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1.
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.

2.
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.

3.
Article in Chinese | WPRIM | ID: wpr-910067

ABSTRACT

Objective:To characterize the radial head fracture combined with capitulum cartilage injury (CCI).Methods:The data of 110 patients were analyzed retrospectively who had been treated for radial head fracture at Department of Orthopaedics, The Ninth People's Hospital of Wuxi from January 2011 to May 2020. They were 62 males and 48 females, aged from 17 to 74 years (average, 44.10 years). According to the finding of intraoperative exploration whether CCI was complicated or not, they were assigned into a CCI group and a CCI-free group. The diagnosis, location, size, type, operation method and postoperative recovery of CCI were observed in CCI group. The 2 groups were compared in terms of preoperative general data, range of forearm motion before and after operation and functional recovery of the limb by Mayo elbow performance score (MEPS).Results:CCI was complicated in 25 cases (type Ⅰ in 7 ones, type Ⅱ in 12 ones and type Ⅲ in 6 ones), involving all Mason types of radial head fracture, and located at the lateral capitellum in 13 cases, at the posterolateral capitellum in 9 cases and at the anterolateral capitellum in 3 cases. CCI was diagnosed before operation in 13 cases by physical examination after local anesthesia and imaging examination with a rate of 48% (12/25) for missed diagnosis. The preoperative flexion and extension (61.8°±13.7°) and rotation (60.0°±24.2°) in CCI group were significantly less than those in CCI-free group (77.7°±23.0° and 79.9°±21.9°) ( P<0.05); the Mason types of radial head fracture in CCI group were significantly more serious than those in CCI-free group ( P<0.05). There was no significant difference between the 2 groups in age, gender, combined injury, treatment of radial head fracture, follow-up time, range of forearm motion at the last follow-up or MEPS score ( P>0.05). Conclusions:CCI was complicated in 22.73%(25/110) of the radial head fractures in this cohort and found in all Mason types of radial head fracture, and mostly located at the lateral and posterolateral capitellum. CCI is likely to be missed by imaging examination. In patients with mild radial head fracture and suspected CCI, positive physical examination after local anesthesia is valuable for diagnosis of CCI complication and operative indication. Care should be taken to detect CCI complication by intraoperative exploration in surgery of radial head fracture.

4.
Chinese Journal of Trauma ; (12): 635-640, 2021.
Article in Chinese | WPRIM | ID: wpr-909914

ABSTRACT

Objective:To explore the clinical efficacy of periosteum-covered iliac crest autografts for treatment of severe osteochondral lesions of talus (OCLTs).Methods:A retrospective case series study was used to analyze the clinical data of 26 patients with severe OCLTs treated at Zhejiang Armed Police Corps Hospital from January 2013 to October 2019. There were 21 males and 5 females,aged 17-49 years [(36.3 ± 10.9)years]. All patients were treated using periosteum-covered iliac crest autografts. The visual analogue scale (VAS),American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and ankle joint range of motion (ROM) were assessed before operation,6 months after operation and at the last follow-up (≥ 12 months). The area of talus injury with MRI at the same level was recorded before operation and at the last follow-up. The healing of talus and joint surface was detected with CT at the last follow-up. The healing of the incision and osteotomy site and complications were observed.Results:All patients were followed for 12 to 22 months[(15.1 ± 3.2)months]. The VAS was (2.4 ± 0.9)points and (1.7 ± 0.6)points at postoperative 6 months and at the last follow-up,significantly lower than the preoperative (5.4 ± 1.2)points ( P < 0.01). Meanwhile,the VAS at the last follow-up was significantly lower than that at postoperative 6 months ( P < 0.01). The AOFAS ankle-hindfoot score was (71.7 ± 7.8)points and (87.8 ± 6.2) points at postoperative 6 months and at the last follow-up,significantly lower than the preoperative (66.5 ± 7.5) points ( P < 0.01). Meanwhile,the AOFAS ankle-hindfoot at the last follow-up was significantly lower than that at postoperative 6 months ( P < 0.01). The ankle ROM was (58.4 ± 5.5)° and (70.0 ± 4.9)° at postoperative 6 months and at the last follow-up,significantly improved when compared to the preoperative (42.3 ± 8.1)° ( P < 0.01). Meanwhile,the ankle ROM at the last follow-up was significantly improved when compared to that at postoperative 6 months ( P < 0.01). The area of talus injury with MRI at the same level was 0.67(0.55,0.89)cm 2 at the last follow-up,significantly improved when compared to preoperative 2.64(1.98,3.68)cm 2 ( P < 0.01). The transplantation had neither obvious defects nor joint surface steps based on CT findings. All surgical incisions were healed by first intention. There were no complications such as incision infection,skin necrosis,nonunion of osteotomy,malunion or severe ankle joint disorder except that 8 patients had residual local subchondral bone?marrow?edema-like?signal?and 2 patients showed delayed healing of medial malleolus osteotomy. Conclusion:For patients with severe OCLTs,periosteum-covered iliac crest autografts can effectively relieve ankle pain,improve ankle function,and reduce the area of injury.

