Latest ArticlesObjective To investigate the effect and potential mechanism of Taohong Siwu decoction(THD) on paclitaxel-induced peripheral nerve injury in rat. Methods Twenty-four female SD rats were randomly divided into control group, model group, THD low-dose group and THD high-dos group (6 each). Rats in control group were given saline of the same volume, while paclitaxel (8 mg/kg) was slowly injected intraperitoneally into rats in other three groups on the 1, 3, 5, and 7th day for 4 times. Rats with mechanical withdrawal threshold under 4 g indicated model success. The THD low-dose group and THD high-dose group was given 1 g/ml or 2 g/ml of THD 2 times/d, for 4 weeks. The threshold of mechanical stimulation, cold and hot stimulation to rats was detected after administration. The pathological morphology of sciatic nerve was observed by HE staining.The contents of inflammatory factor Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), thiobarbituric acid reactive substances (TBARS) and L-Glutathione (GSH) in the sciatic nerve were measured with automatic biochemical analyzer.The relative contents of myelination pieces were determined by red oil O staining and expression level of autophagy associated proteins microtubule-associated protein 1 light chain3-I (LC3-I), LC3-Ⅱ, and Beclin1 were detected by Western blotting. Results Compared with control group, rats in model group showed lower threshold to mechanical stimulation and lower sensitivity to hot and cold stimulation (P<0.05), expression levels of IL-6, TNF-α and TRABS elevated (P<0.05), while GSH levels decreased (P<0.05). HE staining showed tissue injury, atrophy, inflammatory infiltration, and myelination pieces increased significantly and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 reduced (P<0.05). The results of THD low-dose group and THD high-dose group showed that the response of rats to mechanical stimulation, hot and cold stimulation was obviously improved (P<0.05), levels of IL-6, TNF-α and TRABS significantly decreased (P<0.05), while level of antioxidant GSH significantly elevated (P<0.05). Compared with THD low-dose group, rats in THD high-dose group showed elevated threshold to mechanical stimulation and more sensitive to mechanical stimulation, hot and cold stimulation (P<0.05), myelination pieces decreased significantly (P<0.05) and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 increased (P<0.05). Conclusion Taohong Siwu decoction can alleviate rat peripheral nerve injury caused by paclitaxel, and its mechanism may be related to reducing inflammatory reaction and inducing autophagy to remove damaged debris.
Objective To investigate the regulatory effect and molecular mechanism of circAPLP2 on invasion and metastasis of colorectal cancer cell SW480. Methods The online database Starbase was used to predict the binding sites of circAPLP2 and miR-497-5p, and TargetScan was used to predict the binding sites of miR-497-5p and FGFR1. The relative expression levels of circAPLP2 and miR-497-5p in LoVo, DLD1, SW480, SW620, Caco-2 and HCoEpiC cells were detected by qRT-PCR, and the relative expression level of FGFR1 protein was detected by Western blotting. SW480 cells were taken and set up as follows:(1) siNC group (transfected with siControl) and sicircAPLP2 group (transfected with sicircAPLP2), the expressions of circAPLP2, miR-497-5p, FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting.(2) Vector group (transfected with empty plasmid) and circAPLP2 group (transfected with circAPLP2 overexpression plasmid), the expressions of miR-497-5p and FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting. (3) siNC group (transfected with siControl), sicircAPLP2 group (transfected with sicircAPLP2) and sicircAPLP2+miR-497-5p inhibitor group (transfected with sicircAPLP2 and miR-497-5p inhibitor), the cell invasion was detected by Transwell, the cell migration was detected by scratch test, and the expressions of EMT marker proteins (E-cadherin, Twist1, N-cadherin and Vimentin) were detected by Western blotting. (4) NC miRNA group (transfected with NC-miRNA) and miR-497-5p mimics group (transfected with miR-497-5p mimics), or NC-inhibitor group (transfected with NC-inhibitor) and miR-497-5p inhibitor group (transfected with miR-497-5p inhibitor), the expression of FGFR1 was detected by qRT-PCR and Western blotting.(5) pcDNA-Control group (transfected with pcDNA-Control) and pcDNA-FGFR1 group (transfected with pcDNA-FGFR1), the expression of FGFR1 protein was detected by Western blotting. (6) NC-miRNA group (transfected with negative control), miR-497-5p mimics group (transfected with miR-497-5p mimics) and miR-497-5p mimics+pcDNA-FGFR1 group (co transfected with miR-497-5p mimics and pcDNA-FGFR1), the cell invasion, migration and the expression of FGFR1 and EMT marker proteins(E-cadherin, Twist1, N-cadherin, Vimentin) were detected by Transwell, scratch test or Western blotting. The circAPLP2-WT or circAPLP2-MT report plasmid was co-transfected with NC-miRNA or miR-497-5p mimics respectively for 48 h in SW480 cells, and the FGFR1-WT or FGFR1-MT report plasmid was co-transfected with miR-497-5p mimics and circAPLP2 respectively for 48 h in SW480 cells, and the luciferase activity was detected by the luciferase reporter gene detection system. Results The analysis results by Starbase and TargetScan showed that binding sites existed between circAPLP2 and miR-497-5p, and between miR-497-5p and FGFR1. Compared with human colon epithelial cell HCoEpiC, the relative expression level of circAPLP2 in colorectal cancer cells LoVo, DLD1, SW480, SW620 and Caco-2 increased significantly, while of miR-497-5p significantly decreased, and the relative expression level of FGFR1 protein significantly increased (P<0.05). After knocking down the expression of circAPLP2, compared with siCN group, the number of invasive cells in sicircAPLP2 group decreased (P<0.001), and the cell healing rate of scratches decreased (P<0.001), the expression of E-cadherin protein increased, and the protein expressions of Twist1, N-cadherin and Vimentin decreased (P<0.05). The results of dual luciferase reporter assay showed that miR-497-5p mimics decreased circAPLP2-MT luciferase activity significantly (P<0.001); MiR-497-5p inhibitor reverses the inhibitory effect of sicircAPLP2 on EMT, migration and invasion of colorectal cancer cells, as the number of invasive cells increased (P<0.001), the scratch healing rate increased (P<0.01), the expression of E-cadherin protein decreased, and the expression of Twist1, N-cadherin, and Vimentin protein increased (P<0.05). Dual luciferase reporter assay results showed that miR-497-5p mimics significantly reduced FGFR1-MT luciferase activity (P<0.001). Over-expression of FGFR1 reversed the inhibition of miR-497-5p overexpression on colorectal cancer cell migration and invasion, manifested as increased number of invasive cells (P<0.001), increased scratch healing rate (P<0.01), decreased expression of E-cadherin, increased expressions of N-cadherin, Twist1 and Vimentin (P<0.05). Conclusion The expression level of circAPLP2 increases in colorectal cancer cells, it may promote the expression of FGFR1 through competitive combination with miR-497-5p, thus promoting EMT, invasion and migration of colorectal cancer cells.
