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ObjectiveTo investigate the mechanism of Xumingtang in Gu Jin Lu Yan （《古今录验》） in regulating cell pyroptosis through the hypoxia-inducible factor-1α （HIF-1α）/NOD-like receptor pyrin domain-containing protein 3 （NLRP3） pathway in ischemic stroke （IS）. MethodSD rats were randomly divided into a sham operation group， a model group， low- and high-dose Xumingtang groups， and a metformin group， with 20 rats in each group. Oral administration was performed for 3 days， and tissue samples were collected. Differential messenger RNA （mRNA） was screened using high-throughput sequencing， and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were performed on key differentially expressed genes. The modified neurological severity score （mNSS） and 2，3，5-triphenyltetrazolium chloride （TTC） staining were used to evaluate the effect of brain infarction. Hematoxylin-eosin （HE） staining was used for pathological morphological observation of brain tissue. Enzyme-linked immunosorbent assay （ELISA） was used to compare the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the ischemic cortical region. Double staining immunohistochemistry was used to detect the co-localization of HIF-1α and NLRP3. Real-time quantitative polymerase chain reaction （PCR） was performed to detect the mRNA expression of NLRP3， HIF-1α， Caspase-1 （CASP-1）， and gasdermin D （GSDMD）. Western blot was used to detect the protein expression of HIF-1α， NLRP3， CASP-1， and GSDMD. ResultA total of 5 705 differentially expressed genes （2 733 downregulated and 2 972 upregulated） were obtained by mRNA sequencing. After conversion to homologous genes and intersection with the pyroptosis gene set， 95 key differentially expressed pyroptosis genes were obtained. Compared with the sham operation group， the model group showed significantly increased mNSS scores， larger brain infarction areas （P<0.01）， diverse neuronal morphology， disordered arrangement， widened cell gaps， significantly increased levels of IL-1β and IL-18 in the ischemic cortical region （P<0.01）， enhanced co-localization fluorescence intensity， and significantly increased mRNA and protein expression levels of HIF-1α， NLRP3， CASP-1， and GSDMD （P<0.01）. Compared with the model group， the high-dose Xumingtang group showed the most significant improvement in neurological function scores and brain infarction areas （P<0.01）. The neuronal integrity and arrangement were more complete， and the cell gaps were narrower in all groups with drug treatment， with significantly reduced co-localization fluorescence intensity. Xumingtang could reduce the levels of IL-1β， IL-18， and the mRNA and protein expression of HIF-1α， NLRP3， CASP-1， and GSDMD （P<0.05， P<0.01）， with the high-dose Xumingtang group showing the most significant effect （P<0.01）. ConclusionXumingtang in Gu Jin Lu Yan can inhibit cell pyroptosis and promote neurological function recovery after IS， which may be related to the inhibition of the HIF-1α/NLRP3 pathway.
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Objective:To observe the effects of Traditional Chinese Medicine (TCM)ultrasound drug permeation electrotherapy device on the inflammatory response of rats with cerebral ischemia, and to provide an experimental basis for the clinical application of TCM ultrasound drug permeation electrotherapy device in the treatment of cerebral ischemia.Methods:A total of 72 SD rats were randomly divided into sham-operation group (12 rats) and modeling group (60 rats). The middle cerebral artery occlusion (MCAO) model was prepared by thread embolism in the model group. The rats were divided into model group, Chinese medicine tablet group, blank tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "blank tablet + electrotherapy group"), Chinese medicine tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "Chinese medicine tablet + electrotherapy group") and butylphthalide group according to the random number table method, with 12 rats in each group. The corresponding treatment was given continuously for 7 days. The neurological function was scored using Longa method evaluation criteria; TTC staining was used to observe the infarct volume and calculate the percentage of infarct volume; HE staining was used to observe the cell morphology of cortical area in each group of rats; ELISA was used to detect the serum TNF-α and IL-1β levels in each group of rats; TLR4, MyD88 and NF-κBp65 protein expressions in hippocampal tissue of each group of rats on the infarct side were detected by Western blot method.Results:Compared with the model group, the neurological function scores of rats in the blank tablet + electrotherapy group, the herbal tablet + electrotherapy group, and the butylphthalein group significantly decreased ( P<0.05), the percentage of cerebral infarct volume significantly decreased ( P<0.05), the contents of serum TNF-α and IL-1β significantly decreased ( P<0.05), and the expressions of TLR4 (0.42±0.07, 0.31±0.07, 0.19±0.04 vs. 0.68±0.14), MyD88 (0.39±0.12, 0.30±0.07, 0.23±0.11 vs. 0.67±0.10), NF-κBp65 (0.32±0.03, 0.27±0.02, 0.17±0.03 vs. 0.57±0.12) protein in hippocampal tissue significantly decreased ( P<0.05). Conclusion:The TCM ultrasound drug permeation electrotherapy device can inhibit TLR4, MyD88, NF-κBp65 protein expressions and reduce the release of serum inflammatory factors TNF-α and IL-1β, thus exerting cerebral ischemic protective effects.