5.
Chinese Critical Care Medicine ; (12): 529-534, 2021.
Article in Chinese | WPRIM | ID: wpr-909353

ABSTRACT

Objective:To evaluate the effects of noise, bright light and mechanical stimulation on sleep, blood-brain barrier and cognitive function in septic rats.Methods:Forty male Sprague-Dawley (SD) rats were selected and intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) was used to establish sepsis model. 0, 30, 45, 60, 75 dB noise stimulation or 0, 50, 100, 200, 400 Lux light stimulation were given to rats (all n = 4). The serum levels of cortisol and melatonin, and the cerebral content of Evans blue (EB) were measured 96 hours after the stimulation to determine the optimal intensity of intervention. The other 40 SD rats were randomly divided into control group (Con group), LPS group, noise intervention group (LPS+60 dB group), 200 Lux light intervention group (LPS+200 Lux group) and mechanical stimulation group (LPS+MS group), with 8 rats in each group. The open fields test and fear conditioning test were used to evaluate the exploratory behavior and cognitive function 96 hours after corresponding stimulation. The enzyme linked immunosorbent assay (ELISA) was used to detect cerebral level of interleukin-6 (IL-6) and serum levels of cortisol and melatonin. The blood-brain barrier integrity was assessed by EB staining. The protein levels of ZO-1, Claudin-5 and caspase-3 in the hippocampus were detected by Western blotting to assess the blood-brain barrier integrity and neuronal apoptosis. Results:Compared with 0 dB group or 0 Lux group, the serum melatonin concentration in 60 dB group and 200 Lux group were significantly reduced, while the serum cortisol concentration and cerebral EB content were significantly increased. Therefore, 60 dB noise and 200 Lux light were selected in the subsequent experiments. Compared with Con group, the horizontal score and vertical score in the open field test in LPS group were significantly decreased. There were no significant differences in the proportion of freezing time, the cerebral contents of EB and IL-6, the serum levels of melatonin and cortisol, and the hippocampal expressions of ZO-1, Claudin-5 and caspase-3. Compared with LPS group, the horizontal score, vertical score and the percentage of freezing time in LPS+60 dB group, LPS+200 Lux group and LPS+MS group were significantly reduced [horizontal score: 73.8±9.7, 80.3±9.4, 64.5±8.3 vs. 103.6±15.5; vertical score: 9.4±1.7, 11.2±1.9, 6.8±0.9 vs. 15.9±2.8; the percentage of freezing time: (45.3±4.7)%, (53.3±5.8)%, (42.1±5.1)% vs. (66.1±6.3)%], the serum level of melatonin was significantly decreased (ng/L: 53.62±6.20, 44.25±6.41, 45.33±5.84 vs. 74.39±7.54), the serum level of cortisol was significantly increased (nmol/L: 818.34±95.53, 710.04±65.41, 989.73±91.63 vs. 398.82±72.59), the levels of EB, IL-6 in the brain tissue were significantly increased [EB (μg/g): 2.80±0.35, 2.38±0.31, 3.24±0.42 vs. 1.59±0.26; IL-6 (ng/g): 31.56±4.11, 26.69±3.75, 37.47±4.56 vs. 16.28±2.69], the expressions of ZO-1 and Claudin-5 were significantly decreased (ZO-1/β-actin: 0.37±0.04, 0.32±0.05, 0.24±0.04 vs. 0.80±0.09; Claudin-5/β-actin: 0.62±0.08, 0.47±0.06, 0.35±0.05 vs. 0.97±0.20), and the expression of cleaved caspase-3 was significantly increased (caspase-3/β-actin: 0.56±0.06, 0.39±0.04, 0.72±0.12 vs. 0.20±0.03), with statistically significant differences (all P < 0.05). Conclusion:60 dB noise, 200 Lux light or mechanical stimulation for 96 hours could inhibit the secretion of serum melatonin, promote the secretion of cortisol, and activate neuroinflammation in septic rats, and lead to neuronal apoptosis in hippocampus and hyper-permeability of blood-brain barrier, which in turn could cause sleep disturbance and cognitive impairment.

