The Keap1-Nrf2 pathway has been shown to be an important defense mechanism against oxidative stress, which may be an effective therapeutic strategy for many diseases. The research progresses on Keap1-Nrf2 pathway in inflammatory diseases were mainly reviewed. The basic components and activation mechanism of Keap1-Nrf2 pathway were introduced. The relationship between Keap1-Nrf2 pathway and the crosstalk between NF-κB pathway and HO-1 pathway, the expression of inflammatory mediators and enzymes, and inflammatory bodies were expounded. Natural product-derived inhibitors, small molecule inhibitors targeting Keap1-Nrf2 pathway and their clinical progress were introduced, and the potential application value of Keap1-Nrf2 pathway in the treatment of inflammation was discussed.

Objective:To systematically compare the analgesic efficacy of pericapsular nerve group (PENG) block and fascia iliaca compartment block (FICB) after hip fracture surgery.Methods:Databases including Pubmed, Embase, Cochrane, CNKI, Wanfang and VIP were searched for randomized controlled trials involving comparison of the analgesic efficacy of PENG block and FICB after hip fracture surgery from inception to August 2022. The primary outcome was the postoperative pain score, and the secondary outcome was the amount of postoperative analgesics and incidence of postoperative adverse reactions. The data were analyzed using Revman 5.4 software.Results:Eight studies were included ( n=374), and the pain score at rest 30 min after block was significantly lower in PENG group than in FICB group ( MD=-0.35, 95% CI -0.60--0.11, I2=14%, P<0.05). There was no statistically significant difference between PENG group and FICB group in pain scores at rest and during activity at 6, 12, 24 and 48 h after operation ( P>0.05). Compared with FICB group, the amount of analgesics used was significantly reduced at 24 and 48 h after operation in PENG group ( MD=-9.10, 95% CI -19.11-0.91, I2=95%, P<0.05). There was no statistically significant difference in the incidence of adverse reactions after operation between the two groups ( P>0.05). Conclusions:PENG block provides better efficacy when used for analgesia following hip fracture than FICB.

Intestinal microbiota plays an important role in maintaining liver metabolic homeostasis and affects the development and progression of hepatocellular carcinoma by participating in bile acid metabolism. Gut-liver axis plays an important role in the pathogenesis of liver diseases， and it might be one of the effective methods to prevent the progression of hepatocellular carcinoma by correcting intestinal ecological imbalance to restore normal bile acid level. This article summarizes the mechanism of bile acid receptor affecting hepatocellular carcinoma and the latest therapeutic targets， in order to provide a reference for the early prevention and treatment of hepatocellular carcinoma.

OBJECTIVE To study the imp rovement effects of total flavonoids of Psidium guajava leaves on myocardial hypertrophy in hypertensive model rats. METHODS Ten rats were randomly selected from 60 healthy SD rats as the normal group ； other 50 rats established hypertensive model ，and 44 rats with successful modeling were randomly divided into model group ， anisomycin group [p38 mitogen-activated protein kinase （p38 MAPK）activator，1 mg/kg]，total flavonoids of P. guajava leaves+ anisomycin group （200 mg/kg total flavonoids+ 1 mg/kg anisomycin ）and total flavonoids of P. guajava leaves group （200 mg/kg） by random volume mass ranking method ，with 11 rats in each group. Rats in normal group and model group were given 3％ hydroxymethylcellulose sodium solution ，and other groups were given relevant solution intragastrically ，once a day ，for consecutive 6 weeks. Blood pressure （systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ），cardiac index and left ventricular index were measured. The levels of tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β）and IL- 6 in myocardial tissue were detected. The pathomorphological changes of myocardial tissue were observed. The expression of p 38 MAPK， phosphorylated p 38 MAPK （p-p38 MAPK），extracellular regulated protein kinase 1/2 （ERK1/2），phosphorylated ERK 1/2 （p-ERK1/2），c-Jun N-terminal kinase （JNK）and phosphorylated JNK （p-JNK）in myocardial tissue were detected. RESULTS Compared with normal group ，the systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ，cardiac index ，left ventricular index as well as the levels of TNF-α，IL-1β and IL-6 and protein expression of p-p 38 MAPK，p-ERK1/2 and p-JNK in myocardial tissue were increased significantly in anisomycin group and model group （P＜0.05）；it was also found that hypertrophy of cardiomyocytes ，disorder of myocardial fibers ，looseness，edema and proliferation of connective tissue between myocardial fibers，increased infiltration of inflammatory cells ，etc. Compared with anisomycin group and model group ，the le vels of above indexes in total flavonoids of P. guajava leaves+ anisomycin group and total flavonoids of P. guajava leaves group were decreased significantly （P＜0.05）； cardiomyocytes were 163.com slightly larger and arranged reasonably ；the degree of myocardial hypertrophy，looseness，edema and proliferation of connective tissue were relieved ，and the improvement effect of total flavonoids of P. guajava leaves group was more significant （P＜0.05）. CONCLUSIONS The total flavonoids of P. guajava leaves can reduce blood pressure and improve myocardial hypertrophy in hypertensive model rats. Its mechanism may be related to the inhibition of p38 MAPK signal pathway activity and the expression of inflammatory factors.

