摘要:Officers and soldiers exposed to high temperature and high-humidity environments are highly susceptible to exertional heat illness and even heatstroke. Reports indicated that after conventional treatment, the heat endurance damage in officers/soldiers with exertional heat illness can persist for months or even years. Therefore, the Expert Group of Heatstroke Prevention and Treatment of Heatstroke of Chinese PLA has specially formulated a technical proposal for the reconstruction of heat endurance in officers/soldiers suffering from exertional heatstroke, aiming to provide a safeguard for reconstruction of heat endurance in affected personnel. This article mainly elaborates on the basic concepts, technical requirements, initiation timing, implementation assessment, and follow-up of the heat endurance reconstruction for officers/soldiers with exertional heatstroke.
摘要:ObjectiveTo compare the outcomes of transplant kidneys and patient survival between simultaneous pancreas-kidney transplantation (SPKT) recipients and deceased donor kidney transplant (DDKT) recipients in patients with type 2 diabetes mellitus (T2DM) complicated with end-stage renal disease (ESRD), and to analyze the risk factors affecting patient survival post-SPKT.MethodsClinical and prognostic data of patients who underwent kidney transplantation from January 27, 2003, to January 1, 2021, were retrieved from the United Network for Organ Sharing (UNOS) database. A total of 50 230 cases were selected based on inclusion criteria, with 48 669 cases in DDKT group and 1561 cases in SPKT group. Kaplan-Meier analysis was employed to compare transplant kidney and patient survival between the two groups, and propensity score matching (PSM) was utilized to balance confounding factors between the groups. Cox regression model was used to analyze independent risk factors affecting patient survival post-SPKT.ResultsCompared with DDKT group, recipients in SPKT group had a younger median age (P<0.001), a higher proportion of males (P<0.001), lower BMI (P<0.001), shorter dialysis and transplant waiting times (P<0.001), a higher percentage of private medical insurance (P<0.001), a lower proportion of previous transplants (P<0.001), a younger age at diabetes diagnosis (P<0.001), and a lower incidence of peripheral vascular disease (P=0.033). Compared with DDKT group, the donors in SPKT group had a younger median age (P<0.001), a higher proportion of males (P<0.001), lower BMI (P<0.001), and a lower prevalence of hypertension and diabetes history (P<0.001). In terms of transplant-related factors, the SPKT group had a shorter donor kidney cold ischemia time (P<0.001), a higher degree of HLA mismatch (P<0.001), and a lower Kidney Donor Profile Index (KDPI) (P<0.001) when compared with DDKT group. The SPKT group had lower serum creatinine levels at discharge (P<0.001), lower rates of postoperative delayed graft function (DGF) and acute rejection (AR) (P<0.001), but longer hospital stays (P<0.001) when compared with DDKT group. Kaplan-Meier survival analysis curves, both original and after propensity score matching (PSM), consistently showed significantly higher transplant kidney and patient survival rates in SPKT group compared with DDKT group (P<0.001). Cox regression model analysis indicated that recipient age, recipient race, donor age, and donor kidney cold ischemia time were independent risk factors influencing patient survival post-SPKT.ConclusionsFor ESRD patients with T2DM, SPKT offers improved long-term graft and patient survival rates compared with DDKT. Recipient age, recipient ethnicity, donor age, and cold ischemia time for the donor's kidney are independent risk factors affecting post-SPKT patient survival.
