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Objective:To investigate the relationship between spinal Mas-related gene receptor C (MrgC) and pathophysiological mechanism of bone cancer pain in mice.Methods:Forty male C3H/HeNCrlVr mice, aged 5-7 weeks, weighing 20-25 g, were selected and divided into 4 groups ( n=10 each) using a random number table method: sham operation group (group S), bone cancer pain group (group P), bone cancer pain + MrgC agonist group (group P-agonist) and bone cancer pain + Mrg C antagonist group (group P-Ab). Preparation of the bone cancer pain model: mouse fibrosarcoma cells (NCTC2472) were injected into the upper tibia of mice in P, P-agonist and P-Ab groups, and the equal volume of D-Hanks balanced salt solution was given instead in S group. Fourteen days later cerebrospinal fluid was intrathecally injected in S and P groups, and MrgC agonist and MrgC antibody were intrathecally injected in P-agonist and P-Ab groups. The mechanical paw withdrawal threshold (MWT) to von Frey stimuli was measured before developing the model (T 0), at 7 days after developing the model (T 1), at 14 days after developing the model (before intrathecal injection, T 2), and at 4, 8 and 12 h after intrathecal injection (T 3-5). Results:Compared with group S, no significant change was found in the MWT at T 0 ( P>0.05), and the MWT was significantly decreased at T 1-T 5 in the other groups ( P<0.05). Compared with group P, the MWT was significantly increased at T 3-T 5 in group P-agonist, and the MWT was significantly decreased at T 3-T 5 in group P-Ab ( P<0.05). Conclusions:Spinal MrgC plays an endogenous protective role in the pathophysiological mechanism of bone cancer pain to a certain extent in mice.
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Objective:To explore the prognostic value of circulating tumor cell (CTC) for colorectal cancer.Method:We analyze the correlation between CTC and clinicopathological data, survival curve and overall survival.Results:The positive rates of preoperative and postoperative CTC in 181 colorectal cancer patients were 66.3% and 65.7% respectively ( χ2=0.012, P=0.912). The postoperative CTC positive rates for recurrence and non-recurrence of stage Ⅱ colorectal cancer were 29.2% and 8.0%, respectively ( χ2=4.303, P=0.038). The progress free survuval of CTC-positive and CTC-negative in postoperative stage Ⅱ colorectal cancer patients were 28.7 months and 34.0 months, respectively ( χ2=4.096, P=0.043). Conclusion:Postoperative CTC detection has predictive prognostic value for patients with stage Ⅱ colorectal cancer.
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Objective:To investigate the correlation between migraine and overall burden of cerebral small vessel disease (CSVD).Methods:Migraine patients who visited the headache clinic of Jiangyin People's Hospital from January 2021 to October 2021 were selected as the case group, and healthy people who had no previous primary headache of any type and matched age and sex in the same period were selected as the control group. Various CSVD phenotypes, including vasogenic lacuna, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs) and enlarged perivascular space (EPVS) were detected by the multimodal MRI, and the overall burden score of CSVD was calculated. The detection rates of CSVD and its phenotypes and the overall burden of CSVD were compared between the case group and the control group. The subjects with CSVD were divided into mild group, moderate group and severe group according to the overall burden score of CSVD. The independent influencing factors of the overall burden of CSVD were identified by the ordinal multi-classification logistic regression model. Results:A total of 109 migraine patients and 100 healthy controls were enrolled. The detection rate of CSVD (65.13% vs. 46.00%; P=0.005) and the proportion of patients with severe CSVD overall burden (24.77% vs. 10.00%; P=0.005) in the case group were significantly higher than those in the control group. In terms of specific CSVD phenotypes, the detection rates of WMHs (48.62% vs. 33.00%; P=0.022) and CMBs (35.80% vs. 19.00%; P=0.007) in the case group were significantly higher than those in the control group, while there were no significant differences in vasogenic lacuna and moderate to severe EPVS. Univariate analysis showed that the overall burden of CSVD was significantly associated with age, migraine, hypertension, baseline diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C) and glycosylated hemoglobin (all P<0.05). Multivariate logistic analysis showed that age (odds ratio [ OR] 3.731, 95% confidence interval [ CI] 1.051-1.217; P=0.001), migraine ( OR 2.812, 95% CI 1.045-5.124; P=0.012), hypertension ( OR 2.112, 95% CI 1.525-4.021; P=0.032), and LDL-C ( OR 2.512, 95% CI 1.541-4.312; P=0.023) were independently associated with the overall burden of CSVD. Conclusions:The detection rate of CSVD in migraine patients is higher than that in the general population, especially WMHs and CMBs. Migraine is independently associated with the overall burden of CSVD.
