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Endometriosis is a common chronic gynecological disease,and its pathogenesis has not been fully elucidated.Mesenchymal stem cells are a kind of pluripotent stem cells with multi-directional differentiation potential derived from mesoderm,which can differentiate into a variety of tissues and organs.Endometrial mesenchymal stem cells,menstrual blood-derived mesenchymal stem cells,adipose mesenchymal stem cells,bone marrow mesenchymal stem cells and umbilical cord blood mesenchymal stem cells can participate in the pathogenesis of endometriosis from cell proliferation and differentiation,ectopic migration,angiogenesis,inflammatory response and fibrosis formation,and play a certain role in progression of the disease.Mesenchymal stem cells provide new ideas for elucidating the pathogenesis of endometriosis,and may also become a potential method for the treatment of endometriosis.
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Objective To establish the methods of galvanic vestibular stimulation-vestibular evoked myogenic potentials(GVS-VEMPs)in healthy children and to obtain the normal value of GVS-cVEMP and GVS-oVEMP in these children in China.Methods Twenty(3～14 years)healthy children and 24 healthy adults(18～30 years)were enrolled for conventional examinations of GVS-cVEMP and GVS-oVEMP.Using the galvanic stimulation in-tensity under 3 mA/1 ms for children and 5 mA/1 ms for adults.The characteristics of elicitation and parameter re-sults of GVS-cVEMP and GVS-oVEMP in children and adults,as well as the pain scores and the elicitation of differ-ent stimulus intensities in the two age groups were recorded.Results The elicitation of GVS-cVEMP and GVS-oVEMP were both 100.0％in children and adult groups.The p1 latency,n1 latency and p1-n1 interval latency of GVS-cVEMP were 10.46±1.84 ms,16.98±2.12 ms and 6.52±1.42 ms respectively in children group,the n1 la-tency and p1-n1 interval latency were significantly shorter than the adult group(P＜0.05).The n1 latency,p1 la-tency and p1-n1 interval latency of GVS-oVEMP were 8.87±1.40 ms,12.25±1.80 ms and 3.39±1.07 ms re-spectively in children group with no significant difference between the two groups.The thresholds of GVS-cVEMP and GVS-oVEMP in children group were significantly lower than adult group(P＜0.01),but no differences were found in adult group regarding on the amplitude and interaural amplitude asymmetry ratio.In addition,with the in-crease of the intensity of galvanic stimulation,the correlation between pain scores and the elicitation rates of GVS-cVEMP and GVS-oVEMP also increased.Conclusion Using appropriate stimulus intensity and recording methods,GVS-cVEMP and GVS-oVEMP could be successfully assessed and detected in healthy children over 3 years old and adolescents.The latency of GVS-cVEMP in children is slightly shorter than that in adults,therefore we recommend selecting the matched age group for assessment in the children group.
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Objective To explore the effects and mechanism of Baishile Capsules regulating SHH/Gli1 signaling pathway on hippocampal neurogenesis of depression model rats.Methods Totally 32 SD rats were randomly divided into control group,model group,fluoxetine(5.4 mg/kg)group and Baishile Capsules(2.88 g/kg)group,with 8 rats in each group.A depression rat model was established using chronic unpredictable mild stress and single cage feeding method.The model was established and administered simultaneously for 21 consecutive days.Depression-like behavior in rats were evaluated by sucrose preference experiment and open field experiment,ELISA was used to detect brain derived neurotrophic factor(BDNF)contents in rat serum and hippocampal tissue,the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus was observed by immunofluorescence,immunofluorescence and Western blot were used to detect the fluorescence intensity and protein expression of SHH,Gli1,Smo,Ptch in hippocampal tissue.Results Compared with the control group,the degree of sucrose preference significantly decreased in the model group(P<0.01),the number of horizontal and vertical movements significantly decreased(P<0.01),the contents of BDNF in serum and hippocampal tissue significantly decreased(P<0.05),the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus significantly decreased(P<0.01),and the fluorescence intensity and protein expression of SHH,Gli1,Smo,Ptch in hippocampal tissue significantly decreased(P<0.01,P<0.05).Compared with the model group,the degree of sucrose preference and the number of horizontal and vertical movements in fluoxetine group and Baishile Capsule group increased significantly(P<0.05,P<0.01),the contents of BDNF in serum and hippocampal tissue significantly increased(P<0.05,P<0.01),and the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus significantly increased(P<0.01,P<0.05),the fluorescence intensity and protein expressions of SHH,Gli1,Smo,Ptch in hippocampal tissue significantly increased(P<0.01,P<0.05).Conclusion Baishile Capsule can promote the hippocampus neurogenesis in depression model rats by regulating SHH/Gli1 signaling pathway,and play an antidepressant role.