6.
Article in Chinese | WPRIM | ID: wpr-908984

ABSTRACT

In this study, 15 second-year resident doctors who had standardized training of OBGYN were taken as research subjects to discuss the effect of training resident doctors with obstetrics forceps by using simulation teaching method. The simulation teaching process includes theoretical study, theoretical examination, simulation teaching of forceps skills and Assessment of forceps skills. In theoretical study section: before learning to use forceps, the students acquired the theoretical knowledge by flipped teaching micro-video mode. In theoretical examination section: the mastery of basic clinical knowledge of using forceps was evaluated through online assessment. In simulation teaching of forceps skills: students who scored 8/10 points were admitted to enter the simulation teaching process, and they had practical training of scenario simulation skills in Clinical Skills Center. In assessment of forceps skills: the mastery of forceps skills was evaluated by standardized forceps delivery procedure items. The results showed that the students in the simulation teaching group had excellent teaching assessment results, and the resident doctors had more confidence in operating forceps independently, and the teaching effect was ideal, which could further promote the simulation teaching of obstetric clinical skills.

7.
Article in Chinese | WPRIM | ID: wpr-908303

ABSTRACT

In order to meet the needs of national development and people′s health, the development of nursing education is facing unprecedented challenges. Nursing practice teaching undertakes the important task of providing talents for the national health cause, and it is urgent to explore a teaching mode that can adapt to the development of the times. In order to provide reference for the further development of clinical nursing education in China, we can establish the clinical nursing practice teaching mode with professional competence as the core from the aspects of clarifying the current situation, innovating the teaching model and improving the ideological and political education quality.

8.
Article in Chinese | WPRIM | ID: wpr-908257

ABSTRACT

Objective:To establish and apply the intervention model of professional attitude for nursing undergraduates in universities of Traditional Chinese Medicine (TCM), and to explore its effect on the professional attitude of the nursing undergraduates.Methods:The study started in August 2018 included two steps. The first step was to develop intervention model of professional attitude for nursing undergraduates in universities of TCM based on the three-stage theory of Kelman ′s attitude formation and with Delphi method. After two rounds of expert consultation, the intervention model of professional attitude for nursing undergraduates in universities of TCM was finally formed, including three intervention stages, a total of 41 intervention measurements. The second step was to use the historical control research method. Grade 2016 nursing undergraduate (the year 2016—2020) in Beijing University of Chinese Medicine was taken as the experimental group ( n=86) and adopted the intervention model. Grade 2012 nursing undergraduate (the year 2012—2016) in the same university was taken as the control group ( n=56) and did not adopted the intervention model during their university study. The two groups were continuously evaluated by "Scale for Nurse ′s Professional Attitude" during their four years in the university. The measurement time was within one week of admission and the 16th week of the second semester of each academic year, with a total of 5 times of measurement. Results:Repeated measurement design showed that the scores of Scale for Nurse′s Professional Attitude of the two groups changed with time. At the end of the first year, the score of the scale in the experimental group was (6.06±0.95) points, higher than (5.41±1.08) points of the control group ( t value was 3.765, P<0.001). There was no difference between the two groups at other time points ( P>0.05). Conclusions:The intervention model of professional attitude for nursing undergraduates in universities of TCM has good operability and can improve the professional attitude of nursing undergraduates in universities of TCM during their freshman year. The intervention model needs to be further adjusted to improve the professional attitude in the subsequent learning stage.

9.
Article in Chinese | WPRIM | ID: wpr-908205

ABSTRACT

PhaseⅡexercise rehabilitation of patients with myocardial infarction is the core stage of the whole exercise rehabilitation process, which plays a vital role in disease rehabilitation and prevention. Previous reviews are difficult to highlight the changes and focus of phaseⅡexercise rehabilitation in patients with myocardial infarction. This article provides a general introduction from the perspective of myocardial infarction patients′ phaseⅡexercise rehabilitation. It summarizes the current status and deficiencies of exercise load assessment method, the types of exercise and effect of the myocardial infarction patient′s phaseⅡexercise rehabilitation, in order to provide reference for the improvement of related studies on exercise rehabilitation.

