Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Purpose To investigate the clinicopathological features,diagnosis and differential diagnosis of the primordial odontogenic tumour(POT).Methods Clinical data of 4 cases of jawbone POT were collected.Imaging examination,HE,and immunohistochemical EnVision two-step staining was used to an-alyze their clinical and pathological characteristics,and relevant literatures were reviewed.Results The age arranged from 5 years to 21 years.2 cases were male and 2 case were female.There were 2 cases in maxilla and 2 cases in mandible.The clinical presentation was a slow growing painless mass.Cut sur-face of the tumor was appeared grayish yellow and grayish white,the tumor involved the crown of an unerupted tooth.The tumour consisted of a proliferation of spindled and stellate cells in myx-oid stroma.Surfaced by cuboidal to columnar epithelium forming papillary structures and invaginations.Calcification was observed in 2 cases.Conclusion POT is a rare benign mixed odontogen-ic tumor that is more common in children and adolescents.Mas-tering its characteristic histological morphology can make a cor-rect diagnosis.Local complete resection of the tumor has a good prognosis.

Objective To investigate the effect of osimertinib combined with aspirin on the survival pe-riod of the advanced lung adenocarcinoma patients with epidermal growth factor receptor(EGFR)mutation.Methods Sixty lung adenocarcinoma patients with EGFR mutation in advanced non-small cell lung cancer(NSCLC)first diagnosed in Banan District Second People's Hospital of from August 2020 to October 2021 were selected as the study subjects and divided into the observation group and control group by the random number table method,30 cases in each group.The observation group adopted osimertinib combined with aspi-rin,and the control used osimertinib merely.The overall response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and the adverse reactions occurrence were compared between the two groups.Results ORR and DCR after 3,6,12 months medication in the observation group were higher than those in the control group,but the differences were not statistically significant(P＞0.05).Compared with the control group,PFS and OS in the observation group were longer,and the differences were statistically significant[14.9(11.8,17.2)m vs.10.5(8.9,12.5)m;24.1(19.5,27.4)m vs.18.1(16.1,21.1)m,P＜0.05].In addition,PFS and OS in male and female patients with brain metastasis,EGER19 and 21 ex-on mutation in the observation group were longer than those in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in overall and≥Ⅲ degree adverse reactions between the two groups(P＞0.05).Conclusion Osimertinib combined with aspirin could prolong PFS and OS of the advanced lung adenocarcinoma patients with EGFR mutation without increasing the risk of adverse reactions.

The gut microbiota plays a crucial role in the development of colorectal cancer (CRC). The imbalanced gut microbiota causes damage to the body and disrupts bile acids metabolism, increases susceptibility to CRC, and affects the signaling of farnesol X receptor (FXR), thereby promoting CRC progression. Traditional Chinese medicine has unique advantages in the treatment of CRC due to its synergistic regulatory effects of multiple components, targets, and pathways. It can regulate gut microbiota, intervene in bile acids metabolism, and activate its receptor FXR to inhibit the occurrence and development of CRC. Based on this, this article discusses the main role of the gut microbiota-bile acids-FXR axis in the development of CRC, and reviews the anti CRC effects and mechanisms of traditional Chinese medicine intervention on gut microbiota-bile acids-FXR axis, in order to provide new ideas and methods for the prevention and treatment of CRC.

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally.Programmed death protein-1(PD-1)/programmed death protein ligand-1(PD-L1)inhibitors promote the reactivation of anti-tumor immune response by bloc-king the negative modulatory signaling pathway of T cells'activa-tion and inhibiting the immune escape pathway of tumor cells.PD-1/PD-L1 inhibitors become a novel therapeutic strategy to treat HCC.However,long-term clinical outcomes show that HCC patients treated with anti-PD-1/PD-L1 monotherapy still have high rates of recurrence and metastasis.Combination immuno-therapy is a novel therapeutic strategy to treat advanced HCC pa-tients,among which PD-1/PD-L1 inhibitors in combination with anti-vascular endothelial growth factor(VEGF)agents have showed promising efficacy and better safety.PD-1/PD-L1 inhib-itors plus anti-VEGF agents combined therapy inhibit the growth of hepatoma cells by participating in the cancer immunity cycle pathway.This review focuses on the research progress of PD-1/PD-L1 inhibitors,anti-VEGF agents and their combined therapy in the clinical treatment of HCC.

Objective To investigate the effect of iTBS stimulation on walking function in patients with stroke.Methods Fifty patients with post-stroke walking dysfunction who met the inclusion criteria were selected for 3-week rehabilitation treatment,and were randomly divided into iTBS group(n=25)and sham group(n=25).The iTBS group was treated with conventional rehabilitation therapy combined with iTBS stimulation of contral-esional cerebellum,and the sham group was treated with conventional rehabilitation therapy plus iTBS stimulation of contralesional cerebellum.Relevant indicators were analyzed before treatment and at 21 days of treatment.Lower limb motor function scores of the two groups were compared before and after treatment.Fugl-Meyer motor function lower limb activity score,Berg Balance Scale score,Brunnstrom stage(lower limb),hamstring/quadriceps(H/Q)on the affected side,Modified Barthel index(MBI),gait analysis parameters,and TMS-MEP were used to evaluate the effectiveness of cerebellar iTBS in the rehabilitation of walking dysfunction after stroke.Results After 21 days of treatment,the improvements of Brunnstrom stage,Holden grade,Berg score,FMA score,6-minute walking dis-tance,NIHSS score and MBI score in iTBS group were significantly better than those in sham group(P<0.05).Af-ter treatment,the H/Q in iTBS group was significantly higher thanbefore(P<0.05),but there was no significant difference between the two groups(P>0.05).Stride speed,stride frequency,stride width,single support phase on the affected side and GDI score in iTBS group were significantly improved compared with sham group(P<0.05),and there was no significant difference in stride length between the two groups after treatment(P>0.05).The amplitude of MEP in the affected cerebral cortex of iTBS group was lower after treatment than before(P<0.05).Conclusion Contralesional cerebellar iTBS combined with routine rehabilitation could improve lower limb walk-ing function and daily living ability of stroke patients.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.