Background: Co-infections of the porcine reproductive and respiratory syndrome virus (PRRSV) and the Haemophilus parasuis (HPS) are severe in Chinese pigs, but the immune response genes against co-infected with 2 pathogens in the lungs have not been reported. Objectives: To understand the effect of PRRSV and/or HPS infection on the genes expression associated with lung immune function. Methods: The expression of the immune-related genes was analyzed using RNA-sequencing and bioinformatics. Differentially expressed genes (DEGs) were detected and identified by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and western blotting assays. Results: All experimental pigs showed clinical symptoms and lung lesions. RNA-seq analysis showed that 922 DEGs in co-challenged pigs were more than in the HPS group (709 DEGs) and the PRRSV group (676 DEGs). Eleven DEGs validated by qRT-PCR were consistent with the RNA sequencing results. Eleven common Kyoto Encyclopedia of Genes and Genomes pathways related to infection and immune were found in single-infected and co-challenged pigs, including autophagy, cytokine-cytokine receptor interaction, and antigen processing and presentation, involving different DEGs. A model of immune response to infection with PRRSV and HPS was predicted among the DEGs in the co-challenged pigs. Dual oxidase 1 (DUOX1) and interleukin-21 (IL21) were detected by IHC and western blot and showed significant differences between the co-challenged pigs and the controls. Conclusions These findings elucidated the transcriptome changes in the lungs after PRRSV and/or HPS infections, providing ideas for further study to inhibit ROS production and promote pulmonary fibrosis caused by co-challenging with PRRSV and HPS.

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distri-bution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were system-atically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavail-ability in rats(0.6％-1.6％)and dogs(4.5％-9.3％).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.So-dium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a con-stant area under the concentration-time curve ratio(CSF/plasma)of approximately 5％.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7％(male)and 26.3％(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.

Objective:This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients. Methods:This prospective, single-arm, and open clinical study enrolled 30 adult Ph + ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results:All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS ( P=0.004) , HRFS ( P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS ( P=0.030) and EFS ( P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions:The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph + ALL patients. Clinical trial registration:ClinicalTrials.gov, NCT02523976.

Histone modification plays an important role in the process of cellular DNA damage repair. In recent years, a great number of studies have shown that histone modification affectsradiation responses including recruitment of DNA damage repair factors, creation of chromatin open structures and establishment of repressive histone marks.Regulation of histone modification may influence the process of DNA damage repair and thus affect radiation sensitivity. In this paper, the effects of histone modification on DNA damage repair, cellular radiosensitivity and the underlying mechanisms are reviewed.

Objective:To analyze the clinical characteristics of intestinal tuberculosis improving the diagnosis rate of intestinal tuberculosis.Methods:From January 2014 to June 2018, at Wuhan Pulmonary Hospital, the data of clinical symptoms, laboratory examination, imaging, endoscopy, surgery and pathological examination of 205 patients with intestinal tuberculosis were retrospectively analyzed. Descriptive analysis was performed for statistical analysis.Results:Among 205 patients with intestinal tuberculosis, 145 cases were male and 60 cases were female, aged 14 to 85 years old. A total of 189 cases (92.2%) were complicated with lung tuberculosis, of which 151 cases (79.9%) were positive for sputum acid fast staining. A total of 126 cases were tested for feces acid fast staining, of which 83 cases (65.9%) were positive. A total of 60 cases (29.3%) were tested for GeneXpert Mycobacterium tuberculosis/rifampicintablet (GeneXpert MTB/RIP), of which 49 cases (81.7%) were positive. A total of 44 cases of intestinal tuberculosis were diagnosed by biopsy under electronic enteroscopy, and 21 cases were pathologically diagnosed with intestinal tuberculosis after surgical resection. The 21 patients were tested for GeneXpert MTB/RIP, of which 19 cases (90.5%) were positive and 10 cases (47.6%) were positive for tuberculin test. Six patients were clinically diagnosed with intestinal tuberculosis after effective treatment of antituberculosis drugs. Conclusions:Combination of clinical symptoms and laboratory, imaging, endoscopic and pathological examination, as well as the therapeutic effect of diagnostic antituberculosis treatment could make comprehensive diagnosis of intestinal tuberculosis. The GeneXpert MTB/RIP examination is of great value in the diagnosis of intestinal tuberculosis.

AIM: To identify the differentially expressed lncRNAs related to myelodysplastic syndromes by method of bioinformatics. METHODS: The GSE145733 was downloaded from GEO database; the differentially expressed lncRNAs were screened out by GEO2R. miRNA and mRNA associated with the differentially expressed lncRNAs were analyzed by the platform miRDB. lncRNA-miRNA-mRNA network was constructed and visualized by Cytoscape software. We annotated and enriched the lncRNAs to biological functions and pathways by GO and KEGG tools. RESULTS: Five differentially expressed lncRNAs were screened out. These lncRNAs were associated with 19 miRNAs and 84 mRNAs. They mainly affected the functions such as substance synthesis and transportation, gene transcription, and nervous system. CONCLUSION: We discovered the lncRNA expression characteristics in MDS patients, predicted the functions of these lncRNAs, which may provide new drug targets for the precise medication in MDS.