Objective To explore the risk factors related to coronary heart disease (CHD) complicated with carotid plaque, and compare the effects of different lipid-lowering treatment schemes on carotid plaque. Methods The data of 335 patients with CHD, hospitalized in the Department of Cardiology of Wuhan First Hospital and undergone coronary angiography and percutaneous coronary intervention (PCI) from January 2017 to December 2019, were collected and analyzed retrospectively. The biochemical indexes of CHD with carotid plaque group (n=257) and CHD without carotid plaque group (n=78) were compared,and the factors affecting the distribution of blood lipid levels were screened and analyzed in the CHD with carotid plaque group. Univariate and multivariate logistic regression were performed to analyze the risk factors of CHD complicated with carotid plaque.Then the patients in CHD complicated with carotid plaque group were divided into four subgroups according to the actual oral lipid-lowering drug regimen: atorvastatin 20 mg group (n=90), atorvastatin 10 mg + ezetimibe 10 mg group (n=51), rosuvastatin 10 mg group (n=71), and pivastatin 2 mg group (n=36). The number and size changes of carotid plaques were analyzed before and one year after PCI. Results The BMI, blood pressure (including systolic pressure and diastolic pressure), serum creatinine and uric acid levels, low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), glycosylated hemoglobin (HbA_1c) and lipoprotein phospholipase A₂ (Lp-PLA2) increased obviously in CHD complicated with carotid plaque group compared with without carotid plaque group (P<0.01). In patients with CHD complicated with carotid plaque, gender, age and BMI were the factors affecting blood lipid levels (P<0.05). The results of univariate and multivariate logistic regression analysis showed that HbA_1c, Lp-PLA2,LDL-C, creatinine, albumin and uric acid were the risk factors affecting carotid plaque (P<0.05). The number and/or size decreased of carotid plaques could be reduced by different lipid-lowering treatment schemes one year after PCI in the four subgroups, but there was no significant difference between the groups. Conclusions Biochemical indicators such as HbA_1c, Lp-PLA2, LDL-C,creatinine, albumin and uric acid can be used for screening and targeted prevention and treatment of high-risk population. Different lipid-lowering treatment schemes have no significant effect on carotid plaque.

Objective To construct a PAEH/PEG DA hydrogel sustained-release system containing combined Pseudomonas aeruginosa (PA) outer membrane protein F (OprF) and Pseudomonas V antigen (PcrV) gene DNA vaccine, and evaluate the in vivo immune efficacy of the system. Methods The PAEH/PEG DA hydrogel containing combined PA DNA vaccine was prepared with a simple mixing method. The gelation time was tested, and the cytotoxicity (DC 2.4), degradation and cumulative release rate in vitro of the hydrogel were evaluated. Nine mice were randomly divided into 3 groups (3 each): 30 min group, 2 d group and 7 d group, the in vivo degradability and security of the hydrogel were evaluated by gelation volume changes at the injection site and histopathological sections of the skin, respectively. Eighteen mice were randomly divided into 6 groups (3 each): control group (PBS),hydrogel group (Gel), En/pVAX1-OprF group (O), En/pVAX1-PcrV group (P), En/(pVAX1-OprF+pVAX1-PcrV) group (OP), and hydrogel + En/(pVAX1-OprF+pVAX1-PcrV) group (GOP). Mice were immunized 3 times with a 10-day interval, then sacrificed 2 weeks after last immunization. The levels of serum specific IgG antibody, splenic lymphocyte stimulation index (SI) and interferon-γ(IFN-γ) in the supernatant of splenic lymphocytes were detected. Results The PAEH/PEG DA hydrogel sustained-release system required only about 30 min to form a gelation state. There was no significant toxicity to DC 2.4 cells in vitro, and approximately 85%of plasmid DNA was released after 36 hours of in vitro release. The degradation time of the hydrogel was nearly the same in vitro and in vivo. It could be almost completely degraded in about 7 days, and had good in vivo biodegradability and biosafety. The results of in vivo immune test showed that, compared with PBS group, no significant changes existed in the levels of specific IgG antibodies,splenic lymphocyte SI and IFN-γ in the Gel group (P>0.05). Compared with the corresponding DNA vaccine groups (O group or P group) and PBS group, the specific IgG antibody levels, spleen lymphocyte SI and IFN-γ level increased obviously in OP group and GOP group (P<0.05, P<0.01). While compared with OP group, the levels of specific IgG antibodies, splenic lymphocyte SI and IFN-γ increased markedly in GOP group (P<0.05, P<0.01). Conclusion The PAEH/PEG DA hydrogel sustained-release systems containing PA OprE and PcrF gene combined DNA vaccines, which can slowly release the combined DNA vaccine and further enhance the immune efficacy of combined DNA vaccine, are one of the promising strategies for the development of PA vaccines.