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BackgroundInternet-based cognitive behavioral therapy （ICBT） is progressively emerging as an efficacious alternative to alleviate anxiety and depression in cancer patients. To date， no Meta-analysis has been conducted specific to the effect of ICBT on anxiety， depression， distress and quality of life in cancer patients. ObjectiveTo assess the effect of ICBT on distress， depression， anxiety and quality of life in cancer patients through a systematic review of the literature. MethodsOn March 28， 2022， PubMed， PsycINFO， Embase， Cochrane Library， Web of Science， CNKI， VIP， Wanfang Data and CBM were retrieved for the randomized controlled trials （RCTs） involving ICBT targeting either distress， depression， anxiety， quality of life or all in cancer patients. After the risk of bias assessment， Stata 17.0 software was used for Meta-analysis. ResultsA total of 12 RCTs with a total sample size of 1 686 patients were included. Meta-analysis revealed that the superiority of ICBT over controls was evident for interventions targeting distress in cancer patients （SMD=-0.547， 95% CI： -1.090~-0.145， P<0.01）， while appeared to be less evident for the interventions targeting depression （SMD=-0.652， 95% CI： -1.734~0.002， P=0.051）， anxiety （SMD=-1.045， 95% CI： -3.656~0.101， P=0.088） and quality of life （SMD=0.234， 95% CI： -0.064~0.449， P=0.112） in cancer patients，and dropout rate was higher in ICBT group than that in control group （OR=1.795， 95% CI：1.358~2.374， P<0.01）. ConclusionICBT is reported to be effective in alleviating distress in cancer patients， whereas results inconsiderable improvements over depression， anxiety and quality of life in cancer patients.
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Rosacea is a chronic recurrent inflammatory skin disease that mainly occurs on the face. A large number of studies have confirmed that rosacea is related to a variety of systemic diseases, including neuropsychiatric diseases such as anxiety, depression, migraine, Alzheimer′s disease and Parkinson′s disease. This review summarizes research progress in the correlation between rosacea and neuropsychiatric diseases, as well as the underlying mechanisms.
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Rosacea is a chronic inflammatory disease. In addition to subjective evaluation, some objective quantifiable indices are needed for the diagnosis and treatment of rosacea. Some skin imaging and noninvasive measurement tools have been applied to clinical practice, and can provide quantitative or semi-quantitative indices to assist the diagnosis and treatment of rosacea. This review summarizes relevant research progress to provide evidence for clinical standardized application.
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Localized neurovascular dysregulation is an important factor for the occurrence of rosacea, and it has been confirmed that neurogenic inflammation is a key step in neurovascular dysregulation. Intradermal injection of botulinum toxin can relieve facial flushing and burning sensations, which may be attributed to the inhibition of neuropeptide release from nerve endings and degranulation of mast cells. This review summarizes the research progress in neurogenic inflammation in the pathogenesis of rosacea and botulinum toxin in the treatment of rosacea, aiming to provide a basis for nerve-related basic research and clinical treatment of rosacea.