Objective To evaluate the usability of tablet-based digital complex figure test (dCFT) software on assessment of drawing strategies of patients with amnestic mild cognitive impairment (aMCI). Methods A total of 64 patients treated in a hospital from Nov. 2020 to Nov. 2021 were selected, including 26 cognitively normal people (control group) and 38 aMCI patients(aMCI group). All subjects underwent standardized neuropsychological assessments, including the mini-mental state examination(MMSE), the montreal cognitive assessment (MoCA), the Rey–Osterrieth Complex Figure (ROCF) test, and other cognitive domain scales. And then use the dCFT (including copying and recall) developed by our team to collect drawing parameters, such as stroke length, time, speed and number. The Pearson correlation coefficient was used to evaluate the correlation between the original and simplified ROCF test scores, and partial correlation used to analyze the correlation between the dCFT parameters and the comprehensive scores of each cognitive domain. Results (1) In the copying test, all dCFT parameters had no statistically significant between the two groups (P>0.05). In the immediate recall test, the total thinking time and element delay time in aMCI group were significantly longer than those in the control group [27.15(21.49, 33.94) vs. 21.85(18.26, 24.81), 1.99(1.36, 3.62) vs.1.32(1.03, 1.99), P<0.05]. In the delayed recall test, the transition time of short and long stroke sequence, total thinking time, total completion time, first thinking time and element delay time of the aMCI group were significantly higher than those of control group [1.89(1.12, 3.93) vs. 1.19(0.42, 2.41), 23.94(18.86, 36.87) vs. 19.93(16.59, 23.00), 40.30(34.83, 56.21) vs. 34.52(29.96, 42.15), 7.92(6.20, 9.83) vs. 5.92(5.16, 8.04), 1.63(1.25, 2.47) vs. 1.08(0.83, 1.55), P<0.05]. The first 5 stroke ratios (%), speed of the longest stroke (cm/s) and strokes per minute of aMCI group were significantly lower than those of control group [60(40, 80) vs. 80(60, 100), 4.65(3.53, 6.07) vs. 6.00(4.54, 7.13), 21(18, 25) vs. 26(21, 27), P<0.05]. Other dCFT parameters had no statistically significance between the two groups (P>0.05). (2) Correlation analysis showed that the transition time was negatively correlated with attention and executive function (r=–0.292, r=–0.275, P<0.05); the speed of the longest stroke was positively correlated with the executive function (r=0.302, P<0.05); the total thinking time was negatively correlated with memory, attention, executive function and visuospatial ability (r=–0.26, r=–0.408, r=–0.448, r=–0.264, P<0.05); the total completion time was negatively correlated with attention, executive function and visuospatial ability (r=–0.342, r=–0.429, r=–0.273, P<0.05); the first stroke latency was negatively correlated with memory and visuospatial ability (r=–0.365, r=–0.407, P<0.01); the average element latency was negatively correlated with memory and attention (r=–0.377, r=–0.33, P<0.01); the strokes per minute was positively correlated with memory, attention, executive function and visuospatial ability (r=0.326, r=0.311, r=0.376, r=0.263, P<0.05). Conclusions Visuospatial memory impairment of aMCI patients was presented in 3-minute recall test of the complex figure test, and their drawing strategy was acceptable. But after 20 minutes, the memory and the organization strategy of drawing were significantly affected. Visual perception is not significantly impaired in the process. The dCFT software is a convenient, objective assessment tool for aMCI.
Objectives To understand the natural course of infection complications in elderly patients with tunnel-cuffed catheter (TCC) blood purification; and analyze the prognostic significance of blood routine test parameters detected before catheterization. Methods Collect 2430 patients who underwent blood purification treatment at the First Medical Center of the Chinese PLA General Hospital from January 2008 to January 2023, and follow up the patients who used TCC and had blood routine tests 24 hours before catheterization. Analyze the natural course of infection complications after TCC; Using all-cause death as the endpoint, Kendall correlation analysis was used to investigate the relationship between clinical data of first infection after TCC and prognosis. The nested case-control study was used to match the case group with the control group according to the ratio of hypertension and diabetes 1:1. The first infection within 6 months of TCC was taken as case group (n=34), and the first infection after 6 months of TCC was taken as control group (n=34). The risk factors related to the first infection within 6 months of TCC were analyzed by logistic regression. Validate the results of nested case-control studies across the entire group of patients and analyze the value of mean platelet volume (MPV) before catheterization in predicting the prognosis of first-time infections. Results A total of 77 patients were followed up, aged (78.4±7.3) years, with a median follow-up time of 28.0(13.8-70.5) months. After the first infection, 32 died and 45 survived. Compared with first-time infected survivors, deceased patients had a higher age and lower catheter age (P<0.05). The first infection within 6 months of TCC is positively correlated with death (r=0.336, P=0.003), and the cumulative survival rate is significantly lower than that in infected patients after 6 months of TCC (P<0.001). The results of a nested case-control study showed that the MPV of infected group within 6 months of TCC was significantly higher than that in control group [(10.64±1.05) fl vs. (9.89±0.80) fl, P=0.001]. Logistic regression analysis showed that the risk of infection was 3.222 times higher in high MPV group compared with control group. In the entire group of 77 cases, it was confirmed that high MPV values were associated with the occurrence of first infection within 6 months of TCC (P=0.037). Conclusions First infection within 6 months after TCC catheterization is associated with death; Patients with high MPV values before catheterization have a significantly increased risk of first infection within 6 months after TCC. The MPV level before catheterization may indicate a poor prognosis for infected individuals after TCC, and this indicator may be a personalized decision-making reference for TCC.