10.
Article in Chinese | WPRIM | ID: wpr-908164

ABSTRACT

With the development of human centered medical nursing model, empowerment as a new and effective nursing intervention model has been widely concerned. In this paper, from the overview of empowerment theory, the influencing factors of the implementation of empowerment theory in patients with chronic heart failure and the strategies to improve the implementation effect of empowerment theory for patients with chronic heart failure. The purpose of this review is to provide reference for the implementation of empowerment theory for patients with chronic heart failure in China.

11.
Acta Pharmaceutica Sinica ; (12): 3285-3299, 2021.
Article in Chinese | WPRIM | ID: wpr-906851

ABSTRACT

Plant natural products (PNPs) are important sources of innovative drugs. They are mainly obtained by isolation or extraction from plants. Low content and with structural analogues in plants result in high production cost, which restricts the research and application of PNPs. While biopathway construction by synthetic biology provides an alternative for production of PNPs. By biosynthetic pathway analysis of PNPs and reconstructing the biopathway in microorganisms, we can produce PNPs in cell factories efficiently. Recently, several predominantly international reports about biosynthesis of PNPs and its synthetic biology production, triggered the researches of PNPs. Abundant traditional Chinese medicine resources and profound cultural heritage of Chinese medicine make biosynthesis pathway analysis of PNPs to be a research hotspot. And some of the studies have achieved significant progress. Here, recent progress in the biosynthesis of plant natural products and its synthetic biology was reviewed. In particular, the application of new methods and technologies in recent years were summarized and discussed. This will provide reference for the biopathway construction of plant natural products.

12.
Article in Chinese | WPRIM | ID: wpr-906631

ABSTRACT

Objective To explore the different diagnostic values of acid-fast staining, tuberculosis culture, tuberculosis DNA detection (TB-DNA), tuberculosis RNA constant temperature amplification technology (SAT-TB) in the detection of Mycobacterium tuberculosis in sputum specimens. Methods A total of 200 pulmonary tuberculosis patients and 80 non-tuberculosis patients who were hospitalized in Hebei Chest Hospital between September 2015 and September 2019 were selected for this study. Sputum samples were collected after admission, and the detection values of acid-fast staining, tuberculosis culture, TB-DNA, and SAT-TB in sputum samples were statistically analyzed. Results The differences in the sensitivity, accuracy, positive predictive value, and negative predictive values of the four diagnostic methods of acid-fast staining, tuberculosis culture, TB-DNA, and SAT-TB were statistically significant (P TB-DNA> tuberculosis culture> acid-fast staining. In terms of the positive predictive value of diagnosis, the values of SAT-TB, TB-DNA, and tuberculosis culture were higher than that of acid-fast staining. The Kappa values of the four methods and the gold standard were: Kappa (acid-fast staining) = 0.145, Kappa (tuberculosis culture) = 0.395, Kappa (TB-DNA) = 0.602, and Kappa (SAT-TB) = 0.770. Conclusion The four diagnostic methods of acid-fast staining, tuberculosis culture, TB-DNA, and SAT-TB all had certain detection value with their advantages and disadvantages. SAT-TB was a better detection method with high specificity, good sensitivity, and a short detection timer, which could quickly identify bacteria and distinguish live bacteria.

