OBJECTIVE:To estabilish a HPLC-MS method for determining enalapril in human plasma METHODS:Alprozalam was added into plasma sample as an internal standard,then supernate of the sample was extracted through solid-phase extration column,washed with methanol and detected by HPLC-MS method:column,ODS C18;mobile phase,methanol-0 01% formic acid(45∶55);flow rate,0 8ml/min;capillary voltage,3 81kV;cone voltage,39 0V The selected ion was determined by EST RESULTS:The calibration curve was linear within the range of 2 5～400ng/ml r=0 9 996,the recovery was 102 2%,RSDs of intra -day and inter-day were 4 0% and 5 4%,respectively CONCLUSION:The method is accurate and sensitive with no endogenous interference It can be applied to studying the pharmacokinetics and bioavailability of enalapril tablets in humans

0.05). But the determined values in the above two dose groups of Astragalus Injection were obviously lower than that in cisplatin group. There were remarkable differences.( P

Objective To analyze clinical characteristics of gastroesophageal reflux disease(GERD) in aged patients for improvement of diagnosis and treatemcnt. Methods The reflux disease questionnaire was performed in patients diagnosed as GERD based on Montreal definition and classification as well as Rome Ⅲ criteria.All patients were divided into elderly group (≥65 years) and control group(＜65 years). The incidence of hita[ hernia (HH), the frequencies of esophagitis (based on Los Angeles classification), clinical features, and quality of life were compared between two groups. Results There was no difference between two groups in male/female ratio and morbidity of HH(P＞0.05). In comparison with control group, the frequency of esophagitis graded as LC or LD increased and extra-esophageal symptoms were higher in elderly group (P＜ 0.05), but the lower typical symptoms (heartburn and regurgitation) were seen in the elderly group(P＜0.05). The scores of role physical, bodily pain and role emotional were higher in elderly group than those in control group (P＜0.05). There was no significant differences between two groups in physical function, vitality,social functioning, mental health, and general health. Conclusion The elderly GERD patients often have lower score of typical reflux symptoms (heartburn and regurgitation) and high incidence of severer esophagitis, but their quality of life is not significantly influenced.

Objective To analyze the occurrence of clinical adverse drug reaction (ADR) of tonic Chinese medicinal herbs. Methods Articles about ADR of tonic Chinese medicinal herbs reported from January 1990 to February 2014 were collected from databases of CNKI, VIP, CBM, Pubmed and Embase according to incorporation and exclusion standard. Metrology analysis was also conducted. Results Totally 378 effective articles showed tonic Chinese medicinal herbs most likely to induce ADR were as follows:individual Chinese medicinal herbs including Polygoni Multiflori Radix, Ginseng Radix et Rhizoma, Lycii Fructus and Astragali Radix;injection containing Shenmai Injection, Shengmai Injection and Acanthopanax Injection;other herbal preparation covering Polygoni Multiflori tablets. The most common ADR involved the damage on skin tissue, nervous system and digestive system, with prominent relevant clinical symptoms such as itching, skin rash, dizziness, unconsciousness, nausea, vomiting, and liver dysfunction. Conclusion Correct understanding adverse reaction of tonic Chinese medicinal herbs will be conducive to rational drug use and avoiding risk.

Objective To analyze ultrasonic manifestations of intrahepatic and perihepatic abnormalities after liver transplantation.Methods Ultrasonograms of intrahepatic and perihepatic abnormalities in 114 patients after liver transplantation were retrospectively analyzed.Results Among 114 patients,perihepatic effusion was observed in 96,perihepatic hematoceles or hematoma formation in 19,intrahepatic hematoma in 1,ischemic necrosis of hepatic segments in 2,bile leakage in 7,biloma in 3,focal fatty infiltration of transplanted liver in 3 and intrahepatic solid masses in 6 patients.Conclusion Ultrasonography has great application value in diagnosis of intrahepatic and perihepatic abnormalities after liver transplantation.

OBJECTIVETo explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats.

METHODSTwenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared.

RESULTSCompared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in the model group (P < 0.05), while that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of Ach in the model group was obviously; lower than that in the control group (P < 0.05), and that in the 7-d treatment group was higher than that in the model group (P < 0.05).

