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1.
Acta Pharmaceutica Sinica ; (12): 233-241, 2022.
Article in Chinese | WPRIM | ID: wpr-913175

ABSTRACT

This paper aims to develop folic acid-modified paclitaxel nanocrystals (PTX NC@FA) with good stability, high drug loading and tumor cell targeting for endoscopic injection for preoperative local chemotherapy of gastric cancer. PTX NC@FA was prepared by the "bottom-up" followed by ultrasonic to study its morphology, particle size, ζ-potential, drug loading, folic acid-modified phospholipid (FA-DSPE-PEG2000) content, crystalline characteristics, stability, in vitro release, cytotoxicity against human gastric cancer cell line SGC-7901, and anti-tumor effect in two different tumor sizes (tumor volume 100 mm3 or 300 mm3) after single peri-tumor injection in a murine subcutaneous SGC-7901 tumor model. Animal experiments were approved by the Experimental Animal Ethics Committee of the School of Pharmacy, Fudan University. The resulting PTX NC@FA was of short rod-like shape, average particle size 175.3 ± 2.5 nm (PDI 0.17 ± 0.02), ζ- potential -2.5 ± 0.2 mV, PTX loading (28.23 ± 0.74) % (w/w) and FA-DSPE-PEG2000 content (4.40 ± 0.60) % (w/w). The size of the PTX NC@FA remained unchanged for 4 days in phosphate buffer with or without serum. Cellular growth inhibition effect on SGC-7901 showed the superiority of PTX NC@FA over nanocrystals without FA modification. PTX NC@FA inhibited tumor growth more efficiently than both nanocrystals without FA modification and commercially available paclitaxel injection (Taxol) 12 days after peri-tumor injection. For model tumor with the volume of 100 mm3, tumors of all animals in the PTX NC@FA group disappeared completely. For model tumor with the volume of 300 mm3, tumors of 3 animals in the PTX NC@FA group completely disappeared and tumors of the rest 4 animals also became significantly smaller with a tumor volume inhibition rate of 90%. PTX NC@FA showed good potential for preoperative chemotherapy of increase the chances of function preserving gastrectomy and improve the quality of life of patients.

2.
Organ Transplantation ; (6): 88-2022.
Article in Chinese | WPRIM | ID: wpr-907038

ABSTRACT

Objective To evaluate the effect of high mobility group box 1 (HMGB1)/ cysteinyl aspartate specific proteinase (Caspase)-1/Gasdermin D (GSDMD) signaling axis-mediated hepatocyte pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57BL/6 mice were randomly divided into the sham operation group (Sham group), IRI 2 h group, IRI 6 h group, IRI 12 h group, glycyrrhizic acid (GA)+Sham group and GA+IRI 12 h group (n=8 in each group). AML12 cells were evenly divided into the Sham group, IRI 12 h group, GA+Sham group and GA+IRI 12 h group. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β and IL-6 in each group were detected by enzyme-linked immune absorbent assay(ELISA). The messenger ribonucleic acid (mRNA) levels of IL-1β and IL-6 were detected by reverse transcription polymerase chain reaction(RT-PCR). The pathological score of liver ischemia and cell apoptosis were compared among all groups. The expression level of HMGB1 in the liver tissues of each group was determined by immunohistochemistry. The expression levels of HMGB1, Caspase-1 and GSDMD proteins in the mouse liver tissues and AML12 cells were measured by Western blot. Results Compared with the Sham group, the serum levels of ALT, AST, IL-1β and IL-6 and the relative expression levels of IL-1β and IL-6 mRNA in the liver tissues were all significantly up-regulated after IRI in each group (all P < 0.05), and showed significant time-dependent pattern along with the prolongation of reperfusion time. Compared with the Sham group, the pathological score of hepatic ischemia and the apoptosis rate of hepatocytes were significantly increased after IRI in each group (all P < 0.05). Immunohistochemical results showed that the expression level of HMGB1 in the liver tissues was significantly up-regulated after IRI, which showed an increasing trend along with the prolongation within the period of 2-12 h. Western blot showed that compared with the Sham group, the relative expression levels of HMGB1, Caspase-1 and GSDMD proteins in vivo and in vitro were up-regulated in the IRI 12 h group. The relative expression level of HMGB1 protein was significantly up-regulated, whereas those of Caspase-1 and GSDMD proteins were significantly down-regulated in the GA+IRI 12 h group compared with those in the IRI 12 h group (all P < 0.05). Conclusions Hepatocytes probably activate the Caspase-1/GSDMD signaling pathway by releasing HMGB1, thereby triggering hepatocyte pyroptosis and leading to liver IRI. Inhibition of extracellular release of HMGB1 by GA may mitigate liver IRI.

