ArchiveObjective To investigate the role of autophagy in acute lung injury in rats with exertional heat stroke (EHS). Methods A total of 60 male Wistar rats were randomly divided into four groups: control group, EHS group, EHS+bafilomycin A1 (Baf A1) group, and EHS+rapamycin (RAPA) group, with 15 rats in each group. The EHS+Baf A1 group (Baf A1, 1 mg/kg)and EHS+RAPA group (RAPA, 1 mg/kg) were injected intraperitoneally for 4 consecutive days before modeling the rats. After establishing the EHS model, we observed for 5 hours, followed by anesthesia for these rats to collect tissues. We observed and compared the morphological changes in lung tissue, performed arterial blood gas analysis, and measured the lung coefficient and Evans blue (EB) leakage. We also examined the lung tissue pathological changes using HE staining, evaluated lung tissue apoptosis through the TdT-mediated dUTP Nick-end labeling (TUNEL) method, and detected microtubule-associated protein Ⅰ light chain 3(LC3)-Ⅱ/LC3-Ⅰ ratio in lung tissue and p62 protein level through Western blotting. Results Compared with control group,the lung tissue of the EHS group was obviously swollen and more fluid exuded; the arterial blood oxygen partial pressure (PaO2)decreased, while the arterial blood carbon dioxide partial pressure (PaCO2) increased; the lung coefficient and EB leakage were significantly increased; HE staining and apoptosis staining showed uneven thickening of alveolar septum and alveolar wall, alveolar exudation increased and the number of apoptotic cells increased, the difference was statistically significant (P<0.05); Compared with EHS group, the EHS+Baf A1 group had more severe lung tissue swelling, lung coefficient and EB leakage were increased; PaO2 further decreased, while PaCO2 further increased; HE staining and apoptosis staining showed that lung tissue lesions and damage were significantly worsened, and the number of apoptotic cells increased significantly (P<0.05). Compared with EHS group, the EHS+RAPA group had a significant decrease in various pulmonary edema indicators; PaO2 increased, PaCO2 is close to the normal range; HE staining and apoptosis staining showed lung tissue lesions and the degree of damage was significantly reduced, and the number of apoptotic cells was reduced, and the difference was statistically significant (P<0.05); Western blotting results showed that compared with control group, the ratio of LC3-Ⅱ/LC3-Ⅰ in the lung tissue of rats in the EHS group was significantly reduced(0.3±0.1 vs. 1.0±0.1, P<0.05), the expression of p62 increased (1.4±0.2 vs. 0.8±0.1, P<0.05). Compared with EHS group, the ratio of LC3-Ⅱ/LC3-Ⅰ in the lung tissue of the EHS+Baf A1 group was reduced (0.10±0.04), and the expression of p62 was further increased (1.7±0.1), while the ratio of LC3-Ⅱ/LC3-Ⅰ in the lung tissues of rats in the EHS+RAPA group was significantly increased (0.5±0.1), and the expression of p62 was significantly decreased (1.1±0.1), the differences were statistically significant(P<0.05). Conclusion The reduction of autophagy levels is one of the mechanisms of EHS leading to lung injury. Up-regulation of autophagy can reduce the acute lung injury of EHS.
Objective To explore the effect and mechanism of phosphatase and tensin homolog (PTEN) on renal interstitial fibrosis in diabetic nephropathy. Methods We culture NRK52E cells in vitro, cells were randomly assigned to three groups: normal glucose group (NG), high glucose group (HG) and mannitol group (MA), Western blotting was used to detect the protein levels of PTEN, LC3, P62, collagen-Ⅰ and Ⅲ in vitro. To detect the effect of PTEN on autophagy and collagen, the NRK52E were randomly assigned to three groups: NG group, HG group and HG+pPTEN group, the autophagy changes were observed by laser confocal microscopy, and the changes of collagen were observed by fluorescence microscopy. Results Western blotting in vivo showed that, compared with NG group, the expression levels of PTEN and LC3 were decreased, but of P62, collagen-Ⅰ and Ⅲ obviously increased in HG group (P<0.01), while no obvious change of the expression of PTEN and LC3, P62, collagen-Ⅰ and Ⅲ in MA group. The confocal microscope showed that, the number of red spots and yellow spots were decreased and significant autophagy inhibition in HG group, there were no significant autophagy inhibition in other two groups. The cellular immunofluorescence staining showed that, the red fluorescence of PTEN and protein expression were decreased, the collagen fluorescence staining and protein expression were increased in HG group, there were no significant change in other two groups. Conclusions In NRK52E cells under high glucose, PTEN expression reduced significantly,autophagy was inhibited, and then aggravate renal fibrosis. Overexpression of PTEN can restore autophagy and alleviate the progression of renal interstitial fibrosis.