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@#Objective To explore the relationship between the total burden of cerebral small vessel disease (CSVD) and the progression of large artery atherosclerosis (LAA) cerebral infarction in acute stage.Methods One hundred and forty-three patients with acute LAA cerebral infarction were collected.The CSVD total load score (0~4 points) was calculated according to MRI and CSVD total load scale.According to the progress of the disease in the acute phase,the patients were divided into two groups:non progressive cerebral infarction group (NPCI) and progressive cerebral infarction group (PCI).The baseline data,CSVD sub items and total load scores were compared between two groups.Logistic regression analysis was used to analyze the relationship between CSVD total load score and the progression of LAA type cerebral infarction.Results There was significant difference in CSVD total load score between PCI group and NPCI group (P<0.05).In group PCI,smoking history,diabetes history,baseline diastolic blood pressure,fasting blood glucose,vascular lacuna,moderate and severe WMH,CMBs and CSVD total load score were all higher than those in NPCI group (P<0.05),and LDL-C level was lower than that in NPCI group (P<0.05).Logistic regression analysis showed that fasting blood glucose,moderate and severe WMH and CSVD total load score were independent risk factors for the progression of LAA cerebral infarction in acute stage (P<0.05).Conclusion The severity of CSVD in patients with LAA type cerebral infarction is closely related to the progress of the disease in acute phase.
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ObjectiveTo investigate the distribution of traditional Chinese medicine (TCM) syndrome types and syndrome elements of nonalcoholic fatty liver disease (NAFLD). MethodsRelated databases (CNKI, Wanfang Dota, and VIP)were searched for articles on the syndrome differentiation of NAFLD published up to July 2020. Two investigators independently performed literature screening and collection and summarization of syndrome types based on the inclusion and exclusion criteria, and an Excel 2010 database was established after the standardization of syndrome names, re-decomposition of syndrome types, and extraction of syndrome elements. The data were imported into SPSS 25.0 statistical software for the analysis of frequency distribution. ResultsA total of 45 qualified articles were collected, with a total of 8703 cases reported. A total of 14 syndrome types were obtained after standardization, and 10 syndrome elements reflecting the nature of disease and 4 syndrome elements of disease location were obtained after the syndrome types were disassembled. Stagnation of liver Qi and spleen deficiency syndrome (26.47%) and damp-heat accumulation syndrome (22.16%) were the most common syndrome types, followed by stagnation of phlegm dampness, intermingled phlegm and blood stasis, and stagnation of liver Qi and Qi stagnation. Dampness (23.75%), Qi stagnation (19.82%), Qi deficiency (17.12%), phlegm (15.43%), and heat (12.13%) were the most common syndrome elements reflecting the nature of disease, followed by stasis, Yin deficiency, and Yang deficiency, while fire and cold were relatively uncommon. Qi stagnation and Qi deficiency (26.63%), dampness and heat (22.30%), phlegm and dampness (16.17%), and phlegm and stasis (12.19%) were the most common combinations of syndrome elements. The liver and the spleen were the most common syndrome elements of disease location, accounting for 90.95% of the constituent ratio, and the combination of the liver and the spleen with the same disease accounted for 54.01%. The combination of one, two, three, or four syndrome elements was observed, and the combination of two syndrome elements accounted for 76.03%. ConclusionStagnation of liver Qi and spleen deficiency are the basic pathogeneses of NAFLD, and liver, spleen, dampness, Qi stagnation, Qi deficiency, phlegm, and heat are common syndrome elements. Dampness, phlegm, and heat are important factors for the development and progression of this disease.