Objective To investigate the effect of Rhopaladins' analogs RPDPC on cell biological properties of human cervical cancer HeLa cells and miR-21-5P/PTEN/PI3K signaling pathway. Methods CCK-8 assay was used to detect the effects of different concentrations of RPDPC on the cell viabilities of HeLa cells treated for different time. DMSO (control), 12.5 μmol/L,25.0 μmol/L and 50.0 μmol/L RPDPC were selected to treat HeLa cells for 48 h. Hoechst 33258 staining and Annexin-FITC/PI double staining were used to detect the effect of RPDPC on HeLa cell apoptosis; The expression levels of miR-21 and mRNA of E6,E7, PTEN, PI3K, Akt were detected by qRT-PCR; The expression levels of PTEN, p-PI3K, p-PI3K, p-Akt and Akt were detected by immunoblotting (WB). Results Compared with the control group, viabilities of HeLa cells decreased significantly treated by RPDPC in different concentration and time (P<0.05); The apoptosis rate of HeLa cells tended to increase with increasing concentration of RPDPC (P<0.05); qRT-PCR results showed that compared with the control group, the expression level of miR-21-5P and mRNA of E6, E7, PI3K, Akt decreased significantly (P<0.05), the expression levels of PTEN mRNA increased significantly(P<0.05). WB results showed that compared with the control group, the expression level of PTEN protein increased significantly(P<0.05); The expression levels of p-PI3K, PI3K, p-Akt and Akt proteins decreased significantly (P<0.05). Conclusions RPDPC could inhibit the proliferation and promote the apoptosis of cervical cancer cells. The mechanism may be the inhibition of expression of E6 and E7, and may be related to mir-21/PTEN/PI3K/Akt signaling pathway.

Diabetic cardiomyopathy is one of the chronic irreversible and serious cardiovascular complications in diabetic patients. Recent studies have shown that the mitochondrial dysfunction caused by the disturbance of mitochondrial dynamic balance is closely related to the occurrence of diabetic cardiomyopathy. Dynamin related protein 1 (Drp1) is an important regulator of mitochondrial fission. Studies have shown that increased activity of Drp1 in diabetes cardiomyocytes can lead to increased mitochondrial fission and decreased mitochondrial fusion which leads to mitochondrial dysfunction. Drp1 can lead to the occurrence and development of diabetic cardiomyopathy by inducing oxidative stress, energy metabolism disorders, apoptosis,insulin resistance, and lipotoxicity in cardiomyocytes. In addition, inhibition of Drp1 activity may improve cardiac function in diabetic cardiomyopathy. Therefore, the mechanism of Drp1 in diabetic cardiomyopathy have been reviewed in present paper in order to provide new ideas for the prevention and treatment of diabetic cardiomyopathy and drug development.

Low back pain caused by intervertebral disc degeneration (IVDD) has become an important disease affecting human health, the current conservative treatment and surgical treatment cannot prevent its progression. Therefore, targeted therapy starting from the molecular level has become a current research hotspot. The matrix metalloproteinases (MMPs) carried by exosomes are closely related to the disorder of extracellular matrix (ECM) components in the IVDD process, MMP-1, MMP-2,MMP-3, MMP-9, and MMP-14 overexpression is positively correlated with the severity of IVDD. MMP-8, MMP-10, and MMP-12 also participate in the occurrence and progression of IVDD to varying degrees, but the specific mechanism is still unclear. Therefore,in-depth study of the mechanism of MMP-8, MMP-10, MMP-12 involved in the occurrence of IVDD, and the development of targeted drugs for exosomes and MMP-1, MMP-2, MMP-3, MMP-9, MMP-14 have certain potential value to the molecular level treatment of IVDD. This article aims to summarize the recent research progress in the involvement of MMPs carried by exosomes in the process of IVDD, in order to provide new targets and directions for the treatment of IVDD at the molecular level.