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Photobiomodulation, also known as photochemical modulation, refers to the use of low-power light from various sources to induce photophysical and photochemical modulation without thermal injury in the body. Photobiomodulation is related to the wavelength and energy of light. Target chromophores for light of different wavelengths include cytochrome C oxidase, opsin, porphyrin, etc., and the parameters such as power density, spot size, and energy density determine the energy of light. At present, many in vivo and in vitro studies have confirmed the application potential of photobiomodulation in the treatment of various skin diseases.
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Objective To explore relationship between the nature of carotid atherosclerotic plaque and the number and function of endothelial progenitor cells in peripheral blood.Methods A prospective study of 80 carotid atherosclerotic plaque patients were selected from June 2016 to March 2017 in Guangdong Second Provincial General Hospital.All patients were examined with Cranial magnetic resonance imaging or X-ray computed tomography,pathological examination,carotid artery color Doppler ultrasonography.Patients were divided into hard plaque group (n =42) and soft plaque group (n =38) according to the nature of carotid atherosclerotic plaque.Forty healthy subjects were selected as controls.Monocytes were obtained from 10 ml of elbow venous blood by density gradient centrifugation.Adherent cells were cultured and identified by confocal laser microscopy.The number,migration,proliferation and adhesion of EPCs in soft plaque group and hard plaque group were evaluated.Results The number of proliferating cells (0.847 ± 0.037),migrating cells(27.697±8.248) and adherent cells (46.184± 7.876) in the normal control group were significantly higher than those in the hard plaque group ((0.647±0.019),(18.643±3.289),(32.165±4.325)) and the soft plaque group ((0.679± 0.023),(23.576± 6.327),(40.587±6.523)) (all P＜ 0.001),while the proliferation,migration and adherent cells in the hard plaque group were lower than those in the soft plaque group (all P＜0.001).Conclusion The nature of carotid atherosclerosis plaque is closely related to the number and function of endothelial progenitor cells in peripheral blood.The number of endothelial progenitor cells in carotid atherosclerosis patients with hard plaque is small,and their proliferation,migration and adhesion ability are impaired.
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Objective To study the effect and mechanism of S1PR2 inhibition on epithelial ovarian cancer SKOV3 cell proliferation in vitro and in vivo. Methods(1)A pair of S1PR2 gene small interference RNA(siRNA),namely si-S1PR2,and a pair of negative control siRNA were designed.Western blot methods were used to detect the silence efficiency of the S1PR2 in the si-S1PR2 group,blank control group and negative control group.(2)Study in vitro: the experiment included three groups, namely si-S1PR2 group, blank control group and negative control group. Cell counting kit-8(CCK-8)assay was used to detect the proliferation inhibition rates of the transfected cells. The cell cycles of the transfected cells were measured by flow cytometry. Western blot was used to detect the levels of phosph-extracellular regulated protein kinase 1/2(p-ERK1/2)of the transfected cells.(3)Study in vivo:to establish intraperitoneal transplantation models, 8 mice in each group were intraperitoneally injected with 5×106SKOV3 cells. Phosphate buffered saline(PBS)or JTE-013 were administered into mice twice per week starting on day 7 after the injection of the cancer cells. Twenty-eight days after nude mice intraperitoneal injection with JTE-013 or PBS,the mice were sacrificed and the number and the weight of visible tumors were calculated. Results(1)The results of western blot showed that the relative S1PR2 protein expression levels were 0.24±0.04 in the si-S1PR2 group,which was lower than that in the blank control group(1.10±0.14,P<0.01) and negative control group(1.07 ± 0.13, P<0.01).(2)The results of CCK-8 assay indicated that after transfected for 24, 48 and 72 hours, the proliferation inhibition rate of si-S1PR2 group were respectively (26.6±3.3)%,(35.0±3.4)%,and(34.0±2.8)%,significantly lower than those in the blank control group (all 0;all P<0.01)and negative control group[(1.7±0.9)%,(2.5±0.5)%,and(2.4±1.1)% respectively;all P<0.01].The results of flow cytometry showed that the G0/G1ratio in the si-S1PR2 group[(70.9±2.8)%]was significantly higher than those in the blank control group[(61.7±2.4)%,P<0.01]and negative control group [(62.1 ± 3.3)%, P<0.01]. Western blot showed that the relative expression level of p-ERK1/2 in si-S1PR2 group(0.11±0.03)was significantly lower than those in the blank control group[(0.62±0.09),P<0.01]and negative control group[(0.68±0.09),P<0.01].