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Objective:To investigate the effect of preoperative old muscular calf vein thrombosis on the safety and efficacy of total knee arthroplasty (TKA).Methods:A total of 411 patients with end-stage knee osteoarthritis who underwent primary TKA in the First Affiliated Hospital of Nanjing Medical University from September 2021 to March 2023 were retrospectively analyzed. There were 89 males and 322 females, aged 68.05±5.91 years (range, 50-82 years). The body mass index was 26.8±3.7 kg/m 2 (range, 17.4-39.8 kg/m 2). The group was divided into a preoperative thrombosis group (47 cases) and a preoperative none-thrombosis group (364 cases) according to whether or not there was a combination of old muscular calf vein thrombosis before TKA. The clinical characteristics (location and size) and lower limb swelling were observed, and the American Knee Society (AKS) score, visual analogue scale (VAS) and Villalta score were recorded to compare the differences between the two groups. Results:All patients successfully completed the operation and were followed up for 7.4±1.1 months (range, 6-9 months). Postoperative deep venous thrombosis (DVT) occurred in 96% (45/47) of the patients in the preoperative thrombus group, which was greater than the 38.5% (140/364) in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=55.184, P<0.001). 29% (13/45) of the patients who developed DVT postoperatively in the preoperative thrombus group had DVT located in the main vein, which was greater than the 9% (12/140) in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=12.028, P<0.001). 51% (23/45) of patients with DVT after operation had thrombosis ≥6 mm, which was higher than 34% (47/140) of patients in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=4.454, P=0.035). The rate of thigh swelling on postoperative day 3 was 8.42%±3.50% in the group with preoperative thrombus and 7.80%±4.12% in the preoperative none-thrombus group, and the differences were not statistically significant ( t=-0.995, P=0.320). The rate of calf swelling on postoperative day 3 was 8.14%±3.40% in the preoperative thrombus group, which was greater than the 5.51%±3.45% in the preoperative none-thrombus group, and the difference was statistically significant ( t=-4.923, P<0.001). Postoperative AKS scores were elevated in both groups and were greater than preoperative scores at 3 and 6 months postoperatively, with statistically significant differences ( P<0.05). There was no significant difference in AKS score between the two groups before operation ( P>0.05), and the AKS scores in the preoperative thrombus group were smaller than those in the preoperative none-thrombus group at 3 and 6 months postoperatively, with a statistically significant difference ( P<0.05). Postoperative VAS scores were reduced in both groups and were smaller than preoperative scores at 3 and 6 months postoperatively, with statistically significant differences ( P<0.05). There was no significant difference in preoperative VAS scores between the two groups ( P<0.05), and the VAS scores in the preoperative thrombus group were greater than those in the preoperative none-thrombus group at 3 and 6 months postoperatively, with a statistically significant difference ( P<0.05). The Villalta score of patients with DVT after operation in the preoperative thrombus group was 4.47±2.47 at the last follow-up, which was greater than that of the preoperative none-thrombus group, which was 2.90±1.92, and the difference was statistically significant ( t=-4.395, P<0.001). Conclusion:Preoperative combined old muscular calf vein thrombosis increases the incidence of postoperative DVT and the dangerousness of DVT is higher.
