Objective:To investigate the effectiveness of heart rate deceleration capacity (DC) measurement in predicting the car-diotoxicity of malignant tumor patients treated with epirubicin-based chemotherapy. Methods:The clinical medical records, including CK-MB and cTnI levels and dynamic electrocardiogram (ECG) parameters before and after each chemotherapy cycle, of 140 patients treated with epirubicin-based chemotherapy were analyzed. Patients were divided into the DC>4.5 ms group and the DC≤4.5 ms group based on the calculated DC values. The CK-MB and cTnI levels and the dynamic ECG parameters of the two groups were compared af-ter two and four cycles of chemotherapy. Results:Patients in the two groups exhibited no statistically significant difference in their rele-vant clinical and pathological data before receiving chemotherapy (P>0.05). However, after four cycles of chemotherapy, the DC≤4.5 ms group showed a significantly greater increase in serum CK-MB and cTnI concentrations over the pre-chemotherapy levels compared with the DC>4.5 ms group. After two and four cycles of chemotherapy, the DC≤4.5 ms group also exhibited a significantly greater in-crease in mean heart rate (beats/min) and supraventricular and ventricular arrhythmia counts (times/24 h) over the pre-chemotherapy values compared with the DC>4.5 ms group (P<0.05). After four cycles of chemotherapy, 23 cases showed abnormally elevated cTnI levels in the DC≤4.5 ms group. In this group, patients with elevated cTnI level exhibited no statistically significant difference in CK-MB and cTnI concentrations, mean heart rates, and supraventricular and ventricular arrhythmia counts compared with those with nor-mal cTnI level before chemotherapy (P>0.05). However, the DC values of patients with elevated cTnI were significantly lower than those with normal cTnI level (P<0.05). Conclusion:The risk of epirubicin-induced cardiotoxicity increased with decrease in DC value. The DC test was shown to be an effective predictor of the risk of epirubicin-induced cardiotoxicity.

Resveratrol possesses a wide range of biological activities, such as anti-cancer, anti-oxidation, induction of apoptosis, etc., but its poor drug properties, rapid metabolism, low target selectivity and bioavailability limit its application value. Studies have shown that modification of the structure of natural compounds can improve their pharmacological activities. To improve the bioavailability of resveratrol, many researchers have undertaken the synthesis and activity evaluation of resveratrol derivatives and analogues. They have modified the phenolic hydroxyl groups, double bonds and benzene ring of resveratrol so as to further understand the interactions among functional groups and its structure-activity relationship. In this paper, we review the chemical structures, synthetic methods and mechanisms of biological activity of resveratrol monomer derivatives as well as their related therapeutic applications, especially in the anticancer area over the last decade. This will provide some reference value for the further research and development of resveratrol-related drugs.

Objective:To investigate the changes of blood pressure and heart rate in patients aged over 80 years undergoing intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs under topical anesthesia without anesthetic monitoring in ophthalmology surgery, and to analyze the potential risk for surgery-induced acute cardiovascular and cerebrovascular events.Methods:This was a prospective observational cohort study.A total of 100 patients(aged 80 to 95 years, 47 males and 53 females)included 85 cases of wet age-related macular degeneration, 14 cases of retinal vein occlusion with macular edema, and 1 case of diabetic macular edema.These patients received anti-VEGF drugs injection, with accumulated injections of 1 to 36 times per patient.Blood pressure and heart rate were measured at visit to a medical clinic(as baseline), before operation, 0 min and 30 min after operation.The operation anxiety and pain scores were investigated by questionnaires.Comparison of systolic blood pressure, diastolic blood pressure and heart rate among four different time points was performed by Wilcoxon symbol rank test.Results:At four different time points i. e.at the baseline, before injection, 0 min and 30 min after injection, systolic blood pressure, diastolic blood pressure and heart rate showed an important regularity.The median systolic blood pressure at the four time points was 130(120-140)mmHg(1 mmHg=0.133 kPa), 142(129-149)mmHg, 153(139-164)mmHg and 143(130-151)mmHg, with ranges of 100-160 mmHg, 106-176 mmHg, 118-197 mmHg and 115-187 mmHg, respectively.The median diastolic blood pressure at the four time points was 70(65-75)mmHg, 76(69-83)mmHg, 81(73-87)mmHg and 75(69~81)mmHg, with ranges of 45-90 mmHg, 55-98 mmHg, 58-99 mmHg and 50-93 mmHg, respectively.The median heart rate at the four time-points was 70(65-80)beats/min, 72.5(65-81)beats/min, 73(66-80)beats/min and 70(65-76)times/min, with ranges of 50-95 beats/min, 48-101 beats/min, 51-93 beats/min and 50-87 beats/min, respectively.Systolic blood pressure and diastolic blood pressure were significantly increased from preoperative time to 0 min and 30 min after operation( P<0.01). Compared to the baseline, heart rate was increased before operation( P<0.01)and was decreased at 30 minutes after operation( P<0.01). Conclusions:Blood pressure fluctuation may exceed the safe range with an obvious increase of systolic blood pressure during the current intravitreal injection of anti-VEGF drugs in the patients aged over 80 years.Systolic blood pressure rises significantly before operation and falls back after operation, but it may last till 30 minutes after operation.The range of heart rate change is relatively small.Perioperative management and monitoring measures should be strengthened to reduce the risk of acute cardiovascular and cerebrovascular events.