Objective To explore the role and mechanism of β-hydroxy-β-methyl butyric acid (HMB) in intensive care unit-acquired weakness (ICU-AW) associated with acute respiratory distress syndrome (ARDS). Methods Forty SPF grade male C57BL/6 mice were randomly divided into control group, sham operation group, model group, and HMB group, with 10 mice in each group. Model group and HMB group were treated with 3 μg/g lipopolysaccharide (LPS) by intratracheal injection to prepare the ICU-AW model associated with ARDS. Sham operation group received the same amount of sterile water. No procedures for control group. On the second day of modeling, mice in HMB group were given 340 mg/(kg·d) HMB by intragastric administration,and mice in the other three groups were given an equal volume of normal saline for continuous intragastric administration for two weeks. Additional 20 mice were randomized into the ARQ-092 group and Akt inhibitor control group, with 10 mice in each group.On the second day of modeling, both groups were given Akt inhibitor (ARQ-092 group) or an equivalent volume of the carrier (Akt inhibitor control group) orally for 10 hours after HMB intragastric administration for 12 days. We evaluated the grasping force of forelimb muscles and measured the sarcopenia index (SI). HE staining was used to observe the pathological changes in lung and muscle tissues. The mRNA expressions of Akt, FoxO3a, Atrogin1, and MuRF1 in mouse gastrocnemius were tested by qRT-PCR, and the expression levels of Akt/FoxO3a pathway related proteins in mouse gastrocnemius was further detected by Western blotting. Results Compared with the model group, the grasping force and SI of forelimb muscle in HMB group were significantly higher(P<0.05). HE staining revealed regular lung tissue structure in control group and sham operation group. Alveolar septa in model group were thickened and fractured, with structural disorder and inflammatory cell infiltration. The injury degree of lung tissue in HMB group was lighter compared with the model group. We observed normal phenotypes of the muscle tracts of gastrocnemius in control group and sham operation group. In model group, we detected muscle fiber atrophy and decreased quantity, muscle bundle structure destruction, and decreased cross-sectional area. The injury degree of the gastrocnemius muscle in HMB group was mild. In addition, compared with model group, the mRNA expressions of Akt and FoxO3a in the gastrocnemius of HMB group were significantly increased (P<0.05), and the phosphorylation levels of Akt and FoxO3a protein were also increased (P<0.05), the levels of Atrogin1 and MuRF1 mRNA and protein expressions decreased (P<0.05). Conclusion HMB can play a protective role in ICU-AW by regulating the Akt-FoxO3A-MurF1/Atrogin1 signaling pathway, which may be valuable for ICU-AW prevention and treatment. The Akt inhibitor ARQ-092 reversed the protective effect of HMB.

Objective To explore the independent influencing factors of the prognosis of patients after radical resection for colon cancer and establish a nomogram prognosis prediction model based on preoperative inflammatory immune indexes neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR) and tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9). Methods The clinicopathological data of 185 patients with colon cancer who underwent radical resection for colon cancer in the General Surgery Department of the Lanzhou University Second Hospital from April 2014 to December 2018 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to analyze the preoperative NLR, LMR, CEA and CA19-9 for predicting the best cut-off value of overall survival situation and grouping was performed according to the best cut-off value of NLR and LMR. The χ² test was used to analyze the relationship between different NLR and LMR groups and clinicopathological characteristics in colon cancer patients. Kaplan-Meier method and log-rank test were used to analyze the influence of different clinicopathological characteristics on the overall survial (OS) and disease-free survival (DFS) of patients. Multivariate Cox regression analysis was used to analyze the independent factors influencing patient prognosis. R4.1.1 software was used to draw a nomogram prediction model of DFS for patients after radical colon cancer surgery at 1, 2 and 3 years, and the performance of the prediction model was evaluated, and then using X-tile software stratified the model according to the nomogram risk score to explore further the clinical value of this model. Results The ROC curve results showed that the area under the curve (AUC) of NLR, LMR, CEA and CA19-9 were 0.784, 0.672, 0.727 and 0.656 respectively, and the optimal cut-off values were 3.40, 3.25, 4.30 ng/ml and 21.82 U/ml respectively. NLR was related to the the depth of invasion, maximum tumor diameter and preoperative CEA (P<0.05), and LMR was related to the depth of invasion, tumor location and maximum tumor diameter (P<0.05). Univariate analysis showed that lymph node metastasis, histological type, clinical stage, NLR, LMR, CEA and CA19-9 were associated with OS and DFS of patients with colon cancer after radical resection(P<0.05). Multivariate Cox regression analysis showed that NLR, CEA and histological type were independent factors influencing OS of patients after radical resection for colon cancer (P<0.05); NLR, LMR, CEA, CA19-9 and clinical stage were independent factors influencing DFS of patients after radical resection for colon cancer (P<0.05), of which LMR is a protective factor. A nomogram prediction model including NLR, LMR, CEA, CA19-9 and clinical stage was constructed. The internal validation consistency index (C index) of the model was 0.851. The calibration curve indicated that the model had a good degree of discrimination, and the DFS of patients in the low-risk group was obviously better than that in the middle- and high-risk groups (P<0.001). Conclusions Preoperative NLR, LMR, CEA,CA19-9 and clinical stage are related to the prognosis of colon cancer patients. The nomogram model constructed based on NLR, LMR,CEA, CA19-9 and clinical stage has good accuracy, discrimination and clinical utility.