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Objective:To evaluate the relationship between phosphorylation of glycogen synthase kinase-3β (GSK-3β) and high glucose-caused abolition of cardioprotection induced by sevoflurane postconditioning.Methods:H9c2 cells were incubated in normal glucose (5.56 mmol/L) DMEM culture medium or high glucose (33 mmol/L) DMEM culture medium.The cells were divided into 8 groups ( n=24 each) using a random number table method: normal control group (group NC), normal glucose-cultured hypoxia/reoxygenation (H/R) group (group NH/R), normal glucose-cultured sevoflurane postconditioning group (group NS), normal glucose-cultured GSK-3β inhibitor SB216763 group (group NSB), high glucose-cultured group (group HC), high glucose-cultured H/R group (group HH/R), high glucose-cultured sevoflurane postconditioning group (group HS) and high glucose-cultured GSK-3β inhibitor SB216763 group (group HSB). The model of cardiomyocyte H/R was established by subjecting cardiomyocytes to 3 h of hypoxia followed by reoxygenation.Immediately after onset of reoxygenation, cardiomyocytes were exposed to 2.4% sevoflurane for 30 min in Ns and HS groups.Before the beginning of reoxygenation, GSK-3β inhibitor SB216763 was added to the culture medium with the final concentration of 10 μmol/L in NSB and HSB groups.At 3 h of reoxygenation, the apoptosis rate was determined by Anexin V-PI flow cytometry, the expression of GSK-3β and phosphorylated GSK-3β (p-GSK-3β) was detected by Western blot, superoxide dismutase (SOD) activity was measured using xanthineoxidase method, and lactic dehydrogenase (LDH) activity and malondialdehyde (MDA) content were determined by colorimetric assay. Results:Compared with group NC, apoptosis rate, LDH activity and MDA content were significantly increased, and SOD activity was decreased in group NH/R and group HC, expression of GSK-3β was up-regulated, and expression of p-GSK-3β was down-regulated in group NH/R, expression of p-GSK-3β was up-regulated in group NS, and expression of p-GSK-3β was down-regulated in group HC ( P<0.05). Compared with group NH/R, apoptosis rate, LDH activity and MDA content were significantly decreased, and SOD activity was increased in group NS and NSB groups, and expression of GSK-3β was down-regulated, and expression of p-GSK-3β was up-regulated in group NS ( P<0.05). Compared with group HC, apoptosis rate, LDH activity and MDA content were significantly increased, SOD activity was decreased, expression of GSK-3β was up-regulated, and expression of p-GSK-3β was down-regulated in group HH/R ( P<0.05). Compared with group HH/R, apoptosis rate, LDH activity and MDA content were significantly decreased, and SOD activity was increased in group HSB ( P<0.05). Conclusion:The mechanism by which high glucose abolishes cardioprotection induced by sevoflurane postconditioning is related to inhibiting phosphorylation of GSK-3β.
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Objective To explore the clinical and neuroimaging features in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) caused by mutation of the colony stimulating factor 1 receptor gene (CSF1R). Methods The proband and another patient from a HDLS pedigree were assessed respectively through standardized clinical evaluation (medical history inquiry, physical examination),neuropsychology assessment,MRI,genetic sequencing, as well as brain PET imaging with carbon11-labelled Pittsburgh compound-B(11C-PIB). Results A HDLS pedigree with three patients was recruited to this study. Apathy, memory decline, slow behavior were the first symptoms for two of the patients. Being bedridden, urinary incontinence and epilepsy were developed at the later stage. A missense mutation c. 2381T>C(p. I794T) in exon 18 of the CSF1R gene of chromosome 5 was identified in the proband. The brain DWI illustrated multiple patchy high signal in periventricular white matter and centrum semiovale which was characterized by persistence, and the corpus callosum was affected in the early stage. Conclusion The multiple patchy high signal with persistence in periventricular white matter and centrum semiovale of DWI is helpful for the early diagnosis of HDLS.