AIMTo explore the role of endogenous and exogenous hydrogen sulfide (H2S) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and the underlying mechanisms.

METHODS120 Sprague-Dawley rats were randomly divided into four groups: control, LPS (instilled intratracheally to induce ALI), NaHS (H2S donor) + LPS, and propargylglycin (PPG) + LPS. Animals were sacrificed at 4 h or 8 h after agent administration. Lung weight/body weight ratio (LW/BW) was measured and calculated. Morphological changes of lung tissues were observed. H2S concentration, NO concentration (NO) and carbon monoxide (CO) level in plasma were tested. Malondialdehyde (MDA) content, CSE activity, inducible nitric oxide synthase (iNOS) activity and hemeoxygenase (HO) activity of the lung were determined. PMN and protein content in BALF were also tested. Immunohistochemisty technique was performed to examine the expression of iNOS and HO-1 protein in lung tissues. The correlation of H2S content with the above indices was analyzed.

RESULTSCompared with control conditions, severe injuries of lung tissues and a raised LW/BW, MDA content, PMN and protein content in BALF were observed in rats treated with LPS. LPS also lead to a drop in plasma H2S concentration and lung CSE activity. The enzyme activity of iNOS and HO, the protein expression of them and plasma NO, CO level increased after LPS instillation. Administration of NaHS before LPS could attenuated the changes induced by LPS. Pre-administration of PPG exacerbated the injuries induced by LPS, increased PMN and protein content in BALF, the plasma NO level, lung iNOS activity and its protein expression, but there was no prominent variation in CO level, HO activity and HO-1 protein expression compared with those of LPS group. The H2S content was positively correlated with CSE activity, CO content and HO-1activity (r = 0.945-0.987, P < 0.01), and negatively correlated with the other indices (r = -0.994 - -0.943, P < 0.01).

CONCLUSIONDownregulation of H2S/CSE was involved in the pathogenesis of acute lung injury induced by LPS. Endogenous and exogenous H2S provided protection against the lung injuries, which might be explained by its anti-oxidative effects, attenuating inflammatory over-reaction in lung induced by PMN,the downregulation NO/iNOS system and the upregulation of CO/HO-1 system.

Acute Lung Injury ; chemically induced ; physiopathology ; Animals ; Antioxidants ; metabolism ; pharmacology ; Bronchoalveolar Lavage Fluid ; Carbon Monoxide ; metabolism ; Heme Oxygenase (Decyclizing) ; metabolism ; Hydrogen Sulfide ; metabolism ; pharmacology ; Lipopolysaccharides ; antagonists & inhibitors ; toxicity ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To investigate the effects of antihypertension and reversing left ventricular hypertro- phy by carvedilol or bisoprolol in patients with mild to moderate essential hypertension.Methods 40 cases of mild to moderate essential hypertension patients were selected for this random single-blind,paralleling controlled clinical study.Results Patients were randomized to take 12.5～25mg carvedilol tablet orlce daily or bisoprolol 2.5～5mg once daily if DBP was still in the range of 12.0～14.6kPa(90～110mmHg)after 2 weeks' placebo baseline. Carvedilol group included 20 cases,bisoprolol group included 20 cases,and the course was 24 weeks.Blood pressure and heart rate were measured and symptoms and signs were recorded.At the end of placebo and in 24 weeks heart ultrasound,blood routine,serum glucose,blood lipid,hepatic function and renal function were examined.SBP,DBP and heart rate of patients in two groups decreased obviously.There were significant differences between the two groups.Ventricular hypertrophy of carvedilol group improved than that in pretherapy.There were significant differ- ences between the two groups.Conclusion Carvedilol was well-tolerated with less side effects such as mild headache,tiredness,dizziness,slightly elevating of serum glucose.Carvedilol could well treat the mild moderate essen- tial hypertension effectively and safely by 12.5～25mg once daily.

