Latest ArticlesObjective To investigate whether Huaier can reverse the drug resistance of CEM-C1 cells to glucocorticoid(GC) in human acute T lymphocytic leukemia (T-ALL) and its possible mechanism. Methods CEM-C1 and CEM-C7 cells were set as control group (0 μg/ml) and experimental groups (200 and 600 μg/ml) after treated with different concentrations of Huaier; T-ALL CEM-C1 cells were set as Huaier (100 μg/ml) combined with dexamethasone (DEX)(12.5, 25, 50, 100, 200 μg/ml)groups; CCK-8 was used to detect the affect of Huaier on the inhibition rate to proliferation of each group of cells; Flow cytometry(FCM) was employed to detect the effect of different concentrations Huaier (200 and 600 μg/ml) on the apoptosis and cell cycle of CEM-C1 and CEM-C7 cells; Western blotting was performed to detect the MDR1 and Pim3 protein expression levels in CEM-C1, CEM-C7 cells and CEM-C1 cells treated with different concentrations of Huaier (200 and 600 μg/ml); qRT-PCR was used to detect the expression level of Pim3 mRNA in CEM-C1 and CEM-C7 cells and CEM-C1 cells treated with different concentrations of Huaier(200 and 600 μg/ml). Results Huaier inhibited the proliferation of CEM-C1 and CEM-C7 cells in a dose-dependent manner;For CEM-C1 cells, compared with DEX alone, the drug resistance was reversed by 1.34 times in Huaier+DEX group, and Huaier(100 μg/ml) combined with low concentration of DEX (12.5, 25, 50 μg/ml) increased the proliferation inhibition rate of CEM-C1 cells (P<0.05); the coeffcient of drug interaction (CDI) values of all groups were <1. Compared with control group, the apoptosis rate of CEM-C1 and CEM-C7 cells increased significantly with the increase of Huaier concentration (P<0.05). Compared with control group, the number of CEM-C1 and CEM-C7 cells decreased in G0/G1 stage and increased in S stage in 200 and 600 μg/ml Huaier groups. The expression levels of MDR1 and Pim3 protein and Pim3 mRNA in CEM-C1 cells were higher than those of CEM-C7 cells (2.41±0.32 vs. 1.34±0.43; 0.39±0.10 vs. 0.13±0.05; 1.00 vs. 0.37±0.02, respectively, P<0.05). Compared with control group, the expression levels of MDR1 and Pim3 proteins and Pim3 mRNA reduced obviously in CEM-C1 cells after treatment with 200 and 600 μg/ml Huaier (P<0.05). Conclusion Huaier can inhibit the proliferation and promote the apoptosis of CEM-C1 and CEM-C7 cells, and partially reverse the resistance of CEM-C1 cells to GC, the mechanism may be related to the down-regulation of Pim3.
Objective To document the dynamics of secondary liver injury in pigs with traumatic hemorrhagic shock(THS) induced by simulated desert dry heat environment and to explore its possible mechanism. Methods Sixty male Landrace piglets were randomly divided into three groups: Dry heat trauma hemorrhagic shock group (DHS group, n=20), dry heat trauma hemorrhagic shock sham operation group (DHC group, n=20), normal temperature trauma hemorrhagic shock group (NTS group,n=20). DHS group and DHC group were exposed to a dry and hot environment [temperature (40.5±0.5) ℃, humidity 10%±2%];while NTS group were exposed to normal temperature environment [temperature (25.0±0.5) ℃, humidity 35%±5%] for 3 h. Then the model of blood pressure controlled hemorrhagic shock was established. Animals were euthanized at 0 min (T0), 50 min(T1), 100 min (T2) or 150 min (T3) after the successful establishment of the hemorrhagic shock model, blood and live tissue were collected. The pathological changes of liver tissue were observed by HE staining; the levels of TNF-α and IL-1β in liver tissue were detected by ELISA; the expressions of HMGB-1 and ICAM-1 in liver tissue were detected by Western blotting; the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were determined. Results HE staining results showed that the DHS group had different degrees of injury at each time point, and gradually aggravated with time, and gradually appeared different degrees of hepatic sinusoidal expansion, congestion, hepatic lobule, portal area structure disorder, inflammatory cell infiltration, liver cell degeneration, necrosis and so on. In the NTS group, the injury began to appear at T2 and gradually worsened. In the DHC group, there was no obvious pathological change at each time point (P>0.05). In the DHS group, ALT