(3)Twenty-eight days after nude mice intraperitoneal injection with JTE-013 or PBS,the tumor number of the control group and JTE-013 group were respectively 15.4±4.3 and 8.2±3.7,the tumor weight were(0.45±0.12)and(0.21±0.07)g,respectively.The tumor number and weight in the JTE-013 group were significantly less than those in the control group(all P<0.01). Conclusions The growth of ovarian cancer cells could be decreased by S1PR2 inhibition in vitro and in vivo. One of the mechanisms of the growth inhibitory effect is probably that S1PR2 inhibition lower the phosphorylation level of extracellular regulated protein kinase 1/2(ERK1/2)pathway, which prevent the transformation of ovarian cancer cells from phase G1to S.
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Objective To investigate the correlations among homocysteine(Hcy)level,serum cystatin C (Cys-c)and diabetic peripheral neuropathy(DPN).Methods Two hundred and three diagnosed cases of type 2 diabetes were enrolled,including 123 DPN patients(DPN+)and 80 non-DPN(DPN-)patients.Levels of serum Hcy,Cys-c,high-sensitivity C-reactive protein(hs-CRP)and fiber fibrinogen(Fg)were detected.The above indi-cators and the baseline data such as sex,age,duration,BMI,WHR,HOMA-IR(CP),HOMA-islet(CP)were statistically analyzed. Results Hcy,Cys-c,and the duration of the DPN+ group were significantly higher than those in the DPN-group(P<0.05,respectively).HOMA-islet(CP)in the DPN-group was markedly higher than that in the DPN+group(P<0.01).The prevalence of DPN in the high level of Hcy group was much higher than that in the low and the normal level of Hcy group.Hcy was still significantly correlated with the Cys-c after taking the controlled procedure such as duration and fibrinogen. Conclusion High levels of Hcy and Cys-c are the criti-cal risk factors of DPN,collaborative determination of Hcy and Cys-c level might be of quitevaluable in early diag-nosis of DPN.
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Objective:To explore the effect of inherent depression on chronic visceral hypersensitivity. The differences of visceral sensitivity, colitis, and brain activation between Fawn-Hooded ( FH/Wjd) and Sprague-Dawley( SD) rats were identified after neonatal colon acetate stimulation.Methods:The specific pathogen free Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were used to establish irritable bowel syndrome (IBS) model.The visceral sensitivity was measured by colorectal distension (CRD). The expression of 5-hydroxytryptamine (5-HT), mast cell (MC), indoleamine 2,3-dioxygenase (IDO) in colon and IDO in specific cerebral regions were detected through immunohistochemistry.Results:Ab-dominal withdrawal reflex ( AWR) scores showed that visceral sensitivity of acetate-enema groups was sig-nificantly higher than that of saline-enema groups ( FH/Wjd:2.44 ±0.04 vs.1.96 ±0.07, P Besides, the MC amounts of control and IBS group of FH/Wjd rats were significantly more than that of SD IBS group rats ( P<0 .01 ) .The IDO and 5-HT positive cells in colonic mucosa of IBS group of both SD and FH/Wjd rats were significantly more than those of their control groups, respectively(P <0.01). The IDO, 5-HT positive cells in colonic mucosa of both control and IBS group of FH/Wjd rats were significantly more than those of both control and IBS group of SD rats ( control:IDO,24.64 ±2.22 vs. 15.52 ±1.39;5-HT,21.32 ±1.26 vs.12.72 ±1.12.IBS: IDO,44.92 ±2.31 vs.20.85 ±1.72;5-HT, 31.84 ±1.57 vs.19.65 ±1.09.P <0.01).The expression of IDO in prelimbic cortex (PrL) areas of FH/Wjd IBS rats was significantly higher than that of IBS group of SD rats (49.60 ±4.31 vs. 35.60 ±2.42, P <0.01) , and the expression of IDO in rostral anterior cingulate cortex ( rACC) areas of FH/Wjd IBS rats was significantly more than that of FH/Wjd control rats (45.44 ±1.16 vs.34.08 ± 2.76, P <0.01) .Conclusion:Inherent depressive FH/Wjd rats were more sensitive to neonatal colon acetate stimulation, presenting as visceral hypersensitivity which maybe associated with increased MC amounts and over-expression of 5-HT and IDO in colon, suggesting that depression disorder may aggra-vate functional disturbance of gastrointestinal tract by regulating the response to inflammatory stimulation.