Objective To investigate the effect of activated protein kinase C receptor 1 (RACK1) on the proliferation and apoptosis of human cervical cancer cells and its potential mechanism. Methods The cervical cancer tissues of 24 patients diagnosed as cervical squamous cell carcinoma (CSCC), admitted in the First Affiliated Hospital of Xinjiang Medical University from Dec. 2020 to Dec. 2021, were collected as the experimental group (CSCC group), and 24 normal cervical (NC) tissues were collected as the control group (NC group). The expression levels of RACK1 mRNA in CSCC tissues and NC tissues and in proliferation and apoptosis related genes c-myc, caspase-3, caspase-9, Bax and Bcl-2 in CSCC tissue samples were detected by qRT-PCR, and the correlation between RACK1 mRNA expression and apoptosis-related genes was analyzed by Spearman rank correlation. qRT-PCR and Western blotting were used to detect the expression of RACK1 in cervical cancer cells C33a and SiHa and normal cervical epithelial cells H8. C33a and SiHa cells were transfected with lentivirus to silence the expression of RACK1. According to different treatments, they were divided into: normal control (NC) group, sh-NON (RACK1 silent expression no-load group), shRACK1-1(RACK1 silent expression group 1), shRACK1-2 (RACK1 silent expression group 2), and the transfection efficiency was verified.MTT assay and plate cloning assay were used to detect cell proliferation, and flow cytometry was performed to detect cell apoptosis.After RACK1 was silenced, qRT-PCR was used to detect the expression levels of c-myc, caspase-3, caspase-9, Bax and Bcl-2. Western blotting was used to detect the expression levels of c-myc, caspase-3, caspase-9, Bax, Bcl-2, phosphorylated Janus kinase 2 (p-JAK2),JAK2, phosphorylated cell signal transduction and transcription activating factor 3 (p-STAT3) and STAT3. Results The expression level of RACK1 mRNA was significantly higher in CSCC tissue than that in NC tissue (P<0.001). Spearman rank correlation analysis showed that the expression level of RACK1 mRNA in cervical cancer tissues was significantly negative correlated with caspase-3(r=–0.679, P<0.001), caspase-9 (r=–0.735, P<0.001), Bax (r=–0.691, P<0.001) mRNA expression, but positively correlated with c-myc (r=0.713, P<0.001) and Bcl-2 (r=0.846, P<0.001) mRNA expression. qRT-PCR and Western blotting showed that compared with H8 cells, RACK1 mRNA and protein were highly expressed in C33a and SiHa cells (P<0.001). After RACK1 silence, the expression levels of RACK1 mRNA and protein declined obviously, the proliferation and colony formation ability also decreased,while the apoptosis level was significantly increased (P<0.001) in shRACK1-1 and shRACK1-2 groups than those in sh-NON group (P<0.001). In addition, compared with sh-NON group, the expression of caspase-3, caspase-9, Bax, p-JAK2 and p-STAT3 were significantly increased in shRACK1-1 and shRACK1-2 groups, but of c-myc and Bcl-2 decreased significantly (P<0.001 or P<0.01). Conclusion RACK1 is highly expressed in cervical cancer tissues and cells. Targeted silencing RACK1 gene can effectively reduce the expression of proliferation related protein c-myc and anti-apoptotic protein Bcl-2, but significantly increase the expression of apoptosis related protein caspase-3, caspase-9 and Bax in cervical cancer cells, which may be related to the activation of JAK2/STAT3 signaling pathway.
