Sphingolipids, especially ceramide and S1P, are structural components of biological membranes and bioactive molecules which participate in diverse cellular activities such as cell division, differentiation, gene expression and apoptosis. Emerging evidence demonstrates the role of sphingolipids in hepatocellular death, which contributes to the progression of several liver diseases including ischaemia-reperfusion liver injury, steatohepatitis or hepatocarcinogenesis. Furthermore, some data indicate that the accumulation of some sphingolipids contributes to the hepatic dysfunctions. Hence, understanding of sphingolipid may open up a novel therapeutic avenue to liver diseases. This review focuses on the progress in the sphingolipid metabolic pathway with a focus on hepatic diseases and drugs targeting the sphingolipid pathway.

Objective To evaluate the efficacy and safety of sequential treatment of newly diagnosed de novo acute myeloid leukemia (AML) patients with IA and low-dose HA combined with G-CSF regimens as remission induction therapy.Methods Fifty-seven patients with AML were enrolled,which marrow biopsy was hypocellular or active proliferation on the third day from the end of the first course with IA regimen.32 cases of them received the second course with low-dose HA combined with G-CSF regimen,compared with other 25 cases received the second course with another IA regimen.Clinical manifestations,blood count,blood biochemical parameters and bone marrow smears were measured during the courses.Results In study group,21 of 32 cases reached CR,4 PR,and 11 of 20 cases reached CR,2 PR in control group.Overall remission rate (ORR) was higher in study group than that in control group (78.1％ vs 52.0 ％,P =0.038).Both median duration of agranulocytosis and median time for PLT to reach 50×109/L from the lowest were shorter in study group than those in control group (9.5 d vs 28.0 d,U=32.5,P＜ 0.001; 11 d vs 19 d,U=193.0,P=0.001).Component transfusion,not only RBC but PLT,decreased in study group,compared with control group (8 U vs 16 U,U =206.5,P =0.002; 20 U vs 60 U,U =149,P ＜ 0.001).Median durable time of antibiotic intravenous injection was shorter in study group than that in control group (14 d vs 21 d,U=249.5,P=0.015).Visceral hemorrhage rate reduced in study group,compared with control group (x2 =3.90,P =0.048).Conclusion IA and low-dose HA combined with G-CSF regimens sequential treatment as remission induction therapy for newly diagnosed de novo AML patients is effective and well tolerated.

Objective To evaluate the effects of two different dosage of rosuvastatin on endothelial dysfunction in diabetic rats. Methods The 24 diabetic rats were randomly divided into three groups (n=8,each): diabetic control group, 20 mg rosuvastatin daily (RV 20 mg group) and 10mg rosuvastatin daily for 8 weeks (RV 10 mg group) and normal control group (SD group). The levels of blood glucose, lipid, nitric oxide(NO) and endothelin-1 (ET-1) were measured before and 8 weeks after treatment. Results The levels of blood glucose were higher in all diabetic rats groups than in SD group before experiment (P＜0. 01). Compared with diabetic rats control group, blood glucose was slightly lower in RV 10 mg group and RV 20 mg group at 8 weeks (P＞0. 05). The plasma NO level was significantly lower in diabetic rats control group than in SD group (P＜0. 05).After 8 weeks, plasma NO levels were significantly higher in RV 20 mg and RV 10 mg groups than in diabetic rats control group (P＜0. 01 or P＜0. 05). The plasma levels of ET-1 was significantly higher in diabetic rats control group than in SD group (P＜0. 01). After 8 weeks, plasma ET-1 levels were significantly lower in RV 20 mg and RV 10 mg group than in diabetic rats control group (P＜0. 01).Meanwhile, the plasma lipids were lower in RV 20 mg and RV 10 mg group than in diabetic control group (P＜0. 05 or P＜0. 01). Conclusions Rosuvastatin can adjust blood lipids and significantly improve endothelial function in diabetic rats by increasing plasma NO level and decreasing plasma ET-1 level.