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Objective To develop an Exercise Behavior Perception Scale for Lung Cancer Patients in China,and to test its reliability and validity.Methods According to the health belief model,the first draft of the scale was formed through literature review,semi-structured interview,research group discussion,2 rounds of expert correspondence and pre-survey.A total of 842 patients with lung cancer who received treatment in a tertiary A hospital in Zhengzhou City from October 2022 to April 2023 were selected for investigation,and item analysis,validity analysis,and reliability analysis were applied to adjust the items to form a formal scale.Results The Exercise Behavior Perception Scale for Lung Cancer Patients contained 24 items,and exploratory factor analysis generated 6 common factors,including physical rehabilitation benefits,emotional and mental benefits,information disorders,disease symptom disorders,condition disorders,and psychological disorders.The cumulative variance contribution rate reached 73.916％,and the results of confirmatory factor analysis showed that the model fit was good,the x2/df was 2.371,the root mean square error of approximation was 0.057,the normed fit index was 0.924,and the comparative fit index was 0.954,the scale score was moderately positively correlated with the total score of the Frenchay activities index(r=0.529,P＜0.001).The Cronbach's α,coefficient,half reliability,and retest reliability of the scale were 0.884,0.741,and 0.889,respectively.Conclusion The Exercise Behavior Perception Scale for Lung Cancer Patients had good reliability and validity,and it can be used to effectively evaluate the exercise behavior perception status of lung cancer patients.
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ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.
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ObjectiveTo investigate the possible mechanisms of modified Xiaoyao Powder （逍遥散） in the treatment of hyperprolactinemia （HPRL） with liver constraint and spleen deficiency. MethodsNinety-six female SD rats were randomly divided into a normal group （n=16） and a modeling group （n=80）. In the modeling group， rats were subjected to chronic unpredictable stress combined with intraperitoneal injection of metoclopramide to establish a rat model of HPRL with liver constraint and spleen deficiency. The 80 successfully modeled rats were randomly divided into a model group， a high， medium， and low-dose group of modified Xiaoyao Powder， and a bromocriptine group， with 16 rats in each group. The high， medium， and low-dose groups of modified Xiaoyao Powder were orally administered doses of 60， 30， and 15 g/（kg·d） respectively， the bromocriptine group was orally administered bromocriptine tablets at a dose of 1 mg/（kg·d）， and the normal group and model group were orally administered 10 ml/（kg·d） of normal saline for 14 consecutive days. ELISA was used to detect serum prolactin （PRL） level； immunohistochemistry was used to determine the expression of tumor necrosis factor-alpha （TNF-α） and tyrosine hydroxylase （TH） in the hypothalamus； Western blot was used to detect the protein expression of tumor necrosis factor receptor 1 （TNFR1） in the hypothalamus； Real-time PCR was used to detect the mRNA expression of receptor interacting protein kinase 3 （RIP3） in the hypothalamus； immunofluorescence was used to detect the co-expression of RIP3 and dopamine neurons in the hypothalamus. ResultsCompared with the normal group， the serum PRL levels were increased in the model group， and the expression of hypothalamic TNF-α， TNFR1， RIP3 mRNA， and the co-expression of RIP3 with dopamine neurons were significantly increased， while TH expression was decreased （P＜0.05 or P＜0.01）. Compared with the model group， the expression of hypothalamic TNF-α was decreased in the bromocriptine group and low-dose group of modified Xiaoyao Powder， and the expression of TH was significantly increased in the medium and high-dose groups of modified Xiaoyao Powder and the bromocriptine group. The serum PRL levels， hypothalamic TNFR1 and RIP3 mRNA expression， and the co-expression of RIP3 with dopamine neurons were significantly decreased in all dose groups of modified Xiaoyao Powder and the bromocriptine group （P＜0.05 or P＜0.01）. Compared with the bromocriptine group， the serum PRL level were significantly increased in the high and low-dose groups of modified Xiaoyao Powder， TH expression was significantly increased in the medium-dose group of modified Xiaoyao Powder， hypothalamic RIP3 mRNA expression was decreased in the low-dose group of modified Xiaoyao Powder， and the co-expression of RIP3 with dopamine neurons was significantly increased in the high-dose group of modified Xiaoyao Powder （P＜0.01）. ConclusionModified Xiaoyao Powder can regulate the programmed cell death of hypothalamic dopamine neurons， affect DA expression， and regulate PRL levels， which may be one of its mechanisms in the treatment of HPRL with liver constraint and spleen deficiency.
