Fatal Outcome ; Female ; Fever ; Humans ; Infant ; Purpura, Schoenlein-Henoch ; diagnosis ; therapy

OBJECTIVE: To observe the inhibitive effect of pirenzepine on form deprivation myopia in guinea pigs and to explore the mechanism of Smad3 signaling pathway and connective tissue growth factor (CTGF) in the inhibition of myopia by pirenzepine. METHODS: Forty 1-week-old guinea pigs of either sex were randomly divided into 4 groups: a control group (Group I), a form deprivation group (Group II), a pirenzepine ophthalmic solution group (Group III), and a sodium chloride ophthalmic solution group (Group IV). Translucent blinders were used in the right eyes of Group II, III and IV. The left eyes were not given any treatment as the normal control group. Covered eyes of Group III and IV were given 3% pirenzepine ophthalmic solution and 0.1% azone ophthalmic solution respectively twice every day. Six weeks later, refraction and axial length were measured at the end of the experiment, and immunohistochemistry and Western blot were used to analyze the expression levels of Smad3 and CTGF in the sclera of all 4 groups. RESULTS: There was no significant difference between Group III and I in relative refraction and changes of axial length (P>0.05). The difference of Group II and IV compared with Group I was statistically significant (P<0.05). The number of Smad3 and CTGF positive cells in the sclera between Group III and I was not significantly different (P>0.05), while the difference in Group II, IV and I was significant (P<0.05). Western blot showed that the expression levels of Smad3 and CTGF in Group II and IV were much lower than those in Group I (P<0.05), but not evident in Group III and I (P>0.05). CONCLUSION Pirenzepine ophthalmic solution can inhibit the development of form deprivation myopia. Pirenzepine may affect Smad3 signaling pathway in the sclera by inhibiting the development of form deprivation myopia.
Animals ; Connective Tissue Growth Factor ; metabolism ; Guinea Pigs ; Humans ; Muscarinic Antagonists ; administration & dosage ; Myopia ; prevention & control ; Pirenzepine ; administration & dosage ; Random Allocation ; Sensory Deprivation ; Signal Transduction ; drug effects ; Smad3 Protein ; metabolism

Objective Exploration of the efficacy of different drugs in the treatment of retinopathy caused by type 2 diabetes. Methods 120 type 2 diabetic retinopathy patients were randomly divided into treatment group of 60 patients and the control group of 60 patients based on random number table method, the control group were selected intravitreal injection with triamcinolone aetonide, and the treatment group were selected intravitreal injection with conbercept, all treatments were done three times and visual acuity, retinal and macular leakage of two groups were observed. Results The best corrected visual acuity after treatment in the treatment group and the control group were 40.45 ± 14.38 and 45.33 ± 12.89 respectively and that were significantly higher than the value before treatment, the statistically significant differences also happened between the two (P < 0.05). The CRT and TMV values of the two groups after treatment were significantly lower than that before treatment (P < 0.05) , while the CRT and TMV values in the treatment group were also significantly lower than the control group (P < 0.05). The typing leakage before and after treatment were mostly with diffuse and there were also no statistically significant differences in intra-group or inter-group. Conclusion Intravitreal injection of conbercept in the treatment of type 2 diabetic retinopathy can effectively recover vision and retinal conditions, it can stable patients' macular edema, thereby improve prognosis.

