OBJECTIVE To explore the ameliorative effect of ursolic acid on carbon tetrachloride-induced acute liver injury in mice,and the feasibility of multispectral optoacoustic tomography(MSOT)for characteristic structural and functional imaging of liver tissues.METHODS Kunming mice were randomly divided into the normal control group,model group,model+ursolic acid 30,60 mg·kg-1 groups and model+bifendate 5.625 mg·kg-1 group,with 14 mice in each.Each group was given the corresponding drug once daily for 7 days.An acute liver injury model was established in mice by intraperitoneal injection of 0.2％carbon tetrachloride in olive oil solution after the last administration.Blood was collected,liver tissues were taken 24 h after modeling,and the liver index was calculated,8 mice from each group and the levels of serum glutamic pyruciv transaminase(GPT)and glutamic oxaloacetic transaminase(GOT),as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content in liver tissues were measured.The enzyme-linked immunosorbent assay(ELISA)method was used to detect the level ofα-glutathione S-transferase(α-GST)in serum.The histopathological changes of the liver were observed under a light microscope.The remaining 6 mice in each group underwent MSOT technique was used for characteristic structural and functional imaging of liver tissue.Levels of oxygenated hemoglobin(HbO2)and deoxygenated hemoglobin(Hb)were analyzed,oxygen saturation was calculated,and the extent of liver injury was assessed by examining the intrahepatic distribution of indocyanine green(ICG).RESULTS Compared with the normal group,the levels of GPT,GOT and α-GST in serum,content of MDA in liver tissues and the liver index in the model control group were significantly increased while the activity of SOD in liver tissues were significantly decreased.Compared with the model group,ursolic acid in each dose group significantly reduced the liver index of mice,lowered the serum levels of GPT and GOT as well as the level of α-GST,decreased the content of MDA in liver tissues,and elevated the activity of SOD in liver-injured mice.Hematoxylin-eosin staining showed that significant steatosis and hepatocyte necrosis and inflammatory cell infiltration in hepatocytes of mice in the model group.Ursolic acid significantly attenuated the degree of hepatocellular lesions and markedly reduced steatosis in mice.MSOT imaging showed that the HbO2 level and oxygen saturation were significantly lower while the Hb level was remarkably higher in the liver of mice in the model group.In each administration group,the level of HbO2 significantly increased,the level of Hb was significantly decreased,oxygen saturation was significantly increased in the liver of model mice and the accumulation of ICG dye probe was atten-uated in the body after hepatocyte injury.CONCLUSION Ursolic acid can elevate the hepatic oxygen saturation,improve the metabolism of ICG,reduce the degree of hepatic necrosis in mice,and help protect against carbon tetrachloride-induced hepatic injury in mice.The mechanism is probably related to the inhibition of oxidative stress.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