摘要:ObjectiveTo explore the relationship between serum ferritin levels and body fat distribution in patients with type 2 diabetes mellitus (T2DM).MethodsA retrospective analysis was conducted on 151 patients with T2DM who were hospitalized in the Department of Endocrinology of the First Hospital of Lanzhou University from June to November 2020, and all the patients were divided into high serum ferritin (n=50) and normal serum ferritin (n=101) groups according to their serum ferritin levels. The visceral fat area (VFA), subcutaneous fat area (SFA), liver fat, height, weight and waist circumference (WC) were measured, as well as blood glucose, lipid indexes, body mass index (BMI) and visceral adiposity index (VAI) were also calculated. t-test or nonparametric test was used to compare the differences between the two groups, and the relationship between serum ferritin levels and body fat distribution was analyzed by Pearson or Spearman correlation analysis, multiple linear regression and logistic regression.ResultsThe VAI and WC were significantly higher in high serum ferritin group [3.13(2.16,4.58) and (96.66±7.78) cm] than in normal serum ferritin group [2.66(1.66,3.81) and (91.96±9.75) cm, P<0.05]. The prevalence of central obesity and dyslipidemia was higher in high serum ferritin group (88.0% and 90.0%) than in normal serum ferritin group (68.3% and 75.2%); and the composition ratios of poor glycemic control and insulin resistance (96.0% and 62.0%) were also higher than in normal serum ferritin group (78.2% and 40.6%) (P<0.05), there were no statistically significant differences in BMI, VFA, and SFA levels, as well as antidiabetic drug use and chronic complications of diabetes mellitus between the two groups (P>0.05). Serum ferritin levels in T2DM patients were positively correlated with VAI, WC, triglyceride (TG), fasting blood glucose (FPG), HbA1c, dyslipidemia and serum creatinine (r=0.171, 0.207, 0.187, 0.243, 0.270, 0.162, 0.162; P<0.05), and negatively correlated with age, sex and diabetes course (r=-0.191, -0.434, -0.352; P<0.05). Multivariate linear regression analysis showed that in male T2DM patients, duration of diabetes and FPG were risk factors for increased levels of serum ferritin. However, WC and VAI did not significantly affect serum ferritin levels. In female patients with T2DM, the course of diabetes, TG and VAI were the factors influencing serum ferritin (P<0.05).ConclusionDyslipidemia and visceral fat accumulation are risk factors for elevated serum ferritin levels in female T2DM patients.
关键词:diabetes mellitus, type 2;serum ferritin;body fat distribution;visceral obesity index;insulin resistance
摘要:ObjectiveTo analyze the prognostic significance and biological effects of cytochrome P450 family 27 subfamily A member 1 (CYP27A1) in hepatocellular carcinoma (HCC), and to preliminarily explore its molecular mechanism of regulating the malignant growth of HCC.MethodsThe Cance Genome Atlas (TCGA) database was used to analyze the expression level of CYP27A1 and its prognostic effect on HCC patients. The samples were divided into CYP27A1 high-expression group (n=170) and low-expression group (n=170) based on the median expression of CYP27A1 in HCC, gene set enrichment analysis (GSEA) was performed to investigate gene sets associated with CYP27A1 expression. The subcellular localization of CYP27A1 was detected by immunofluorescence staining and search database. The over-expression plasmid of CYP27A1 was constructed and then transfected into the HCC cells MHCC-97H and HCCLM3 cell lines, including two groups, namely control group (transfecting empty vector) and CYP27A1 over-expression group (transfecting CYP27A1 over-expressed vector). CCK-8, flow cytometer, and reactive oxygen species (ROS) fluorescence probe were applied to detect the effects of CYP27A1 over-expression on cell viability, apoptosis and ROS levels in HCC cells. Combining bioinformatics to analyze the correlation between CYP27A1 and the expression of ROS generation-related genes and HCC proliferation-related genes.ResultsCompared with the normal liver tissue, the expression level of CYP27A1 mRNA in HCC tissue was significantly reduced (P<0.01). The expression of CYP27A1 was significantly correlated with sex, T stage, tumor grade and tumor stage of HCC patients (P<0.05). Compared to the CYP27A1 high-expression group, patients in CYP27A1 low-expression group had lower survival rate (P<0.01). GSEA enrichment analysis revealed that the levels of HCC stem cell-related gene clusters and HCC proliferation gene clusters were remarkably increased in CYP27A1 low-expression group. The immunofluorescence showed that CYP27A1 was mainly located in nucleus in MHCC-97H and HCCLM3, whereas CYP27A1 was mainly located in mitochondria in HepG2. CYP27A1 over-expression attenuated cell viability (P<0.01), and reduced the ROS levels (P<0.05), whereas it had no effects on the apoptosis in HCC cells (P>0.05). The expression of CYP27A1 and the expression of inhibiting ROS generation-related genes were positively correlated (P<0.05), while the expression of inhibiting ROS generation-related genes and the expression of HCC proliferation-related genes were negatively correlated (P<0.05).ConclusionsThe expression of CYP27A1 was decreased in HCC, and down-regulated CYP27A1 promoted cell growth by enhancing ROS generation, although the precise mechanism requires future educidation.
