Objective To observe the inhibition of asON phosphorothioate to the TIMP-1 gene and protein expression in the liver tissue of immune- induced hepatic fibrosis rats. Methods According to the analysis of modulator, structure protein, encoding sequence of TIMP-1 genome, we designed four different groups of asONs. These asONs were injected into the hepatic fibrosis rat models through coccygeal vein. The results were observed by RT-PCR, immunohistochemistry and in situ hybridization with collagen Ⅰ、Ⅲ, special staining of collagen fiber, electron microscope. Results The asON phosphorothioate of TIMP-1 could be expressed in vivo, and could block the TIMP-1 gene and protein expression in the liver of immune- induced hepatic fibrosis rats on the level of mRNA, which could promote the degradation of collagen Ⅰ、Ⅲ(P

Objective To study the expression and distribution of TIMP 1 and TIMP 2 in liver tissue of cirrhosis patient and to investigate the roles and pathogenesis of TIMP 1 and TIMP 2 in liver cirrhosis. Methods TIMP 1 and TIMP 2 proteins and mRNA were detected with immunohistochemistry and in situ hybridization methods using monoclonal antibodies and cDNA probes. Results mRNA and proteins of TIMP 1 and TIMP 2 were detected in all the liver tissues from 40 liver cirrhosis patients, all in cytoplasm but not nucleus. TIMP 1 and TIMP 2 were found co exist in all samples, while TIMP 1 concentration was higher. Conclusions mRNA and protein of TIMP 1 and TIMP 2 are found in all the cirrhosis patient samples. Liver TIMP 1 and TIMP 2 concentrations increase with the progression of liver cirrhosis, decrease the degradation of extracellular matrix proteins, resulting in the initiation and the development of liver fibrosis and liver cirrhosis.

An experimental immunity hepatic fibrosis rat model was prepared by means of immunologic assault with human serum albumin, and normal rats served as a control group. The immunohistochemistry methods and in situ hybridization were respectively used to detect TIMP 2 mRNA and related antigens in the liver,and to investigate the localization and expression of TIMP 2 in the liver of both normal and experimental hepatic fibrosis rats. The results showed that TIMP 2 mRNA and related antigens in the livers of experimental group were expressed in myofibroblasts and fibroblasts, especially in the portal area and fibrous septum. The positive signal was located in the cytoplasm, but not in the nucleus. On the other hand, there was a high level of expression of TIMP 2 in the liver of the experimental group.It is suggested that in the process of hepatic fibrosis, fibroblasts and myofibroblasts are the major cells expressing TIMP 2. The severer the hepatic fibrosis in the injured liver is, the higher the levels of TIMP 2 related antigens and gene expression are.

Objective To investigate the risk factors of hypertension patients combined with coronary artery disease(CAD)and analyze the correlation. Methods A total of 258 hospitalized hypertension patients from August 2015 to December 2016 were divided into hypertension group(n = 124)and hypertension combined with CAD group(n = 134),according to the results of coronary angiography. The general data,platelet parame-ters,blood lipid level and renal function indexes of all objects were recorded. The differences of all indexes between 2 groups were compared,and the correlation between these indexes and CAD in hypertensive patients was analyzed. Results(1)More smokers and older patients were found in hypertension combined with CAD group;the values of mean platelet volume(MPV),platelet distribution width,creatinine,serum uric acid were higher, but HDL-C level was lower and all the differences were statistically significant(P < 0.05).(2)Multivariable logistic regression analysis demonstrated that age,smoking history,MPV,serum uric acid and low level of HDL-C were independent hazardous factors of CAD in hypertensive patients[OR = 1.062,95% CI:1.032 ~ 1.093;OR =2.048,95% CI:1.078~3.893;OR=2.737,95% CI:1.193~6.278;OR=1.006,95% CI:1.001~1.010;OR=0.280,95% CI:0.115~0.681(all,P<0.05)].(3)Pearson correlation analysis showed that MPV was positively correlated with serum uric acid(r = 0.17,P < 0.05). Conclusions Age,smoking history,MPV,serum uric acid and lower HDL-C value are risk factors of CAD in hypertensive patients and active detection and prevention will benefit reducing the risk for the occurrence of CAD in hypertensive patients.

