Energy metabolism disorders and potential therapeutic drugs in heart failure

Heart failure (HF) is a global public health problem with high morbidity and mortality. A large number of studies have shown that HF is caused by severe energy metabolism disorders, which result in an insufficient heart energy supply. This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure, which determine the development of HF and recovery of heart. Current HF therapy acts by reducing heart rate and cardiac preload and afterload, treating the HF symptomatically or delaying development of the disease. Drugs aimed at cardiac energy metabolism have not yet been developed. In this review, we outline the main characteristics of cardiac energy metabolism in healthy hearts, changes in metabolism during HF, and related pathways and targets of energy metabolism. Finally, we discuss drugs that improve cardiac function

Preparation and Study on in vitro Transdermal Characteristics of Tetramethylpyrazine Pellicle / 中国药房

OBJECTIVE：To preliminarily optimize the preparation technology of Ligustrazine pellicle ，and to study its in vitro percutaneous permeation characteristics. METHODS ：With the amounts of PVA- 124，ethyl alcohol ，glycerin，tween-80 and azone as factors ，single factor experiment was used to optimize the Ligustrazine pellicle matrix formulation ；modified scoring standard was used to evaluate the film formation time ，film formation ability ，ductility，uniformity and the presence of bubble. On the basis of the optimal matrix formulation ，the pellicle with different loading amount of ligustrazine （300，250，200，150，100，50 mg/mL） was prepared and its maximum loading amount was investigated. HPLC method was adopted to determine the content of ligustrazine，and methodology investigation was conducted. Isolated back skin of rats were collected ，the percutaneous permeation test was conducted for high ，medium and low loading amount （100，75，50 mg/mL）of Ligustrazine pellicle. At 15，30，45，60， 75，90，120，150，180 min，the sample was taken and the permeation rate of ligustrazine was calculated. RESULTS ：When the amounts of PVA- 124，ethyl alcohol，glycerin，tween-80 and azone were 2.5 g，7.0 mL，1.97 mL，0.07 mL，0.28 mL（in terms of 50 mL formulation amount ），the optimal matrix formulation of Ligustrazine pellicle was obtained. The maximum drug loading amount of ligustrazine was 100 mg/mL. The linear ranges of ligustrazine was 3.125-100 μg/mL. The specificity，precision， reproducibility，recovery and stability investigation of content determination method of ligustrazine were all in line with the requirements（RSD＜2％）. The permeation rate of high ，medium and low loading amount of Ligustrazine pellicle were 608.42， 384.19，158.20 μg（/ cm2·h）. CONCLUSIONS ：According to the optimized formulation ，the prepared Ligustrazine pellicle had a short film forming time ，stable and re liable quality ； the drug-loading amount was up to 100 mg/mL. The pellicle with drug-loading amount of 75 mg/mL had reached the penetration rate range of effective plasma concentration of ligustrazine treatment.

Characteristics of blood uric acid level and its correlation with metabolic indexes in obese adolescentsu / 公共卫生与预防医学

Objective To explore the characteristics of blood uric acid levels and its correlation with calcium and phosphorus levels, and glucose and lipid metabolism in obese adolescents in weight-loss training camps. Methods In this study, 357 obese adolescents aged 12-18 were selected as the research subjects, and 135 normal-weight adolescents were selected as the controls. The body shape and blood uric acid characteristics of the subjects were measured and analyzed. Further, 59 subjects were selected from the obese adolescents for blood calcium, blood phosphorus and glucose and lipid metabolism index tests to analyze the correlation between blood uric acid level and calcium, phosphorus, and glucose and lipid metabolism indicators. Results The average blood uric acid level of obese adolescents was (527.12±122.94)μmol/L, (566.58±122.51)μmol/L for boys, and (468.35±97.79)μmol/L for girls. The blood uric acid level of the obesity group was significantly higher than that of the control group (P<0.001 for boys, P<0.05 for girls), and it was higher in boys than in girls (P<0.01). Obese adolescents with high uric acid accounted for 73.39%. The HOMA-IR of obese adolescents was 5.79±3.04. The blood uric acid level was significantly correlated with blood calcium, total cholesterol, and low-density lipoprotein cholesterol (P<0.05). Gender and low-density lipoprotein cholesterol were the main influencing factors of blood uric acid (P<0.05). Conclusion Obese adolescents have high blood uric acid levels, low calcium and high phosphorus in the body, and a higher incidence of insulin resistance. There exists a positive correlation between the blood uric acid level and the body's calcium and phosphorus metabolism and glucose and lipid metabolism in obese adolescents. Clinical monitoring of lipid metabolism indicators such as low-density lipoprotein has certain reference value for the prevention and treatment of hyperuricemia.