关键词:hepatocellular carcinoma;cytochrome P450 family 27 subfamily A member 1;malignant growth
摘要:ObjectiveTo observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation (NPWTi) for the treatment of stage Ⅲ-Ⅳ pressure injury (PI), and to preliminarily explore its action mechanism.Methods(1) Clinical research: from January 2019 to October 2022, 60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group, with 30 cases in each group. Both groups underwent NPWTi under the premise of systemic basic treatment, before treatment, after removing the negative pressure device in the 1st, 2nd and 3rd weeks of treatment, the pressure ulcer scale for healing (PUSH) score, the wound bacterial culture detection rate and the wound healing time were counted, and the vascular endothelial growth factor (VEGF) content of wound tissue was detected by ELISA method. (2) Animal experiments: 24 SD rats were randomly divided into blank group, model group, normal saline NPWTi group and compound Wufengcao liquid NPWTi group, 6 rats in each group. PI rat model was established by local tissue ischemia/reperfusion injury method, and the negative pressure device was removed at the end of each day of treatment. Before treatment and 3, 7 and 10 days after treatment, the wound morphology of each group of rats was observed, the wound histopathology was observed by HE staining, the CD34 positive cells rate of wound tissue was detected by immunohistochemistry, and the expressions of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor-κB p65 (NF-κB p65), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), arginase-1 (Arg-1) and transforming growth factor-β (TGF-β) in rat blood and wound tissue were detected by ELISA and RT-qPCR.Results(1) Clinical research: Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate, shorten the wound healing time, and promote the expression of VEGF in wound tissue, the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group (P<0.05). (2) Animal experiments: Compared with blank group, the rats in the model group showed obvious wound inflammatory response and tissue damage, and the CD34 positive cells rate, blood and wound tissue p38 MAPK, NF-κB p65, iNOS and TNF-α levels were significantly increased, Arg-1 and TGF-β level was significantly reduced (P<0.05); Compared with model group, after 7 days of treatment, the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score, the histopathological morphology was significantly improved, the CD34 positive cells rate was significantly increased (P<0.05), the levels of blood and wound tissue p38 MAPK, NF-κB p65, iNOS, and TNF-α were significantly reduced, and the levels of Arg-1 and TGF-β were significantly increased (P<0.05), and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group (P<0.05).ConclusionCompound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds, and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway, thereby regulating the polarization balance of M1/M2 macrophages.
摘要:ObjectiveTo investigate the association between the serum creatinine/cystatin C ratio (SCr/Cys C) as a Sarcopenia index (SI) and the incidence of in-hospital adverse events in patients with acute myocardial infarction (AMI) undergoing emergency percutaneous coronary intervention (PCI). Additionally, we evaluate the predictive efficacy of the SI in predicting major adverse cardiovascular events (MACEs) during hospitalization.MethodsA total of 306 patients with AMI who underwent emergency PCI in the 904th Hospital of PLA Joint Logistics Support Force from January 2020 to March 2023 were consecutively included in this retrospective analysis. Patients were divided into two groups based on the occurrence of MACEs during hospitalization: MACEs group (n=43) and non-MACEs group (n=263). Clinical characteristics and pre-PCI laboratory test results were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for MACEs. The predictive performance of SI was assessed using receiver operating characteristic (ROC) curve analysis.ResultsThe incidence of in-hospital MACEs in AMI patients was 14.1%.The results of the independent samples t-test showed that the SI level in MACEs group was significantly lower than that in non-MACEs group, with a statistically significant difference (P<0.001). The results of the multivariate logistic regression analysis suggested that new-onset atrial fibrillation, Killip class 2-4, SI, and TG were independent risk factors for in-hospital adverse events after emergency PCI. The ROC curve results showed that the predictive value of SI (AUC=0.741, 95%CI 0.666-0.816) using the SCr/Cys C ratio was superior to that of single Cys C (AUC=0.658, 95%CI 0.570-0.746) for predicting post-PCI MACEs, with a statistically significant difference (P<0.05), and the optimal cutoff value for SI was 78.14. After stratifying SI based on the cutoff value, the results of the independent samples t-test showed that compared to the higher SI group, the lower SI group had a higher occurrence of specific adverse events such as heart failure (P<0.001), malignant arrhythmias (P=0.009), and strokes (P=0.003), with statistically significant differences.ConclusionsThe results highlight SI as an independent risk factor for MACEs during hospitalization after emergency PCI in AMI patients. Furthermore, SI has proven to be an effective prognostic index for patient outcomes.