13.
Article in Chinese | WPRIM | ID: wpr-906493

ABSTRACT

Objective:To study the quality inspection standard of seeds of <italic>Belamcanda chinensis</italic> and establish the quality grading standard of seeds of <italic>B. chinensis</italic>. Method:The purity of seeds of <italic>B. chinensis</italic> from different producing areas was analyzed,and the 1 000-grain weight,water content,viability and germination rate of seeds of <italic>B. chinensis</italic> with different diameters were determined after diameter classification. K-means was used for cluster analysis to preliminarily formulate the quality grading standard of seeds of <italic>B. chinensis</italic>. Result:There were obvious regional differences in the size of seeds of <italic>B. chinensis</italic>. The particle size of seeds of <italic>B. chinensis</italic> of Xiaochang,Dawu and Huanggang Academy of Agricultural Sciences in Hubei Province was larger and mostly between 4.5 mm to 5.5 mm. The seeds of<italic> B. chinensis </italic>from Tuanfeng,Qujing,Yunnan,and Anguo,Hebei province had smaller particle sizes than those from the other three producing areas,which were mostly between 3.5 mm to 5.0 mm. Arils in seeds of <italic>B. chinensis</italic> were removed by 10% NaClO to effectively break seed dormancy and significantly improve the seed germination rate. On this basis,the seed diameter was taken as the main grading index,and the seed moisture content,viability,germination rate and purity were taken as important reference indexes. The quality of seeds of <italic>B. chinensis</italic> was preliminarily divided into three grades,grade Ⅰ:seed diameter≥5.5 mm,moisture content≤10%,viability≥94%,germination rate≥60%,and cleanliness≥93%;grade Ⅱ:seed diameter≥4.5 mm,moisture content≤10%,viability≥90%,germination rate≥55%,and cleanliness≥85%;and grade Ⅲ:seed diameter≥3.5 mm,moisture content≤10%,viability≥84%,germination rate≥45%,cleanliness≥80%. Conclusion:In this study,the quality grading standard of seeds of <italic>B. chinensis</italic> was preliminarily established to provide reference for the quality evaluation of seeds of <italic>B. chinensis</italic> and the breeding of improved varieties. In addition,the maturity and the storage time of seeds of <italic>B. chinensis</italic> have a greater impact on the quality of seeds,so it is recommended to select fully mature(dark black) seeds and new seeds for production.

14.
Article in Chinese | WPRIM | ID: wpr-906456

ABSTRACT

Objective:To determine the contents of inorganic arsenic(iAs),monomethylarsonic acid(MMA) and dimethylarsinic acid(DMA) in brain tissues and blood by using hydride generation-cold trap-atomic absorptionspectrometry(HG-CT-AAS), and to explore the toxic effects of Realgar on central nervous system of rats. Method:The 96 Wistar rats were randomly divided into 4 groups:normal control group,0.3,0.9 and 2.7 g·kg<sup>-1</sup> Realgar groups. They then received intragastric administration for 14,28 and 42 days respectively, so a total of 12 groups were formed, with 8 animals in each group. The normal group was given the same dose of sodium carboxymethyl cellulose (CMC-Na) by gavage. The contents of iAs,MMA and DMA in blood and brain tissues were determined by HG-CT-AAS. The novel object recognition test was conducted to observe the learning and memory ability of rats. The changes of hippocampal neuron ultrastructure were observed by transmission electron microscopy. Result:There was no difference in the growth,weight and hippocampal coefficient of the experimental animals. The method of HG-CT-AAS showed a good linearity,precision,accuracy and recovery in content determination of arsenic (at various forms) in rat brain and blood. MMA and DMA were detected in the brain of realgar groups at time-dose-effect relationship. iAs,MMA and DMA were detected in the blood of Realgar groups. The nuclear membrane, mitochondria and endoplasmic reticulum in hippocampus neurons of rats were gradually damaged with the increase of Rhubarb exposure dose and time. After 14 days of exposure to Realgar,compared with the normal control group,there was no significant difference in the novel object recognition index among Realgar groups. After 28 days of exposure,only 2.7 g·kg<sup>-1</sup> Realgar group showed statistically significant difference with the control group (<italic>P</italic><0.05). After 42 days of exposure, the novel object recognition index of 0.9 and 2.7 g·kg<sup>-1</sup> Realgar groups was significantly lower than that in normal control group(<italic>P</italic><0.05). Conclusion:The metabolites of Realgar in rats are iAs,MMA and DMA. MMA and DMA can be accumulated in the brain tissue through the blood-brain barrier,causing the decline of the ability of learning and memory and leading to damage of hippocampal neurons.