and AST showed dynamic changes, and the changing trend was the same, compared with the DHC group, it began to rise at T0, the difference was statistically significant (P<0.01), and reached the peak at T1 and T3, respectively, and the differences were statistically significant compared with DHC group and NTS group at the same time point (P<0.01); however, there was no significant change in DHC group at each time point. TNF-α and IL-1β began to increase at T0 in the DHS group, and the differences were statistically significant compared with the DHC group and NTS group at the same time point (P<0.01). Both the DHS group and NTS group showed a continuous growth trend in a time-dependent manner with a significantly faster growth rate in the DHS group than that of the NTS group (P<0.01). There were no statistical significances on ALT or AST levels in the DHC group (P>0.05). As time went on, the expression of ICAM-1 and HMGB-1 in the DHS group was higher than that in the previous time point (P<0.05 or P<0.01). Conclusion In desert dry and hot environment, the secondary liver injury of THS occurs early and progresses seriously. This can activate more Kupffer cells in the liver to promote the release of TNF-α and IL-1β leading to elevated expression of HMGB-1 and ICAM-1 resulting in further liver injury.
Intervertebral disc degeneration (IDD) is a common disease in orthopedics, and its pathogenesis is complicated. The main pathological changes are cell apoptosis and extracellular matrix degradation. Clinical therapies are mainly symptomatic and cannot cure diseases at the etiological level. IDD targeted therapy has become the focus of current research due to its small side effects and broad prospects. The apoptosis of nucleus pulposus cells caused by activation of the Fas signaling pathway is an important cause of IDD. It affects IDD's pathophysiological process through genetic factors and is closely related to the pathogenesis of IDD inflammation, immunity, and abnormal vascular growth. Targeting Fas signaling inhibition may be a new type of therapy to slow down the process of IDD effectively. This paper reviews Fas apoptotic pathway, etiology of IDD, the relationship between Fas pathway and IDD, and targeted inhibition of Fas pathway in the treatment of IDD.
Cardiac computed tomography angiography (CCTA) has become an important non-invasive method to evaluate coronary artery disease. With the extensive application and increased image analysis features, more demands on operational technique and efficiency are asked. Machine learning (ML) is the subarea of artificial intelligence (AI), which is completely data driven, by computer algorithm to identify and analyze the potential relationship of centralized variables in large data sets for realizing the prediction of external data. In the field of cardiac CT, the application of various ML algorithms would improve the efficiency and quality of CCTA, helping accurate lesion assessment and risk stratification. It also brings new applications in cardiac functional imaging. The applications of ML in cardiac CT have been reviewed in present paper including CT-image analysis, risk stratification, CT-myocardial perfusion and CT-fractional flow reserve.
Percutaneous coronary intervention (PCI) is one of the effective treatments for coronary heart disease (CHD), but it may cause stress events since its invasive might lead to various somatization symptoms, and then bring about anxiety, depression and other psychological disorders, thus affecting its curative effect and prognosis. In recent years, due to the extensive development of PCI treatment, such patients are not rare in clinic. It has been proved that anxiety and/or depression and CHD are reciprocal and influenced by multiple factors, but the pathophysiological mechanism is still not clear. With the continuous development of "double-heart medicine" model, clinical workers have paid more attention to the identification and diagnosis of cardiovascular disease complicated with psychological problems. The research progress of clinical diagnosis and treatment of patients with complicated anxiety and/or depression after PCI has been reviewed in present paper, thus provides a reference for the implementation of clinical work.