Objective To explore the mechanism of nodakenin (NDK) affecting the invasion and migration of cervical cancer cells by regulating epithelial-mesenchymal transformation (EMT), and analyze its effect on microRNA (miR)-324-3P/WNT3a axis. Methods Human cervical cancer HeLa cells in logarithmic growth phase were divided into four groups: blank group(cultivated in a 37 ℃, 5% CO2-saturated humidity incubator), NDK group (20 mmol/L NDK was added to culture), miR-324-3P inhibitor group (hsa-miR-324-3p inhibitor transfection), and miR-324-3P inhibitor+NDK group (after transfection of miR-324-3P inhibitor, 20 mmol/L NDK was added to culture) all were treated for 48 h. Transwell test was used to detect the invasion ability of cells in each group. Cell scratch test was performed to detect cell migration ability of each group. qRT-PCR to detect the mRNA level of miR-324-3P and WNT3a in each group of cells. Western blotting was carried out to detect the expression of EMT-related marker proteins E-cadherin, vimentin, Neural cadherin (N-cadherin), WNT3a, and β-catenin protein in each group of cells. Dual luciferase reporter gene was used to detect the targeting relationship between miR-324-3P and WNT3a gene. Results Compared with the blank group, the number of transmembrane HeLa cells increased in miR-324-3P inhibitor group, the scratch healing rate increased, the mRNA expression level of miR-324-3P decreased, and of WNT3a increased; the relative expression of E-cadherin protein decreased, while the relative expressions of vimentin, N-cadherin, WNT3a and β-catenin increased (P<0.05). While for NDK group and miR-324-3P inhibitor+NDK group, the number of transmembrane HeLa cells decreased, the scar healing rate was also decreased, the mRNA expression level of miR-324-3P increased, the expression level of WNT3a mRNA decreased, the relative expression of E-cadherin protein increased, and the relative expression of vimentin, N-cadherin, WNT3a and β-catenin protein decreased (P<0.05); All the indexes mentioned above were lower in NDK group than those in miR-324-3P inhibitor+NDK group.The dual luciferase reporter gene results showed that miR-324-3P mimic could reduce WNT3a WT luciferase activity (P<0.05), but did not affect WNT3a mut luciferase activity (P>0.05). Conclusion NDK can inhibit the invasion and migration of cervical cancer cells by regulating EMT, and the mechanism of such action may be related to the regulation of miR-324-3P/WNT3a axis.
Objective To establish an improved method for estimating the mean blood glucose by glycosylated hemoglobin(HbA1c) in diabetic patients with renal insufficiency. Methods The clinical data were retrospectively analyzed of 329 patients with type 2 diabetes mellitus who were hospitalized in the Department of Hypertension and Endocrinology of Daping Hospital of Army Medical Center of PLA from January 2018 to December 2021. All patients were divided into control group [estimated glomerular fraction rate, eGFR≥60 ml/(min.1.73 m2), n=165] and renal insufficiency group [eGFR<60 ml/(min.1.73 m2), n=164]based on their eGFR levels. The basic demographic data, oral glucose tolerance test (OGTT) 2 hours post plasma glucose, and other laboratory test results of the patients were collected. The HbA1c and OGTT models were adopted separately to estimate the 24-hour average blood glucose of the enrolled patients, and the gap glucose level of the two methods was calculated. The influencing factors of estimating blood glucose deviation with HbA1c in patients with renal insufficiency were analyzed, and a correction model of estimating average blood glucose with HbA1c was established. A total of 29 patients with type 2 diabetes mellitus and renal insufficiency hospitalized in the Department of Hypertension and Endocrinology of Daping Hospital of Army Medical Center of PLA from January to March 2022 were collected for external verification. Results Compared with control group, diabetic patients with renal insufficiency were relatively older (P=0.001), with longer course of diabetes (P<0.001), and had lower HbA1c (P=0.034),eGFR (P<0.001), Hb (P<0.001), and ALB (P<0.001) levels. The mean blood glucose of the two groups was estimated by HbA1c. The gap of estimated blood glucose was significantly higher in renal insufficiency group than in control group [(0.88±1.64) mmol/L vs.(–0.09±2.10) mmol/L, P<0.001], and was negatively correlated with the Hb level (r=–0.377, P<0.001), while with no relation with ALB level (P=0.551). A linear regression model was used to include HbA1c, Hb, age, diabetes course, eGFR and ALB into the analysis,and to establish an estimation model for estimating the daily mean blood glucose of diabetic patients with renal insufficiency: mean blood glucose (mmol/L) =4.539+0.95×HbA1c-0.016×Hb (adjusted R2=0.829, P<0.001). Using this model, the gap glucose level between the estimated mean blood glucose and the detected blood glucose were remarkably reduced in renal insufficiency group [(0.02±1.05) mmol/L vs. (0.88±1.64) mmol/L, P<0.001]. The goodness-of-fit index RNL=0.830 was obtained by external validation of 29 patients, indicating that the model obtained is highly feasible. Conclusions A correction model of estimating mean blood glucose by HbA1c for diabetic patients with renal insufficiency has been successfully established. It is of great significance to further develop individualized HbA1c control and improve the prognosis of diabetes patients.