摘要:ObjectiveTo investigate the independent risk factors of comprehensive complication index (CCI) ≥26.2 after radical resection of colon cancer, and use these factors to establish and verify a dynamic web-based nomogram model.MethodsThe clinical data of colon cancer patients who underwent radical resection in the Affiliated Hospital of Jiangnan University from November 2020 to April 2022 were retrospectively collected, and divided into main cohort (November 2020 to October 2021,n=438) and validation cohort (November 2021 to April 2022, n=196). CCI scores of all patients were obtained based on CCI calculator (http://www.assessurgery.com). Univariate and multivariate logistic regression analysis were performed to identify the risk factors for CCI ≥26.2, and a nomogram model was constructed. Receiver operator characteristic curve (ROC), C index and calibration curve were used to evaluate the differentiation and consistency of predictive nomogram model, and the decision curve analysis was conducted to assess the clinical benefits of the model. Internal validation of the model is performed in the validation cohort.ResultsA total of 438 patients were identified in present study, of which 63 cases (14.4%) had CCI ≥26.2. Multivariate logistic regression analysis revealed that age ≥60 years (OR=2.662, 95%CI 1.341-5.285, P=0.005), low third lumbar spine skeletal muscle mass index (L3MI; OR=4.572, 95%CI 2.435-8.583, P<0.001), NRS2002 ≥3 (OR=4.281, 95%CI 2.304-7.952, P<0.001), and preoperative bowel obstruction (OR=3.785, 95%CI 1.971-7.268, P<0.001) were significant independent risk factors for postoperative CCI ≥26.2. Based on these results, a static and web-based dynamic nomogram was established (https://jndxfsyywcwksyf.shinyapps.io/DynNomCCI/). The C-index and area under the curve (AUC) of the nomogram were 0.742 and 0.787, respectively. The calibration curve indicated a good consistency between the predicted probability and the actual probability. In the validation cohort, the nomogram also presented good discrimination (C-index=0.722, AUC=0.795) and predictive consistency. The decision curve analysis indicated the clinical benefit and application value of the nomogram prediction model.ConclusionThis easy-to-use dynamic nomogram based on 4 independent risk factors can conveniently and reliably predict the probability of CCI ≥26.2 after radical resection of colon cancer, which helps optimize the preoperative evaluation system, formulate precise individualized treatment strategies, and enhance recovery after surgery.
