Objective To investigate the role and mechanism of myotubularin-related protein 7 (Mtmr7) in proliferation and migration of mouse vascular smooth muscle cells (VSMCs). Methods The mouse aortic smooth muscle cell line (MOVAS)was cultured. 30 ng/ml of platelet-derived growth factor-BB (PDGF-BB) was used to induce proliferation and migration of VSMCs in vitro. The changes of mRNA and protein expression levels after PDGF-BB intervention in Mtmr7 was assessed by qRT-PCR and Western blotting. To explore the role of Mtmr7 in proliferation and migration of mouse VSMCs, the adenovirus carrying Mtmr7(Ad-Mtmr7) was used to infect VSMCs for overexpression of Mtmr7. MOVAS was divided into control group, Ad-Mtmr7 group,PDGF-BB group and Ad-Mtmr7+PDGF-BB group. The proliferation capacity of VSMCs was analyzed by Ki-67 immunofluorescence staining and cell counting kit-8 (CCK-8) assay. The migration capacity was assessed by scratch assay. The downstream target protein levels of mammalian rapamycin target protein complex 1 (mTORC1) were determined by Western blotting. Insulin (5 mg/L)was used to restore the activity of mTORC1. MOVAS were divided into PDGF-BB group, Ad-Mtmr7+PDGF-BB group and Ad-Mtmr7+PDGF-BB+insulin group. The proliferation, migration and protein levels were measured by methods as the same mentioned above. A model of carotid endothelial injury was established. At 28 days after operation, the protein level of Mtmr7 was determined by Western blotting. The mice were randomly divided into 4 groups (10 each): sham group, sham+Ad-Mtmr7 group,carotid endothelial injury group and carotid injury+Ad-Mtmr7 group. To overexpress Mtmr7, Ad-Mtmr7 (5×10¹⁰ pfu/ml) was injected into the carotid artery immediately after operation and then partly incubated for 30 min. At 7th, 14th and 21st day after operation, the mice were injected the adenovirus via tail vein. Twenty-eight days after modeling, the morphology of carotid artery and the degree of intimal hyperplasia were analyzed by HE staining. Results Compared with control group, the mRNA and protein levels of Mtmr7 were obviously reduced (P<0.001 and P<0.05), the rate of Ki-67 positive cells and the relative number of VSMCs increased (P<0.01 and P<0.001), the rate of wound healing and the protein expression levels of p-S6^Ser235/236 and p-4EBP1^Thr37/46 increased (P<0.001 and P<0.05) in PDGF-BB group. Compared with the PDGF-BB group, the rate of Ki-67 positive cells, the relative number of VSMCs (P<0.01 or P<0.001), the rate of wound healing (P<0.001) and the protein levels of p-S6^Ser235/236 and p-4EBP1^Thr37/46 (P<0.05) were decreased in Ad-Mtmr7+PDGF-BB group. Compared with the Ad-Mtmr7+PDGF-BB group, the protein levels of p-S6^Ser235/236 and p-4EBP1^Thr37/46 (P<0.01), the rate of Ki-67 positive cells, the relative number of VSMCs (P<0.01 or P<0.001) and the rate of wound healing (P<0.01) were increased in Ad-Mtmr7+PDGF-BB+insulin group. Compared with the sham group, the protein expression level of Mtmr7 decreased significantly (P<0.01) and the ratio of intima/media area increased (P<0.001)in carotid endothelial injury group. Compared with the carotid endothelial injury group, after overexpression of Mtmr7, the ratio of intima/media area decreased significantly (P<0.01) in carotid endothelial injury+Ad-Mtmr7 group. Conclusion Overexpression of Mtmr7 may inhibit the proliferation and migration of VSMCs induced by PDGF-BB in mice, alleviating intimal hyperplasia after vascular injury, which is closely related to the mTORC1 activity reduced by Mtmr7.

Functional metabolomics is an extension of metabolomics, through detecting changes in endogenous metabolites that are stimulated and disturbed by a particular organism, after obtaining the biomarker, experiments were conducted to verify the functions of the biomarker and the associated enzymes, genes and proteins. The molecular mechanism of pathophysiology can be revealed systematically from the perspective of "metabolite-enzyme-gene-protein", solving the upstream and downstream biological mechanisms of metabolite association. This article reviews and analyzes the current common methods and research strategies of functional metabolomics, the exploration of disease targets and pathogenesis, and the analysis of drug action mechanisms in the field of biomedicine. At the same time, the extended research on the combination of functional metabolomics with network pharmacology and reprogramming metabolomics is summarized, and finally the application prospects of functional metabolomics are analyzed and prospected in the field of biomedicine.