Objective To investigate the effect of dexmedetomidine on perioperative anxiety of patients under general anesthesia in thoracic surgery. Methods One hundred and twenty patients undergoing elective surgery under general anesthesia in the Department of Thoracic Surgery, the Sixth Medical Center of Chinese PLA General Hospital, from June 2021 to September 2021, were enrolled and randomly divided into control group (no dexmedetomidine perioperative), D1 group (dexmedetomidine 0.6 μg/kg intraoperatively), and D2 group (dexmedetomidine 0.6 μg/kg intraoperative, dexmedetomidine 2.4 μg/kg postoperative analgesia pump), 40 patients in each group. Perioperative anesthetic dosage, anesthetic time, operation time, time from operation completion to extubation, time from extubation to out-room and time from postoperative to discharge were compared among the three groups. The patients' average arterial pressure (MAP) and heart rate (HR) at entry (T0), after intubation (T1), immediately after dexmedetomidine pump injection (T2), before catheterization (T3), at exit (T4), and 24, 48, 72 h after operation were recorded.Self-rating anxiety scale (SAS), visual analogue scale-anxiety (VAS-a), visual analogue scale (VAS), and sedation score (Ramsay)were measured before and 24, 48, 72 h postoperatively. Results No significant differences were observed in operation time,anesthesia time, time from operation completion to extubation, time from extubation to out-room and anesthesia dosage among the three groups (P>0.05), but the time from postoperative to discharge was significantly shorter in D2 group than in control group[(7.13±3.83) d vs. (8.93±3.67) d, P=0.027]. Compared with control group, the MAP of patients in D1 group and D2 group decreased at T3 (P<0.05). No significant differences were observed in MAP, HR and Ramsay scores among the three groups at 24,48 and 72 h postoperatively (P>0.05). The SAS scores of patients in the three groups decreased significantly at 48 and 72 h after operation, and the decrease was most obvious in D2 group (P<0.05); The VAS-a score was significantly lower in D2 group than in control group and D1 group at 24, 48 and 72 h after surgery (P<0.05). The VAS scores of patients in the three groups decreased gradually at 48 and 72 h after surgery than that at 24 h after surgery (P<0.05). Multivariate linear regression analysis showed that age, sex and length of preoperative hospital stay were significantly correlated with preoperative anxiety in thoracic surgery patients(P<0.05). Conclusion Intra- and post-operative application of dexmedetomidine can significantly improve perioperative anxiety,synergistic analgesia and shorten postoperative hospital stay in patients of thoracic surgery.