关键词:colon cancer;comprehensive complication index;skeletal muscle mass index;nomogram model
摘要:ObjectiveTo investigate the changes of serum neuroglobulin (NGB) levels in patients with aneurysmal subarachnoid hemorrhage (aSAH) and its clinical value in predicting of delayed cerebral ischemia (DCI).MethodsA total of 217 patients with aSAH who were diagnosed and treated in the Department of Neurology of Wuwei People's Hospital from October 2019 to October 2022 were selected. They were divided into DCI group and non-DCI group according to the occurrence of DCI after aSAH. The clinical data, and serum NGB levels on day 1 and day 3 after admission were compared between the two groups, and the value of serum NGB in prediction of DCI was evaluated by ROC curve. Logistic regression was used to analyze the risk factors to DCI in aSAH patients.ResultsDCI occurred in 43 of 217 patients with aSAH (19.8%). Hunt-Hess grade and modified Fisher grade in DCI group were higher than those in non-DCI group (P<0.05). The level of serum NGB in DCI group was higher than that in non-DCI group on day 1 and day 3 after admission (P<0.05), and the levels of serum NGB on day 3 after admission were lower than that on day 1 in two groups (P<0.05). The decrease of serum NGB level in DCI group was lower than that in non-DCI group (P<0.05). ROC curves showed that serum NGB at 3 d after admission predicted a greater AUC for DCI (0.838) than serum NGB at 1 d after admission (0.706)(Z=2.139, P<0.05), with an optimal cutoff of 10.19 ng/ml of serum NGB, the sensitivity and specificity were 74.4% and 86.8% respectively. Logistic regression analysis showed that the risk factors of DCI in patients with aSAH were modified Fisher Grade Ⅲ-Ⅳ (OR=3.790, 95%CI 1.531-9.382), Hunt-Hess grade Ⅲ-Ⅴ(OR=2.448, 95%CI 1.023-5.858) and increased serum NGB at 3 d after admission (OR=1.835, 95%CI 1.496-2.251).ConclusionsThe serum NGB level is relatively high in patients with DCI after aSAH in the early stage. The serum NGB level, modified Fisher grade, and Hunt-Hess grade are related to the development of DCI after aSAH, and the serum NGB level on 3 d after admission has high predictive value.
摘要:ObjectiveTo investigate the genotypic and phenotypic characteristics of AB type GM2 gangliosidosis (GM2-GLS) with onset during childhood.MethodsThe report analyzed the clinical data and gene detection results of a 4-year-old child with AB type GM2-GLS diagnosed by Trio whole exome detection in March 2022 admitted to the Department of Pediatrics of Guangxi Zhuang Autonomous Region People's Hospital. The clinical data and genetic testing results are analyzed. A literature review was also conducted on relevant studies published between 1991 and 2022 in the PubMed database.ResultsThe results of Trio whole exome sequencing and Sanger verification showed that the GM2A gene carried two compound heterozygous mutations: c.158_159delTG and c.496G>A, which caused p.L53Rfs*3 frameshift mutation and p.G166R missense mutation, respectively. A total of 20 cases were reported in 22 articles. A total of 11 mutation types of GM2A gene were included in the ClinVar Database.ConclusionsAB type GM2-GLS is a rare autosomal recessive lysosomal storage disease, and its gene test is helpful for definite diagnosis.
关键词:ganglioside deposition;gene, GM2A;GM2 activating protein
摘要:ObjectiveTo investigate the protective effect of placental mesenchymal stem cells (P-MSCs) on pancreatic trauma (PT) in rats.MethodsSixty healthy adult male SD rats were randomly divided into control group, pancreatic trauma group (inject 1 ml of PBS solution locally in the pancreatic injury area and around the trauma area), and P-MSCs group [inject 1 ml of P-MSCs (1×106/ml) locally in the pancreatic injury area and around the trauma area], with 20 rats in each group. The pancreatic trauma rat model was established using a traumatic pressure of 400 kPa. Five rats were sacrificed at 1, 3, 5, and 7 d after modeling in each group, and serum and pancreatic tissue were collected. HE staining was used to observe the pathological changes of pancreatic tissue and pathological scores were performed. The ELISA method was used to measure the concentrations of serum amylase (AMS), lipase (LPS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, and transforming growth factor-β1 (TGF-β1), as well as the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in pancreatic tissue. The TUNEL method was used to observe the level of apoptosis in pancreatic tissue was observed by the TUNEL method.ResultsCompared with control group, pancreatic trauma group and P-MSCs group showed significant differences after pancreatic trauma, including the generation of peritoneal fluid increased (P<0.05), the ratio of pancreas to body weight and the total score of pancreatic tissue pathological damage increased (P<0.05), and serum levels of AMS, LPS, TNF-α, IL-6, and MPO activity increased early and showed a decreasing trend over time (P<0.05), while anti-inflammatory factors IL-10 and SOD activity showed an increasing trend over time (P<0.01), level of TGF-β1 in the early decline showed an upward trend over time (P<0.01), and the apoptosis index (AI) significantly increased (P<0.001). Compared with pancreatic trauma group, P-MSCs group showed an improvement in the overall morphology of pancreatic tissue, the generation of peritoneal fluid decreased (P<0.001), the pancreas to body weight ratio and the total score of pancreatic tissue pathological damage decreased (P<0.05), and serum levels of AMS, LPS, IL-6, TNF-α and MPO activity returned to normal levels faster (P<0.05); and the rate of anti-inflammatory factors IL-10, TGF-β1 and SOD activity elevation increased (P<0.05), the AI increased (P<0.001).ConclusionP-MSCs can achieve therapeutic effects on pancreatic trauma in rats by promoting pancreatic tissue repair, reducing local and systemic inflammation, improving tissue oxidative stress, and enhancing pancreatic acinar cell apoptosis.