CONCLUSIONElectrical stimulation at auricular vagus nerve combined with sound masking) could regulate the threshold of ABR, especially in the 15-d treatment group. This may be ascribed to modulating the levels of neurotransmitter of γ-GABA, 5-HT and Ach in inferior colliculus.

Acupuncture Points ; Animals ; Brain Stem ; physiopathology ; Electric Stimulation ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Inferior Colliculi ; physiopathology ; Male ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Tinnitus ; physiopathology ; therapy ; Vagus Nerve ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo analyze the etiology, clinical features and prognosis of liver injuries caused by different drugs.

METHODSThe types of suspected drugs related to liver injury, clinical manifestations, liver biochemical parameters, clinical outcomes and other associated data were retrospectively assessed for 140 patients with drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method (RUCAM) was used to assess the causality between drugs and liver injury.

RESULTSThe most prevalent agents inducing DILI were Chinese traditional drugs (62.1%), followed by antipyretic analgesic drugs (10%) and antibiotics (5%). The ratio of male to female patients in the study cohort was 1:1.69, with 71 of the total patients (50.7%) being between the ages of 40 and 60 years-old. The RUCAM scale was not less than 3 points for any of the patients.In general, the clinical manifestations and biochemical results were not specific. The percentages of hepatocellular injury type, cholestatic injury type and mixed injury type were 51.4%, 30.7% and 17.9% respectively. The median age of patients with cholestatic liver injury was 55.6 years, which was older than that of patients with hepatocellular injury (47.1 years) or mixed injury (49.9 years).

CONCLUSIONAlthough antipyretic analgesics and antibiotics are considered as common drugs that can induce DILI, Chinese traditional drugs have emerged as another important group of liver injurious agents. Cholestatic DILI was found to occur more often in elderly patients than in younger patients.

Adult ; Anti-Bacterial Agents ; Chemical and Drug Induced Liver Injury ; Cholestasis ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Prevalence ; Prognosis ; Retrospective Studies

Background and purpose:Silent information regulator proteins(sirtuins,SIRT)are a class Ⅲ histone deacetylases with nicotinamide adenine dinucleotide(NAD+)as coenzyme.YME1 like 1 ATPase(YME1L1)is essential for the maintenance of mitochondrial morphology,function and plasticity.Optic atrophy 1(OPA1)mainly mediates mitochondrial fusion.The aim of this study was to explore the expression of SIRT3 in the endocrine resistance of breast cancer,the relationship between SIRT3 and YME1L1 and OPA1,and the mechanism of SIRT3 in the endocrine resistance of breast cancer.Methods:4-hydroxytamoxifen was used to induce tamoxifen-resistant MCF-7/TAM cells.cell counting kit-8(CCK-8)was used to detect cell proliferation and verify drug resistance.The mitochondrial morphology was observed by transmission electron microscopy(TEM)and immunofluorescence staining.The expressions of SIRT3 and OPA1 were detected by real-time fluorescent quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.JC-1 staining was used to detect mitochondrial membrane potential,and dihydroethidium(DHE)staining was used to detect reactive oxygen species(ROS)to verify mitochondrial function.SIRT3 was knocked down in drug-resistant cells by RNA interference,and SIRT3 and YME1L1 wild type(WT),simulated acetylation state mutant(MUT K237Q),and simulated deacetylation state mutant(MUT K237R)were overexpressed in parental cells by overexpression plasmid.Immunoprecipitation assay(IP)and immunofluorescence(IF)were used to verify the interaction between SIRT3 and YME1L1.Results:RTFQ-PCR and Western blot results showed that SIRT3 gene expression and protein level was significantly higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in parental cells decreased the sensitivity of breast cancer cells to tamoxifen.Knockdown of SIRT3 in drug-resistant cells enhanced the sensitivity of drug-resistant cells to tamoxifen.DHE staining showed that the ROS level was lower in tamoxifen resistant cells than in parental cells at the same concentration.Transmission electron microscopy and fluorescence staining showed that the mitochondria of the drug-resistant cells were elongated compared with the parental cells.Western blot results showed that the expression level of L-OPA1 protein was higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in the parental cells resulted in enhanced mitochondrial function and longer mitochondrial morphology compared with the control cells.Western blot showed that the expression of L-OPA1 was upregulated.When SIRT3 was knocked down in drug-resistant cells,the opposite result was obtained.We further verified how SIRT3 regulated OPA1 protein,affected the morphology and function of mitochondria,and promoted drug resistance of breast cancer.Overexpression of YME1L1(wild-type and mutant plasmids)in parental cells showed that overexpression of YME1L1 in the simulated deacetylation state resulted in similar results as overexpression of SIRT3,and overexpression of YME1L1 in the acetylated state resulted in similar results as knockdown of SIRT3.IP assay confirmed the interaction between SIRT3 and YME1L1 in breast cancer cells.The acetylation level of YME1L1 was different at different SIRT3 expression levels.IF assay showed that YME1L1 was co-localized with SIRT3 in MCF-7 cells.Conclusion:SIRT3 is highly expressed in tamoxifen-resistant breast cancer cells.SIRT3 upregulates L-OPA1 expression by deacetylating YME1L1,thereby promoting mitochondrial fusion and enhancing mitochondrial function,and promotes tamoxifen resistance in breast cancer.