OBJECTIVE To explore the ameliorative effect of ursolic acid on carbon tetrachloride-induced acute liver injury in mice,and the feasibility of multispectral optoacoustic tomography(MSOT)for characteristic structural and functional imaging of liver tissues.METHODS Kunming mice were randomly divided into the normal control group,model group,model+ursolic acid 30,60 mg·kg-1 groups and model+bifendate 5.625 mg·kg-1 group,with 14 mice in each.Each group was given the corresponding drug once daily for 7 days.An acute liver injury model was established in mice by intraperitoneal injection of 0.2％carbon tetrachloride in olive oil solution after the last administration.Blood was collected,liver tissues were taken 24 h after modeling,and the liver index was calculated,8 mice from each group and the levels of serum glutamic pyruciv transaminase(GPT)and glutamic oxaloacetic transaminase(GOT),as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content in liver tissues were measured.The enzyme-linked immunosorbent assay(ELISA)method was used to detect the level ofα-glutathione S-transferase(α-GST)in serum.The histopathological changes of the liver were observed under a light microscope.The remaining 6 mice in each group underwent MSOT technique was used for characteristic structural and functional imaging of liver tissue.Levels of oxygenated hemoglobin(HbO2)and deoxygenated hemoglobin(Hb)were analyzed,oxygen saturation was calculated,and the extent of liver injury was assessed by examining the intrahepatic distribution of indocyanine green(ICG).RESULTS Compared with the normal group,the levels of GPT,GOT and α-GST in serum,content of MDA in liver tissues and the liver index in the model control group were significantly increased while the activity of SOD in liver tissues were significantly decreased.Compared with the model group,ursolic acid in each dose group significantly reduced the liver index of mice,lowered the serum levels of GPT and GOT as well as the level of α-GST,decreased the content of MDA in liver tissues,and elevated the activity of SOD in liver-injured mice.Hematoxylin-eosin staining showed that significant steatosis and hepatocyte necrosis and inflammatory cell infiltration in hepatocytes of mice in the model group.Ursolic acid significantly attenuated the degree of hepatocellular lesions and markedly reduced steatosis in mice.MSOT imaging showed that the HbO2 level and oxygen saturation were significantly lower while the Hb level was remarkably higher in the liver of mice in the model group.In each administration group,the level of HbO2 significantly increased,the level of Hb was significantly decreased,oxygen saturation was significantly increased in the liver of model mice and the accumulation of ICG dye probe was atten-uated in the body after hepatocyte injury.CONCLUSION Ursolic acid can elevate the hepatic oxygen saturation,improve the metabolism of ICG,reduce the degree of hepatic necrosis in mice,and help protect against carbon tetrachloride-induced hepatic injury in mice.The mechanism is probably related to the inhibition of oxidative stress.

Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.

A middle-aged male patient initially appeared scattered erythema with pruritus all over the body without obvious cause. According to the skin manifestations of the patient, combined with pathological diagnosis, direct immunofluorescence examination, and different serum autoantibody spectrum, the diagnosis and differential diagnosis of the patient was made by clinicians. The diagnosis of dermatitis herpetiformis was confirmed by the use of autoantibodies in the absence of any apparent history of pasta discomfort. With targeted treatment, the patient′s symptoms and laboratory indicators improved significantly.

Thymic stromal lymphopoietin (TSLP) , a cytokine similar to interleukin-7 (IL-7) , can promote the differentiation and proliferation of a variety of cells, promote the secretion of Th2 cytokines by these cells, and plays an important role in the immune system. In recent years, abnormal expression of TSLP has been found in many skin diseases, and its level is also related to the severity of some skin diseases, suggesting that TSLP may be a potential target for the treatment of various skin diseases. This review summarizes recent research progress in the role of TSLP in the occurrence and development of various skin diseases, including inflammatory diseases, immune diseases, genetic diseases and tumors, and provides a basis and some ideas for the diagnosis and treatment of related diseases.

Objective:To investigate the relationship of eosinophil cationic protein (ECP) levels in sera and blister fluids with bullous pemphigoid (BP) .Methods:From January 2012 to October 2019, 40 patients with newly diagnosed BP and 40 healthy individuals were enrolled from Department of Dermatology, Peking Union Medical College Hospital, and serum ECP levels were detected by enzyme-linked immunosorbent assay. Meanwhile, another 33 patients with newly diagnosed BP and 41 patients with non-autoimmune bullous diseases were enrolled, and the ECP level was detected in blister fluids by enzyme-linked immunosorbent assay. Pathological sections of skin lesions of 1 patient with BP and 1 with contact dermatitis were subjected to immunohistochemical staining for ECP. Normally distributed data were compared between 2 groups by using t test or t′ test, while enumeration data were compared by using chi-square test. Pearson′s correlation coefficient was used to analyze the relationship between serum levels of ECP and proportions of peripheral blood eosinophils in patients with BP. Results:The serum level of ECP was significantly higher in the BP group (116.9 ± 19.3 ng/L) than in the healthy control group (93.3 ± 15.9 ng/L, t = 5.96, P<0.001) , and the blister fluid level of ECP was also significantly higher in the BP group (665.8 ± 189.0 ng/L) than in the non-autoimmune bullous disease group (547.5 ± 240.6 ng/L, t = 2.31, P = 0.02) . Immunohistochemical study showed more brown-yellow particles in the cytoplasm of ECP-positive cells in the BP group than in the contact dermatitis group. There was no significant correlation between the serum level of ECP and proportion of peripheral blood eosinophils in the BP patients ( r = -0.15, P = 0.35) . Conclusion:The levels of ECP in the sera and blister fluids markedly increased in the patients with BP, and blister fluid levels of ECP were much higher than serum levels of ECP, suggesting that ECP may be involved in the occurrence of BP.