Cachexia is a serious chronic wasting syndrome, which is a common complication of cancer, end-stage heart failure and other diseases. The abnormal inflammatory response in the process of cachexia plays an important role in the loss of muscle and fat, the proliferation and metastasis of tumors. In recent years, it has been found that microRNA and long non-coding RNA (lncRNA) carried in exosomes can mediate cell-to-cell communication, activate related signaling pathway to secrete various inflammatory factors. It mediates the inflammatory response of cachexia, affects the formation of local and distal inflammatory microenvironment, promotes tumor cell proliferation, metastasis and inhibits its apoptosis, thereby accelerating the progression of cachexia. This review mainly summarizes the relationship between exosome and cachexia inflammation response, the harm of cachexia inflammation response and the mechanism of action, and provides new ideas for preventing it and slowing down the cachexia progress.
Liver fibrosis is a response to chronic liver injury caused by a variety of factors, such as alcohol consumption, viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD) and cholestatic liver disease. The combined effect of all these factors on the liver is to produce chronic inflammation leading to an abnormal wound-healing response. Mesenchymal stem cells (MSCs) are pluripotent stem cells that are able to implant into target tissues and secrete a variety of factors that can alter or improve the function of damaged tissues. Stem cells have the advantages of self-renewal, pluripotent differentiation and low immunogenicity. Due to their differentiation potential and paracrine characteristics, MSCs are the key for repair. This review focuses on the mechanism and progress of MSCs and their modifiers in liver fibrosis.
Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury and subsequent acute respiratory failure caused by various intrapulmonary and extrapulmonary pathogenic factors, with respiratory distress and refractory hypoxemia as clinical features. At present, the "standardized" mechanical ventilation for ARDS patients is a lung protective ventilation strategy with low tidal volume and high positive end-expiratory pressure. However, the results are often unsatisfactory, and most related clinical studies have ended up unsuccessfully. Because of the high heterogeneity of ARDS, accurate classification and individualized treatment are very important. In this paper, we reviewed the phenotypes of ARDS from the perspectives of etiology, onset time, disease severity, inflammation level, imaging characteristics pathology, etc., and preliminarily explained the ARDS phenotype associated with COVID-19, and summarized the individualized treatment strategies for ARDS with different phenotypes, hoping to provide evidence for the individualized and precise treatment of ARDS.
corona virus disease 2019 (COVID-19), which emerged at the end of 2019, is caused by infection with the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Due to the high mutability of SARS-COV-2, a variety of different types of mutant strains have emerged around the world, making the COVID-19 epidemic continues to spread around the world, posing a great threat and severe challenge to the global public health system. In November 2021, the Omicron (B.1.1.529)variant found in Botswana, southern Africa, is rapidly spreading globally with super infectivity, and has immediately attracted great attention worldwide because of its strong infectivity and immune evasion ability. In this paper, the latest research progresses on pathogenic characteristics, molecular mechanisms of immune evasion, vaccine tolerance and antibody tolerance of Omicron variant are briefly reviewed.
Cardiac arrest (CA) induced by army combat trauma is a specific type of traumatic cardiac arrest. Since it is inextricably intertwined with tactical combat casualty care (TCCC), the diagnosis and therapeutic strategy is dependent on various stages, i.e., care under fire/threat, tactical field care, and tactical evacuation care. In addition, active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR) should be considered among patients with lung, pleural and heart injury resulted from chest trauma. Moreover, portable ultrasound to identify reversible etiologies in CA should be highlighted.