Objective:To explore the incidence, diagnosis and treatment of retinopathy of prematurity(ROP) in preterm infants born in the Guangdong Women and Children′s Hospital and transported from other hospital.Method:s Clinical data of 755 premature infants with ROP at Neonatal Intensive Care Unit, Guangdong Women and Children′s Hospital from January 2013 to December 2015 were retrospectively analyzed.There were 239 cases born in the hospital and 516 cases transported from other hospitals.Their gestational age, birth weight, gender, severity of ROP lesion and clinical data were collected and compared.Result:s The birth weight in the group of transported from other hospital was lower than that in the group of born in the hospital[(1 290.64±392.87) g vs.(1 586.21±512.74) g], and the difference was statistically significant( P<0.001). The ROP diagnosis of gestational age in the group of transported from other hospital was higher than that in the group of born in the hospital[(35.53±2.81)weeks vs.(34.51±2.17)weeks], and the difference was statistically significant( P<0.001). On the proportion of severe condition [such as lesion area Ⅰ, aggressive posterior retinopathy of prematurity(AP-ROP) and plus combined lesions], in the group of transported from other hospital was higher than that in the group of born in the hospital, and the differences was statistically significant( P<0.001). In the comparison of the proportion of laser photocoagulation, vitreous injection, combination of the two operations and supplementary laser therapy, in the group of transported from other hospital were higher than those in the group of born in the hospital[60.1%(310/516 cases) vs.20.9%(50/239 cases); 10.9%(56/516 cases) vs.2.5%(6/239 cases); 8.1%(42/516 cases) vs.1.7%(4/239 cases); 4.5%(23/516 cases) vs.1.3%(3/239 cases)], and the differences were statistically significant(all P<0.001). Conclusions:Premature infants with ROP transported from other hospitals have lower birth weight, severe ROP lesions and high surgical intervention rate.Improving ROP screening level in primary hospitals, timely diagnosis and efficient transportation can help to effectively prevent the deterioration of ROP in premature infants and improve their quality of life.

OBJECTIVE To study the toxicokinetics and tissue distribution characteristics of alpha-amanitin in rats.METHODS The tail venous blood was collected from SD rats before and 5,10,20,30 and 45 min,1,1.5,2.5,4 and 8 h after intraperitoneal injection of alpha-amanitin(1.5 mg·kg-1),and the concentration of alpha-amanitin in blood was determined by liquid chromatography-mass spectrometry(LC-MS/MS).DAS 2.0 software was used to analyze and plot the drug-time curve with toxicokinetic parame-ters.Based on the toxicokinetics results,18 SD rats were randomly divided into three groups.The rats were sacrificed,and left ventricular arterial(LVA)blood and 9 types of tissue samples involving the heart,liver,spleen,lung,kidney,whole brain,small intestine,stomach wall and testis were collected 15 min,40 min and 2.5 h after dosing,and the concentrations of alpha-amanitin were measured by LC-MS/MS to obtain the tissue distribution results of alpha-amanitin in SD rats.RESULTS Toxicokinetics studies revealed that the peak blood concentration(Cmax)was(633±121)μg·L-1,the elimination half-life(T1/2)was(0.72±0.37)h,and the peak time(Tmax)was(0.52±0.16)h.The total clearance rate(CLz)was(1.62±0.26)L·h·kg-1,the area under the curve(AUC0-t)was(946±183)μg·h·L-1,and the mean reten-tion time(MRT0-t)was(1.18±0.17)h.The apparent volume of distribution(Vz)was(1.65±0.86)L·kg-1.The results of tissue distribution study showed that alpha-amanitin was widely distributed in SD rats with the highest concentration in the kidney,followed by the lung,small intestines,stomach wall,LVA blood and liver,but was low in the heart,spleen,testicles and other tissues,and very low in the brain.Alpha-amanitin was absorbed and eliminated quickly,peaked at 40 min in each tissue,and the concen-tration was minimized after 2.5 h.CONCLUSION The absorption and elimination of alpha-amanitin by intraperitoneal injection are rapid in SD rats,and the blood concentration reaches the peak about 31 min after administration,but can not be detected 4 h later.Alpha-amanitin is mainly distributed in the kidney,followed by the tissues and metabolic organs with rich blood flow,such as the lung,small intestines,stomach wall,LVA blood and liver.The content of alpha-amanitin is low in the heart,spleen,testicles and other tissues,and very low in the brain.It is speculated that it may have toxic targeting effect on the kidney and low blood-brain barrier permeability.