Objective To investigate the cytotoxicity of vascular endothelial growth factor (VEGF) siRNA combined with fusion suicide gene yCDglyTK on human gastric cancer cell line in vitro.MethodsThe gastric cancer cell line SGC7901 was transfeeted with blank plasmid pcDNA3.1 (-) null [pcDNA3.1 (-) group], or VEGF-siRNA expression plasmid pGenesil-shVEGF (SGC7901/shVEGF group),or fusion suicide gene plasmid pcDNA3.1 (-)CV-yCDglyTK (SGC7901/CDTK group),or combined gene plasmid pcDNA3.1 (-)shVEGF-yCDglyTK (SGC7901//shVEGF-CDTK group) with calcium phosphate nanoparticles (CPNPs).Un-transfected gastric cells were set as control group.The stable transfected cells were selected by G418.The target gene expression was verified by RT-PCR and Western-blot.After given prodrug 5-fluorocytosine (5-FC), the biologic characters variation, apoptotic morphology and apoptotic rate of cells in each group were observed through cell growth curve by MTT assays, by-stander effect, Hoechst 33258 staining and flow cytometry.The data was analyzed with SPSS 13.0 software and multiple groups’ comparison was analyzed with LSD test.ResultsFour gastric cancer cells lines transfected with different plasmids were successfully established.The expression of gene yCDglyTK was detected both in SGC7901/CDTK cells and SGC7901/shVEGF-CDTK cells.By MTT assays, the cell growth curve indicated that the A570 value of SGC7901/shVEGF cells, SGC7901/CDTK cells and SGC7901/shVEGF-CDTK cells decreased significantly compared with that of SGC7901 and SGC7901/null cells after a 24-hour 5-FC treatment (P＜0.01).When the percentage of stable gene trasfected SGC7901 cells was 60％, 80％and 100％, the cell relative viability was 13.09％±2.40％, 9.74％±2.83％ and 5.68％±1.03％,respectively. A large number of cells in SGC7901/CDTK and SGC7901/shVEGF-CDTK group appeared typical apoptotic morphology under fluorescence microscope.The result of flow cytometry showed that the apoptosis rates in SGC7901/shVEG group、 SGC7901/CDTK group and SGC7901/shVEGF-CDTK group were 16.40％ ±4.68％, 57.63％ ± 4.96％ and 69.07％ ± 4.69％,respectively, and there were significant differences compared with control (P＜0.01).Conclusion VEGF siRNA combined with suicide gene can effectively kill gastric cancer cell line SGC7901.Apoptosis induction may be one of the important mechanisms of killing tumor cells.

Objective To investigate the effects of connective tissue growth factor (CTGF) siRNA delivered by pRetro-Super (PRS) retrovirus vector on extracellular matrix and VEGF expression in human peritoneal mesothelial cells (HPMC). Methods Four pairs of oligonucleotides including 64 bp DNA were designed and synthesized in vitro according to siRNA target sequence and PRS retrovirus desire.PRS-CTGF-siRNA1-4 recombinant retrovirus vectors were constructed.The recombinant retrovirus vectors containing CTGF-siRNA were transferred into PT67 packaging cell lines with lipefectamine 2000,then infected HPMC.mRNA expression was determined by semi-quantitative RT-PCR and protein expression was determined by Western blot.Results Both mRNA and protein expressions of CTGF,FN,Col I,laminin (LN) and VEGF were significantly increased in HPMC with 5 μg/L TGF-β1 stimulation (P＜0.01,respectively).CTGF,FN,Col I,LN mRNA and protein and VEGF mRNA expression stimulated by TGF-β1 were significantly decreased in HPMC infected with PRS-CTGF-siRNA1～4 retrovirus vectors (P＜0.01,respectively).The inhibitory rates on CTGF were 69.3%,22.2%,27.4% and 38.8%,respectively (P＜0.01).At the same time,there was also a significant reduction of VEGF protein expression in HPMC infected with PRS-CTGF-siRNA1 vector (P＜0.01).There was no significant difference in HPMC infected with PRS void vector. Conclusion CTGF siRNA delivered by PRS retrovirus vector can effectively inhibit the enhancement of extracellular matrix and VEGF expression stimulated by TGF-β1 in HPMC.

