AIM: To study apoptotic injury induced by aeactive oxygen species - hydrogen peroxide (H2O2) on cardiac myocytes. METHODS: Cultured rat neonatal cardiac myocytes were treated with H2O2 of various concentra- tion to observe apoptoitic injury of cardiomyocytes by agarose gel electrophoresis, Giemsa - stained smears of cell, and flow cytometry, meanwhile lactate dehydrogenas (LDH) and malondialdehyde (MDA) were determined to assess the effect of H2O2 on lipid peroxidation and permeability of the plasma membrane. RESULTS: 5 mmol/L H2O2 caused culted cardiomyocytes apoptotic morophological characteristics, including nucleosomal DNA fragmentation in my- ocytes by agarose gell electrophoresis (DNA ladder), cell shrinkage, nuclear condensation, and chromatin margin by Giemsa-stained cell smears, and aneuploid peak (AP) - apoptotic bodies occurence by flow cytometry. CONCLU- SONS: H2O2 - induced apotosis in myocytes was a the - and concentration - dependent process, Treatment with low concentration of H2O2(10 mmol/L) rapidly induced a necrotic form of death characterized by smeared patterns of DNA digestion on agarose gel electrophoresis and lethal membrane disuption (as measured by LDH release). Exposure of 5 - 10 mmol/ L H2O2 induced cardiomyocytes apoptosis concurrently with biochemical changes of LDH and MDA increase in the medium.

Objective To investigate the effect of curcumin pretreatment on endoplasmic reticulum stress induced by global cerebral ischemia-reperfusion (I/R) in rats. Methods One hundred forty-four male SD rats weighing 200-250 g were randomly divided into 4 groups (n = 36 each): sham operation group (group S) ; I/Rgroup; curcumin group (group Cur) and vehicle control group (group VC). Global cerebral I/R was produced by four-vessel occlusion technique in S, I/R, Cur, VC groups. Bilateral vertebral arteries were cauterized. Bilateral common carotid arteries were occluded by clipping for 15 min. Curcumin 200 mg/kg was injected intraperitoneally (IP) at 1 h before cerebral ischemia. Global cerebral ischemia was confirmed by unconsciousness and disappearance of papillary and righting reflex. Animals were sacrificed at 12 h, 1,3 and 7 d of reperfusion. Neuronal apoptosis in hippocampal CA1 region was detected by TUNEL assay. Apoptosis index (AI) was calculated. The expression of glucose regulated protein 78 (GRP78) ,growth arrest and DNA damage inducible gene 153 (GADD153) and caspase-12 protein in hippocampal region was assessed by Western blot analysis. Results Cerebral I/R significantly increased AI and GRP78 and caspase-12 protein expression in hippocampus as compared with group S( P <0.05) . Curcumin pretreatment significantly decreased AI, increased GRP78 protein expression and decreased caspase-12 protein expression as compared with group I/R ( P < 0.05) . There was no significant difference in the GADD153 protein expression among Cur, VC and I/R groups ( P > 0.05) . Conclusion Curcumin pretreatment can significantly reduce global cerebral I/R-induced neuronal apoptosis in hippocampus by increasing GRP78 expression and decreasing easpase-12 expression in hippocampus.

Objective To explore the effects of pretreatment with different doses of curcumm on the expression of p-CREB and PGC-1α in hippocampus after global cerebral ischemia-reperfusion (IR) injury in rats.Methods Three hundred male SD rats weighing 200-250 g were randomly divided 5 groups ( n = 60 each): sham operation group (group S), IR group, low, median and high dose curcumin group (group LC, MC, HC). Global cerebral ischemia was produced by occlusion of 4 vessels (cauterization of bilateral vertebral arteries and 15 min occlusion of bilateral common carotid arteries) according to the method described by Finkbeiner. Bilateral common carotid arteries were only exposed but not ligated in group S. Intraperitoneal curcumin 30, 100 and 300 mg/kg were injected at 1 h before ischemia in group LC, MC and HC respectively. Equal volume of dimethylsulfoxide (DMSO) was injected intraperitoneally in group S and IR. The rats were killed at 2, 6, 24 and 72 h and 7 d after reperfusion (12 at each time point). Brains were immediately removed and hippocampus was isolated. The number of apoptosis neurons was counted using TUNEL. The expression of p-CREB and PG C-1α protein in hippocampus was detected by Western blot. Results The number of apoptosis neurons, p-CREB and PG C-1α protein expression were significantly higher at each time point in the other 4 groups than in group S ( P ＜ 0.05). The number of apoptosis neurons was significantly lower at T2-4 in group LC and MC, while p-CREB and PG C-Ⅰα protein expression wes significantly higher at T1-4 in group LC, MC and HC than in group IR (P ＜ 0.05). The number of apoptosis neurons was significantly higher, while p-CREB and PGC-1α protein expression was significantly lower at T2-4 in group LC and HC than in group MC ( P ＜ 0.05). Conclusion Curcumin can inhibit neuronal apoptosis in hippocampus and reduce global cerebral IR injury by up-regulating p-CREB and PG C-1α expression in rats and the effect was dose-related.