Catalyst system in patient positioning during breast cancer radiotherapy: clinical application and influencing factors / 中华放射肿瘤学杂志

Objective To evaluate the clinical application of Catalyst system in patient positioning during breast cancer radiotherapy,and to analyze its correlation with age and body mass index (BMI).Methods Twenty-four patients with breast cancer who were admitted to our hospital from May to August,2016 were enrolled as subjects.For all patients,auxiliary positioning was made by the optical surface imaging system (CRad Catalyst) before each treatment.The kV-kV imaging was executed weekly to verify positioning.Age,BMI,and setup errors of the two systems in the anterior-posterior (AP),superior-inferior (SI),and left-fight (LR) directions were recorded and analyzed by independent samples t-test and Pearson correlation analysis.Results The C-Rad Catalyst system had a significantly larger setup error in the AP direction than the kV-kV imaging (0.22±0.17 vs.0.18±0.13 cm,P＜0.05).There were no significant differences in setup errors in the SI or LR direction between the two systems (0.23±0.18 vs.0.19±0.15 cm,P＞0.05;0.28±0.28 vs.0.20±0.15 cm,P＞ 0.05).Age and BMI of patients had significant impacts on the C-Rad Catalyst system but the kV-kV imaging (P＞0.05):there were significant differences in setup errors in the AP and SI directions between patients ≤44 years of age and those 45-59 years of age (all P＜0.05);there were significant differences in setup errors in the AP and LR directions between patients ≤44 years of age and those ≥60 years of age (all P＜0.05);there was a significant difference in setup error in the LR direction between patients 45-59 years of age and those ≥ 60 years of age (P＜0.05);there was a significant difference in setup error in the SI direction between patients with BMIs of＜ 25 and ≥ 25 kg/m2 (P＜ 0.05).For patients ≥ 60 years of age,setup error of the C-Rad Catalyst system in the SI direction was correlated with age (r=-0.496,P＜0.05).For patients with BMI of＜25 kg/m2,setup error of the C-Rad Catalyst system in the AP direction was correlated with BMI (r=-0.445,P＜ 0.05).For patients with a BMI of ≥ 25 kg/m2,setup error of the C-Rad Catalyst system in the SI direction was correlated with BMI (r=-0.252,P＜0.05).Conclusions There is significant difference in setup error in the AP direction between the C-Rad Catalyst system and the kV-kV imaging.Age and BMI have impacts on patient positioning by the C-Rad Catalyst system.

A novel quantified bitterness evaluation model for traditional Chinese herbs based on an animal ethology principle

Traditional Chinese herbs (TCH) are currently gaining attention in disease prevention and health care plans. However, their general bitter taste hinders their use. Despite the development of a variety of taste evaluation methods, it is still a major challenge to establish a quantitative detection technique that is objective, authentic and sensitive. Based on the two-bottle preference test (TBP), we proposed a novel quantitative strategy using a standardized animal test and a unified quantitative benchmark. To reduce the difference of results, the methodology of TBP was optimized. The relationship between the concentration of quinine and animal preference index (PI) was obtained. Then the PI of TCH was measured through TBP, and bitterness results were converted into a unified numerical system using the relationship of concentration and PI. To verify the authenticity and sensitivity of quantified results, human sensory testing and electronic tongue testing were applied. The quantified results showed a good discrimination ability. For example, the bitterness of Coptidis Rhizoma was equal to 0.0579 mg/mL quinine, and Nelumbinis Folium was equal to 0.0001 mg/mL. The validation results proved that the new assessment method for TCH was objective and reliable. In conclusion, this study provides an option for the quantification of bitterness and the evaluation of taste masking effects.

