Objective To explore the effect of propofol on human gastric cancer transplant BALB/c mice model treated with oxaliplatin. Methods We established a human gastric cancer model in the BALB/c mice using MGC 803 cells subcutaneous transplantation. Then the mice were randomly divided into control group (n=6), propofol group (n=6, 5 mg/kg propofol), oxaliplatin group (n=6, 6 mg/kg oxaliplatin), and propofol with oxaliplatin group (n=6, 5 mg/kg propofol+6 mg/kg oxaliplatin). The mice in each group received a total of 3 consecutive drug administrations through intraperitoneal injection once every 3 days. Mice were sacrificed two days after the last injection. Blood samples were then collected. The tumor volume and mass tumor inhibition rates were analyzed, respectively. The histological features of the tumor were evaluated with HE staining. The expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum were quantified using ELISA. In addition, the expression levels of epidermal growth factor (EGF), matrix metal protease-2 (MMP-2) and MMP-9 proteins in transplanted tumor tissue were quantified using ELISA. Results Compared with control group, the volume tumor inhibition rates (F=248.717, P<0.05) and mass tumor inhibition rates (F=376.205, P<0.05) of propofol group, oxaliplatin group, and propofol+oxaliplatin group were significantly reduced. The tumor volume inhibition rate and mass tumor inhibition rate of propofol+oxaliplatin group were significantly lower than those of oxaliplatin group, and the differences were statistically significant (tumor volume inhibition rate: 82.44%±4.69% vs.47.18%±5.71%, P<0.05; mass tumor inhibition rate: 77.95%±3.64% vs. 46.43%±3.99%, P<0.05). Compared with control group, cancer cell volume was reduced to varying degrees as well as the number of cancer cells was decreased in the remaining drug-treated groups using HE staining. In addition, the most significant decrease in cancer cell number happened in propofol+oxaliplatin group.The cell nucleus shrinks into a uniform blue-black dense body with an increased cytoplasmic density, increased cancer cell nuclear fragments, and large areas of necrosis. ELISA results showed that the levels of TNF-α and IL-6 in serum and EGF, MMP-2 and MMP-9 in transplanted tumor tissues of propofol group, oxaliplatin group and propofol+oxaliplatin group were significantly lower than those in control group, and those in propofol+oxaliplatin group were significantly lower than those in oxaliplatin group, and the differences were statistically significant (P<0.05). Conclusion Propofol can increase the sensitivity of gastric cancer cells to oxaliplatin, inhibit the proliferation, invasion and metastasis of gastric cancer cells, and enhance the anti-tumor effect of oxaliplatin.The mechanism may be related to the inhibition of inflammatory response by propofol and the regulation of EGF expression.