Objective To investigate the role of mitochondrial respiratory chain in the hyperpermeability of human peritoneal mesothelial cells (HPMCs) induced by high glucose peritoneal glucose PDS was also added. Transmesothelial electrical resistance (TER) measurement was examined for detection of permeability damage in HPMCs. Immunostaining and Western blotting analysis were used to detect claudin-1 expression. Mitochondrial superoxide (MitoSOX) Red staining and respiratory chain complexes activities were determined for detection of mitochondrial reactive oxygen species (ROS) production and mitochondrial complexes activities. Results TER was decreased in a time- and concentration-dependent manner after culture with high glucose PDS for was also down-regulated significantly by high glucose PDS (P＜0.01). Complex Ⅲ activity was inhibited (10.8% of control, P＜0.01) accompanied with increased mitochondrial ROS generation.These changes were partially prevented by glutathione. Conclusion Mitochondrial respiratory complex Ⅲ pathway has crucial importance in maintaining TER of HPMCs, which may reveal a valuable target for novel therapies to fight hyperpermeability of peritoneum during the prolonged PD treatment.

Objective To establish the different degrees of rat diffuse axonal injury (DAI) model by using a self‐made DAI device .Methods A total of 70 healthy adult clean SD rats were selected and randomly divided into the normal control group (n=10) and DAI group (n=60) ,then the DAI group was randomly subdivided into the group A ,B ,and C ,20 cases in each group .The rat head injury model was prepared by using the self‐made experimental device ,which made the rat head to simultaneously produce instant oversized linear and angular accelerations ,different degrees of rat DAI model ,including mild DAI(group A) ,moderate DAI (group B) and severe DAI(group C) ,were induced by different rotation back and forth ,accelerated movement times under the con‐stant air pressure .The pathological and behavior effect evaluation was performed .Results With the injury degree aggravating ,the time interval of nerve physiological reflex recovery and awakening time in the acute DAI groups were increased (P<0 .05) .The nerve function score after 7 d in the DAI groups was decreased (P<0 .05);the death rates within 14 d after injury in the group A , B and C were 5 .0% ,25 .0% and 50 .0% respectively .With the injury degree aggravating ,the DAI pathological characteristics were more significant .Conclusion This device could effectively establish different injury degrees of DAI animal model .

OBJECTIVETo observe the cytotoxicity of indirubin derivative PHII-7 against human breast cancer MCF-7 cells and to study its primary mechanisms.

METHODSThe proliferation of MCF-7 cells was detected using MTT colorimetry. Annexin V/PI double staining was applied to detect the apoptosis rate of MCF-7 cells. The distribution of cell cycles was detected using PI staining and flow cytometry (FCM). The levels of reactive oxygen species (ROS) in MCF-7 cells were detected by DCFH-DA staining. The mRNA and protein levels of c-fos were detected using RT-PCR and Westem blot analysis.

RESULTSPHII-7 at different concentrations inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, with the inhibitory rate ranging from 43.13% to 90.90% (P < 0.05). The inhibition was strengthened along with increased concentrations. PHII-7 at different concentrations could induce the apoptosis of MCF-7 cells. The early apoptosis rate was 1.43% +/- 0.02%, 9.14% +/- 0.36%, and 45.79% +/- 8.46%, respectively with the action of 1.25, 2.50, and 5.00 micromol/L PHII-7, respectively, showing dose-dependent manner. FCM analysis found that the proportion of MCF-7 cells in the G0/G1 phase and the S phase decreased after treatment with PHII-7, and the ratio of MCF-7 cells in the G2/M phase obviously increased (P < 0.01). The intra-cellular ROS level was significantly elevated 2 h after pretreatment with PHII-7. The levels of the protooncogene c-fos mRNA and protein were down-regulated in a dose-dependent manner after action of PHII-7.

CONCLUSIONSPHII-7 exerted obvious in vitro cytotoxic effects on MCF-7 cells. Its mechanisms might be associated with arresting the cell cycle, regulating the redox equilibrium, and down-regulating the expression of the protooncogene.

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Female ; Humans ; Indoles ; pharmacology ; MCF-7 Cells