Aims To compare hippocampus between CUMS rats and normal rats, to find differentially ex-pressed proteins and to explore the pathogenesis of de-pression in the protein levels and biological marker. Methods Chronic unpredicted mild stress was taken to establish rat depression model. The ITRAQ-labeled proteins and peptides were separated by the cation col-umn, and differentially expressed proteins were detec-ted and identified by 2D LC-MS/MS. The functions of proteins were analyzed by bioinformatics. Results To-tally 5 109 proteins were identified, 33 differentially expressed proteins were identified, the expressions of 8 proteins were increased and 25 proteins downregulated. Conclusion ITRAQ based sereening is effective in discovering the nosogenesis of depression and new bio-logical marker.

AIM:To evaluate the effect of curcumin on impaired learning-memory ability and the expression of high mobility group box protein 1 ( HMGB1 ) and c-Jun N-terminal kinase ( JNK ) in a rat model of Alzheimer disease (AD).METHODS:Male Sprague-Dawley rats, weighing 250~270 g, were randomly divided into 4 groups (n=9):blank control group (group A), model group (group B), curcumin treatment group (group C, curcumin injected intraper-itoneally at 100 mg· kg-1· d-1 for 6 consecutive days) and solvent control group (group D).The rats of AD model were induced by injection of ibotenic acid into the nucleus basalis of Meynert ( NBM) bilaterally.All rats were trained in Morris maze to assess the ability of learning and memory .The expression of HMGB1 and JNK in the hippocampus was detected by the methods of immunohistochemistry and Western blotting .RESULTS:Compared with group A , the average escape laten-cy (AEL) in groups B and D were obviously longer (P<0.05), while AEL in group C in the 5th and 6th days were signif-icantly shorter (P<0.05).The releases of HMGB1 in the CA1 and CA3 areas in groups B and D from the nucleus were a-bundant.Compared with groups B and D , HMGB1 in hippocampal CA1 and CA3 areas in group C secreted out of the nu-cleus decreased obviously (P<0.05).No significant difference of the release of HMGB1 between group A and group C was observed (P>0.05).No significant difference in the expression of HMGB1 in the hippocampus among the 4 groups was found (P>0.05).However, compared with groups B and D , the expression of JNK in group C was decreased obvi-ously (P<0.05).CONCLUSION: Curcumin significantly improves the learning and memory ability of AD rats .The probable mechanisms may be related to inhibiting the release of HMGB 1 from the nucleus of hippocampal neurons and de-creasing the expression of JNK in the hippocampus .

Objective:To analyze the clinico-pathological characteristics, pathological diagnosis, and treatment of rhabdoid tu-mor. Methods:The medical records of four rhabdoid tumor patients that were admitted to the Tianjin Medical University Cancer Insti-tute and Hospital since 2000 were analyzed based on existing literature. Results:In one of the four cases, the tumor originated from the kidney, whereas in the other three, the tumor occurred from extra-renal soft tissues. Histologic analysis revealed that the tumor cells were loosely arranged with diffuse growth, vesicular nuclei, dyed cytoplasm, visible eosinophilic inclusions, and more nuclear fission. The results of immunohistochemical staining showed that the vimentin and epithelial membrane antigen were positive, whereas CK, CD99, CD34, and S-100 were positive at different degrees. MyoD1, Desmin, and INI-1 were negative. Conclusion:Rhabdoid tumor is rare and highly aggressive. It occurs mainly in the kidney and can also be found in other systems. The unique pathological form and im-munohistochemical staining observed on the tumor can be used as reference for diagnosis.

Most diploid cells proliferate by proceeding through the canonical G1 (DNA pre-synthesis), S (DNA synthesis), G2 (DNA post-synthesis), and M(mitosis) phases of the cell cycle. However, there is another type of cell cycle that occurs frequently in both plants and animals, known as endoreplication. Endoreplication consists of alternating periods of G and S phases without cytokinesis, which results in polyploidy. It is indispensable for normal development, organ formation, and wound healing in humans. In recent years, con-siderable attention has been paid to delineating the connections of endoreplication with tumorigenesis and tumor progression. Here, we review the role of endoreplication in normal human development and discuss its possible role in tumor development and the un-derlying molecular mechanisms.