Objective To explore the effect and mechanism of ivermectin (Ive) in enhancing oxaliplatin (L-OHP) against colon cancer HCT116/L-OHP cells. Methods In vitro establishment of colon cancer HCT116/L-OHP cells model with L-OHP low-concentration gradient increasing and low-concentration L-OHP (4 μmol/L) continuous culture. Set control group, L-OHP 25 μmol/L group, and L-OHP 25 μmol/L combined with 1, 2, 4, and 8 μmol/L Ive groups, and used MTT assay to detect cell viability. Set control group, L-OHP 25 μmol/L group, L-OHP+Ive 2 μmol/L group, and L-OHP+Ive 4 μmol/L group, and use cloning experiment to detect cell clone formation ability and flow cytometry apoptosis and cell cycle distribution, Western blotting was used to detect the expression levels of nuclear factor κB p65 (NF-κB p65), pregnane X receptor (PXR) and P-glycoprotein (P-gp). The colon cancer HCT116/L-OHP cells model with high expression of NF-κB p65 was constructed by LPS induction(setting control group, LPS group, LPS+L-OHP group, LPS+L-OHP+Ive 2 μmol/L group and LPS+L-OHP+Ive 4 μmol/L group), using lentiviral transfection to construct a colon cancer HCT116/L-OHP cells model with high PXR expression (setting control group, Ad-PXR group, Ad-PXR+L-OHP group, Ad-PXR+L-OHP+Ive 2 μmol/L group and Ad-PXR+L-OHP+Ive 4 μmol/L group), Western blotting was used to detect the expressions of NF-κB p65, PXR and P-gp protein levels. Twenty nude mice were injected subcutaneously with HCT116/L-OHP cells to establish a colon cancer drug-resistant cell transplantation tumor model and were divided into control group, L-OHP group, Ive group and Ive+L-OHP group, 5 mice in each group, and the tumor volume was calculated, the tumor weight was measured, and use immunohistochemistry to detect the expression of NF-κB p65, PXR and P-gp protein in the tumor tissues. Results Ive can potentiate L-OHP to inhibit colon cancer HCT116/L-OHP cells proliferation and clone formation (P<0.05), and promote colon cancer HCT116/L-OHP cells apoptosis and cell cycle S phase block (P<0.05).Western blotting showed that, in colon cancer HCT116/L-OHP cells, the expression levels of NF-κB p65, PXR and P-gp proteins in L-OHP+Ive 2 μmol/L group and L-OHP+Ive 4 μmol/L group were lower than those in control group, those in L-OHP+Ive 4 μmol/L group were lower than in L-OHP group (P<0.05). In the HCT116/L-OHP cells model with high NF-κB p65 expression, the expression levels of the NF-κB p65, PXR and P-gp protein in LPS+L-OHP+Ive 2 μmol/L group and the LPS+L-OHP+Ive 4 μmol/L group were lower than those in LPS group (P<0.05). In HCT116/L-OHP cells model with high PXR expression, the expression levels of the NF-κB p65, PXR and P-gp protein in Ad-PXR+L-OHP+Ive 2 μmol/L group and Ad-PXR+L-OHP+Ive 4 μmol/L group were lower than those in Ad-PXR group and Ad-PXR+L-OHP group, those in Ad-PXR+L-OHP+Ive 4 μmol/L group were lower than those in Ad-PXR+L-OHP+Ive 2 μmol/L group (P<0.05). In vivo experimental results showed that Ive can cooperate with L-OHP to inhibit the growth of HCT116/L-OHP cells xenograft tumors (P<0.05). The results of immunohistochemistry showed that the relative expression density of NF-κB p65, PXR and P-gp protein in the tumor tissues of Ive group, L-OHP group and Ive+L-OHP group was lower than that of control group. The L-OHP group and Ive+L-OHP group were lower than those in Ive group, and the Ive+L-OHP group were lower than those in L-OHP group (P<0.05). Conclusion Ive can enhance the effect of L-OHP against colon cancer HCT116/L-OHP cells, and its potential mechanism of action is to reduce the mediating effect of P-gp protein on L-OHP resistance by inhibiting the expression of NF-κB p65/PXR signaling pathway.

Objective To explore the effect and mechanism of carbazochrome sodium sulfonate on acute lung injury in septic rats. Methods Healthy male Wistar rats were randomized into 5 groups: sham group (n=25), sepsis group (n=25), low dose group (carbazochrome sodium sulfonate: 8 mg/kg)(n=25), middle dose group (carbazochrome sodium sulfonate: 40 mg/kg)(n=25), and high dose group (carbazochrome sodium sulfonate: 80 mg/kg)(n=25). Two additional groups, the autophagy inhibition group(3-MA)(n=10) and the sepsis middle dose group (carbazochrome sodium sulfonate: 40 mg/kg)(n=10), are also included in this study. After the preparation of septic rats by cecal ligation and puncture, the different doses of carbazochrome sodium sulfonate or 3-MA were given by intraperitoneal injection. The survival curve is drawn. After CLP 24 hours, the lung Micro-CT of those survival rats were examined. The arterial blood gas, pulmonary index and vascular permeability of lung tissue were measured. Pathological changes of lung tissues were observed by HE staining. The level of autophagic marker (LC3-Ⅱ/LC3-Ⅰ) of lung tissue was measured by Western blotting. Results Compared with sepsis group, the survival rate of the rats of carbazochrome sodium sulfonate groups increased, the arterial blood oxygen partial pressure and oxygenation index increased, the pulmonary index and vascular permeability decreased, and the differences were statistically significant (P<0.05). Both lung Micro-CT and HE staining showed that the lung lesions were more serious in sepsis group, while carbazochrome sodium sulfonate alleviated these lesions. Western blotting results showed that, the ratio of LC3-Ⅱ/LC3-Ⅰ in lung tissue of septic rats was higher than sham group (5.1±2.7 vs. 2.7±0.7, P<0.05), while the ratio of LC3-Ⅱ/LC3-Ⅰ in lung tissue in the low dose and middle dose carbazochrome sodium sulfonate groups was further increased than sepsis group (6.8±2.6, 8.9±1.4 vs. 5.1±2.7, both P<0.05). The value of LC3-Ⅱ/LC3-Ⅰ in the lung tissue of rats in 3-MA group was significantly lower than that in the middle dose carbazochrome sodium group (3.1±1.7 vs. 8.7±1.6), and the difference was statistically significant (P<0.05). Conclusion The mechanism by which carbazochrome sodium sulfonate-alleviating lung injury is related to the up-regulation of autophagy level in septic rats.