Immune system dysfunction in Niemann-Pick type C1 mice / 中华微生物学和免疫学杂志

Objective To analyze the differences in immune system between Npc1 gene mutant (Npc1-/ -) and wild-type (Npc1+/ +) mice for better understanding the pathogenesis of Niemann-Pick disease type C1 (NPC1) from an immunological perspective and providing reference for NPC1 treatment in clinic.Methods Body, thymus and spleen weight of Npc1-/ -and Npc1+/ + mice aged (14±2) days, (42±2) days and (63±2) days (Day14±2 , Day42±2 and Day63±2 ) were recorded and the associated organ index were calcu-lated. White blood cell count in peripheral blood of mice aged Day42±2 was examined by routine blood test. Expression of cytokines at mRNA level in mouse peripheral blood was detected by qPCR. Percentages of CD4+, CD8+ and CD19+ lymphocytes in peripheral blood and spleen of mice aged Day42±2 were measured by flow cytometry. Apoptosis and senescence of spleen in mice aged Day63±2 were examined by immunofluores-cence and β-galactosidase staining. Results Compared with Npc1+/ + mice, there was no significant differ-ence in the weight of spleen and thymus in Npc1-/ - mice aged Day14±2; the weight of spleen in Npc1-/ - mice aged Day42±2 significantly increased, but the weight of thymus showed a significant decrease; furthermore, both the weight of spleen and thymus in Npc1-/ - mice aged Day63±2 significantly decreased; and the body weight of Npc1-/ - mice of each age group significantly decreased. Moreover, compared with Npc1+/ + mice, the absolute number of lymphocytes in the peripheral blood of Npc1-/ - mice aged Day42±2 showed no signifi-cant difference, but the percentage in whole white blood cells significantly decreased due to the significantly increased neutrophils. Expression of cytokines ( IL-1, IL-2, IFN-γ, TNF-α, IL-4, granzyme A and granzyme B) at mRNA level in the peripheral blood leukocytes of Npc1-/ - mice aged Day42±2 was abnormal as compared with that in Npc1+/ + mice. The number of T (CD4+ and CD8+) lymphocytes in Npc1-/ - mice aged Day42±2 significantly decreased, while the number of B (CD19+) lymphocytes increased significantly as com-pared with those in the Npc1+/ + mice. Compared with Npc1+/ + mice, apoptosis and senescence of the spleen in Npc1-/ - mice aged Day63±2 aggravated significantly. Conclusion The abnormal lipid metabolism triggered by Npc1 gene mutation causes severe immune dysfunction in Npc1-/ - mice. Therefore, immune dysfunction should be taken into full consideration when treating patients with NPC1, which might help improve the life quality and prolong the survival time.

Pathologic changes of spontaneous tumors in Sprague-Dawley and Wistar rats / 中华病理学杂志