Objective To investigate the role and mechanism of circRNA BRAF_2 in proliferation and apoptosis of placental trophoblast cells in preeclampsia (PE). Methods Placental tissues of pregnant women with normal pregnancy and PE were collected (n=21) in the General Hospital of Ningxia Medical University from January 2018 to February 2019. The expression level of circRNA BRAF_2 in placental tissues of the two groups was detected by qRT-PCR, and the correlation between circRNA BRAF_2 expression level and blood pressure was analyzed. Human placental trophoblast cell lines (HTR8-S/Vneo) were cultured in vitro, (1) Cells were divided into control group and hypoxia group, and the expression of circRNA BRAF_2 were detected by qRT-PCR. (2) HTR8-S/Vneo was transfected with circRNA BRAF_2 lentivirus empty vector and circRNA BRAF_2 overexpression lentivirus, and then divided into control group, circRNA BRAF_2 negative control group and circRNA BRAF_2 overexpression group. The overexpression of circRNA BRAF 2 was verified with qRT-PCR. (3) Based on the successful transfection of circRNA BRAF_2 overexpressing lentivirus, the cells were divided into control group, circRNA BRAF_2 negative control group, circRNA BRAF_2 overexpression group, hypoxia group, hypoxia +circRNA BRAF_2 negative control group, and hypoxia +circRNA BRAF_2 overexpression group. EdU and CCK-8 methods were used to detect the proliferation. Flow cytometry was used to detect the changes of apoptosis level. Western blotting was used to detect the expression levels of apoptosis-related proteins caspase-3, caspase-9,Bcl-2 and Bax. qRT-PCR was used to detect the expression levels of circRNA BRAF_2 in HTR8-S/Vneo cytoplasm and nucleus.Bioinformatics analysis was performed to screen out the miRNA that might bind circRNA BRAF_2 and detect their expression levels in tissues and cells. Results Compared with normal pregnancy group, the expression level of circRNA BRAF_2 was significantly decreased in placenta of PE group (P<0.001), and of circRNA BRAF_2 was negatively correlated with systolic pressure and diastolic pressure (r=-0.4531, P<0.01; r=-0.4381, P<0.01). qRT-PCR showed that compared with control group, the expression level of circRNA BRAF_2 in hypoxia group was significantly decreased (P<0.01), and the relative expression level of circRNA BRAF_2 in negative control group showed no significant difference when ompared with control group (P>0.05). Compared with that in circRNA BRAF_2 negative control group, the circRNA BRAF_2 expression level increased significantly in circRNA BRAF_2 overexpression group (P<0.001). The detection results of EdU and CCK-8 showed that, compared with control group, the percentage of positive EdU cells decreased significantly (P<0.001) in hypoxia group, trophoblast proliferation ability decreased (P<0.001); Compared with the hypoxia +circRNA BRAF_2 negative control group, the percentage of EdU positive trophoblast cells increased significantly in hypoxia +circRNA BRAF_2 overexpression group (P<0.001), and the proliferation ability of trophoblast cells was significantly enhanced (P<0.001). The detection results of flow cytometry showed that, compared with control group, the apoptosis rate of hypoxia group increased obviously (P<0.001); Compared with the hypoxia +circRNA BRAF_2 negative control group, the apoptosis rate of the hypoxia + circRNA BRAF_2 overexpression group decreased significantly (P<0.001). Western blotting showed that compared with control group, the relative expressions of caspase-3, caspase-9 and Bax proteins increased (P<0.01 or P<0.001), and of Bcl-2 protein decreased (P<0.01) in hypoxia group; Compared with the hypoxia + circRNA BRAF_2 negative control group, the relative expressions of caspase-3, caspase-9 and Bax proteins decreased (P<0.001 or P<0.01), and of Bcl-2 protein increased (P<0.05) in hypoxia + circRNA BRAF_2 overexpression group. The results of qRT-PCR showed that circRNA BRAF_2 was expressed mainly in cytoplasm, and bioinformatics analysis showed that binding sites existed between circRNA BRAF_2 and miR-7855-5p. and miR-7855-5p was highly expressed in PE placental tissue than that in normal pregnancy group (P<0.05); Compared with control group, miR-7855-5p was obviously highly expressed in hypoxia group (P<0.001). Conclusion circRNA BRAF_2 can promote proliferation and inhibit apoptosis of PE placental trophoblast cells, and the mechanism may be related to miR-7855-5p.