摘要:ObjectiveTo investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1) A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation. To observe the effects of hypoxia on the expression of TH, Ub-K48 and Ub-K63, MN9D cells were divided into normoxia group and hypoxia (12 h, 24 h and 48 h) groups. To observe the effects of MG132 on the expression of the above-mentioned proteins, MN9D cells were divided into normoxia group, hypoxia group and hypoxia + MG132 (25, 50, 100, 200 μmol/L) group. (2) A mouse model of memory impairment was established using a hypobaric chamber. To observe the effects of hypobaric hypoxia on the expression of TH, Ub-K48 and Ub-K63 in the substantia nigra compacta (SNc) of mice, thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia (3 d and 21 d) groups, 10 in each group. To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia, twenty-four C57BL/6 mice were randomly and equally divided into normoxia group, hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group, 8 in each group. (3) The protein expression levels of TH, Ub-K48, and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting (WB). The novel object recognition test was used to detect the memory function of mice. Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region. The expression levels of TH, Ub-K48, and Ub-K63 in the SNc region were detected by WB.Results(1) Compared with normoxia group, MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63 (P<0.05), and decreasing expression of TH (P<0.05), and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH (P<0.05). Compared with hypoxia group, MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group (P<0.05). (2) Compared with the mice in normoxia group, mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH (P<0.001), and increasing expression of Ub-K48/TH and Ub-K63/TH (P<0.05) in the SNc region. Compared with normoxia group, the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index (P<0.01), and the proportion of positive immunoreactive area of TH response in the SNc region (P<0.05). Compared with 21 d hypobaric hypoxia group, the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index (P<0.01).ConclusionThe proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice, and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48, which in turn upregulates expression of TH in dopaminergic neurons.
摘要:ObjectiveTo investigate the expression of prolyl 4-hydroxylase β‑polypeptide (P4HB) in glioblastoma multiforme (GBM) and its impact on clinical prognosis, as well as on the proliferation and migration of U87 cells.Methods(1) According to the Cancer Genome Atlas (TCGA) database, GTEx database and GEPIA2 database, the difference expression of P4HB in GBM and normal brain tissues were analyzed by R software. (2) A total of 52 patients with GBM who underwent surgical treatment from February 2017 to December 2019 were collected from Department of Neurosurgery, the Second People's Hospital of Guiyang. The normal brain tissues of 10 patients were selected as controls. Immunohistochemical method was used to detect the expression level of P4HB in tumor tissues and normal tissues. The Kaplan-Meier method with the log-rank test was employed for survival analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive valuable of P4HB expression in survival rate of GBM. Univariate and multivariate Cox regression analysis were used to identify the expression of P4HB and related clinicopathological factors affecting the survival and prognosis of the patients. (3) Human GBM U87 cells were randomly assigned into three groups: control group, NC-siRNA group and P4HB-siRNA group. P4HB expression was interfered with by the transfection of siRNA in P4HB-siRNA group. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the content of P4HB mRNA in U87 cells. Cell counting kit-8 (CCK-8) and immunofluorescence assay were used to analyze the effects of P4HB on the proliferation of U87 cells. Scratch test was used to analyze the effects of P4HB on cell migration.ResultsThe expression of P4HB was significantly upregulated in GBM tissues compared with normal brain tissues (P<0.05). The γδ T cells (r=-0.227) and follicular helper T cells (r=-0.226) were negatively correlated with the expression of P4HB, while natural killer cell (r=0.417), macrophages (r=0.374), neutrophils (r=0.344), and immature dendritic cells (r=0.263) were positively correlated with the expression of P4HB. Kaplan-Meier survival