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ObjectiveTo investigate the mechanism of Baitouweng Tang in inhibiting the growth of esophageal cancer （EC） cells by regulating budding uninhibited by benzimidazoles 1 （BUB1）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodGene chip technology was used to explore the differential gene expression between esophageal cancer tissues and normal tissues and identified differentially expressed genes. The differentially expressed genes were analyzed by bioinformatics methods. EC cells were treated with 25， 50， 100， 200， 400， 800 mg·L-1 Baitouweng Tang. EC cell viability was detected by Thiazolyl Blue （MTT） colorimetry. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 was measured by real time quantitative polymerase chain reaction （Real-time PCR）. The protein levels of BUB1， STAT3， phosphorylated （p）-STAT3， Cyclin B1 （CCNB1）， cyclin-dependent kinase 1 （CDK1）， B-cell lymphoma-2 （Bcl-2）， cysteinyl aspartate-specific proteinase（Caspase）-3， and Caspase-9 were measured by Western blot. The migration and invasion abilities of the cells were measured by wound-healing and Transwell invasion assays. ResultDifferentially expressed genes were primarily involved in biological processes， signaling pathways， and network construction related to cell mitosis， with BUB1 identified as a key core gene. Compared with the control group， Baitouweng Tang inhibited BUB1 expression （P<0.05，P<0.01）. In vitro experiments showed that compared with the control group， Baitouweng Tang could significantly inhibit the growth （P<0.05，P<0.01）， migration and invasion （P<0.05，P<0.01） of EC cells， induce apoptosis （P<0.05，P<0.01）， and cause G2/M phase increase （P<0.01）. After treatment with Baitouweng Tang， compared with the results in the control group， the expression of Caspase-3， and Caspase-9 in EC cells increased significantly （P<0.05，P<0.01）， while the expression of Bcl-2， BUB1， CCNB1， and CDK1 decreased significantly （P<0.05，P<0.01）. Moreover， the STAT3 signaling pathway was also found to play an important role in this process. ConclusionBaitouweng Tang may inhibit the growth of EC cells by downregulating BUB1 and mediating the STAT3 signaling pathway.
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Purpose@#Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer. @*Methods@#This retrospective study included all patients with stage I–III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore.Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests. @*Results@#A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13–3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16–0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17–0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07–2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11–3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36–0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09–2.44; p = 0.018). @*Conclusion@#NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.
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Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/ 6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.
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AIM:To investigate the mechanism of Piezo1 channel activation promoting the increase in intra-cellular Ca2+ concentration([Ca2+]i)of rat coronary artery smooth muscle cells(CASMCs).METHODS:The primary CASMCs of SD rats were cultured,and the expression and subcellular localization of Piezo1 in the cells were observed by immunofluorescence staining.The Piezo1 and stromal interaction molecule 1(STIM1)in CASMCs were knocked down by siRNA transfection,and the expression levels of the proteins were detected by Western blot.Utilizing laser confocal mi-croscopy,the change of[Ca2+]i in CASMCs was detected by Fluo-4 AM fluorescent probes.RESULTS:It was confirmed by immunofluorescence staining that the expression of Piezo1 existed in primary rat CASMCs.Immunofluorescence staining also showed that Piezo1 was co-located with sarco-/endoplasmic reticulum Ca2+-ATPase 2(SERCA2),mitochondrial outer membrane protein TOM20 and nuclear membrane protein lamin B1.Western blot results showed that the protein expres-sion levels of STIM1 and Piezo1 were significantly down-regulated by siRNA transfection(P<0.05).Compared with con-trol group,Yoda1,the agonist of Piezo1,could increase the extracellular Ca2+ influx of CASMCs(P<0.01).However,the Ca2+ influx mediated by Yoda1 was not affected by the inhibition of L-type calcium channels.Treatment with Yoda1 in-creased the intracellular Ca2+ release of CASMCs(P<0.01).However,inhibition of calcium channels on endoplasmic re-ticulum,ryanodine receptor and inositol 1,4,5-triphosphate receptor,did not affect intracellular Ca2+ release mediated by Yoda1.After the Ca2+ in endoplasmic reticulum was emptied using thapsigargin(TG),Yoda1 also mediated the Ca2+ re-lease of other organelles in CASMCs(P<0.01).After inhibition of L-type calcium channels,treatment with store-operated calcium channel(SOCC)inhibitor BTP2 or knockdown of STIM1 led to the decrease in extracellular Ca2+ influx of CASMCs mediated by Yoda1(P<0.01).Treatment with TG increased the release of Ca2+ from the endoplasmic reticulum of CASMCs after knockdown of Piezo1(P<0.05),but the extracellular Ca2+ influx mediated by TG was not affected.After inhibition of L-type calcium channels and SOCC,knockdown of Piezo1 led to the decreases in intracellular Ca2+ release and extracellular Ca2+ influx induced by Yoda1(P<0.01).CONCLUSION:The Piezo1 agonist orchestrates the influx of extracellular Ca2+ by activating Piezo1 channels on the cell membrane and inducing the indirect activation of SOCC.More-over,it facilitates the release of Ca2+ from organelles.Consequently,these pathways synergistically elevate the[Ca2+]i of rat CASMCs.