Objective@#To investigate the spontaneous neoplastic lesions and their incidences in Sprague-Dawley (SD) and Wistar rats, and to accumulate background data for carcinogenicity studies.@*Methods@#One hundred and eighty SD rats and 240 Wistar rats (4-week old) , half in each sex, were used in this study. The rats were housed routinely under specific pathogen-free environment and euthanized after 104 weeks. Histopathological examination was undertaken for all animals including deaths and scheduled euthanasia. The types and incidences of spontaneous tumors were gathered statistically.@*Results@#Total 411 rats (176 SD rats and 235 Wistar rats) were examined in this study. The total tumor incidence of the 411 rats was 57.7%(237/411). The total tumor incidence in SD rats was 55.7%(98/176), benign tumor incidence was 48.9%(86/176) and malignant tumor incidence was 15.9%(28/176). The total tumor incidence in Wistar rats was 59.1%(139/235), benign tumor incidence was 51.5%(121/235) and malignant tumor incidence was 14.5%(34/235). The main benign tumors were pituitary adenoma (23.3% in SD rats, 12.3% in Wistar rats), breast fibroadenoma (21.3% in SD rats, 12.9% in Wistar rats) and breast adenoma (16.9% in SD rats, 9.5% in Wistar rats) in females; testis Leydig cell tumor (0 in SD rats, 14.3% in Wistar rats) in males. The main malignant tumors were breast carcinoma (10.1% in SD rats, 3.4% in Wistar rats) and uterine leiomyosarcoma (0 in SD rats, 2.6% in Wistar rats) in females; squamous cell carcinoma of skin (2.3% in SD rats, 0.9% in Wistar rats); subcutaneous fibrosarcoma (1.1% in SD rats, 2.1% in Wistar rats); brain malignant glioma (1.1% in SD rats, 1.7% in Wistar rats).@*Conclusions@#In the study, a high incidence of spontaneous tumors is reported in both SD and Wistar rats housed for 2 years. The incidence of benign tumors is higher than that of malignant rumors. The benign tumors mainly are pituitary adenoma, breast fibroadenoma and breast adenoma in females, and testis Leydig cell tumor in males. The malignant tumors mainly are breast carcinoma and some soft tissue sarcomas. The results of the study enrich the data of spontaneous tumor in SD and Wisar rats and provide background data for carcinogenicity studies for new drugs.

Effects of degreasing-frosting on reducing toxicity and enhancing efficacy of Periplaneta americana / 中成药

AIM To study the effects of degreasing-frosting on reducing toxicity and enhancing efficacy of Periplaneta americana L..METHODS The 95％ ethanol extracts from P.americana raw powder and processed products were extracted by petroleum ether,ethyl acetate,n-butanol and water.TLC was applied to comparing the component changes in various fractions.GC-MS was used for analyzing the kinds and contents of liposoluble constituents before and after processing.Shaking flask method combined with UV spectrophotometry method was adopted in the determination of Papp values in octanol-water and different pH values (2.23,3.28,4.22,5.23,6.12,7.24,8.23,9.10,10.15 and pure water) of buffer solutions.RESULTS After the petroleum ether fraction was processed,the colors of TLC spots became much shallower,which changed more significantly with the prolonging of processing time and increase of pressure.The TLC spots in the n-butanol and water fractions were clear without obvious changes.And no TLC spots were found in the ethyl acetate fraction.The kinds of liposoluble constituents were the same before and after processing,whose absolute contents were decreased after processing.Compared with raw powder,the Papp values of minor polypeptides in various processed products at different pH values exhibited significant differences (P ＜0.05,P ＜0.01),which also showed certain differences at the same pH values.CONCLUSION Degreasing-frosting can affect the contents of liposoluble constituents in P.americana and Papp values of minor polypeptides,which may be the mechanism of reducing toxicity and enhancing efficacy.

The study of angular dependence of gamma index for Delta4 phantom / 中华放射肿瘤学杂志

Objective To study the effect of the uncertain deflection of the Delta4 phantom (ScandiDos AB,Sweden) in setting up on the Gamma index passing rate during the VMAT plan verification.Methods Two patients with head and neck cancer,two with lung cancers and one with pelvic cancer receiving VMAT radiotherapy were randomly chosen.By means of Eclipse8.6 TPS the treatment plans elaborated for the five patients were picked up to make the verification plans and Delta4 was used to perform dose verification On VARIAN Clinac Ⅸ.The Delta4 phantom was precisely set up first,and then it was deflected in a given angle towards the horizontal direction in relation to the center of the linear accelerator isocenter to perform the dose verification for 11 times successively.To figure out the relationship between the deflection angle of the Delta4 phantom and the Gamma index passing rate.Results As the Delta4 phantom was deflected by 0.0°,0.2°,0.4°,0.6°,0.8°,1.0°,1.2°,1.4°,1.6°,1.8° and 2.0° in sequence,the measured Gamma index passing rates presented a slight decline,but all greater than 90％ (DD 3％,DTA 3 mm).Conclusions In the VMAT plan verification,the Gamma index passing rate of Delta4 has no dependence on the uncertain deflection of the Delta4 phantom provided that the uncertain deflection of the Delta4 phantom is no greater than 2°,but the passing rates of DD and DTA vary significantly with the uncertain deflection of the Delta4 phantom.