Objective To investigate the correlations of the serum level of interleukin-21 (IL-21) with anti-BP 180 antibodies,peripheral eosinophil level,bullous pemphigoid disease area index (BPDAI)in patients with bullous pemphigoid (BP).Methods A total of 31 patients with bullous pemphigoid and 31 healthy controls were enrolled into this study.Blood samples were collected from all the subjects,and enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum level of IL-21 and serum titer of anti-BP180 antibodies.BPDAI was assessed among 13 patients,and the correlation of the IL-21 level with anti-BP180 antibody titers,eosinophil count and BPDAI were analyzed.Results No significant difference in the serum level of IL-21 was observed between the patients (M [P25-P75]:255.28 [156.19-361.59] ng/L) and healthy controls (150.47 [72.4-268.73] ng/L,P =0.14).There was no correlation between the serum level of IL-21 and serum titer of anti-BP180 antibodies (82.98 [26.82-132.92] U/ml,rs =0.18,P =0.332).Among the 27 BP patients who underwent blood cell count,no correlation was found between the serum levels of IL-21 and whole-blood eosinophil counts (rs =0.104,P =0.606).Among the 13 BP patients who underwent assessment of BPDAI,there was no correlation between the serum levels of IL-21 and BPDAI scores (rs =0.233,P =0.464).Conclusion The IL-21 level is uncorrelated with anti-BP 180 antibody level,peripheral eosinophil level or BPDAI in patients with BP.

Objective To explore the correlation between ATF5 protein expression level and drug sensitivity of gastric cancer AGS cells.Methods We established the high,middle and low ATF5 expression groups by transfecting the AGS cells with ATF5 pcDNA3.1 plasmid,ATF5 siRNA and empty plasmid using the liposome transfection technique.Then we detected the expression of the ATF5 protein of the 3 groups using the Western Blot.The drug sensitivity of AGS cells in 3 groups to paclitaxel and cisplatin was detected using the MTT experiments and plate clone formation experiments then the correlation between ATF5 protein expression level and drug sensitivity of gastric cancer AGS cells was analyzed.Results With the effect of paclitaxel or cisplatin on AGS cells in 3 groups,the surviving fraction and the IC50 of high ATF5 expression group were higher than those of control group,which indicated statistical significance (all P ＜ 0.05);while the surviving fraction and the IC50 of low ATF5 expression group were lower than those of control group (all P ＜ 0.05,P cisplatin =0.00,P paclitaxel =0.002).We found that cell clone formation of AGS cells to paclitaxel and cisplatin was significantly increased after the transfection with ATF5 protein plasmid and decreased after transfection with ATF5 siRNA plasmid (all P ＜ 0.05).Conclusion The expression of ATF5 protein is related to the drug sensitivity of gastric cancer AGS cells that upregulation of ATF5 protein expression can decrease the drug sensitivity of AGS cells to paclitaxel and cisplatin in gastric cancer.

Bullous pemphigoid (BP) is a group of autoimmune blistering skin diseases.There are special measures for the assessment of disease severity and therapeutic response in autoimmune bullous skin diseases.Common scoring indexes include autoimmune bullous skin disorder intensity score (ABSIS),bullous pemphigoid disease area index (BPDAI),and so on.ABSIS has been validated,and is widely applied in evaluation of pemphigus vulgaris and other autoimmune blistering diseases.BPDAI is still in the process of verification,and has been applied in only a few clinical trials.The evaluation of diseases by ABSIS and BPDAI is both based on a global assessment of skin and mucosal lesions,and degree of subjective pruritus.