3.
Protein & Cell ; (12): 261-278, 2021.
Article in English | WPRIM | ID: wpr-880901

ABSTRACT

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

4.
Article in English | WPRIM | ID: wpr-880526

ABSTRACT

OBJECTIVE@#To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment.@*METHODS@#A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets.@*RESULTS@#Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway.@*CONCLUSIONS@#The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

5.
Article in Chinese | WPRIM | ID: wpr-880087

ABSTRACT

OBJECTIVE@#To investigate the effect of etoposide (ETO) on elimination of chronic myeloid leukemia (CML) stem cells by imatinib mesylate(IM) in vivo.@*METHODS@#SCL-tTA/BCR-ABL mice were used as CML animal model. Flow cytometry was used to assess the effect of ETO alone or in combination with IM on the number of leukemia stem cell (LSC) in bone marrow and spleen, and peripheral blood neutrophils in CML mice and normal control FVB mice.@*RESULTS@#The results showed that in CML mice, the number and proportion of LSC in bone marrow and the proportion of neutrophils in peripheral blood decreased significantly after ETO and IM combined treatment, and the degree of decrease was more significant than that of both alone. While in wild type FVB mice, the combination of ETO and IM showed no significant effect on the number and proportion of LSK cells in bone marrow and the proportion of neutrophils in spleen.@*CONCLUSION@#ETO can selectively enhance elimination of CML LSC by IM in vivo.


Subject(s)
Animals , Drug Resistance, Neoplasm , Etoposide , Fusion Proteins, bcr-abl , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Mice , Stem Cells
6.
Article in Chinese | WPRIM | ID: wpr-905318

ABSTRACT

The nervous system controls eccentric exercise in a special way. During eccentric exercise, excitability increases in cortex, and inhibition decreases, causing excitability decrease in spinal cords. In another hand, increased cortical excitability results in extra excitatory compensation for spinal inhibition. The excitability of the corticospinal pathway depends on the balance between excitability and inhibition of the spinal cord level finally, which usually decreases. Many factors, such as the intensity of contraction, can affect the balance of corticospinal excitability. There is a cross-over effect in eccentric exercise, which promotes corticospinal excitability in untrained limbs. However, the effects and mechanisms of muscle length, fatigue and training duration are still unclear, and current researches have focused in the healthy populations. More researches are needed to explore the effects of eccentric exercise on ill populations.

7.
Article in Chinese | WPRIM | ID: wpr-905167

ABSTRACT

Objective:To investigate the knowledgement and clinical application of neurogenic bladder and intermittent catheterization among nurses in Guangdong. Methods:From December, 2020 to January, 2021, 241 nurses in Guangdong were investigated with a questionnaire designed by ourselves. Results:The score was low in understanding the neurogenic bladder rehabilitation nursing management and intermittent catheterization through self-assessment. The awareness was deficient in the complication and risk management of neurogenic bladder. Although there were a lot of patients with dysuria in clinical practice, 67.2% of nurses still used indwelling catheter, and only 24.1% used intermittent catheterization. Only 9.9% nurses thought that patients with dysuria were treated positively by doctors. Most of nurses would like to participate in the training and nursing alliance in neurogenic bladder rehabilitation nursing management and intermittent catheterization, and manage patients with neurogenic bladder after discharge. Conclusion:The knowledge of guidelines related with neurogenic bladder and intermittent catheterization among nurses is insufficient, and is not applied in clinical practice. More work should be done to improve the knowledge and standardization of management of neurogenic bladder.