A meta-analysis on randomized clinical trials comparing single-incision with conventional laparoscopic cholecystectomy / 中华肝胆外科杂志

Objectives To evaluate the efficacy and safety of single-incision versus conventional laparoscopic cholecystectomy.Methods We searched electronic databases (PubMed,EMBASE,Cochrane Library,Chinese Biomedicine databases) from January 2000 to April 2012.Personal contact with experts in the field of laparoscopic cholecystectomy was performed to identify further potentially relevant clinical trials.Randomized controlled trials conducted on single-incision versus conventional laparoscopic cholecystectomy were analysed to compare conversion rates,blood loss,operation time,postoperative complications,wound satisfaction score,postoperative pain score and postoperative duration of hospitalization.Data were extracted by two reviewers independently.Statistical analysis was performed by using the RevMan 5.1 software.Results Twelve studies involving 915 patients met the inclusion criteria.When compared with conventional laparoscopic cholecystectomy (LC),the singleincision laparoscopic cholecystectomy (SILC) group showed no significant difference in conversion rate (OR=0.70,95％CI: 0.13～3.77,P=0.68),postoperative complications (OR=1.13,95％CI:0.72～1.78,P＝0.59) and postoperative pain scores (WMD＝-0.18,95％CI:-0.78～-0.43,P=0.57) . There was a significant increase in operative blood loss (WMD ＝ 1.43,95 ％ CI: 0.09 ～2.78,P＜0.05),increase in operative time (WMD=16.79,95％CI: 9.05～24.52,P＜0.01),but an increase in wound satisfaction score (WMD=1.28,95％CI..1.09～1.47,P＜0.01).The postoperative duration of hospitalization was significantly shorter (WMD =-0.30,95％ CI:-0.58 ～-0.02,P＜0.05).Conclusions Current evidence suggests that there is no significant difference in conversion rate or postoperative complications between SILC and LC.Although SILC requires a longer operative time and there is more blood loss when compared with LC,the SILC is superior in wound satisfaction score and in duration of hospitalization.

Relationship between expression of G-protein-coupled bile acid receptor 1 in gallbladder mucosa and lithogenic bile of gallstone / 中华肝胆外科杂志