Objective To investigate the predictive value of lactate (Lac) and complex model for the occurrence of prolonging mechanical ventilation (PMV) after off-pump coronary bypass grafting (OPCABG) based on dose-response analysis and decision curve analysis. Methods A retrospective analysis was conducted on 683 patients who underwent OPCABG from January to December 2019 in the Department of Cardiovascular Surgery of the General Hospital of the Northern Theater Command. These patients were divided into PMV group (n=107) and non-PMV group (n=576) based on whether duration of prolonged mechanical ventilation was longer than 24 h. The arterial blood lactate at 0 h and 6 h after admission to the ICU of cardiovascular surgery,baseline data and other clinical indicators of the patients were recorded. Preoperative, intraoperative and postoperative risk factors affecting PMV time were analyzed by univariate analysis, and a prediction model was established by indicators selected by logistic regression. Restricted cubic spline model, decision curve analysis (DCA) and receiver operating characteristic (ROC) curve were used to evaluate the predictive value of arterial blood lactate and complex model. Results There were no significant differences between PMV group and non-PMV group in gender, age, BMI, NYHA cardiac function classification, history of myocardial infarction, history of PCI, smoking history, hypertension, diabetes, hypercholesterolemia, >50% stenosis with of 3 coronary artery branches and left aortic stenosis >50%, number of blood vessel bridge, arterial blood lactate at 0 h after admission to ICU,preoperative serum creatinine, hemoglobin after operation, preoperative total bilirubin, preoperative direct bilirubin (P>0.05). There were statistically significant differences in the use of IABP, left ventricular ejection fraction (LVEF), pulmonary arterial pressure,preoperative red blood cell distribution width (RDW), arterial blood lactate at 6 h after admission to ICU, preoperative hemoglobin,preoperative hypersensitive CRP (hs-CRP), postoperative hs-CRP, preoperative troponin T (TNT) and preoperative amino-terminal pro-brain natriuretic peptide (NT-proBNP) (P<0.05). Multivariate logistic regression analysis showed that preoperative RDW, arterial blood lactate 6 h after admission to ICU, pulmonary arterial pressure, preoperative NT-proBNP were risk predictors of PMV, and use of IABP was protective predictor of PMV (P<0.05), OR of five factors were 1.242 (95%CI 1.001-1.539), 1.370 (95%CI 1.171-1.604), 1.043 (95%CI 1.002-1.087), 2.065 (95%CI 1.333-3.200), 0.146 (95%CI 0.071-0.301), respectively (P<0.05). The area under the receiver operating characteristic curve of arterial blood lactate 6 h after admission to ICU and complex model were 0.582 (95%CI 0.518-0.646), 0.727 (95%CI 0.674-0.781), respectively. Intensity of association between Lac 6 h and the development of PMV exhibited a non-linear dose response relationship (P<0.01). Decision curve analysis showed that compared with Lac 6 h, the complex model had a higher net benefit when the threshold probability was between 0.05 and 0.75. Conclusions Compared with Lac 6 h, complex model has a higher predictive value for the occurrence of PMV after OPCABG.
Objective To compare whether the differences existed of collateral circulation in patients with acute anterior circulation intracranial large vessel occlusion induced by large artery atherosclerosis (LAA) and cardioembolism (CE) stroke, and explore the influencing factor to collateral circulation. Methods A total of 70 patients with acute ischemic stroke induced by anterior circulation intracranial large vessel occlusion, admitted to the Second Hospital of Lanzhou University, were retrospectively collected from January 2020 to August 2021, and divided into LAA group (n=50) and CE group (n=20) based on the etiological classification of stroke. The baseline data of the two groups were compared, and CT angiography iconography data were used to score the collateral circulation. On a 3-point scale, the collateral circulation scores were dichotomized into poor (grade 0 or 1, n=31) vs. good (grade 2 or 3, n=39), the clinical data of the two groups were compared, and multivariate logistic regression analysis was performed to determine the independent risk factors for collateral circulation. Results The proportion of good collateral circulation was higher in LAA group than that in CE group(64% vs. 35%, P=0.027), and the proportion of the thrombus load score (CBS) ≥6 and admission systolic pressure was also higher in LAA group than those in CE group (P<0.05). The score of US. National Institutes of Health Stroke Scale (NIHSS) at admission was significantly lower in LAA group than that in CE group [5.50(3.00, 10.00) vs. 13.50(8.25, 17.00), P=0.003]. The proportion of LAA was higher, while of previous hypertension and diabetes history and NIHSS score at admission were lower in good collateral circulation group than those in bad collateral circulation group with statistical significance (P=0.027, P=0.044, P=0.003, P=0.017, respectively).Multivariate logistic regression analysis showed that the etiological types of stroke were CE (OR=4.607, 95%CI 1.337-15.877, P=0.016),history of hypertension (OR=3.357, 95%CI 1.059-10.642, P=0.040) and diabetes history (OR=4.589, 95%CI 1.530-13.766, P=0.007),which were the independent risk factors for collateral circulation. Conclusions Patients with stroke due to LAA had a more extensive cerebral collateral circulation than those with CE. Etiological type of stoke was CE, the history of hypertension and diabetes, are the independent risk factors for the poor collateral circulation in patients with acute anterior circulation intracranial large vessel occlusion.