analysis showed that the progression-free survival and disease-specific survival of GBM patients with high P4HB expression were significantly lower than those with low expression (P<0.05). ROC curve showed that the area under the curve (AUC) of P4HB in predicting overall survival rate of GBM patients was 0.982, and 1-year, 3-year, and 5-year survival was 0.655, 0.724, 0.861, respectively. The immunohistochemistry results suggested that P4HB protein was significantly highly expressed in GBM tumors. Survival analysis indicated that high expression of P4HB was associated with bad prognosis in GBM patients (P<0.05). Multivariate Cox regression analysis indicated that high expression of P4HB and TERT promoter mutations were the independent prognostic risk factors for GBM (P<0.05). Compared with control group and NC-siRNA group, the expression levels of P4HB were decreased significantly after transfected with siRNA in U87 cells of P4HB-siRNA group (P<0.01), and the proliferation ability and the wound healing rate were decreased significantly in P4HB-siRNA group (P<0.001).ConclusionsP4HB is significantly highly expressed in GBM, which indicates that the prognosis of patients is poor. Knockout of P4HB could inhibit cellular proliferation and migration of GBM U87 cells. P4HB may be used as the relevant predictive marker and potential therapeutic target in GBM.
摘要:Histone deacetylases (HDACs) can deacetylate histones, leading to tighter DNA binding, and thereby playing a role in inhibiting gene transcription. On the contrary, histone deacetylase inhibitors (HDACis) can promote chromatin relaxation, enabling various transcription factors to bind specifically to DNA and activate transcription genes. Dental stem cells (DSCs) are human adult stem cells. These cells have the characteristics of less damage and low immune rejection during sampling, and are especially important seed cells in the process of osteogenesis, odontogenesis and other differentiation. A large number of experimental studies have shown that HDACs and HDACis together play important roles in cell division and differentiation, signal transduction, regulation of cellular inflammation and other life processes. This review summarizes the research progress of HDACs and HDACis in regulating osteogenic and odontogenic differentiation of DSCs, aiming to provide insights into the study of the interaction between HDACs and HDACis, and potentially guide clinical application of DSCs in the treatment of tooth and bone injury.
摘要:Epilepsy is a chronic disease characterized by recurrent, sudden, and excessive synchronous discharge of neurons in the brain, leading to transient brain dysfunction, and inflammatory responses in specific regions within the central nervous system are common features of epilepsy. In recent years, there has been increasing evidence that endoplasmic reticulum stress is involved in the pathology of epilepsy, which activates the unfolded protein response, then regulate and control nuclear factor kappa-B (NF-κB), efficiently induces glial cell activation through the release of pro-inflammatory signals, in turn affects epileptogenesis and seizures by triggering neuroinflammation. This review focuses on the close link between endoplasmic reticulum stress and glial cell activation-mediated neuroinflammation in epilepsy pathology, aiming to provide insights for a deeper understanding of epilepsy.
摘要:Breast cancer is one of the most prevalent malignancies in the world, and many advances have been made in various types of tumor research in recent years. With the deepening understanding of tumors, the microenvironment for tumor cell growth has attracted more and more attention for its impact on the development and progression of cancer. Cancer-associated fibroblasts (CAFs) as the most important components of the tumor microenvironment, can release cytokines, exosomes, and so forth in many ways to regulate immune microenvironment, remodel extracellular matrix and promote formation, migration, invasion, and resistance of tumors, while at the same time CAFs can be regulated by tumor cells. This paper attempts to explain the interaction mode between CAFs and tumors in the immune microenvironment and various ways in which CAFs can promote tumor proliferation, growth, invasion, metastasis, drug resistance and other malignant biological behaviors. Finally, the possibility of using CAFs as an early screening technique and new treatment method for breast tumors is discussed.