Objective To explore the predictive value of fibrinogen (FIB)/albumin (ALB) ratio (FAR), neutrophil (NEU)/lymphocyte (LYM) ratio (NLR) and platelet (PLT)/lymphocyte (LYM) ratio (PLR) to acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods Acute exacerbation COPD (AECOPD) patients hospitalized in the Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical College from September 2019 to July 2021 were selected as AECOPD group (n=96), and patients with stable chronic obstructive pulmonary disease (SCOPD) and without acute exacerbation in the outpatient clinic for nearly three months in the same period were selected as SCOPD group (n=103), and healthy people who had physical examination in the same period were randomly selected as control group (n=80). According to the severity classification, AECOPD patients were divided into grade Ⅰ (n=20), grade Ⅱ (n=33) and grade Ⅲ (n=43). The general data and clinical data of each group were recorded, and the serum C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC),NEU, LYM, PLT, FIB, ALB were detected. In AECOPD patients, carbon dioxide partial pressure (PaCO₂) and arterial oxygen partial pressure (PaO₂) were also detected, the FAR, NLR, PLR and oxygenation index (PaO₂/FiO₂) were calculated. The differences of the above indicators in each group were compared, and their correlation was analyzed. The risk factors of AECOPD were analyzed by multivariate logistic regression, and the receiver operating characteristics (ROC) curves were developed to analyze the significance of each indicator in the prediction of AECOPD. Results The levels of CRP, PCT, WBC, NEU, NLR, PLR and FAR decreased gradually (P<0.05) in control group, SCOPD group and AECOPD group; with the increase of AECOPD severity, the improvement time of patients, the levels of CRP, PCT, WBC, NEU as ell as NLR, PLR, FAR and PaCO₂ increased gradually, and PaO₂/FiO₂ decreased gradually (P<0.05). Pearson or Spearman correlation analysis showed that FAR, NLR and PLR were positively correlated with the severity of AECOPD, improvement time, CRP, PCT, WBC and PaCO₂, but negatively correlated with PaO₂/FiO₂ (P<0.01).Multivariate logistic regression analyses showed that FAR, NLR and PLR were the independent risk factors for AECOPD (P<0.05).ROC curve analysis showed that the AUC value was greater than 0.7 for predicting AECOPD with FAR, NLR and PLR alone or in combined usage, and the sensitivity was 0.990, 0.698, 0.563 and 0.958 respectively, and the specificity was 0.641, 0.883, 0.932 and 0.961. Conclusion FAR, NLR, PLR have certain correlation with the inflammatory level, severity and respiratory function of AECOPD, and joint use of the three indicators for detection may have higher predictive value for its occurrence.

Acute hepatitis of unknown etiology in children has been reported in many countries all over the world since April 2022. As of May 27,there have been at least 650 cases of such patients reported by World Health Organization in 33 countries. The etiology of the hepatitis is still unknown.Adenovirus has been detected in samples of some cases, but it is also suspected that the immune response triggered by SARS-CoV-2 infection maybe contribute to the mechanism of the disease. In this paper, we overview the research and reports about the acute hepatitis of unknown etiology in children about its epidemiology,clinical features and possible etiology, then for the aim to make our country doing well in the monitoring and controlling of the acute hepatitis of unknown etiology in children. Here, we present some points of view from the perspective of infectious diseases and liver diseases in children.

Objective To investigate the effects and mechanism of short chain fatty acids (SCFAs) on lipopolysaccharide(LPS) induced acute respiratory distress syndrome (ARDS) in rats. Methods Twenty male SD rats were randomly divided into control group, model group, low-dose SCFAs group and high-dose SCFAs group (5 each). Rats in control and model groups were given normal saline, in low-dose SCFAs group were given sodium acetate 300 mg/kg, sodium propionate 100 mg/kg and sodium butyrate 100 mg/kg, and in high-dose SCFAs were given sodium acetate 600 mg/kg, sodium propionate 200 mg/kg and sodium butyrate 200 mg/kg by gavage for 7 days in advance. And then the rats in control group were perfused with normal saline, and in the other 3 groups were perfused with LPS (5 mg/kg) into trachea to establish ARDS model. The rats were sacrificed 12 hours after modeling, and the arterial oxygen partial pressure (PaO₂) and lung wet/dry weight ratio (W/D) were measured, and HE staining was performed to observe the pathological changes of lung tissues. The concentrations of tumour necrosis factor (TNF)-α, interleukin(IL)-6 and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA. Western blotting was used to detect c-Jun N-terminal kinase (JNK), p-JNK, extracellular regulated protein kinases (ERK), p-ERK, p38 mitogen-activated protein kinase(MAPK), p-p38 MAPK, nuclear factor kappa-B (NF-κB) p65 and p-NF-κB p65 protein expression in lung tissues. The expression of tight junction protein ZO-1 and Occludin in colonic tissue were detected by immunohistochemistry. Results Compared with control group, PaO₂ decreased, lung W/D and lung pathological injury score increased, the concentration of TNF-α and IL-6 in serum and BALF significantly increased, and the concentration of IL-10 increased, the relative protein expressions of p-JNK/JNK,p-ERK/ERK, p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in lung tissues significantly increased, while the relative expression of ZO-1 and Occludin protein significantly decreased in colonic tissues in model group (P<0.05). Compared with model group, PaO₂ increased, lung W/D and lung pathological injury score decreased, and TNF-α, IL-6 in serum and BALF decreased,the concentration of IL-10 increased further, while the relative expressions of p-JNK/JNK, p-ERK/ERK, p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 protein in lung tissue decreased, and the relative expression of tight junction protein ZO-1 and Occludin in colon tissue increased in low and high dose SCFAs groups (P<0.05). Compared with low-dose SCFAs group, the indexes mentioned above in the high-dose SCFAs group improved more significantly (P<0.05). Conclusion SCFAs could regulate immunity and inflammation, and effectively improved LPS-induced ARDS in rats, the mechanism might be related to enhancement of intestinal barrier and inhibition of MAPK and NF-κB signaling pathway activation, thereby reducing the release of inflammatory factors and increasing the production of anti-inflammatory factors.

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.

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.

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.