Postpartum hemorrhage is the most common cause of maternal death worldwide with an upward trend of incidence recent years. There are many reasons leading to postpartum hemorrhage with very complicated pathogenesis. Recent years, various studies have found that a close relationship existed between the plasma fibrinogen concentration and postpartum hemorrhage and its severity. Prenatal fibrinogen detection is helpful to predict the occurrence of severe postpartum hemorrhage, Detection of postpartum fibrinogen level, and timely correction of transient coagulation dysfunction is an important way to remedy severe postpartum hemorrhage. At the present stage, many domestic hospitals have taken prenatal fibrinogen detection as a routine test item, but it has not yet been taken as an independent risk factor for postpartum hemorrhage. At the same time, the fibrinogen threshold might leading to severe postpartum hemorrhage and whether the lowest fibrinogen level is related to the amount of bleeding are still uncertain. The present review summarized the research progress of the clinical application of plasma fibrinogen measurement in the prediction of severe postpartum hemorrhage and accurate assessment of the amount of bleeding when postpartum hemorrhage occurs, and to explore the clinical value of fibrinogen detection in postpartum hemorrhage. Meanwhile, Suggestions for relative clinical work and future research are presented in order to improve the prognosis of postpartum hemorrhage.

The outbreak of coronavirus disease 2019 has made nucleic acid detection widely known. Fluorescent quantitative polymerase chain reaction (PCR) technique is the most commonly used nucleic acid detection method in this epidemic control. However, its requirements on operators, instruments and sites limited its application in some scenarios with lower resources or outside laboratories. Isothermal amplification technology, especially recombinase polymerase amplification(RPA) technology, has the advantages of mild reaction conditions, high sensitivity, excellent specificity and short reaction time, which let it has a good application prospect in the rapid detection of a variety of pathogenic microorganisms. In this paper, the development and application of RPA technology are reviewed and summarized to provide a reference for the further research and promotion of this technology.

Type 2 diabetes mellitus (T2DM) is often clinically associated with mi- and macrovascular diseases, but is often ignored in the early stage of the disease. Therefore, more auxiliary detection methods are needed clinically for early screening and auxiliary diagnosis of T2DM and high-risk patients. Arteriosclerosis detection--especially pulse wave velocity (PWV), as a non-invasive and effective method for measuring arterial stiffness, has been applied more and more widely in clinic recent years. Existing studies have shown that increased arterial stiffness is an important predictor of the occurrence and development of vascular diseases in T2DM. The value of PWV in the prediction of atherosclerosis is particularly important in order to better predict the occurrence of disease and start health management as soon as possible. Therefore, the relationship between PWV and mi- and macrovasular complications in T2DM is reviewed in present paper to provide early warning for patients with T2DM who have early vascular risk.

Atherosclerotic cardiovascular disease (ASCVD) is a kind of disease including acute coronary syndrome(ACS), history of myocardial infarction (MI), stable or unstable angina pectoris (SAP, UAP), coronary artery or other blood vessel revascularization (PCI), ischemic stroke (IS), transient ischemic attack (TIA), peripheral vascular disease (PAD) and so on. It has a high morbidity rate, high disability rate, and high mortality rate in elderly patients, which puts a heavy burden on patients'families and society. But the early warning markers of ASCVD were still in the exploratory stage. Sarcopenia is a common disease in elderly individuals. A large number of studies showed that sarcopenia may be an independent risk factor for the onset and severity of ASCVD. As a comorbidity, at the same time, it may also be an independent predictor of poor prognosis of ASACVD. In addition, sarcopenia and ASCVD in elderly individuals have some common pathogenesis, such as inflammation, oxidative stress and insulin resistance. The role of sarcopenia in the pathogenesis of ASCVD in the elderly is reviewed in present paper.