Objective: The purpose of this study was to determine the relationship between TCM pattern and Hp infection and apoptosis of stomach mucosa in chronic gastritis, to discover the substance of TCM Pattern of chronic gasuitis on genetic molecular level and to establish syndrome differentiation system of chronic superficial gastritis on molecular level Methods: Get gastric mucosa tissue by electronic gastroscope. Hp infection, expression of Fas and bel-2 of 41 cases of incoordination between the liver and stomach group (IBLS group) and 50 cases of Dampness-beat in spleen and stomach(DHSS group) of chronic superficial gastritis were investigated by immunohistocbemistry examination, with 10 healthy persons as control group. Muti-factor non-condition logistic regression analysis was adopted to analyze the data. Results: The positive rate of HP was of 22%, 52% and 10% respectively in the IBLS group, the DHSS group and the control group. The positive rate of HP in the DHSS group was significant higher than in the IBLS and control group, showing there is a significant correlation between DHSS patern and HP infection. The expression rate of bcl-2 antigen was 24.2%, 76.0% and 30.0% respectively in the IBLS, DHSS and control group. The expression rate of bcl-2 antigen in the DHSS group was significant higher than in and the IBLS and control group(P＜0.01), showing there was significant correlation between DHSS pattern and expression rate of bcl-2 antigen(P＜0.01). The expression rate of Fas antigen was 70.7% and 46% respectively in the IBLS and DHSS group, the expression rate of Fas antigen in the IBLS group was significant higher than in DHSS group(P＜0.01), showing there was a significant correlation between IBLS pattern and expression rate of Fas antigen(P＜0.01).Conclusion: The result suggested that there was a certain relationship between HP infection and TCM pattern, the positive rates of HP was higher in DHSS pattern compared with the IBLS group. There was a certain relationship between the expression of bcl-2 and Fas in DHSS pattern, IBLS pattern may probably promoted apoptosis in gastritis, whereas HP infection performed as a main role in apoptosis in DHSS pattern. Bcl-2, liP and Fas might contribute to syndrome differentiation of chronic gastritis.

Objective To explore the potential mechanisms of mesenchymal stem cell (MSC) therapy in ischemia/reperfusion injury (IRI)-induced acute kidney injury (AKI). Methods Forty-five C57/BL6 male mice were randomly divided into three groups: sham group, IRI group, and IRI+MSCs group, with 15 mice in each group. The IRI-induced AKI model in mice was reproduced by clamping both renal pedicles for 35 minutes. In the sham group, both kidneys were exposed, but their pedicles were not clamped. Six hours after reperfusion, mice in IRI+MSCs group received 100 μL of MSCs (1×104 /μL) isolated from the bone marrow from C57/BL6 mice via tail vein, while the mice in the IRI group received same amount of normal saline. Blood samples were harvested at 48 hours after reperfusion, and levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were determined. The changes in renal pathology were observed by microscopy with PAS staining, and the tubular injury and acute tubular necrosis (ATN) scores were calculated. The number of leukocytes (CD45+) infiltrated in kidney at 24 hours and 72 hours after reperfusion was measured with flow cytometry. The number of neutrophils (Ly-6G+) and macrophages (F4/80+) infiltrated in kidneys at 24 hours and 72 hours after reperfusion was determined by immunofluorescence. Results There was significant increase in the related parameters in IRI group compared with those of sham group. The levels of SCr (μmol/L) and BUN (mmol/L) were 180.3±8.8 vs. 9.7±3.5, and 1 121.1±8.3 vs. 9.4±2.3, both P < 0.01. The score of tubular injury was 4.80±0.55 vs. 0 at 48 hours after reperfusion. The quantity of leukocyte (CD45+) infiltration in kidney at 24 hours and 72 hours after reperfusion was increased (×105 cells/g: 60.50±2.56 vs. 19.46±4.83, 42.00±1.87 vs. 14.70±3.74, both P < 0.01), and the number of neutrophils (Ly-6G+) and macrophages (F4/80+) infiltrated in kidney at 24 hours and 72 hours after reperfusion was also increase although the number of leukocytes infiltrated in kidney was significantly lower at 72 hours after reperfusion than that at 24 hours. There was significant lowering of the levels of SCr and BUN [SCr (μmol/L): 99.0±8.0 vs. 180.3±8.8, BUN (mmol/L): 84.5±7.6 vs. 112.1±8.3, both P < 0.01] in IRI+MSCs group, compared to IRI group. For the degree of tubular necrosis in two groups, the tubular injury scores were 2.60±0.55 vs. 4.80±0.55 (P < 0.05). The number of leukocytes infiltrated in kidney at 24 hours and 72 hours after reperfusion (×105 cells/g) were 24.20±4.53 vs. 60.50±2.56, 31.70±3.15 vs. 42.00±1.87 (both P < 0.01). The number of neutrophils was lowered despite (the number of macrophages was increased). However, the number of infiltrated leukocytes was significantly more in IRI+MSCs group at 72 hours than that at 24 hours (×105 cells/g: 31.70±3.15 vs. 24.20±4.53, P < 0.05). Conclusion MSCs could protect against IRI induced AKI by reducing the total number of leuckocytes, especially that of the neutrophils infiltrating into ischemic kidney and by recruiting macrophages into ischemic kidney.