ObjectiveTo investigate the features of liver injury and related influencing factors in adolescents and adults with infectious mononucleosis (IM). MethodsA retrospective analysis was performed to investigate the features of liver injury in adolescents and adults with IM who were hospitalized in Peking University First Hospital from January 2005 to December 31 2018, and the patients were divided into subgroups based on age, Epstein-Barr virus (EBV) DNA level, and presence or absence of jaundice or infection with cytomegalovirus or hepatitis E virus (HEV). The t-test was used for comparison of continuous data meeting analytical conditions between two groups, and the Mann-Whitney U test was used for comparison of continuous data which did not meet analytical conditions between two groups; the chi-square test was used for comparison of categorical data between two groups, and the Fisher’s exact test was used for comparison of categorical data which did not meet the analytical conditions of the chi-square test. A logistic regression analysis was used for multivariate analysis. ResultsA total of 274 patients were enrolled, with 154 male patients (56.2%) and 120 female patients (43.8%), and the mean age of onset was 22.3±67 years. The incidence rate of liver injury ［defined as alanine aminotransferase (ALT) ＞50 U/L and/or aspartate aminotransferase (AST)＞40 U/L］ was 97.4% (267/274), and that of jaundice was 27.6% (74/268). The patients, aged ≥20 years, tended to have a higher level of gamma-glutamyl transpeptidase (GGT) (Z=2.070, P=0.038). Serum EBV DNA was measured for 167 patients, among whom 90 had positive results and 77 had negative results. The positive serum EBV DNA group had significantly higher levels of GGT (Z=3.005, P=0.003) and lactate dehydrogenase (Z=2.162, P=0.031) than the negative serum EBV DNA group. The patients with cytomegalovirus infection tended to have a higher level of alkaline phosphatase (Z=2.351, P=0.019), and the patients with HEV infection presented with a higher level of GGT (Z=1.988, P=0.047). AST (odds ratio ［OR］=1.006, 95% confidence interval ［CI］: 1.002-1.010, P=0.005) and ALP (OR=1.012, 95%CI: 1.005-1.020, P=0.001) were independent risk factors for jaundice. ConclusionThere is a high incidence rate of liver injury in adolescents and adults with IM, and the patients with an older age or positive serum EBV DNA tend to have more severe liver injury.