Objective To explore the clinical features of patients with end-stage renal disease (ESRD) complicated with pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) and undergoing maintenance hemodialysis (MHD). Methods A total of 133 ESRD patients complicated with tuberculosis, treated at the Tuberculosis Department of the 8th Medical Center of Chinese PLA General Hospital and undergoing MHD at the Blood Purification Center, were selected from July 2012 to February 2021, and divided into PTB group (87 cases) and EPTB group (46 cases). The clinical characteristics, treatment and prognosis of the two groups were compared and analyzed. Results Both PTB group and EPTB group were predominantly male patients (80.5% and 58.7%), but the proportion of female patients was higher in EPTB group (41.3%) than that in PTB group (19.5%, P<0.05). No significant differences existed between the two groups in age, primary kidney disease, comorbidities, dialysis duration, and the detection time-point of tuberculosis after dialysis. Among the first symptoms, the proportion of cough+sputum and fever was significantly higher in PTB group than that in EPTB group (59.8% vs. 23.9% and 60.9% vs. 28.3%, respectively, P<0.05), while the proportion of pain at lesion location was significantly lower in PTB group than that in EPTB group (8.0% vs. 41.3%, P<0.05).CT or MRI imaging was the dominated method for definite diagnosis in both PTB group and EPTB group (67.8% and 76.1%), the secondary method was sputum smear or culture (26.4% and 6.5%) and needle biopsy (5.7% and 17.4%), respectively, with a significant difference between the two groups (P<0.05). No significant difference existed in the positive rate of γ-interferon release assay (γ-IRA) between the two groups. In both PTB group and EPTB group, the proportion of lymphocytes, hemoglobin and albumin decreased markedly, while the proportion of erythrocyte sedimentation rate (ESR) and increased C-reactive protein(CRP) were relatively higher, but there was no statistical difference between the two groups. Both groups were treated with anti-tuberculosis drugs, and one case in EPTB group received anti-tuberculosis drugs plus surgery of tuberculosis focus clearance. No significant difference existed in the incidence of adverse reactions between the two groups, and the improvement rate after treatment was similar. Conclusions Significant differences exist between PTB and EPTB patients with ESRD on MHD in gender ratio, first manifested symptom and diagnosis methods. Paying attention to these differences and conducting individualized monitoring, diagnosis and treatment will be helpful to reduce the morbidity and mortality of patients with PTB and EPTB.
Gastric cancer is the fifth leading incidence and the third leading cause of death in the world. Gastric cancer patients in China are often in advanced stages and have a poor prognosis. Cancer progression depends not only on the cancer cells themselves, but also on the physiological state and composition of the tumor microenvironment in which they are located. Cancer-associated fibroblasts as the major cell type in the tumor microenvironment played an important role in cancer progression. This paper mainly expounds the origin and classification of cancer-associated fibroblasts, and its research progress on gastric cancer invasion and metastasis, growth, angiogenesis, matrix remodeling, immunomodulation and cancer suppression, and summarizes the relevant anti-tumor strategies by targeting cancer-associated fibroblasts in gastric cancer, to provide more information for use of cancer-associated fibroblasts in targeted therapy of gastric cancer.
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is an etiology-unknown, non-specific, chronic inflammatory disorder of the intestinal tract with complex pathogenesis. Generally, patients with IBD present with repeated abdominal pain, diarrhea, mucus and blood in the stool, and even various systemic complications. More and more studies believe that it is a chronic inflammatory disease that occurs through the interaction of environment, genetics, intestinal flora, visceral sensitivity, and mental factors. In recent years, the incidence of IBD has been increasing year by year. Early-life exposure refers to the exposure from fetal period to childhood. Early-life adverse exposure (drug exposure, stress exposure, delivery methods, etc.) can have short-term or long-term effects on the intestines of infants, further affecting the physical and mental health of adolescents, adults, and even the elderly, this leads to long-term health effects. A number of studies have found that early-life adverse exposures are involved in the occurrence and progression of IBD. The occurrence of adverse exposure in early life can promote the occurrence and progression of IBD by changing the intestinal flora, immune function, epigenetic inheritance and visceral sensitivity. However, the mechanism by which early-life adverse exposure changes susceptibility to IBD remains unclear. In-depth study of the relationship between early-life adverse exposure and the occurrence of IBD can help prevent the occurrence of diseases at an early stage and reduce the burden of adulthood. This will greatly benefit the improvement of life and health and the rational use of medical resources. This article reviews the relationship between common early-life adverse exposure and the risk of IBD.