8.
Article in Chinese | WPRIM | ID: wpr-905152

ABSTRACT

Objective:To develop a patient-reported outcomes (PRO) scale for post-stroke aphasia based on the Traditional Chinese Medicine (TCM) holism. Methods:Referring to the TCM holism, the theoretical model was established following the standard process for the development of the PRO scale. An item pool was established and optimized with case review, patient interview, expert questionnaire survey and consensus conference. The PRO scale was established finally. Results:A pool of post-stroke aphasia items based on the holistic view of TCM was constructed in the physical, psychological and social model. The Expert Comment Form for the PRO Scale for Aphasia after Stroke was formed after sorting out the item pool. After expert surveys and meeting discussion, 40 items were finally selected to form the first version of Patient-reported Outcomes Scale for Post-stroke Aphasia-TCM. Conclusion:The first version of Patient-reported Outcomes Scale for Post-stroke Aphasia-TCM has been developed based on the TCM holism and the concept of PRO, which can be evaluated clinically.

9.
Article in Chinese | WPRIM | ID: wpr-904655

ABSTRACT

@#Objective    To analyze the differences in proteins between aneurysm/dissection patients and healthy subjects, and subsequently figure out differential proteins related to medial degeneration of aortic aneurysm/dissection. Methods    Aortic wall samples were collected from 6 male aortic aneurysm patients (an aortic aneurysm group, mean age 56.50±8.19 years), 6 male aortic dissection patients (an aortic dissection group, mean age 54.17±6.68 years) and 6 male healthy subjects (a normal group, mean age 40.50±9.31 years) between December 2019 and May 2020 in West China Hospital of Sichuan University. Quantitative proteomics was performed using tandem mass tag (TMT) techniques, followed by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results    A total of 63 differential proteins were obtained both in the aortic aneurysm group and the aortic dissection group compared with the normal group, with 30 up-regulating and 33 down-regulating. The differential proteins were involved in multiple biological processes and clusted on peroxisome proliferators-activated receptor (PPAR) signaling pathway, extracellular matrix-receptor interaction signaling pathway and complement and coagulation cascades signaling pathway. Conclusion    The identified proteins may help to demonstrate new molecular mechanisms related to medial degeneration of aortic aneurysm/dissection.

10.
Journal of Medical Biomechanics ; (6): E725-E731, 2021.
Article in Chinese | WPRIM | ID: wpr-904463

ABSTRACT

Objective To investigate the effects of shoes type (barefoot, ordinary running shoes, minimalist shoes) and walking speed (jogging, walking at normal speed) on biomechanical parameters of knee joint, so as to provide theoretical reference for scientific fitness. Methods Vicon three-dimensional (3D) motion capture system and Kistler 3D force plate were used to collect biomechanical parameters of lower limbs from 10 subjects during walking at different speed with different shoes. Two-way (2 walking conditions × 3 shoe conditions) repeated measures analysis of variance was used to statistically analyze each dependent variable. Results Compared with jogging, the lateral excursion of plantar center of pressure (COP) was greater, the moment arm in frontal plane, the adduction moment and peak loading rate of knee joint were smaller, but the angular impulse of knee joint in frontal plane was greater. Compared with ordinary running shoes, the stride length was decreased, the lateral excursion of COP was greater, and the moment arm of knee joint in frontal plane, the knee adduction moment, the peak load rate and the angular impulse of knee joint in frontal plane were smaller. Conclusions In order to reduce the angular impulse and peak loading rate of knee joint in frontal plane, it is recommended to jog with small strides for ordinary people with minimalist footwear.

11.
Journal of Medical Biomechanics ; (6): E519-E527, 2021.
Article in Chinese | WPRIM | ID: wpr-904432

ABSTRACT

Objective To extract key parameters from a series of biomechanical parameters of rowing technique, so as to provide useful information for coach training. Methods Based on rowing performance of 16 rowers in national team, the factor analysis was used to extract reducing dimension of biomechanical parameters of rowing technique of 80 oxygen utilisation 2 (UT2) training pieces. Results The biomechanical parameters of rowing techniques were classified as technical characteristic factors (angle of 70% peak force, work portion of per 25% stroke length, drive start time, finish slip, position of peak force and angle of peak force), power factor (rower power, average of boat power, port swivel power and stroke swivel power), stroke length factor (catch angle and finish angle) and oar’s motion factor (recovery time, stroke rate and distance of per stroke). Conclusions Monitoring and analyzing these biomechanical factors would contribute coaches and scientific researchers to accurately judge the technical characteristics and shortcomings of rowers.

