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 investigate the expression and subcellular localization of long non-coding RNA (lncRNA)COL11A1-208, as well as the effect on the proliferation and invasion of oral squamous cell carcinoma (OSCC) cells. Methods The differential expression of COL11A1-208 in seven OSCC cell lines compared with primary cultured normal oral epithelial cells was detected by quantitative real-time PCR (qPCR), and the subcellular localization of COL11A1-208 was evaluated by cell nuclear/cytoplasmic fractionation and fluorescence in situ hybridization (FISH). CAL27 and HN4 cells were respectively transfected with COL11A1-208 Smart Silencer (SS-COL11A1-208 group) and negative control (NC) Smart Silencer (SS-NC group), while HN4 and HN6 cells were stably infected by COL11A1-208 lentivirus overexpression vector (LV-COL11A1-208 group) and NC lentivirus overexpression vector (LV-NC group). Cell proliferation in each group was detected by CCK-8 assay and plate colony formation assay, while cell migration and invasion ability in each group were detected by Transwell assays. Then, the expression of COL11A1 were detected by qPCR and Western blotting assays, while the protein expression of E-cadherin and vimentin was detected by Western blotting assay. Finally, the effect of COL11A1-208 on OSCC cells in vivo was studied by xenograft formation assay. Results COL11A1-208 was highly expressed in OSCC cell lines compared with the normal cells (P<0.05). The results of nuclear and cytoplasmic RNA isolation assay showed that the nuclear proportion of COL11A1-208 in CAL27, HN4 and HN6 cells was significantly higher than that in cytoplasm (P<0.01); similarly, FISH results showed that COL11A1-208 was primarily localized within the nucleus of OSCC cells. The relative expression of COL11A1-208 in SS-COL11A1-208 group was significantly lower than that in the SS-NC group (CAL27: 0.225±0.030 vs. 1.000±0.000; HN4: 0.393±0.028 vs. 1.000±0.000; P<0.01). Compared with the SS-NC group, proliferation activity, colonizing ability, migration and invasion abilities of SS-COL11A1-208 group decreased significantly (P<0.05). The relative expression of COL11A1-208 in LV-COL11A1-208 group was significantly higher than that in the LV-NC group (HN6: 6524.216±3395.926 vs. 1.000±0.000; HN4: 3486.230±743.908 vs. 1.000±0.000; P<0.05).Compared with the LV-NC group, proliferation activity, colonizing ability, migration and invasion abilities of LV-COL11A1-208 group were significantly increased (P<0.05). Compared with the SS-NC group, the relative expression of COL11A1 protein in SS-COL11A1-208 group decreased significantly (P<0.05), while the relative expression of COL11A1 protein in LV-COL11A1-208 group increased significantly than that in the LV-NC group (P<0.01). In addition, compared with the SS-NC group, the relative expression of E-cadherin in SS-COL11A1-208 group increased significantly (P<0.05), and the relative expression of vimentin decreased significantly (P<0.05). In LV-COL11A1-208 group, the relative expression of E-cadherin decreased significantly (P<0.05),and the relative expression of vimentin increased significantly (P<0.01). In vivo experiments showed that the xenograft tumor weight and volume of ASO-COL11A1-208 group were significantly reduced (P<0.05), while the xenograft weight and volume of LV-COL11A1-208 group were significantly enhanced (P<0.05). Conclusion COL11A1-208 could facilitate the cell proliferation and invasion of OSCC, which plays an important role in the development and progression of OSCCs.