Objective To explore the diagnostic value of screening cough variant asthma (CVA) by fractional exhaled nitric oxide (FeNO) combined with lung function and the proportion of peripheral blood eosinophils in patients with chronic cough. Methods Two hundred and sixty-seven patients with chronic cough diagnosed in the Respiratory Medicine Clinic of the Affiliated Hospital of North Sichuan Medical College from March 2016 to November 2017 were selected and divided into CVA group (n=60)and non-CVA group (n=207), and 30 healthy physical examiners in the same period served as the control group. All patients and health examiners were tested of FeNO, routine lung function, pulse oscillatory lung function, bronchodiastolic test, peripheral blood eosinophil proportion. Linear correlation was used to analyze the correlation of FeNO value to pulmonary function and the proportion of peripheral blood eosinophils in patients with CVA. Results The FeNO value and the proportion of peripheral blood eosinophils were obviously higher in CVA group than in non-CVA group and control group [45(34.3, 74.8) μg/L vs. 14(10.0,19.0) μg/L and 10(7.0, 18.0) μg/L, P<0.001; 5.9%±2.3% vs. 2.3%±1.6% and 2.6%±1.3%, P<0.001]. The MEF75pre, MEF50pre,MEF25pre, FEV1pre, PEFpre and MMEFpre were significantly lower in CVA group than the normal range and those in non-CVA group and control group (P<0.01), and the R20pre was significantly higher in CVA group (137.6%±40.7%) than in non-CVA group(127.5%±40.1%) and control group (128.5%±45.4%) (P<0.05). The improvement rates of FEV1, MEF75, MEF50, MEF25, MMEF were significantly higher after using bronchodilator in CVA group than in non-CVA group and control group (P<0.001). Linear correlation results showed that the FeNO value in CVA group showed no correlation with FEV1pre, FEV1/FVC, PEFpre, MEF75pre,Z5, X5, R5pre, R20pre, and Fres (P>0.05), while showed negative correlation with MEF50pre, MEF25pre and MMEFpre (P<0.05),and positive correlation with peripheral blood eosinophil proportion (r=0.863, P<0.001). Conclusion FeNO, pulmonary function and the proportion of peripheral blood eosinophils can be used as the index of screening CVA in patients with chronic cough. The combined effect of the three index may be better.
Objective To investigate the risk factors and predictive value of acute kidney injury (AKI) after laparoscopic partial nephrectomy (LPN). Methods Clinical data of 60 patients with renal cell carcinoma (RCC) who received LPN in Urology Department of the Third Medical Center of Chinese PLA General Hospital from November 2020 to June 2021 were retrospectively analyzed. The diagnosis of AKI according to the kidney disease improving global outcomes standard. According to the occurrence of postoperative AKI, the patients were divided into AKI group (n=26) and non-AKI group (n=34). Patients' age, gender, preoperative hemoglobin (Hb),complicating disease, length of hospital stay, as well as the pre- and 48 h after post-operative serum creatinine (Scr), estimated glomerular filtration rate (eGFR), β2-microglobulin (β2-MG), cystatin C (CysC) and fasting plasma glucose (FPG) were collected. The risk factors for AKI after LPN were analyzed by univariate and multivariate logistic regression, and the predictive value of risk factors for AKI after LPN in RCC patients was analyzed by receiver operating characteristic (ROC) curve. Results Twenty-six of 60 RCC patients(43.3%) were postoperative diagnosed as AKI, among whom 22 patients (84.6%) with stage Ⅰ AKI and 4 patients (15.4%) with stage Ⅱ AKI. Statistical differences existed between the two groups in gender, body mass index (BMI), preoperative hypertension,preoperative diabetes, intraoperative colloid fluid intake, renal artery occlusion time and operation time, preoperative eGFR and β2-MG (P<0.05). Multivariate logistic regression analysis showed that gender (male), BMI, intraoperative colloid fluid intake and renal artery occlusion time were independent risk factors for AKI after LPN (P<0.05). ROC curve analysis showed that the cut-off value of BMI, intraoperative colloid fluid intake and renal artery occlusion time were 24.9 kg/m2, 500 ml, 24 min; the sensitivity was 88.5%,73.1%, 73.1%; the specificity was 64.7%, 70.6%, 73.5%; and the area under curve (AUC) was 0.811, 0.755 and 0.764, respectively. Conclusion BMI, intraoperative colloid fluid intake and renal artery occlusion time were risk factors for AKI after LPN and had certain predictive value, while gender (male) was an independent risk factor for AKI after LPN.