15.
Article in Chinese | WPRIM | ID: wpr-906424

ABSTRACT

Objective:To investigate the hepatotoxicity of different doses of geniposide on the liver of rats and the effects on bile acid profile in serum, liver tissue and feces. Method:The 60 Sprague Dawley rats, half male and half female, were randomly divided into 5 groups according to body weight: blank group and four different doses (50, 100, 200, 400 mg·kg<sup>-1</sup>) geniposide groups, 12 rats in each group. The rats were treated by gavage once a day for 7 consecutive days, and the serum, liver and cecal contents were collected on the 8<sup>th</sup> day of treatment. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), the contents of albumin (ALB), total bilirubin (TBIL), total bile acid (TBA), creatinine (Crea) and carbamide (Urea) were detected in each group. The sections of liver tissue were stained with hematoxylin-eosin(HE), and the protein expressions of cytokeratin 7(CK7) and cytokeratin 19(CK19) were detected by immunohistochemistry. The protein expressions of CK7 and CK19 in the liver tissue were detected by Western blot. And the mRNA expressions of cholesterol 7<italic>α</italic>-hydroxylase (CYP7A1), cholesterol 27<italic>α</italic>-hydroxylase ( CYP27A1) and cholesterol 12<italic>α</italic>-hydroxylase (CYP8B1) were detected by real-time PCR. The contents of 18 kinds of bile acids in serum, liver and cecal contents were determined by ultra-performance liquid chromatography-mass spectrometry(UPLC-MS). Result:Compared with the control group, TBIL level in each dose of geniposide group was increasesd significantly (<italic>P</italic><0.01). ALT, AST activity and TBA content in 400 mg·kg<sup>-1</sup> geniposide group were increased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). HE staining showed that, compared with control group, there was bile duct reaction in the portal area and inflammatory cells infiltrate around bile duct in 200 mg·kg<sup>-1</sup> and 400 mg·kg<sup>-1</sup> geniposide groups, especially 400 mg·kg<sup>-1</sup>. The expressions of CK7 and CK19 in liver tissue of 400 mg·kg<sup>-1</sup> geniposide group were significantly higher than those in the control group (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the control group, the contents of glycoursodeoxycholic acid (GUDCA) and glycohyodeoxycholic acid (GHDCA) in liver tissue of 400 mg·kg<sup>-1</sup> geniposide group decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01), the contents of sodium taurochenodeoxycholate (TCDCA), hyodeoxycholic acid (HDCA), cholic acid (CA) and chenodeoxycholic acid (CDCA) in liver tissue increased significantly (<italic>P</italic><0.01), the contents of glycocholic acid hydrate (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid hydrate (GDCA), glycocholic acid (GLCA), tauroursodeoxycholic acid (TUDCA), GUDCA, GHDCA, ursodeoxycholic (UDCA) and taurolithocholic acid (TLCA) decreased, the proportions of TCDCA, HDCA, CA, CDCA and deoxycholic acid (DCA) in liver tissue increased, the contents of GHDCA and lithocholic acid (LCA) in serum decreased significantly (<italic>P</italic><0.01), while sodium taurohyodeoxycholate hydrate (THDCA), taurocholic acid (TCA), GCA, TCDCA, UDCA, CA, CDCA, DCA in serum decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). The contents of CA, UDCA, CA, CDCA and DCA increased significantly (<italic>P</italic><0.05), the ratio of CA/DCA increased significantly (<italic>P</italic><0.05), and the ratio of CA and CDCA increased by 19.60% and 4.63%, respectively; Compared with the control group, the contents of all bile acids in cecal contents of 400 mg·kg<sup>-1</sup> were decreased, and the contents of GCA, UDCA, HDCA, GCDCA, GDCA, TLCA, GLCA, CDCA, DCA and LCA were decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). In addition, real-time PCR results showed that the mRNA expressions of CYP7A1, CYP27A1 in the 400 mg·kg<sup>-1</sup> geniposide group were significantly higher than those in the control group (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:The 400 mg·kg<sup>-1 </sup>geniposide can cause obvious hepatotoxicity in rats, and the bile acid profile in liver, serum and excrement changes significantly, and the changes of the each bile acid in liver, serum and feces are different. However, the causal relationship between the gardenoside-induced liver injury and the changes in bile acid profile are<italic> </italic>not clear. It needs to be further studied.