Objective To explore the expression of cellular prion protein (PrPC) and its relationship with prognosis in colorectal cancer (CRC). Methods A total of 50 CRC tissues and 30 corresponding normal colorectal tissues were selected from the Department of Gastrointestinal Surgery of the First People's Hospital of Taicang City from January 2016 to January 2017.The expression of PrPC was determined by immunohistochemical SP method. Spearman test was used to analyze the correlation between PrPC positive expression and clinicopathological characteristics in CRC tissue. Kaplan-Meier method was used to analyze the relationship between PrPC expression and prognosis of CRC patients, Cox proportional hazards regression model was used to analyze the influencing factors of CRC prognosis. Results High expression of PrPC was shown in CRC tissues, and positive expression rate in CRC tissues was significantly higher than in corresponding normal colorectal tissues [68.0%(34/50) vs. 20.0%(6/30), P<0.01], and PrPC expression level was associated with patient TNM stage, depth of tumor invasion, degree of tumor differentiation, presence of vascular invasion and lymph node metastasis (P<0.05). Follow up until January 2021, except for 1 case of loss of follow-up, the remaining 49 cases were fully followed up for 6-68 months. During the follow-up, 32 cases died, with a median follow-up of 48 months. Kaplan-Meier survival curve analysis showed that the survival time of the patients in the PrPC negative expression group was (62.0±7.0) months, and the 5-year overall survival rate was 50.3%; the survival time of the PrPC positive expression group was (45.0±4.1) months, the 5-year overall survival rate was 7.0%, the difference was statistically significant in the survival situation was found between the two groups (P=0.015). The results of multivariate Cox regression model analysis showed that TNM stage and positive PrPC expression were independent factors influencing the outcome of CRC patients (P<0.05). Conclusion The high expression of PrPC in CRC tissues is correlated with poor prognosis in CRC patients, suggesting that PrPC is expected to be an important indicator for determining the prognosis of CRC.

Objective To compare the clinical and multidetector computed tomography (MDCT) features of gastroduodenal heterotopic pancreas (HP) and gastrointestinal stromal tumors (GIST) smaller than 3 cm in diameter. Methods A total of 61 patients pathologically confirmed as gastroduodenal HP (n=28) and GIST (diameter <3 cm, n=33) in Daping Hospital during 2012-2021 were included. Their clinical and MDCT features (including lesion location, growth mode, morphology, contour,size and MDCT multi-phase enhancements) were retrospectively reviewed and compared. The characteristics with significant difference between the two were searched as the index of differential diagnosis, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency of each parameter. Results No significant difference existed in gender, body mass index (BMI), clinical symptoms and signs between the patients with gastroduodenal HP and GIST (P>0.05), while statistically significant differences existed in age, MDCT morphological features (location, growth pattern, lobulation sign) and CT values (plain CT value, portal venous phase CT value and enhancement value) between the two groups (P<0.05, P<0.01). Among them, age,location, and portal venous phase CT value had better efficiency, and the areas under ROC curves (AUC) were all greater than 0.700.When the 3 MDCT morphological features (location, growth pattern, lobulation sign) were combined in use, the AUC was improved to 0.954 (95%CI 0.867-0.991). The plain scan CT value, portal venous phase CT value and enhancement value can be separately used to distinguish HP and GIST respectively, and the portal venous phase CT value has the best efficiency. The optimal cut-offs of age, plain scan CT value, portal venous phase CT value and enhancement value were 50 years, 40.33 HU, 72.53 HU and 37.33 HU,respectively, which could be used as reference indicators to differentiate HP from GIST. Conclusion By comprehensively analyze the patient's age, lesion MDCT morphological features and multi-phase enhanced quantitative parameters, a preliminary differential diagnosis can be made between gastroduodenal HP and GIST smaller than 3 cm in diameter.