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Objective To investigate the protection effect of cyclosporine A on spatial memory following chronic cerebral hypoperfusion in rats and its possible mechanism.Me,ods Sixty SD rats were randomly divided into sham operation,vehicle,low-dose cyclosporine A,medium-dose cyclosporine A,and high-dose cyclosporine A groups.A chronic cerebral hypoperfusion model was prepared by permanent bilateral ligation of bilateral common carotid arteries.From 46 days after modeling,olive oil 1 ml/d was used for intragastric administration in the sham-operation group and the vehicle group.Cyclosporine A 3 mg/kg,6 mg/kg,and 12 mg/kg were administrated intragastrically in the low-dose,medium-dose and high-dose cyclosporine A groups,respectively,once a day for 14 days.The spatial memory was assessed using Morris water maze test.Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of NADPH oxidase 4 (NOX4) mRNA in the cerebral cortex.Immunohistochemical staining and Western blot were used to detect the expression of NOX4 protein in the cerebral cortex.Results The Morris water maze test showed that the escape latencies in all cyclosporine A groups were significantly shorter than the vehicle group (all P ＜0.05).Immunohistochemical staining showed that the percentages of the NOX4-positive cells in the sham-operation,vehicle,low-dose,medium-dose,and high-dose cyclosporine A groups were4.43％ ±0.37％,37.44％ ±4.76％,18.05％ ±2.91％,12.51％ ±3.4％,and 11.06％ ±1.74％,respectively (F =262.021,P ＜ 0.001),the vehicle group was significantly higher than the sham-operation group (P ＜ 0.01),and all cyclosporine A groups were significantly less than the vehicle group (all P ＜ 0.01).RT-PCR showed that the expression levels of NOX4 mRNA in cerebral cortex in the sham-operation,vehicle,low-dose,medium-dose,and high-dose cyclosporine A groups were 0.36 ± 0.03,1.04 ± 0.04,0.58 ± 0.02,0.49 ± 0.01,and 0.40 ± 0.02,respectively (F =1 324.941,P ＜ 0.001),all cyclosporine A groups were significantly lower than the vehicle group (all P ＜ 0.01).Western blot showed that the expression levels of NOX4 protein in cerebral cortex in the sham-operation,vehicle,low-dose,medium-dose,and high-dose cyclosporine A groups were 0.02 ± 0.01,0.27 ± 0.04,0.09 ± 0.02,0.06 ± 0.02,and 0.06 ± 0.01,respectively (F =222.692,P ＜ 0.001),all cyclosporine A groups was significantly lower than the vehicle group (all P＜0.01).Conclusion Cyclosporine A may improve spatial memory following chronic cerebral hypoperfusion in rats by down-regulation of NOX4.
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H type hypertension is essential hypertension complicated elevated plasma homocysteine level ,which ac-counts for about 75% in Chinese adults with hypertension and is closely related to cerebral stroke and other cardio-vascular diseases .Lowering homocysteine level in patients with hypertension possesses important significance for preventing stroke .
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Objective:To detect the biological activity of the expression products of the human ?-NGF cDNA in CHO cell line and purified the seperated protein.Methods:Human ?-NGF was transfected with lipofectamine reagent into CHO cell line.The biological activity was analyzed by objection with microscope and the method of MTT.The pure protein was proved by SDS-PAGE analysis.Results:The protein in the culture supernatant of the positive CHO cells transfected with ?-NGF gene could stimulate the growth of PC12 cell line and go into BBB.Conclusion:The target gene expressed successfully in the transfected CHO cell line and had good biological activity. [