16.
Article in Chinese | WPRIM | ID: wpr-906078

ABSTRACT

Objective:To explore the mechanism of Banxia Xiexintang (BXXX) in preventing and treating chronic atrophic gastritis (CAG) through Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. Method:SD rats were divided into a normal group (<italic>n</italic>=12) and an experimental group for CAG model induction. The model rats were then randomly divided into a model group, a vatacoenayme (VG) group (60 mg·kg<sup>-1</sup>), and high- (280 mg·kg<sup>-1</sup>), medium- (140 mg·kg<sup>-1</sup>), and low-dose (70 mg·kg<sup>-1</sup>) BXXX groups. The doses in the BXXX groups were equivalent to 28, 14, and 7 g·kg<sup>-1</sup> crude drugs. The rats in the normal group and the model group received distilled water at an equal volume, and those in the VG group and the BXXX groups were treated correspondingly by gavage. After 12 weeks of treatment, hematoxylin-eosin (HE) staining was carried out to observe pathological changes in the gastric mucosa of CAG rats. Western blot and real-time fluorescence-based quantitative PCR was used to detect the protein and mRNA expression levels of Nrf2, glutathione S-transferase (GST), and NAD (P)H:quinone oxidoreductase 1 (NQO1) in the gastric mucosa of CAG rats. Result:Compared with the normal group, the model group showed increased protein and mRNA expression levels of Nrf2, NQO1, and GST in the gastric mucosa of the rats (<italic>P</italic><0.05), atrophic gastric mucosa, and even intestinal metaplasia. The protein and mRNA expression levels of Nrf2, NQO1, and GST in the VG group and the high- and medium-dose BXXX groups were lower than those in the model group (<italic>P</italic><0.05), and gastric mucosa atrophy and intestinal metaplasia were significantly improved, especially in the high-dose BXXX group. However, the effect in the low-dose BXXX group was not significant. Conclusion:BXXX can blunt the transcriptional activity of Nrf2, shut down Nrf2 signaling pathway, and reduce the expression levels of NQO1 and GST to achieve normal oxidation-anti-oxidation balance, which may be one of its action mechanisms in the treatment of CAG.

17.
Article in Chinese | WPRIM | ID: wpr-905965

ABSTRACT

Objective:To investigate the effect of Ranae Oviductus (RO) on ovarian follicular development, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, and pregnancy function in rats, and the estrogen-like mechanism of OR. Method:Seventy female Wistar rats were randomly divided into a normal group, a progynova+ luteohormone group (1 mg·kg<sup>-1</sup>+40 mg·kg<sup>-1</sup>), a clomiphene group (10 mg·kg<sup>-1</sup>), and high-dose(400 mg·kg<sup>-1</sup>) and low-dose(200 mg·kg<sup>-1</sup>) RO groups. Rats were administered correspondingly by gavage for eight weeks. After seven weeks of intragastric administration, the estrus cycle of all rats was measured. After eight weeks of intragastric administration, four rats from each group were selected to give birth. For other rats, blood was collected on the day of estrus, and the serum levels of estradiol (E<sub>2</sub>),progesterone (P), testosterone (T), follicle-stimulating hormone (FSH), and luteotropic hormone (LH) were detected. Uterus and ovaries were extracted and weighed to calculate organ index. One ovary was made into pathological sections, and the follicles at different developmental stages and corpus luteum were counted. Real-time fluorescence-based quantitative polymerase chain reaction(Real-time PCR)and Western blot were performed on the other ovary to detect mRNA and protein changes in the PI3K/Akt signaling pathway. Forty female Kunming mice were randomly divided into a normal group and RO groups (400 mg·kg<sup>-1</sup>) with 14 days, 28 days, and 56 days of intervention. Mice in the RO groups were raised with male mice in cages after intragastric administration of OR for 14, 28, and 56 days, respectively. After 18 days, the number of intrauterine fetuses on both sides and the number of stunted fetuses were counted. Result:After eight weeks of intragastric administration of OR, the rats showed decreased uterine index (<italic>P</italic><0.05), declining serum LH (<italic>P</italic><0.05), reduced luteum (<italic>P</italic><0.01), dwindled primary follicles (<italic>P</italic><0.05), and increased rate of follicle atresia (<italic>P</italic><0.01). Additionally, more luteal or interstitial glands degenerated into interstitial structures in the ovarian cortex in a short time. The mRNA expression levels of PI3K and Akt in the ovary were elevated (<italic>P</italic><0.01), while the mRNA expression levels of mTOR and PTEN were reduced (<italic>P</italic><0.01). The phosphorylation level of Akt protein showed a downward trend without significant difference. For the rats, the number of fetuses was decreased (<italic>P</italic><0.05). The pregnancy rate of mice was decreased to varying degrees after administration of RO for different durations, with the lowest in the 14 day RO group, as low as 30%. After 28 days of intragastric administration of RO, the difference in left and right uterine pregnancy increased (<italic>P</italic><0.05). Conclusion:Long-term administration of RO can lead to premature ovarian failure by over-stimulating the ovary, which is similar to clomiphene. Short-term administration can result in decreased pregnancy rate, excessive ovulation on one side, and inhibition of ovulation on the other side. The influence on follicles needs further exploration.