Objective To explore the analgesic effect of low-intensity exercise induced by interleukin (IL)-4 on chronic constriction injury of the sciatic nerve (CCI) mice. Methods A total of 48 male C57/BL6 mice were randomized into 6 groups(n=8): sham/sedentary group (SS group), sham/normal saline/exercise group (SNE group), sham/anti-IL-4/exercise group (SAE group), CCI/sedentary group (CS group), CCI/normal saline/exercise group (CNE group), CCI/anti-IL-4/exercise group (CAE group). After inducing CCI, mice were given low-intensity exercise from 1 to 15 days. For the SAE group and the CAE group, mice received 50 μg of IL-4 receptor blocker (IL-4Ra) 30 min before exercise through intraperitoneal injection. Behavioural tests were performed on the 3rd day (T₁), 7th day (T₂), 11th day (T₃) and 15th day (T₄) to analyze the difference of hyperalgesia. On the 15th day after CCI induction, the injured sciatic nerve and lumbar spinal cord (L₁-L₆) of all mice were collected. The levels of IL-4, IL-1Ra, IL-5, TNF-α, IL-1β, brain-derived neurotrophic factor (BDNF) and β-nerve growth factor (β-NGF) were detected by ELISA. Results The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) values of the CNE group at T₃ and T₄ were higher than those of the CS group and CAE group (P<0.05); the IL-4 levels of the sciatic nerve and lumbar spinal cord in CNE group and CAE group were higher than those of CS group (P<0.05); the IL-1Ra and IL-5 levels of the sciatic nerve and lumbar spinal cord in CNE group were higher than those of CS group and CAE group (P<0.05); the TNF-α, IL-1β, BDNF and β-NGF levels of the sciatic nerve and lumbar spinal cord of CNE group were lower than those of CS group and CAE group (P<0.05). Conclusion Low-intensity exercise exerts the analgesic effect on mice with chronic constriction injury of sciatic nerve through IL-4.

Objective To profile transcriptome dynamics in the entecavir resistant hepatitis B virus (ETV-r HBV) stably transfected cell line, and provide fundamental data for future studies to understand mechanisms of infection using this cell line. Methods ETV-r HBV stably transfected cell lines (HepG2.A64) and the corresponding isogenic cell lines (HepG2) were used to profile the transcriptome (n=3). We used DESeq2 software to analyze the sequencing results to identify differentially expressed genes with |log2 Fold Change|>2, padj<0.05. GO and KEGG functional enrichment analysis of differential genes were performed by clusterProfiler software, and then the transcriptional and protein levels of related genes in the DNA repair pathway were detected by RT-qPCR and Western blotting. Results A total of 613 differentially expressed genes were identified in the cell lines before and after stable ETV-r HBV transfection, of which 401 were up-regulated and 212 down-regulated (padj<0.05). GO and KEGG enrichment analysis showed that differentially expressed genes were mainly involved in the inflammatory response, PI3K/Akt signal pathway, PPAR signal pathway, NF-κB signal pathway and immune-related biological processes. Through the analysis of the relevant genes in the DNA repair pathway and the verification by RT-qPCR and Western blotting, it was found that after stable transfection of ETV-r HBV, the mRNA expression of RAD52 and XRCC2 genes in the DNA repair pathway decreased by 68.96%±7.59% and 69.58%±6.32%, respectively, and the protein expression decreased by 69.93%±3.88% and 26.47%±12.7%, respectively, and the differences were statistically significant (P<0.05). Conclusion Compared with the original background cell line HepG2, a lot of genes are differentially expressed at the transcription level in HBV stable cell line, and the DNA repair-related genes in the HepG2.A64 cell line had been decreased significantly.

Objective To investigate the photodynamic effect of IR-820 and perfluoropentane (PFP) loaded phase-transition multifunctional molecular imaging probe (IR-820/PFP@PLGA NPs) on ultrasound/photoacoustic dual-mode imaging and fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) in vitro. Methods The IR-820/PFP@PLGA nanoparticles were prepared by double emulsification method. The basic characteristics, thermal phase transition and photothermal effect of IR-820/PFP@PLGA nanoparticles were determined, the ultrasound/photoacoustic dual-mode imaging ability in vitro of the IR-820/PFP@PLGA nanoparticles were observed, and the generation of reactive oxygen species in vitro were evaluated. The photodynamic therapy effect of the nanoparticles on fibroblast-like synoviocytes was observed by CCK-8 method and flow cytometry. Results The prepared IR-820/PFP@PLGA nanoparticles were dark green, with a particle size of (261.8±3.2) nm and a potential of (–27.4±0.7) mV. The size of the IR-820/PFP@PLGA nanoparticles were uniform and the morphology were regular. The size of nanoparticles and the temperature of nanoparticle solution increased obviously by laser irradiation, it was positively correlated with the concentration of nanoparticles, and enhanced ultrasound imaging was observed. The photoacoustic imaging effect of nanoparticle was linearly correlated with the concentration of IR-820/PFP@PLGA nanoparticles; The singlet oxygen sensor green(SOSG) assay revealed that the nanoparticles produced a large amount of reactive oxygen species after laser irradiation with time-dependent manner; it was found by in vitro cell experiments that the nanoparticles had good biological safety, while the cytotoxicity increased along with the advanced nanoparticle concentration after laser irradiation, and also the apoptosis increased significantly. Conclusion IR-820/PFP@PLGA nanoparticles have a good dual-mode imaging and photodynamic effect on FLSs, which can provide a new idea for the integration of diagnosis and treatment for RA.