Objective To investigate the role and significance of abdominal paracentesis drainage (APD) to pyroptosis in the pancreas of rats with severe acute pancreatitis (SAP), which is mediated by NLRP3 inflammasome-activated-caspase-1. Methods A total of 48 healthy male SD rats were randomly divided into three groups: sham operation (Sham) group, SAP group, and APD group, with 16 rats in each group. 5% sodium sulfonate was retrogradely injected into the pancreaticobiliary duct to establish the SAP model. In the APD group, besides the SAP induction, a drainage tube was placed on the right lower abdomen for drainage. Serum and pancreatic tissue were collected 12 hours after modeling. We examined the activities of serum lipase and amylase using an automatic biochemical analyzer and evaluated pancreatic damage through HE staining. In addition, we quantified the expression of serum inflammatory factors by ELISA and measured the expression level of genes and proteins related to caspase-1 mediated pyroptosis in pancreatic tissue using RT-PCR and Western blotting. Lastly, we observed the structural changes of the subcellular organelles and the characteristic changes of pyrolysis in pancreatic acinar cells using transmission electron microscopy. Results Compared with the SAP group, the pancreas tissue in the ADP group showed alleviated damages with a much lower pathological score; the levels of serum lipase, amylase, tumor necrosis factor(TNF)-α, Interleukin(IL)-6, IL-1β, and IL-18 also showed significant reduction (P<0.05).Compared with the Sham group, the expression levels of NLRP3, ASC, Caspase-1, cleaved caspase-1, GSDMD, and cleaved-GSDMD were all significantly up-regulated in the pancreas in the SAP group. After APD treatment, the expression of these Caspase-1-mediated pyrolysis pathway key genes in pancreatic tissue was significantly down-regulated. In addition, the expression levels of IL-1β and IL-18 mRNA in pancreatic tissue were also significantly reduced (P<0.05). Transmission electron microscopy showed that the SAP group had endoplasmic reticulum and mitochondrial expansion, chromatin condensation, and the characteristic change of pyrolysis, namely the formation of membrane pores in the cell membrane. In the APD group, we observed reduced chromatin condensation in the nucleus and less expansion in the endoplasmic reticulum and mitochondrial. Conclusion SAP showed activated Caspase-1-mediated pyroptosis. Early treatment with APD can alleviate the severity of SAP, possibly by inhibiting the activation of Caspase-1-mediated pyroptosis, thereby reducing local and systemic inflammatory reactions.

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.

Helicobacter pylori (Hp) infection is a common chronic bacterial infection in humans, which is significantly associated with a variety of gastrointestinal diseases. Traditionally, Hp eradication is based on one type of proton pump inhibitors(PPIs) combined with two types of antibiotics. PPIs could increase the pH value in the stomach to strengthen the bactericidal or antibacterial effects of antibiotics. Vonoprazan is a new drug with a stronger acid-suppressing effect compared to PPIs. Vonoprazan-based regimens are not inferior to PPIs-based regimens for eradicating Hp and are well tolerated. This article aims to summarize the effects of vonoprazan-based treatment strategy for Hp eradication, including vonoprazan-based first-line, second-line, and third-line regimens, vonoprazan-based regimens on penicillin-allergic and clarithromycin-resistant patients, vonoprazan-based dual and first-line triple regimens, and 10-14 d vonoprazan-based regimens.

Long non-coding RNAs (lncRNAs) are composed of a group of RNAs with more than 200 nucleotides but lacking protein coding functions. It has been gradually confirmed that it plays an important role of carcinogenic or tumor suppressor genes in the development and progression of human cancer. Small nucleolar RNA host gene 17 (SNHG17) is a lncRNA located on chromosome 20q11.23. In recent years, a large number of studies have explored the potential regulatory roles of SNHG17 in a variety of human cancers [such as oral squamous cell carcinoma, gastric cancer, hepatocellular carcinom, pancreatic cancer,colorectal cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, glioma, melanoma and osteosarcoma, etc.] progression,and high expression is usually closely related to the clinicopathological characteristics of tumor patients. In addition, it can promote the proliferation and metastasis of tumor cells, while inhibiting apoptosis. Therefore, SNHG17 is considered as a potential tumor biomarker and therapeutic target. This review focuses on the relevant research reports of SNHG17 in human cancers at home and abroad in recent years, focusing on the latest insights into the expression, functional role and molecular mechanism of SNHG17 in human malignant tumors, in order to provide a theoretical basis for clinical cancer treatment.

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 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.