12.
Journal of Medical Biomechanics ; (6): E510-E518, 2021.
Article in Chinese | WPRIM | ID: wpr-904431

ABSTRACT

Objective To explore characteristics of flow field around the athletes, change of net flow force, and influences of hip flexion angles at the end of extension kick on the submerged dolphin kick stroke. Methods The body shape data of a swimmer were obtained by three-dimensional (3D) scanning, and the data were reversely reconstructed to obtain the swimmer model. The joints of the swimmer model were separated, and each segment of the athlete was divided into independent rigid body, and simulation of the submerged dolphin kick stroke was realized by controlling movement of each independent rigid body. The computational fluid dynamics (CFD) software package ANSYS Fluent was used as the solver for calculation and solution. Results The vortex structures were shed off from the surface of the swimmer’s body in the area with a large velocity gradient in flow field, and the shedding of vortex structures was different at the stage of extension kick and flexion kick. Propulsion was mainly generated during extension kick phase. At the end of extension kick, the drag decreased as the hip flexion angle increased from 20° to 30°. Conclusions To some extent, increasing flexion angle of the hip joint at the end of extension kick will reduce the drag force and increase the swimming speed in process of the submerged dolphin kick stroke.

13.
Journal of Medical Biomechanics ; (6): E407-E414, 2021.
Article in Chinese | WPRIM | ID: wpr-904416

ABSTRACT

Objective To investigate the effects of athlete’s posture (including bending angle of upper body and angle between body and skis) on aerodynamic characteristics during flight in ski jumping. Methods The athlete and skis were regarded as a multi-body system. By using partially averaged Navier-Stokes (PANS) turbulence model and numerical simulation of computational fluid dynamics (CFD), the aerodynamic characteristics during flight under different postures were predicted. The calculation conditions for bending angle of upper body were 10°, 14°, 18°, 22° and 26°, and the calculation conditions of angle between body and skis were 8°, 12°, 16°, 20° and 24°. Results As the bending angle of upper body increased, the lift force and drag force of the multi-body system, the athlete and skis, and the pitch moment of skis all showed a monotonously decreasing trend, but the ratio of total lift force to total drag force increased first and then decreased. Meanwhile, the pitch moment of the multi-body system decreased first and then increased, and the pitch moment of athlete increased slightly and then decreased. As the angle between body and skis increased, the lift force and drag force of the multi-body system and skis increased first, then decreased and then increased, but the ratio of total lift force to total drag force decreased first, then increased and then decreased. Meanwhile, the lift force, drag force and pitch moment of the athlete increased monotonously, and the pitch moment of the multi-body system and the skis increased first and then decreased. The effect of bending angle of upper body on aerodynamic characteristics during flight in ski jumping was generally significantly larger than that of angle between body and skis. Conclusions The optimal range for bending angle of upper body is 14°-18°, and the optimal range of angle between body and skis is 16°-20°. The influence mechanism for bending angle of upper body and angle between body and skis on aerodynamic characteristics during flight in ski jumping can provide effective auxiliary support for on-the-spot prediction and decisionmaking,

14.
Article in English | WPRIM | ID: wpr-903960

ABSTRACT

Neonatal hypoxia/ischemia (H/I), injures white matter, results in neuronal loss, disturbs myelin formation, and neural network development. Neuroinflammation and oxidative stress have been reported in neonatal hypoxic brain injuries. We investigated whether Paeoniflorin treatment reduced H/I-induced inflammation and oxidative stress and improved white matter integrity in a neonatal rodent model. Seven-day old Sprague?Dawley pups were exposed to H/I. Paeoniflorin (6.25, 12.5, or 25 mg/kg body weight) was administered every day via oral gavage from postpartum day 3 (P3) to P14, and an hour before induction of H/I. Pups were sacrificed 24 h (P8) and 72 h (P10) following H/I. Paeoniflorin reduced the apoptosis of neurons and attenuated cerebral infarct volume. Elevated expression of cleaved caspase-3 and Bad were regulated. Paeoniflorin decreased oxidative stress by lowering levels of malondialdehyde and reactive oxygen species generation and while, and it enhanced glutathione content. Microglial activation and the TLR4/NF-κB signaling were significantly down-regulated. The degree of inflammatory mediators (interleukin 1β and tumor necrosis factor-α) were reduced. Paeoniflorin markedly prevented white matter injury via improving expression of myelin binding protein and increasing O1-positive olidgodendrocyte and O4-positive oligodendrocyte counts. The present investigation demonstrates the potent protective efficiency of paeoniflorin supplementation against H/I-induced brain injury by effectually preventing neuronal loss, microglial activation, and white matter injury via reducing oxidative stress and inflammatory pathways.