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BACKGROUND:The method of ligating or resecting rat lower limb femoral or iliac artery has been widely used to make rat models of lower limb ischemia, but there have been no stable and efective methods used to establish diabetic models of chronic atherosclerotic occlusive diseases and to evaluate the ischemic status of hindlimbs of models. OBJECTIVE: To establish type 2 diabetes rat models of lower limb ischemia by feeding with high-fat diet and to evaluate them. METHODS:Twenty rats were randomly and evenly divided into diabetes group (n=10) and control group (n=10). Rats in the diabetes group were fed with high-fat diet for 6 months, and were intraperitonealy injected with streptozotocin (50 mg/kg) to induce diabetes. Rats in the control group were fed with normal diet for 6 months. Rats in these two groups were subjected to ligation of femoral artery to establish right lower limb ischemia models. RESULTS AND CONCLUSION:At the first day of modeling, color Doppler flow imaging and CT angiography showed obviously decreased blood flow suggesting the success of establishing ischemia model. At 7 and14 days after modeling, the blood flow of rats in these two groups showed a gradual recovery as detected by color Doppler flow imaging. At 28 days after modeling, blood flow of rats in the diabetes group was significantly slower than that in the control group (P < 0.05). CT angiography showed that at 28 days after modeling, only a smal amount of compensatory increase in blood flow of the blood vessels at the ligation position of proximal right lower limb femoral artery was seen in the diabetes group, while no obvious blow was observed in the distal part. Histopathologic and immunohistochemical staining showed that at 28 days after modeling, destroyed tissue structure and inflammatory cel infiltration were observed in the ischemic region and capilary density on the affected side was lower than that on the healthy side. The protein expression of vascular endothelial growth factor in the ischemic muscle tissue of rats in the diabetes group was significantly increased compared with that in the control group (P < 0.05). These results show that diabetic rat models of lower limb ischemia can be successfuly established by long term high-fat diet feeding and femoral artery ligation and they can be validated by CT angiography.
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[Summary] Considerable efforts have been made to understand the cellular and molecular mechanisms of metformin ,a potent antihyperglycemic agent now recommended as the first‐line treatment of patients with T2DM. The main effect of this drug is to reducethe hepatic glucose output ,primarily through inhibition of the mitochondrial respiratory chain complex Ⅰ and then activating AM P‐activated protein kinase (AMPK) ,which provide a generally acceptable mechanism for the action of metformin on hepatic gluconeogenesis. Beyond its effect on glucose metabolism ,metformin has been reported to improve ovarian function of patients with polycystic ovary syndrome (PCOS) and to reduce the risk of microvascular and macrovascular complications in patients with T2DM. In addition ,metfomin has also recently been suggested as an adjuvant treatment of cancer. Here we reviewed the progress of mechanism research and clinical application of metformin.