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AIM:To investigate the influence of fat mass and obesity-associated(Fto)gene on the aberrant contraction of aortic smooth muscle in diabetes mellitus(DM)mice,and to explore the mechanism of Fto gene underlying the calcium regulation.METHODS:Smooth muscle-specific Fto gene knockout(FtoSMKO)mice were generated using Cre-loxP technology.The experiment involved 3 groups of mice:wild-type(WT)group,DM model group and FtoSMKO-DM group,with 15 mice in each group.In DM group and FtoSMKO-DM group,type 1 DM was induced by intraperitoneal injec-tion of streptozotocin.The mice in WT group were injected with equal volume of citric acid-sodium citrate buffer solution.The influences of different drugs on the contraction responses of aortic smooth muscle in mice were analyzed using a multi-myograph system.The expression level of FTO protein in the aortic tissues was detected by Western blot.RESULTS:(1)Compared with WT mice,the expression levels of FTO protein in the aortic tissues of DM mice were significantly in-creased(P＜0.01).(2)The expression level of FTO protein in smooth muscle was significantly decreased after knockout of Fto gene(P＜0.01).Compared with WT group,the mice in DM group exhibited a significant decrease in body weight and a marked increase in fasting blood glucose level(P＜0.05).There were no noticeable differences in body weight or fasting blood glucose level between FtoSMKO-DM group and DM group(P＞0.05).(3)The contraction responses of aortic smooth muscle in DM group were substantially increased by phenylephrine compared with WT group.Specifically,vaso-constriction responses mediated by non-L-type calcium channels and store-operated calcium channels(SOCC)were signifi-cantly enhanced in DM group.In addition,the responses mediated by inositol 1,4,5-trisphosphate receptors(IP3R),which facilitate calcium release from the sarcoplasmic reticulum,were significantly enhanced.However,the responses mediated by caffeine-activated ryanodine receptors(RyR),which also facilitate calcium release from the sarcoplasmic re-ticulum,were significantly inhibited(P＜0.05).(4)Compared with DM group,the phenylephrine-induced contraction re-sponses of aortic smooth muscle in FtoSMKO-DM group were greatly weakened(P＜0.05).In particular,the vasoconstriction responses mediated by non-L-type calcium channels and SOCC in FtoSMKO-DM group were greatly suppressed(P＜0.05),while those mediated by caffeine-activated RyR were dramatically boosted(P＜0.05).However,IP3R-mediated responses were not affected(P＞0.05).CONCLUSION:Smooth muscle-specific Fto gene knockout suppresses contractile hyperre-sponsiveness in the aortic smooth muscle of DM mice,which may be attributed to involvement of FTO protein in calcium regulation in the vascular smooth muscle.
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Different from accounting supervision and audit supervision,financial supervision pays more attention to the standardization of economic behavior from the management and governance level,financial supervision has the characteristics of comprehensiveness,foresightedness and guidance,which is very important for the healthy development of public hospital.By analyzing the main problems and challenges faced by the internal financial supervision in public hospitals,it discusses the construction of supervision system,the perfection of working mechanism,the optimization of supervision means and the construction of supervision environment,to explore the concrete ways and suggestions of improving the efficiency of internal financial supervision in public hospitals.
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Objective To construct a clinical prediction model for the risk of Alzheimer's disease based on ApoE,combined with risk factors and common clinical indicators.Methods There were 61 cases of Alzheimer's disease patients and 111 cases of fuzzy matching healthy physical examination from Nanjing Hospital of Chinese Medicine data platform from January 2019 to January 2021.Using LASSO regression screening of risk factors,constructing logistic regression forecasting model,10 fold cross verifies the degree of differentiation,validation the calibration of the bootstrap method.The clinical guidance of the prediction model was evaluated by the clinical decision curve,and finally,the clinical prediction model was visualized by nomogram.Results 12 variables were screened out and four risk factors were included,which are age,free triiodothyroxine(FT3),gender and ApoE.The AUC of ROC of the whole sample was 0.879,and the average AUC of ROC after 10 folded and 9 crossed training sets verification was 0.864.Bootstrap method and Hosmer-Lemeshow were used to test the calibration degree.Results χ2 =6.496,P=0.592>0.05.The threshold probability of clinical decision curve ranged from 1%to 88.6%.Conclusion Individualized evaluation of patients using clinical prediction models constructed by age,FT3,gender and ApoE can provide early warning of Alzheimer's disease,carry out early prevention intervention and slow down the development of the disease.