Objective To investigate the curative effect of low molecular weight heparin (LMWH) on preventing the formation of deep vein thrombosis (DVT) of high-risk pregnant women during pregnancy and puerperium. Methods A total of 1099 high-risk pregnancy patients were collected as LMWH group who received LMWH for preventing the formation of DVT in Zhujiang Hospital of Southern Medical University from January 2019 to July 2020; and 2107 high-risk pregnancy cases without LMWH were selected as control group from January 2016 to December 2018. SPSS 20.0 was employed for statistical analysis, and the number of thrombosis cases, the incidence of prepartal and puerperal hemorrhage, the cesarean section rate and other indicators were compared and analyzed between the two groups. Results After LMWH treatment, no new case of DVT occurred in LMWH group during pregnancy and puerperium, while there were 24 cases of new thrombosis in control group, the difference was statistically significant between the two groups (P=0.000). There were 2 cases of placental abruption before delivery occurred in the LMWH group, and only 1 case in control group. The 2 h postpartum hemorrhage was (182.25±120.62) ml in LMWH group, and (165.00±68.58) ml in control group. The cesarean section rate was 37.5% in LMWH group and 38.9% in control group. No significant differences existed in the incidence of placental abruption, postpartum hemorrhage and cesarean section between the two groups (P>0.05). Conclusion For pregnant women with high risk factors for thrombosis, LMWH can be used according to the score to prevent thrombosis, and it is safe and effective.
Objective To investigate whether dexmedetomidine alleviates lipopolysaccharide (LPS)-induced acute lung injury(ALI) through alpha-7 nicotinic acetylcholine receptor (α7nAChR) mediated TLR4/NF-κB pathways. Methods Twenty-four Wistar rats were randomly divided into 4 groups: control group (n=6), acute lung injury group (n=6), dexmedetomidine treatment group (n=6), and α7nAChR inhibitor α-BGT group (n=6). After anesthesia, rats in the control group were intraperitoneally injected with normal saline to serve as normal control; the rest rats all received LPS (10 mg/kg) via a femoral vein to induce the ALI model. For the dexmedetomidine treatment group, rats were continuously injected with dexmedetomidine (5 μg/kg per hour) via the femoral vein immediately after LPS administration. For the α7nAChR inhibitor α-BGT group, rats received 1 μg/kg α-BGT half an hour before dexmedetomidine administration as the dexmedetomidine treatment group. The rats were sacrificed 12 hours after LPS injection to collect the blood and lung tissues. Histology of the lungs was examined with HE staining. The lung injury score was calculated. In the blood sample, PaO2, HCO3–, Lac, W/D, MPO activity were measured. The number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) were measured, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10 in serum were measured by ELISA. The protein expression of α7nAChR, TLR4, p-NF-κB were determined by Western blotting. Results Compared with the control group, LPS induced marked lung histological injury, which was less pronounced in the dexmedetomidine treatment group. Compared with the control group, the levels of PaO2 and HCO3– were decreased, Lac, W/D, TNF-α, IL-6, IL-10, MPO, the total number of cells, neutrophils, and macrophages were increased in the acute lung injury group (P<0.01). Compared with the acute lung injury group, PaO2, HCO3– and IL-10 were increased, and Lac, W/D, TNF-α, IL-6, MPO, the total number of cells, neutrophils, and macrophages were decreased in the dexmedetomidine treatment group (P<0.01). Compared with the control group, the protein levels of α7nAChR, TLR4, p-NF-κB were increased in the acute lung injury group (P<0.01). Compared with the acute lung injury group, the protein levels of α7nAChR was increased, and TLR4, p-NF-κB were decreased in the dexmedetomidine treatment group (P<0.01).However, the effect of dexmedetomidine was reversed by the α7nAChR inhibitor α-BGT. Conclusion Dexmedetomidine may reduce LPS-induced ALI through α7nAChR mediated TLR4/NF-κB pathways.