18.
Article in Chinese | WPRIM | ID: wpr-905911

ABSTRACT

Objective:To explore the potential targets and pathways of steroid alkaloids<italic> </italic>from<italic> Solanum</italic> <italic>nigrum</italic> (SASN) in the treatment of non-small cell lung cancer (NSCLC) and analyze the possible mechanism. Method:The active SASN against NSCLC were searched from literature. Then potential targets of SASN were screened through SwissTargetPrediction and PharmMapper, and those of NSCLC through GeneCards. Venny was employed to yield the common targets of the two, and Cytoscape to construct the 'medicinal-component-disease-target' network. Metascape was applied to enrich the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the common targets, and STRING was used to generate the protein-protein interaction (PPI) network, followed by screening of key targets by Cytoscape. Finally, Western blot was used to verify the effects of the medicinal on key targets. Result:A total of 6 active SASN were screened out: solasonine, solamargine, solasodine, solanocapsine, solanidine, and <italic>N</italic>-methylsolasodine, which had 96 potential anti-NSCLC targets. These targets mainly involved the pathways in cancer, proteoglycans in cancer, and Forkhead box protein O (FoxO) pathway. PPI network analysis demonstrated 15 key anti-NSCLC targets of SASN, such as mitogen-activated protein kinase (MAPK)1, MAPK8, MAPK14, protein kinase B (Akt1), signal transducer and activator of transcription 3 (STAT3), and proto-oncogene tyrosine protein kinase (SRC). Meanwhile, Western blot results showed that SASN could significantly down-regulate the expression of the key proteins Akt1, SRC, and STAT3. Conclusion:We predicted the potential targets and pathways of SASN against NSCLC and obtained 15 key targets, from which we selected three key proteins for validation. The validation results were consistent with the prediction results. This paper is expected to lay a scientific basis for the subsequent in-depth study of the mechanisms of SASN against NSCLC.

19.
Article in Chinese | WPRIM | ID: wpr-905833

ABSTRACT

Objective:To observe the effect of tetrahydroxy stilbene glycoside (TSG) on the expression of glycogen synthase kinase 3<italic>β </italic>(GSK3<italic>β</italic>), cyclic adenosine monophosphate-dependent protein kinase (PKA) and Serine/threonine phosphatase 2A(PP2A) in the brain of amyloid precursor protein/presenilin-1/Tau (APP/PS1/Tau) triple-transgenic mice dementia model. Method:A total of forty-five 8-month-old APP/PS1/Tau transgenic mice were randomly divided into model group, positive control group (Huperzine-A, 0.15 mg·kg<sup>-1</sup>), low, medium and high dose TSG groups (TSG, 0.033,0.1,0.3 g·kg<sup>-1</sup>), with 9 mice in each group, and another nine C5B7L/6J mice of the same age were selected as normal control group. After 60 days of intragastric administration, the general structure of hippocampal neurons was observed by hematoxylin-eosin (HE) staining, immunohistochemical (IHC) was used to detect the expression of PKA protein in the brain of mice in each group, the mRNA expression levels of GSK3<italic>β</italic>, PKA and PP2A were detected by real time quantitative reverse transcription polymerase chain reaction (Real-time PCR), and protein expression levels of GSK3<italic>β</italic> and PP2A were detected by Western blot. Result:Compared with the normal control group, the apoptosis level of neurons in the model group was significantly increased, the protein and mRNA expression levels of GSK3<italic>β</italic> and PKA were significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01), and the protein and mRNA expression levels of PP2A were significantly decreased (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the model group, the apoptosis level of neurons in each treatment group was significantly down-regulated, the protein and mRNA expression levels of GSK3<italic>β</italic> and PKA were significantly down-regulated (<italic>P</italic><0.05, <italic>P</italic><0.01), and the protein and mRNA expression levels of PP2A were significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:The mechanism of TSG in the treatment of Alzheimer's disease (AD) may be related to lowering the transcription and expression of GSK3<italic>β</italic> and PKA, increasing the transcription and expression of PP2A.

20.
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.

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