With the change of people's lifestyle and diet structure, hypertriglyceridemia (HTG) has gradually become an important factor causing or aggravating acute pancreatitis (AP). Some studies have pointed out that HTG has become the second major factor of AP following biliary diseases. The concept of hypertriglyceridemic-related acute pancreatitis (HTG-AP) has been put forward, and a large number of studies have been carried out on its mechanism. However, the mechanism of hypertriglyceridemia involved in the progression of AP is still unclear, leading to the lack of specific targets for treatment. This article reviews the pathogenesis of HTG-AP, including excessive free fatty acids (FFA)-induced oxidative stress, Ca2+ overload, endoplasmic reticulum stress, microcirculatory disturbance, etc.
The physical health of military personnel is a prerequisite for maintaining combat effectiveness. Due to the particularity of the military profession, there have been few large-scale high-quality studies on chronic diseases of military personnel.Launched in 2000, the Millennium Cohort Study (MCS) is a large-scale, prospective cohort study of U.S. military personnel, which was sponsored by the U.S. Department of Defense and conducted by the U.S. Naval Health Research Center. MCS covered about 200 000 military personnel in a wide range of services and departments, analysing the impact of career-related factors on the physical and mental health of the U.S. military, and exploring the occupational risk factors for chronic diseases in the military. We reviewed the research progress of chronic diseases in MCS, including chronic multi-symptom diseases, gastrointestinal diseases, respiratory diseases, cardiovascular diseases, metabolic diseases and other chronic diseases, so as to provide further reference for the medical support of the People's Liberation Army.
Glioblastoma (GBM) is a most common primary malignant brain tumor characterized by rapid growth and invasion of surrounding tissues. At present, the standard methods for treatment of GBM include surgical resection, radiotherapy and chemotherapy. Because the existence of blood-brain barrier (BBB) restricts the delivery of anti-cancer drugs into the brain,novel drug deliver approaches are urgently needed to improve the therapeutic effect of GBM. As a non-invasive alternative route for directly targeting the central nervous system (CNS) disease, nose-to-brain delivery could bypass the BBB and reduce the systemic side effects. Recently, several formulations have been developed for further enhancing nose-to-brain transport, mainly with the use of nanostructured drug delivery systems. The application of nose-to-brain delivery combined with different anticancer drugs or methods in clinical treatment of GBM have been reviewed in present paper.
Autophagy has a certain degree of protective effect on cells, but excessive autophagy can lead to programmed cell death, which is called Ⅱ programmed cell death. The blood brain barrier (BBB) plays a protective role between the brain and the peripheral circulation, which helps the inflow and outflow of molecules and ions to maintain the steady state of the central nervous system. A large number of studies have shown that autophagy plays an important role in BBB dysfunction, on the one hand, autophagy can damage or protect the integrity of BBB, and on the other hand, autophagy can also affect the passage of drugs,pathogens and other substances through BBB. Therefore, regulating autophagy level by targeting specific regulatory molecules in autophagy mechanism may affect the function of BBB, and then affect the occurrence and development of central nervous system diseases. The recent advances in the relationship between autophagy and BBB have been reviewed in present paper for hoping to provide new ideas for the prevention and treatment of diseases related to BBB injury.
Liver cancer is a common malignant tumor of digestive system, including primary liver cancer and secondary liver cancer. Primary liver cancer can be divided mainly into hepatocellular carcinoma and cholangiocarcinoma, and secondary liver cancer mostly comes from liver metastasis of colorectal cancer. The treatment of liver cancer include surgical resection, liver transplantation, ablation, transcatheter arterial chemoembolization (TACE), transcatheter arterial chemoperfusion, targeted therapy and immunotherapy. According to Barcelona staging (BCLC) and China's code for the diagnosis and treatment of primary liver cancer (2019 Edition), TACE can be used as the first choice for patients with unresectable medium-term hepatocellular carcinoma.With the rise and development of drug-eluting bead, drug-eluting bead TACE (D-TACE) began to emerge in the treatment of various stages of liver cancer. The application of TACE, especially D-TACE in hepatocellular carcinoma, cholangiocarcinoma and liver metastasis, comparison of the clinical benefits and adverse reactions with other treatment methods, and the molecular mechanisms of tumor recurrence and prognosis after TACE treatment have been focused and summarized in present paper.