15.
Journal of Clinical Hepatology ; (12): 425-428, 2021.
Article in Chinese | WPRIM | ID: wpr-873415

ABSTRACT

Spontaneous bacterial peritonitis (SBP) is a common serious complication of end-stage liver disease. Intestinal microecology is closely associated with the development, progression, and prognosis of SBP, and bacterial translocation is the key pathogenesis of SBP. This article summarizes the intestinal microecology in patients with liver cirrhosis and briefly describes the mechanism of action of intestinal flora in the development and progression of SBP, thus providing a theoretical basis for the clinical regulation of intestinal microecology and treatment of SBP.

16.
Acta Pharmaceutica Sinica ; (12): 1727-1738, 2021.
Article in Chinese | WPRIM | ID: wpr-881568

ABSTRACT

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, 1H NMR, and 13C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

17.
Article in Chinese | WPRIM | ID: wpr-881252

ABSTRACT

@#In the absence of symptoms, silent cerebral infarction can be discovered incidentally during an imaging or neuropathological examination. After cardiovascular surgery with cardiopulmonary bypass, the morbidity is high, and it may contribute to neurocognitive dysfunction, symptomatic cerebral infarction and increased risk of death. The embolus caused by various operations intraoperatively are closely associated with this progress. However, controversies over the prevention still persist. As a result, an overall summary of silent cerebral infarction after cardiovascular surgery with cardiopulmonary bypass will be presented in this review.

18.
Article in Chinese | WPRIM | ID: wpr-913068

ABSTRACT

Objective To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. Methods Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1α, HIF-1β and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1α and VEGF mRNA expression was examined. In addition, and the HIF-1α expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. Results Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1α (F = 132.6, P < 0.05) and HIF-1β mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1α (F = 111.5, P < 0.05) and HIF-1β mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1α and HIF-1β mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1α expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1α expression was detected in mouse uterine specimens. Conclusions HIF-1α expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1α inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes.

19.
Cancer Research and Clinic ; (6): 518-522, 2021.
Article in Chinese | WPRIM | ID: wpr-912917

ABSTRACT

Objective:To investigate the value of paraffin-embedded section of cell block in the diagnosis of lung adenocarcinoma in bloody pleural effusion.Methods:The data of 60 patients with lung adenocarcinoma diagnosed by bloody pleural effusion and confirmed by pathological biopsy in the First Affiliated Hospital of Xi'an Jiaotong University from June 2018 to June 2019 were retrospectively analyzed. Cell smears and paraffin-embedded sections of cell blocks using removed red blood cells sedim entation method were used to make cytological examination in bloody pleural effusion. The expressions of carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), NapsinA, thyroid transcription factor 1 (TTF-1), cytokeratin 5/6 (CK5/6), calretinin, P63 and P40 in the specimens were detected by using immunohistochemistry. The results of histopathological examination were used as the gold standard, and the diagnostic values of cell block paraffin-embedded sections and cell smears for lung adenocarcinoma in bloody pleural effusion were evaluated and compared.Results:The cell block sections had a clear background, clear and easy to distinguish cell morphology, and can be made into permanent specimens. The bloody pleural effusion cell smears results of 60 cases of lung adenocarcinoma showed that 21 cases were diagnosed as atypical cells, 39 cases were diagnosed as adenocarcinoma, and the coincidence rate with the diagnosis of adenocarcinoma by histopathological examination results was 65% (39/60); the immunohistochemistry results of cell block paraffin-embedded sections of bloody pleural effusion showed that CK7, NapsinA, TTF-1 and CEA were positive, and P40, P63, CK5/6 and calretinin were negative, all 60 cases were diagnosed as adenocarcinoma according to the results, and the coincidence rate with the diagnosis of adenocarcinoma by histopathological examination results was 100% (60/60), which was significantly higher than that of cytological smears ( χ2 = 23.088, P < 0.01). Conclusions:The technique of paraffin-embedded section of cell block using removed red blood cells sedim entation method has a high diagnostic rate for lung adenocarcinoma in bloody pleural effusion, and it has a high coincidence rate with histopathological diagnosis. It can improve the accuracy of diagnosis of lung adenocarcinoma in bloody pleural effusion, and it also has a good reference value for cytological typing.