Objective:To investigate the effect and mechanism of Acyl-CoA: lysocardiolipin acyltransferase 1 (ALCAT1) on hepatocyte steatosis and oxidative stress in fatty liver cell model.Methods:A fatty liver cell model was established and induced by free fatty acids (FFA). The expression of ALCAT1 in fatty liver cell model was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The empty siRNA plasmid and ALCAT1 siRNA plasmid were constructed. For the fatty liver cell model group, human normal hepatocytes (L-02 cells) were transfected with empty siRNA plasmid for 24 hours, and then cultured with FFA for 24 hours. For the ALCAT1 interfering group, L-02 cells were transfected with ALCAT1 siRNA plasmid for 24 hours, and then cultured with FFA for 24 hours. And L-02 cells cultured in common medium were used as as blank control group. Lipid droplet deposition and mitochondrial morphology were observed under transmission electron microscopy. The expression levels of autophagy-associated proteins (microtubule-associated protein 1 light chain 3 (LC3)-Ⅱ and Beclin1) and key proteins of autophagy signal pathway (mammalian target of rapamycin (mTOR) and serine/threonine kinase (AKT)) were measured by Western blotting. The expression levels of oxidative stress products (malondialdehyde, 4-hydroxynonenal (4-HNE) and reactive oxygen species (ROS)) and inflammatory factors (interleukin-6(IL-6) and tumor necrosis factor (TNF)-α) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Independent sample t test was used for statistical analysis. Results:The mRNA and protein expression levels of ALCAT1 of the fatty liver cell model group were both higher than that of negative control group (9.26±0.83 vs. 1.02±0.12, 0.35±0.02 vs. 0.17±0.01), and the differences were statistically significant ( t=9.82 and 6.83, both P<0.05). The results of electron microscopy indicated that the deposition of lipid droplets of the fatty liver cell model group and ALCAT1 interfering group were both higher than that of blank control group (17.67±3.52 and 7.67±0.33 vs. 4.33±0.33), the quantity of lipid droplets deposition of ALCAT1 interfering group was lower than that of fatty liver cell model group (7.67±0.33 vs. 17.67±3.52), and the differences were statistically significant ( t=3.76, 7.07 and 2.82, all P<0.05). The degree of mitochondria swelling of fatty liver cell model group was higher than that of blank control group and the degree of mitochondria swelling of ALCAT1 interfering group was lower than that of fatty liver cell model group. The results of Western blotting showed that the expression level of LC3-Ⅱof the fatty liver cell model group was higher than that of the blank control group (0.43±0.01 vs. 0.28±0.02), and the difference was statistically significant ( t=7.32, P<0.05). However there was no significant difference in the expression level of Beclin1 between fatty live cell model group and blank control group (0.93±0.05 vs. 0.98±0.05, P>0.05). The expression levels of LC3-Ⅱ and Beclin1 of the ALCAT1 interfering group were both higher than those of the fatty liver cell model group and blank control group (0.95±0.04 vs. 0.42±0.01 and 0.28±0.02, 2.07±0.06 vs. 0.93±0.05 and 0.98±0.05), and the differences were statistically significant ( t=13.30, 15.63, 14.05 and 13.02, all P<0.05). The expression levels of mTOR of the fatty liver cell model group and ALCAT1 interfering group were both lower than that of the blank control group (1.44±0.02 and 0.74±0.01 vs. 1.93±0.10), the expression level of mTOR of the ALCAT1 interfering group was lower than that of the fatty liver cell model group (0.74±0.01 vs. 1.44±0.02), and the differences were statistically significant ( t=4.83, 12.04 and 32.14, all P<0.05). The expression levels of phosphorylated AKT of the fatty liver cell model group and ALCAT1 interfering group were both lower than that of the blank control group (0.14±0.01 and 0.07±0.01 vs. 0.28±0.01), while the expression level of phosphorylated AKT of the ALCAT1 interfering group was lower than that of the fatty liver cell model group (0.07±0.01 vs. 0.14±0.01), and the differences were statistically significant ( t=8.59, 14.10 and 5.96, all P<0.05). The results of ELISA indicated that the expression levels of ROS, malondialdehyde, 4-HNE, IL-6 and TNF-α of the fatty liver cell model group and the ALCAT1 interfering group were all higher than those of the blank control group ((11.44±0.30) and (5.84±0.36) g/L vs. (1.72±0.38) g/L; (19.94±2.47) and (11.95±1.55) μmol/L vs. (1.47±0.18) μmol/L; (5.00±0.43) and (2.99±0.37) ng/L vs. (1.46±0.23) ng/L; (203.40±5.16) and (92.07±11.98) ng/L vs. (23.32±3.33) ng/L; (123.70±8.38) and (67.42±4.88) ng/L vs. (47.18±4.57) ng/L), and the differences were all statistically significant ( t=19.86, 7.86, 7.45, 6.74, 7.22, 3.49, 29.34, 5.53, 8.02 and 3.03, all P<0.05). While the expression levels of ROS, 4-HNE, IL-6 and TNF-α of the ALCAT1 interfering group were all lower than those of the fatty liver cell model group ((5.84±0.36) g/L vs. (11.44±0.30) g/L, (2.99±0.37) ng/L vs. (5.00±0.43) ng/L, (92.07±11.98) ng/L vs. (203.40±5.16) ng/L and (67.42±4.88) ng/L vs. (123.70±8.38) ng/L), and all the differences were statistically significant ( t=11.99, 3.51, 8.54 and 5.81, all P<0.05). There was no statistically significant difference in the expression of malondialdehyde between ALCAT1 interfering group and fatty liver cell model group ((11.95±1.55) μmol/L vs. (19.94±2.47) μmol/L, P>0.05). Conclusions:The expression of ALCAT1 is up-regulated in fatty liver cell model. Knockdown of ALCAT1 can inhibit the expression of mTOR pathway proteins, activate autophagy, alleviate hepatocyte steatosis, oxidative stress and inflammatory response.

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg^-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg^-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg^-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.