Objective:To investigate the correlation between serum vitamin D and the risk of pre-eclampsia at the early, middle and late stages of pregnancy.Methods:Pregnant women who registered and delivered in Electric Power Teaching Hospital of Capital Medical University from August 2020 to July 2021 were included. Pregnant women with pre-eclampsia during pregnancy were selected as the case group (150 cases), while pregnant women without any complications after delivery were selected as the control group (600 cases) according to the 1∶4 matching principle (age, pre-pregnancy body mass index and last menstruation). The levels of serum vitamin D in differences stages of pregnancy between the two groups were compared. Logistic regression model was used to analyze the association between serum vitamin D levels and the risk of pre-eclampsia.Results:The levels of serum vitamin D at the early, middle and late stages of pregnancy in the case group were lower than those in the control group: (14.32 ± 3.61) μg/L vs. (18.78 ± 4.73) μg/L, (15.06 ± 3.12) μg/L vs. (19.88 ± 4.25) μg/L, (16.04 ± 3.51) μg/L vs. (22.04 ± 5.63) μg/L, there were statistical differences ( P<0.05). Taking pregnant women with adequate serum Vitamin D as a reference, and adjusting for confounding factors such as gain weight and primipara, the risk of pre-eclampsia in early stages pregnant women with serum Vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR and 95% CI were 4.84(1.25 -31.42), 3.09(1.12 - 8.96), 1.48(1.12 - 13.05); the risk of pre-eclampsia in middle stages pregnant women with serum vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR(95% CI) were 4.43(1.23 - 13.55), 2.22(1.05 - 6.78), 1.12(0.45 - 7.73); the risk of pre-eclampsia in late stages pregnant women with serum vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR(95% CI) were 2.13(1.12 - 8.64), 1.76(1.02 - 4.98), 1.22(0.72 - 3.94). Conclusions:The level of serum vitamin D is associated with the risk of pre-eclampsia in pregnant women in the early, middle and late stages of pregnancy, and the risk of pre-eclampsia is significantly increase when the level of serum vitamin D is severely deficient or deficient during pregnancy.

Objective:To analyze the differences of the clinical characteristics and laboratory indexes in children with positive dense fine spot (DFS) type anti-nuclear antibody, and thereby to explore the value of positive DFS in the diagnosis of immunological diseases.Methods:Among 9 613 cases who were routinely tested for antinuclear antibody (ANA) from August 2017 to February 2020, there were 197 cases with DFS positive, who were subjected to a retrospective analysis.These patients were divided into the autoimmune diseases (AID) group (39 cases) and the non-AID group (158 cases) according to clinical diagnosis.Healthy children in the same physical examination were used as healthy control group (40 cases). T test was applied to analyze the differences of humoral immunity markers between AID and non-AID groups.What′s more, DFS positive patients in different clinical departments, initial symptom and the part of body were further compared. Results:Among 9 613 children tested for autoantibodies, 2 654 (27.61%) were ANA positive, with the highest detection rate of the spotted type and 197 DFS positive cases, accoun-ting for 7.42% of ANA positive children; 97 DFS positive male patients accounted for 8.20% (97/1 183 case) of ANA positive male patients, 100 DFS positive female patients accounted for 6.80% (100/1 471 cases) of ANA positive female patients, and there was no significant difference in the positive rate.The departments with high positive ANA detection included the nephrology department (27.88%) and the rheumatology department (24.83%). The departments with a higher ANA positive rate in DFS positive children included the gastroenterology department (13.25%) and the infectious department (11.76%). Among the children with DFS antibody positive, 39 cases had AID, among which 38 cases had organ-specific AID, and juvenile idiopathic arthritis (JIA) had the highest detection rate in 13 cases.The diseases with a high DFS positive rate in 158 non-AID cases included allergic purpura (46 cases). Serum immunoglobulin (IgG) level in the AID group was significantly lower than this in the non-AID group, serum IgM and C 4 levels in AID children were significantly lower than those in the non-AID group and healthy control group, and the serum IgA level of DFS positive group was significantly higher than that of children in the healthy control group.All children with DFS antibody positive had no specific autoantibodies. Conclusions:DFS antibody positive is important for the diagnosis of systemic AID in children.The combined detection with the DFS, other autoimmunity antibody index, humoral immune function index contributes to the early differential diagnosis of autoimmune diseases in children.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.