OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

Objective To establish a hydraulic system model of the aqueous humor circulation in the human eye and explore the characteristics of aqueous humor flow and intraocular pressure changes under various types of glaucoma and surgical conditions.Methods A hydraulic system model of aqueous humor circulation was constructed using AMESim software based on ocular structural parameters to simulate the fluid dynamics of aqueous humor in three types of glaucoma and their surgical interventions.Results Significant elevation in intraocular pressure was observed with pathological changes such as trabecular meshwork obstruction,anterior chamber angle contraction,and narrowing of the iris-lens gap.Through simulations of surgical interventions,including trabeculectomy,iridectomy,and ciliary body ablation,aqueous outflow resistance was effectively reduced,leading to a controlled intraocular pressure.Conclusions By successfully simulating both the pathological conditions of glaucoma and the dynamic intraocular pressure changes under surgical interventions,the hydraulic system model accurately reflects the physiological characteristics of glaucoma.The model not only predicts the effects of therapeutic interventions,but also provides reliable simulation support for the diagnosis and optimization of treatment strategies for glaucoma.

Objective To explore the correlations of spatial distribution frequency map of posterior reversible encephalopathy syndrome(PRES)and cerebral microvascular density map,cerebral blood flow(CBF)map,standard template of cerebral metabolic imaging and the spatial gene transcription map of human brain based on normative analysis strategy,and to analyze the pathophysiological mechanisms of PRES.Methods Cerebral MRI data of 184 patients with PRES were retrospectively analyzed.ROI of the lesions were delineated on T1WI,then registered to Montreal Neurological Institute(MNI)standard space.The spatial distribution frequency map of PRES lesions were obtained with superposition.Spatial correlation analysis were performed to observe correlations of spatial distribution frequency map of PRES and the cerebral microvascular density map,CBF map and standard template of cerebral metabolic imaging based on large sample.The potential related gene expressions were decoded based on gene expression data of Allen human brain atlas,and the correlations of spatial parts of PRES and those expressions were observed.Results No significant correlation was found between spatial distribution frequency map of PRES and cerebral microvascular density,CBF nor distribution of neurotransmitters(all P＞0.05).PLS1 weighted genes,VEGF-A gene,AQP-4 gene and RGS2 gene were all correlated with spatial distribution of PRES(r=-0.363-0.653,all P＜0.05),among which KCNAB3 gene had the highest weight(Z=17.288).Conclusion The spatial patterns of PRES risk or protective genes in brain regions were correlated with regional distribution of PRES lesions,which was consistent with arginine vasopressin(AVP)theory of the occurrence and development of PRES.

Objective To investigate the efficacy of treating adhesive small intestinal obstruction using blind insertion of a nasal ileus catheter in combination with continuous enteral nutrition.Methods The data of patients with adhesive small intestinal obstruction admitted to our department from January 2022 to December 2023 were retrospectively collected.Group A was treated with blind insertion of a nasal jejunal decompression catheter,whereas Group B was managed with a nasogastric tube.Continuous enteral nutrition was initiated after the resolu-tion of intestinal obstruction in both groups.The nutritional indices,abdominal improvement,inflammatory markers,and complication rates were compared between the two groups before and after treatment.Results In terms of nutritional indices,the scores for Alb,Pa,and NRS2002 in Group A were significantly higher than those in Group B on the 7th day(P<0.05).Regarding abdominal improvement indices,Group A demonstrated significantly better outcomes than Group B in daily average decompression drainage volume,daily average reduction in abdominal circumference,relief time for abdominal distension and pain,recovery time for exhaust,defecation,time to resump-tion of enteral nutrition,and total hospitalization duration(P<0.05).Concerning inflammatory indices,CRP,IL-6,and WBC levels in Group A were significantly lower than those in Group B on both the 4th and 7th days post-treatment(P<0.05).With regard to complications,Group A exhibited fewer cases of EN intolerance,reflux,and conversion due to conservative treatment ineffectiveness compared to Group B(P<0.05).Conversely,Group B had fewer instances of water and electrolyte imbalance compared to Group A(P<0.05).Conclusion Adhesive small intestinal obstruction treated with blind insertion of a nasal ileus catheter combined with continuous enteral nutrition is a safe and effective approach,making it worthy of promotion in clinical practice.

Objective To investigate the efficacy of treating adhesive small intestinal obstruction using blind insertion of a nasal ileus catheter in combination with continuous enteral nutrition.Methods The data of patients with adhesive small intestinal obstruction admitted to our department from January 2022 to December 2023 were retrospectively collected.Group A was treated with blind insertion of a nasal jejunal decompression catheter,whereas Group B was managed with a nasogastric tube.Continuous enteral nutrition was initiated after the resolu-tion of intestinal obstruction in both groups.The nutritional indices,abdominal improvement,inflammatory markers,and complication rates were compared between the two groups before and after treatment.Results In terms of nutritional indices,the scores for Alb,Pa,and NRS2002 in Group A were significantly higher than those in Group B on the 7th day(P<0.05).Regarding abdominal improvement indices,Group A demonstrated significantly better outcomes than Group B in daily average decompression drainage volume,daily average reduction in abdominal circumference,relief time for abdominal distension and pain,recovery time for exhaust,defecation,time to resump-tion of enteral nutrition,and total hospitalization duration(P<0.05).Concerning inflammatory indices,CRP,IL-6,and WBC levels in Group A were significantly lower than those in Group B on both the 4th and 7th days post-treatment(P<0.05).With regard to complications,Group A exhibited fewer cases of EN intolerance,reflux,and conversion due to conservative treatment ineffectiveness compared to Group B(P<0.05).Conversely,Group B had fewer instances of water and electrolyte imbalance compared to Group A(P<0.05).Conclusion Adhesive small intestinal obstruction treated with blind insertion of a nasal ileus catheter combined with continuous enteral nutrition is a safe and effective approach,making it worthy of promotion in clinical practice.