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Objective To quantitate coronary tortuosity and provide favorable conditions for understanding the hemodynamic effects caused by coronary tortuosity.Methods We obtained all images from 72 patients who received coronary computed tomo-graphy scanning.After image post-processing,we extracted the medial axis of three main coronary vessel and analysed its coordi-nates on three dimensions.Then we calculated the tortuosity coefficient of coronary artery.Results Tortuosity coefficient was 6.66±7.54 in anterior descending,13.43±12.85 in left circumflex,and 1 7.61 ±7.67 in right coronary artery.We had proved its validity by the changes in morphology with simulated shapes.Conclusion We proposed a new method for quantitating coronary tor-tuosity,by computed tomography coronary imaging.The measurement results would not be affected by projection plane,vessel length or other artificial factors.
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Objective To estimate the prevalence and risk factors for irritable bowel syndrome (IBS) in China.Methods Cross-sectional studies relevant to IBS conducted among Chinese were identified through the databases including PubMed,Web of Science,the Cochrane Library,CBM,CNKI,Wanfang data and VIP.Quality of studies was assessed according to the criteria for cross-sectional studies recommended by Agency for Healthcare Research and Quality(AHRQ).Analysis of data,publication bias and sensitivity were performed with Stata (Version 12.0).Results A total of twenty-three studies were extracted.No obvious publication bias was detected in all analysis except the effect of depression on IBS prevalence.Pooled prevalence of IBS in China was 6.5％.IBS was more common in women than in men (8.1％ vs 6.8％;OR=1.23,95％CI 1.09-1.38) and high rate in age group between 30 to 59 years (6.9％ ; OR =1.22,95％ CI 1.12-1.32).Intestinal infection history(OR =2.39,95％ CI 1.69-3.38),anxiety (OR =2.95,95 ％ CI 1.94-4.49),depression (OR =1.85,95 ％ CI 1.11-3.09),food allergy (OR =2.80,95％ CI 2.12-3.67) and alcohol consumption (OR =1.15,95％ CI 1.07-1.24) might increase the risk for IBS.There were no significant difference of IBS prevalence between urban and rural areas (OR =0.97,95％ CI 0.72-1.29),neither in different education classes (OR =0.85,95％ CI 0.70-1.03).Sub-group analysis showed IBS prevalence varied apparently with different diagnostic criteria:prevalence defined by Manning was 11.8％ and by Rome Ⅱ and Rome Ⅲ prevalence values were 4.4％ and 8.9％ respectively.Conclusions Pooled prevalence of IBS in China was 6.5％.IBS is more common in age group between 30 to 59 years.Female,history of intestinal infection,anxiety,depression,food allergy and alcohol consumption were risk factors for IBS in Chinese population.
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Gut microbiota plays an important role in the maintenance of physiological function and genesis of some gut diseases. Brain-gut axis,as an important link between brain and gastrointestinal tract,is a requisite of gut microbiota stability. The dysfunction of brain-gut axis may lead to intestinal dysbiosis through activation of intestinal immune activity. Conversely,intestinal dysbiosis can influence nervous system development and may cause dysfunction of brain-gut axis,in which vagus nerve and metabolites in serum may be the critical factors. This article reviewed the advances in study on interaction between gut microbiota and brain-gut axis.
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Objective To study the protection against hepatic ischemia-reperfusion injury by human IL-10 gene transduction in rats. Methods Ad-hIL10-EGFP (1. 0 ? 109 plaque forming units/ml) was administered into SD rats by intravenous injection 72 hours before hepatic ischemia-reperfusion injury was induced. Liver function were tested and HE pathology was observed. The expression of hIL-10 was studied with ELISA or immunohistochemical method, the expression of EGFP was observed in frozen sections under the fluoroscopy. The apoptosis of hepatocytes was observed with Tunel's assay. Results Compared with control rats, the expression of EGFP and hIL-10 was observed, serum hIL-10 level was (815.74 ? 284. 76) ng/ml, liver function of treatment rats were improved, the paraffin sections showed that the hepatocytes were not significantly swelling and liver pathology ameliorated, the number of apoptosis cells decreased (P