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Glioma is the most common and lethal intrinsic primary tumor of the brain. Its controversial origins may contribute to its heterogeneity, creating challenges and difficulties in the development of therapies. Among the components constituting tumors, glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation. Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor, in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation. Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states, glial, neural, and immune cell populations in the tumor microenvironment. Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy. Here, we discuss the heterogeneity and relevant functions of tumor cell state, microglia, monocyte-derived macrophages, and neurons in glioma, highlighting their bilateral effects on tumors. Finally, we describe potential therapeutic approaches and targets beyond standard treatments.
Sujet(s)
Humains , Gliome/métabolisme , Névroglie/métabolisme , Carcinogenèse/anatomopathologie , Cellules souches neurales/métabolisme , Microglie/métabolisme , Tumeurs du cerveau/métabolisme , Microenvironnement tumoralRÉSUMÉ
OBJECTIVE To optimize the extraction process and to primarily evaluate the anti-anxiety and anti-depression efficacy of polysaccharide from Baihe dihuang decoction. METHODS Based on Plackett-Burman experimental design， using the comprehensive score of yield and content of polysaccharide as indicators， with extraction time， water amount， alcohol precipitation concentration as factors， Box-Behnken response surface methodology was used to optimize the extraction process of polysaccharide from Baihe dihuang decoction； and the validation test was conducted. Forty ICR mice were divided into control group， venlafaxine group [positive control， 13.5 mg/（kg·d）]， Baihe dihuang polysaccharide high-dose and low-dose groups [5.28， 2.64 g/（kg·d），by raw material]， with 10 mice in each group （half male and half female）. Administration groups were given corresponding drug solution intragastrically， and control group was given water 10 mL/kg intragastrically， once a day， for 7 test， forced swimming test and tail suspension test were used to evaluate the effects of the extract prepared by the optimal process on the anxiety-like and depression-like behavior of mice； enzyme-linked immunosorbent assay was used to detect the effects of the extract on the levels of neurotransmitter in cerebral tissue of mice. RESULTS The optimal extraction process of Baihe dihuang decoction was： the water amount of 25 times， extract time of 1.5 hours， and alcohol precipitation concentration of 70%. In 3 times of validation test， the average yield and content of polysaccharide were 33.10% and 0.62 mg/mg， the relative deviations of which from the predicted values （36.14% and 0.65 mg/mg） were 8.40% and 4.62% respectively （RSD＜2%， n＝3）. The polysaccharide extract of Baihe dihuang decoction could effectively increase the percentages of open-arms entry， the percentages of open-arms time， the total distance of voluntary activities and the activity distance in central area， and significantly shortened the immobility time of forced swimming test and tail suspension test （P＜0.05 or P＜0.01）. The polysaccharide extract could significantly increase the levels of 5-hydroxytryptamine， norepinephrine （except for the Baihe dihuang polysaccharide low-dose group） and gamma-aminobutyric acid in cerebral tissue of mice， while significantly decrease the levels of glutamic acid （except for the Baihe dihuang polysaccharide low-dose group） （P＜0.05 or P＜ 0.01）. CONCLUSIONS The optimized extraction process of polysaccharide from Baihe dihuang decoction is stable and feasible， and the obtained polysaccharide extract has obvious anti-anxiety and anti-depression effect in vivo.