Objective:To provide scientific basis for prevention and control measures of island regions through analyzing the characteristics of malignant tumor incidence and mortality in eastern island areas of China and comparing the data with the national cancer mortality data in the same period. Methods:Using the incidence and mortality data of malignant tumor in Daishan county,Zhoushan collected by the Daishan Center for Disease Control and Prevention(CDC)from 2014 to 2019,which was stratified by gender,the crude incidence rates(CIR)and crude mortality rates(CMR)were calculated,and the top 10 malignant tumors with the highest incidence or mortality rates were then ranked.The Segi's world standard population was used to calculate the age-standardized incidence(ASIR)and age-standardized mortality rate(ASMR).The local data were compared with the national cancer mortality data from 2014 to 2019,and Chi-square test was used to analyze the differences between these two sets of data using the SPSS software.The difference was considered statistically significant when P<0.05. Results:There was a total of 7 305 incidence cases of malignant tumors in Daishan county,Zhoushan from 2014 to 2019.The CIR was 662.39/105 and the ASIR was 306.81/105.Notably,the CIR was the highest in the age group of 75-79 years old.The top 5 malignant tumors with the highest incidence rates were lung cancer(27.15％),gastric cancer(12.76％),liver cancer(10.95％),colorectal cancer(6.92％)and breast cancer(5.42％),whose ASIR were 75.09/105,32.06/105,31.01/105,17.81/105 and 18.36/105,respectively.There was a total of 3 412 mortality cases of malignant tumors in Daishan county,Zhoushan from 2014 to 2019.The CMR was 309.39/105 and the ASMR was 122.73/105.Notably,the CMR was the highest in the age group of 80-85 years old.The top 5 malignant tumors with the highest mortality rates were lung cancer(24.94％),liver cancer(18.64％),gastric cancer(17.00％),colorectal cancer(7.56％)and esophageal cancer(5.72％),whose ASMR were 29.65/105,24.97/105,19.01/105,8.75/105 and 6.60/105,respectively.The total ASMR of malignant tumors in Daishan county,Zhoushan was higher than national total ASMR from 2014 to 2019(100.34/105)(P<0.001).Specifically,the ASMR of gastric cancer,lung cancer and colorectal cancer in Daishan county were significantly higher than national levels(gastric cancer:12.46/105;liver cancer:16.45/105;colorectal cancer:6.63/105)(P<0.01),whereas no significant difference in the ASMR of lung cancer and esophageal cancer between Daishan county and the whole nation(lung cancer:28.06/105;esophageal cancer:7.61/105)was observed. Conclusion:Lung cancer,gastric cancer,liver cancer and colorectal cancer were malignant tumors with higher incidence and mortality rates in Daishan county,Zhoushan from 2014 to 2019.Particularly,the ASMR of gastric cancer,liver cancer and colorectal cancer were significantly higher than the national levels,and these malignant tumors should be considered as the major focus of cancer prevention and control.

RNA methylation is one of the hot topics in the study of epigenetics recently and N6-methyladenosine (m6A) modification is the main type of methylation in mammals RNA. The latest studies have found that RNA m6A methylation plays a significant role in the replication of hepatitis B and C viruses and development of related liver cancer. This paper aims to review the research progress on the roles and mechanisms of RNA m6A in the replication of hepatitis viruses and development of hepatocellular carcinoma (HCC), which might provide the theoretical basis and new research insights for the related diseases.