Objective To investigate the effects of HLA-B27 in disease activity and the clinical features of axial spondyloarthritis(SpA). Methods Clinical data of 112 patients with axial SpA was collected and studied prospectively. Clinical manifestations and laboratory examination results of 82 HLA-B27 positive and 30 HLA-B27 negative patients with axial SpA were analyzed. Data source was from Chinese Rheumatism Data Center. Results (1)The average age of onset of HLA-B27 negative patients was significantly later than that of the positive patients , and there was no significant difference in the course of disease and the proportion of male and female patients. (2)The ratio of severe lesion of hip ,peripheral arthritis ,attachment inflammation and systemic symptoms of HLA-B27 negative group were significantly lower than those of HLA-B27 positive group. Familial aggregation phenomenon,uveitis and spine radiology changes in two groups had no significant difference.(3)The changes of disease activity index including erythrocyte sedimentation rate and C-reactive protein increased in HLA-B 27 negative group was significantly lower than those in HLA-B27 positive group. Conclusion There is strong correlation between axial SpA and HLA-B27. The average age of onset of HLA-B27 negative patients was significantly later than that of the positive patients. HLA-B27 negative patients manifested severe symptoms and worse prognosis.

The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.

Objective To explore the correlation between the level of serum uric acid and metabolic syndrome and associated factors including overweight,abnormality of blood glucose,blood lipid,and hypertension.Methods 654 cases of complete medical records,aging from 30-90with median age of 65 ,were completed were selected,Data base was established by using Excell software,meanwhile,single factor analysis and stepwise regression analysis were performed using SPSS 11.0 software package.Results The levels of serum uric acid of patients with overweight,high fasting blood glucose (FBG),hypertriglyceride (TG),high-density lipid cholesterol (HDL-C)and essential hypertension (EH)were higher than that of patients without overweight,normal fasting blood glucose,normal triglyceride,low high-density lipid cholesterol and without hypertension,respectively [respectively,(270.52 ±81.63 )μmol/L vs.(226.61 ± 67.42)μmol/L,t=-7.387,P=0.000;(265.71±73.50)μmol/Lvs.(235.03 ±75.00)μmol/L,t=-4.459,P=0.000;(262.80 ±74.45 )μmol/L vs.( 235.82±75.04)μmol/L,t=-3.927,P=0.000;(243.97 ±76.33)μmol/L vs.(212.78±57.60)μmol/L,t=-2.412,P=0.016;(282.87±64.79)μmol/L vs.( 180.22±41.60)μmol/L,t=22.59,P=0.000 ].The patients with metabolic syndrome (n=107)and the patients without metabolic syndrome (n=547)were included in our study.The level of serum uric acid of patients with metabolic syndrome was higher than that of patients without metabolic syndrome [(301.22±68.55 )μmol/L vs.(230.72±71.63)μmol/L,t=9.376,P=0.000].Stepwise regression analysis showed that there was positive correlation between systolic blood pressure (SBP),diastolic blood pressure (DBP),the body mass index (BMI),triglyceride (TG),high-density lipid cholesterol (HDL-C),fasting blood glucose (FBG)and the level of serum uric acid,respectively (t=3.409,13.401,6.979,2.943,3.514,4.706 respectively;P=0.000,0.001,0.000,0.003,0.000,0.000 respectively).Conclusion The level of serum uric acid in patients with metabolic syndrome is higher than those without metabolic syndrome.There is positive correlation between the level of serum uric acid and associated factors of metabolic syndrome including overweight,abnormality of blood glucose and blood lipid,and hypertension.

OBJECTIVE: To reveal the characteristics of gene expression in adrenal gland of H22 tumor mice with typical syndromes and in different liver cancer stages. METHODS: By the quantitative four diagnosis and syndrome differentiation methods and GeneChip Mouse Exon 1.0 ST Array, we observed adrenal gland gene expression in H22 tumor mice with pathogenic factor-toxin predominance syndrome and qi deficiency syndrome in the earlier stage, yang-qi deficiency syndrome in the intermediate stage, and qi-yin-yang deficiency syndrome in the advanced stage. Genes highly expressed and remarkably different were analyzed in this study. RESULTS: A total of seventy-three up-regulated coincident genes and twenty-six down-regulated coincident genes in different stages were investigated in the study. Up-regulated coincident genes included Hp, C3, Anxa1, Procr, C2, Il4ra, Cd14, Ptprc, Cd52, C4b, Eno3, Xdh, Gpx3, and so on. Down-regulated coincident genes included nervous system function-related genes such as Plp1, Mbp, Aldh1a1, Cck, Atn1, genes associated with electrolyte metabolism such as Aldh1a1 and Slc22a17, genes related to signal transduction such as Cxcr4, Spag5 and Stmn3, etc, and genes related to transcriptional control and protein biosynthesis such as Hspa1a, Dnajb1, Thra, Hhex and so on. CONCLUSION: With the development of the tumorigenesis, the symptoms and signs and differentially expressed genes in adrenal gland of H22 tumor mice can be measured. Up-regulated and down-regulated coincident genes may be the features of H22 tumor mice different from those of normal mice.

Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.