20.
Chinese Journal of Digestion ; (12): 534-540, 2021.
Article in Chinese | WPRIM | ID: wpr-912208

ABSTRACT

Objective:To investigate the clinical value of systemic immune-inflammation index (SII) based on peripheral blood neutrophils, lymphocytes and platelets counts in predicting the prognosis of patients with gastric cancer after radical resection.Methods:From January 1, 2012 to January 1, 2015, the data of 2 273 patients with gastric cancer who underwent radical surgery at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. SII value was calculated according to the formula (SII=neutrophil cell count (×10 9/L)×platelet cell count (×10 9/L)/lymphocyte count (×10 9/L)). According to receiver operating characteristic curve (ROC), the optimal cut-off value of SII was determined and the patients were divided into high SII group and low SII group. Chi-square test was used to compare the clinicopathological characteristics and prognosis of the two groups. Kaplan-Meier method was applied to draw survival curve, log-rank test was used for univariate survival analysis, and Cox regression model was used for multivariate survival analysis. The ROC of preoperative SII, pathological TNM stage and their combination for predicting prognosis and recurrence were drawn, and the area under the curve (AUC) values were calculated to compare the predictive power of the three. Results:According to the ROC, the optimal cut-off value of SII was 589.5, and there were 1 180 cases (51.91%) in the high SII (SII≥589.5) group and 1 093 cases (48.09%) in the low SII (SII<589.5) group. Compared with those of the low SII group, the maximum diameter of gastric cancer in the high SII group was mostly ≥5 cm (49.04%, 536/1 093 vs. 56.27%, 664/1 180), the histological types were mostly poorly differentiated to undifferentiated (55.63%, 608/1 093 vs. 61.19%, 722/1 180), the depth of tumor invasion was mainly from T4a to T4b (45.11%, 493/1 093 vs. 54.837%, 647/1 180), and the rate of lymph node metastasis, pathological TNM stage, rate of vascular infiltration, incidence of nerve invasion, Ki-67 expression level, serum carcinoembryonic antigen level and carbohydrate antigen 19-9 level in the high SII group were all higher than those in the low SII group (67.70%, 740/1 093 vs. 80.68%, 952/1 180; 57.64%, 630/1 093 vs. 71.10%, 839/1 180; 55.54%, 607/1 093 vs. 67.03%, 791/1 180; 53.89%, 589/1 093 vs. 64.32%, 759/1 180; 45.29%, 495/1 093 vs. 56.69%, 669/1 180; 56.91%, 622/1 093 vs. 63.20%, 734/1 180; 53.25%, 582/1 093 vs. 57.97%, 684/1 180), and the differences were statistically significant ( χ2=8.842, 11.097, 7.225, 21.467, 50.200, 44.984, 31.687, 25.594, 29.549, 6.612 and 5.119, all P<0.05). The 5-year overall survival rate and disease-free survival rate of the low SII group were 75.66% and 67.61%, respectively, which were both higher than those of the high SII group, (24.92% and 23.31%, respectivily), the differences were statistically significant ( χ2=620.700 and 413.00, both P<0.01). The results of multivariate Cox regression analysis showed that tumor histological type, depth of invasion, pathological TNM stage, vascular invasion and preoperative SII were independent risk factors for postoperative prognosis and recurrence of patients with gastric cancer (odds ratios were 4.126, 2.255, 5.123, 3.826, 6.126, 4.683, 2.472, 5.224, 4.416, 6.212, respectively; 95% confidence interval 2.123 to 9.721, 1.632 to 7.427, 3.325 to 10.211, 2.321 to 9.322, 4.127 to 13.782, 2.561 to 9.418, 1.322 to 6.289, 3.315 to 11.526, 2.213 to 9.382, 4.474 to 13.541; all P<0.05). The predictive power of preoperative SII (AUC=0.842, 0.815) and pathological TNM stage (AUC=0.881, 0.827) for the 5-year overall survival and disease-free survival of patients with gastric cancer after radical resection was similar, however the predictive power of combination of the two (AUC=0.943, 0.895) was higher than that of preoperative SII and pathological TNM stage alone. Conclusions:Preoperative SII is an independent risk factor for the prognosis of patients with gastric cancer after radical resection, combined with parthological TNM stage can be used as an indicator to predict the prognosis and recurrence of patients.

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