Objective To explore the correlations of spatial distribution frequency map of posterior reversible encephalopathy syndrome(PRES)and cerebral microvascular density map,cerebral blood flow(CBF)map,standard template of cerebral metabolic imaging and the spatial gene transcription map of human brain based on normative analysis strategy,and to analyze the pathophysiological mechanisms of PRES.Methods Cerebral MRI data of 184 patients with PRES were retrospectively analyzed.ROI of the lesions were delineated on T1WI,then registered to Montreal Neurological Institute(MNI)standard space.The spatial distribution frequency map of PRES lesions were obtained with superposition.Spatial correlation analysis were performed to observe correlations of spatial distribution frequency map of PRES and the cerebral microvascular density map,CBF map and standard template of cerebral metabolic imaging based on large sample.The potential related gene expressions were decoded based on gene expression data of Allen human brain atlas,and the correlations of spatial parts of PRES and those expressions were observed.Results No significant correlation was found between spatial distribution frequency map of PRES and cerebral microvascular density,CBF nor distribution of neurotransmitters(all P＞0.05).PLS1 weighted genes,VEGF-A gene,AQP-4 gene and RGS2 gene were all correlated with spatial distribution of PRES(r=-0.363-0.653,all P＜0.05),among which KCNAB3 gene had the highest weight(Z=17.288).Conclusion The spatial patterns of PRES risk or protective genes in brain regions were correlated with regional distribution of PRES lesions,which was consistent with arginine vasopressin(AVP)theory of the occurrence and development of PRES.

Objective To establish a hydraulic system model of the aqueous humor circulation in the human eye and explore the characteristics of aqueous humor flow and intraocular pressure changes under various types of glaucoma and surgical conditions.Methods A hydraulic system model of aqueous humor circulation was constructed using AMESim software based on ocular structural parameters to simulate the fluid dynamics of aqueous humor in three types of glaucoma and their surgical interventions.Results Significant elevation in intraocular pressure was observed with pathological changes such as trabecular meshwork obstruction,anterior chamber angle contraction,and narrowing of the iris-lens gap.Through simulations of surgical interventions,including trabeculectomy,iridectomy,and ciliary body ablation,aqueous outflow resistance was effectively reduced,leading to a controlled intraocular pressure.Conclusions By successfully simulating both the pathological conditions of glaucoma and the dynamic intraocular pressure changes under surgical interventions,the hydraulic system model accurately reflects the physiological characteristics of glaucoma.The model not only predicts the effects of therapeutic interventions,but also provides reliable simulation support for the diagnosis and optimization of treatment strategies for glaucoma.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

Objective To explore the expression and clinical significance of lysine oxidase (Lox) in primary lesion of esophageal carcinoma (ESCA) and bone metastasis lesion based on bioinformatics. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to screen for differentially expressed genes between ESCA and normal esophageal tissues. Follow-up information of patients with surgery for esophageal cancer in the Fourth Hospital of Hebei Medical University from January 2016 to December 2020 were screened, and the clinical materials of patients diagnosed as bone metastasis during the follow-up period were collected. Western blot was used to verify the expression of Lox in ESCA and normal esophageal tissues; immunohistochemical staining was used to detect the expression of Lox in human ESCA tissue and normal tissue; the impact of Lox expression on survival was explored by Kaplan-Meier curve and Cox regression. Results Through the analysis of ESCA data in GEPIA and TCGA databases, it was found that the expression of Lox in ESCA lesions was significantly higher than that in normal tissues (P<0.05); the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses found that Lox may be involved in the information conduction of various signaling pathways; the Western blot result showed that the expression of Lox in cancer tissue was higher than that in adjacent normal tissue (P<0.05); the analysis of follow-up data found that patients with high expression of Lox were more likely to have multiple bone metastases; survival analysis revealed that patients with high Lox expression had significantly shorter bone metastasis free survival and overall survival compared to patients with low Lox expression (P<0.05); Cox regression found that Lox was an independent risk factor for prognosis of patients with esophageal cancer bone metastasis. Conclusion Lox is highly expressed in ESCA and significantly related to clinical prognosis, which can be used as an effective target for the diagnosis and treatment of ESCA.

Objective:To explore potential biomarkers that can predict the clinical efficacy of PD-1/PD-L1 inhibitors in malig-nancies.Methods:The PubMed,Web of Science,CNKI,Wanfang and VIP databases were searched from the establishment of the database to September 20,2022.After literature screening,data extraction and the risk of bias were evaluated independently by two evaluators,the Meta-analysis was performed using RevMan5.4 and STATA16.0 software.Results:This paper included 18 studies with a total of 4 018 patients.Tumor patients with a high tumor mutational burden(TMB)were found to have higher overall survival(OS)(P=0.003,P=0.01)and progression-free survival(PFS)(P=0.000 2,P=0.04)with PD-1/PD-L1 inhibitors within 1 year and 2 years of follow-up.At different follow-up times,with 1%as the critical value,there was no statistical significance in the level of PD-L1 ex-pression as a biomarker for predicting OS and PFS of PD-1/PD-L1 inhibitors(P>0.05).Conclusion:TMB can be used as a biological indicator to predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant tumors within 2 years after treatment,but whether its efficacy can last longer remains to be further studied.PD-L1 single test is not currently a biomarker for predicting the bene-fit of PD-1/PD-L1 inhibitors.