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AIM: To investigate the clinical efficacy of suture-guided gonioscopy-assisted transluminal trabeculotomy(GATT)combined with phacoemulsification in the treatment of primary open angle glaucoma(POAG).METHODS: A total of 84 patients(84 eyes)with POAG and cataract who underwent surgery in our hospital from January 2021 to July 2022 were selected and randomly divided into two groups. There were 43 cases(43 eyes)in the combined group who underwent suture-guided GATT combined with phacoemulsification, and 41 cases(41 eyes)in the simple group who underwent suture-guided GATT. The two groups were followed up for 3mo to compare the surgical success rate, intraocular pressure, topical intraocular pressure-lowering drugs, visual acuity and postoperative complications.RESULTS: There was no significant difference in overall success rate between the combination and simple groups at 3 mo after surgery(88% vs. 85%, P>0.05). The intraocular pressure levels and topical intraocular pressure-lowering drugs at 1wk, 1 and 3mo after surgery in the two groups were significantly lower than those before surgery(all P<0.05), but there was no significant difference between the two groups(all P>0.05). The visual acuity at 1wk, 1 and 3mo after surgery of patients in the combined group was significantly better than that in the simple group(P<0.01). During the follow-up period, the incidence of anterior chamber hemorrhage and transient hypertension in the combined group was significantly lower than that in the simple group(P<0.05).CONCLUSION: Both suture-guided GATT combined with cataract phacoemulsification and suture-guided GATT are effective treatment for POAG, however, suture-guided GATT combined with phacoemulsification has a lower incidence of anterior chamber hemorrhage and transient ocular hypertension.
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AIM: To investigate the clinical efficacy of femtosecond laser-assisted phacoemulsification combined with goniosynechialysis in the treatment of acute angle-closure glaucoma complicated with cataract.METHODS: A total of 53 patients(60 eyes)with primary acute angle closure glaucoma complicated with cataract admitted to our hospital from April 2020 to February 2021 were selected. They were divided into two groups according to the surgical method, with 28 cases(30 eyes)who were treated with femtosecond laser-assisted phacoemulsification combined with goniosynechialysis in group A, and 25 cases(30 eyes)who were treated with traditional cataract phacoemulsification combined with goniosynechialysis in group B. The effective phacoemulsification time(EPT)and cumulative dissipated energy(CDE)during surgery in two groups were recorded. Patients were followed up to 3mo after surgery, and the intraocular pressure, anterior chamber depth(ACD), best corrected visual acuity, corneal endothelial cell loss rate(ECL)and surgical complications were observed in both groups.RESULTS: The postoperative intraocular pressure was significantly decreased and ACD was significantly increased(all P<0.05), and there was no difference between the two groups(all P>0.05). The postoperative best corrected visual acuity of the two groups was significantly better than that before surgery(P<0.05), and group A was significantly better than group B at 1d after surgery(P<0.05). The EPT, CDE, ECL and incidence of complications(7% vs. 27%)in group A were significantly lower than those in group B(all P<0.05).CONCLUSION: Femtosecond laser-assisted cataract phacoemulsification combined with goniosynechialysis in the treatment of primary acute angle-closure glaucoma combined with cataract has a significant therapeutic effect, which can effectively improve surgical safety, reduce the rate of corneal endothelial cell loss, and have fewer complications.
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Objective@#To construct a model for clinical identification of spotted fever (SF) and severe fever with thrombocytopenia syndrome (SFTS), so as to provide insights into early identification of SF and SFTS.@*Methods@#The clinical data of laboratory-confirmed SF and SFTS patients in secondary and tertiary hospitals in Lu'an City, Anhui Province from May 2017 to May 2021 were retrieved from Chinese Disease Prevention and Control Information System. Factors affecting SF were identified using a logistic regression model, and the model for early identification of SF and SFTS was created. The model fitting effect was evaluated using Hosmer-Lemeshow test, and the value of the model for identification of SF and SFTS was evaluated using the area under the receiver operating characteristic curve (AUC).@*Results@#Data of 62 SF cases and 115 SFTS cases were included. Multivariable logistic regression analysis showed that rash (β=5.994), C-reactive protein (β=4.409), white blood cell (β=-3.176) and platelet (β=-3.234) were included in the model, which were scored 6, 4, -3 and -3, with a total score ranging from -5 to 10. Hosmer-Lemeshow test revealed a high model fitting effect (χ2=3.245, P=0.662). The AUC of the model was 0.992, and the sensitivity and specificity were 0.935 and 0.991 if the cutoff was 1.@*Conclusion@#A model for early identification of SF and SFTS that includes four variables of rash, C-reactive protein, white blood cell and platelet has been created, which has a high accuracy.
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AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.