Objective To study the relationship between expression of G-protein-coupled bile acid receptor 1 (GPBAR1) in gallbladder mucosa and formation of lithogenic bile in patients with gallstones.Methods Gallbladder mucosa,gallbladder wall,bile and plasma were collected from 34 patients with gallstone (GS) and 15 individuals who were gallstone free (GSF).The gallbladder wall was stained with hematoxylin-eosin (HE) and immunohistochemistry to detect pathologic changes and expressions of GPBAR1,mucin 1 (MUC1) and mucin 5AC (MUC5AC).Reverse-transcription polymerase chain reaction (RT-PCR) was used to test mRNA expressions of GPBAR1,MUC1 and MUC5AC in the gallbladder mucosa.The contents of total cholesterol (TC),total bile acid (TBA),triglyceride (TG),low density lipoprotein (LDL) and high density lipoprotein (HDL) in plasma and cholesterol,TBA,phospholipid (PL) and mucin in the bile of gallbladder were measured.Results The gallbladder mucosa in all GS patients showed chronic inflammation on hematoxylin-eosin staining.The expressions of GPBAR1 and MUC5AC were more markedly increased in the GS group than in the GSFgroup (61.34±8.06 vs.43.05±7.83,P＜0.01; 52.11±9.62 vs.45.05±9.27,P＜0.05).The mRNA expressions of GPBAR1 and MUC5AC in the GS group were also more markedly increased than in the GSR group (0.87±0.07 vs.0.80±0.09,P＜0.05; 1.04±0.22 vs.0.8±0.17,P＜0.01).Serum cholesterol,as well as biliary cholesterol,cholesterol mol percentage,cholesterol saturation index and mucin in the GS group were more significantly higher than in the GSF group (5.07±1.64 vs.3.62±1.42,P＜0.01; 17.23±3.67 vs.12.47±2.31,P＜0.01; 7.47±0.65 vs.5.05±0.24,P＜0.01; 1.03±0.58 vs.0.69±0.38,P＜0.01; 92.02±20.89 vs.76.36±19.71,P＜0.05).Biliary total bile acids and bile acids mol percentage were lower in the GS group than in the GSF group (162.68±20.19 vs.180.21±26.05,P＜0.05; 71.28±1.84 vs. 73.29±0.96,P＜0.01). In the GS group,there were negative correlations between the mRNA expression of GPBAR1 and biliary TBA (γ=-0.341,P＜0.05).There were negative correlations in the GS group between the GPBAR1 expression and the level of biliary TBA (γ=- 0.403,P＜0.05),and between the GPBAR1 expression and the level of biliary total lipid (γ=-0.365,P＜0.05).Conclusions This study shows an increase in expression of GPBAR1 in gallbladder mucosa in patients with GS.It is suggested that GPBAR1 may accelerate formation of lithogenic bile by inducing re-absorption of bile acid.

Comparison of RapidArc plans and fixed field intensity modulated radiotherapy planning in cervical cancer radiotherapy / 中华放射医学与防护杂志

Objective To explore the advantages and disadvantages between the RapidArc plans and fixed-field IMRT plan (IMRT).Methods Ten cases of cervical cancer,aged 55 (36-70),who were to receive post-operative radiotherapy were selected randomly.Single arc (Arc 1),two arcs (Arc 2),and three arc (Arc 3) RapidArc plans and fixed-field IMRT plan were designed respectively in the Eclipse 8.6 planning system.The designing,treatment time,target area,and dose distribution of organs at risk by these 4 planning techniques were compared.Results The values of average planned treatment time by the Arc 1,Arc 2,and Arc 3 ten cases was 98,155,185,and 46 min,respectively.The values of average treatment time in the Varian IX accelerator were 2.15,3.32,4.48,and 6.95 min,respectively.The average mean doses were (48.99±1.08),(49.40±0.51) ,(49.51±0.62) ,and (48.65±0.92) Gy,respectively.The values of homogeneity index (HI) of target were 1.11±0.07,1.07±0.02,1.06±0.02,and 1.12±0.05,respectively.The values of eonformal index (CI) of target were 0.73±0.13,0.87±0.06,0.87±0.06,and 0.79±0.06,respectively.The doses at rectum,bladder,and small intestine calculated by IMRT plan were the lowest,and the doses at the femoral neck calculated by these 4 plans were similar.Conclusions The RapidArc plan is superior in dose distribution at target,HI,CI,and treatment time to IMRT,but IMRT plan is superior to RapidArc in planned dose calculation time and protection of organs at risk.However,in general,the RapidArc plan is better in clinical application than IMRT plan.

Role of nuclear receptors in the regulation of lipid metabolism / 国际外科学杂志

Nuclear receptors,the superfamily of ligand-activated transcription factors,play crucial role in the regulation of gene expression of the lipid metabolism,and are involved in many metabolic diseases,such as cholesterol gallstone disease.Recently many domestic and foreign researches on the role of nuclear receptors in the lipid metabolism,help to further elucidate the biomolecular pathogenesis of cholesterol gallstone disease and other diseases associated with the lipid metabolism.