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 role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

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 clinical characteristics and prognosis of malignant melanoma (MM) in the Xinjiang Uygur Autonomous Region.Methods:We collected the clinical and follow-up data of 503 MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University between 2010 and 2022. The Kaplan-Meier method was employed for survival analysis, with Log rank test used for comparing the survival rates between groups. Cox regression analysis was conducted to identify the influencing factors of patient prognosis.Results:From 2010 to 2022, the number of MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University demonstrated an upward trend. Among the 503 MM patients, the primary tumor sites were located in the extremities in 264 cases, the skin in 155 cases, the mucosal in 49 cases, and the ocular uvea in 22 cases, and in 13 cases the primary lesion was unknown. The median follow-up duration was 44 months, with a median overall survival time of 44.0 months. The overall survival rates at 1, 3, and 5 years were 85.2%, 54.3%, and 42.1%, respectively. Univariate analysis revealed that age, Breslow thickness, Clark grading, presence of ulcers, lactate dehydrogenase (LDH) levels, clinical stage at initial treatment, tumor recurrence, distant metastasis (lung, liver, bone, or brain), and postoperative adjuvant therapy were all associated with overall survival in MM patients (all P<0.05). Multivariate Cox regression analysis revealed that age ( HR=1.022, 95% CI: 1.013-1.032), LDH level ( HR=1.696, 95% CI: 1.223-2.353), clinical stage at initial treatment (TxN0M0 vs stage Ⅱ: HR=0.255, 95% CI: 0.096-0.679; TxN0M0 vs stage Ⅲ: HR=0.293, 95% CI: 0.190-0.452; TxN0M0 vs stage Ⅳ: HR=0.414, 95% CI: 0.284-0.603), bone metastasis ( HR=2.032, 95% CI: 1.252-3.298), and postoperative adjuvant therapy ( HR=0.551, 95% CI: 0.426-0.713) are independent factors influencing the overall survival of MM patients. Stratified analysis by different subtype indicated that age, clinical stage at initial treatment, gene mutations, and postoperative adjuvant therapy usage are independent factors affecting the overall survival of patients with limb MM, while age and clinical stage at initial treatment are independent factors influencing the overall survival of patients with skin and mucosal MM. Conclusions:The number of MM patients in Xinjiang Uygur Autonomous Region may be on the rise. Age, LDH level, clinical stage at initial treatment, presence of bone metastasis, and postoperative adjuvant therapy are independent risk factors for the prognosis of MM patients. Among these, age and clinical stage at initial treatment are common independent risk factors that affect the prognosis of different subtypes of MM patients.

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 role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

Objective:To explore the clinical characteristics and prognosis of malignant melanoma (MM) in the Xinjiang Uygur Autonomous Region.Methods:We collected the clinical and follow-up data of 503 MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University between 2010 and 2022. The Kaplan-Meier method was employed for survival analysis, with Log rank test used for comparing the survival rates between groups. Cox regression analysis was conducted to identify the influencing factors of patient prognosis.Results:From 2010 to 2022, the number of MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University demonstrated an upward trend. Among the 503 MM patients, the primary tumor sites were located in the extremities in 264 cases, the skin in 155 cases, the mucosal in 49 cases, and the ocular uvea in 22 cases, and in 13 cases the primary lesion was unknown. The median follow-up duration was 44 months, with a median overall survival time of 44.0 months. The overall survival rates at 1, 3, and 5 years were 85.2%, 54.3%, and 42.1%, respectively. Univariate analysis revealed that age, Breslow thickness, Clark grading, presence of ulcers, lactate dehydrogenase (LDH) levels, clinical stage at initial treatment, tumor recurrence, distant metastasis (lung, liver, bone, or brain), and postoperative adjuvant therapy were all associated with overall survival in MM patients (all P<0.05). Multivariate Cox regression analysis revealed that age ( HR=1.022, 95% CI: 1.013-1.032), LDH level ( HR=1.696, 95% CI: 1.223-2.353), clinical stage at initial treatment (TxN0M0 vs stage Ⅱ: HR=0.255, 95% CI: 0.096-0.679; TxN0M0 vs stage Ⅲ: HR=0.293, 95% CI: 0.190-0.452; TxN0M0 vs stage Ⅳ: HR=0.414, 95% CI: 0.284-0.603), bone metastasis ( HR=2.032, 95% CI: 1.252-3.298), and postoperative adjuvant therapy ( HR=0.551, 95% CI: 0.426-0.713) are independent factors influencing the overall survival of MM patients. Stratified analysis by different subtype indicated that age, clinical stage at initial treatment, gene mutations, and postoperative adjuvant therapy usage are independent factors affecting the overall survival of patients with limb MM, while age and clinical stage at initial treatment are independent factors influencing the overall survival of patients with skin and mucosal MM. Conclusions:The number of MM patients in Xinjiang Uygur Autonomous Region may be on the rise. Age, LDH level, clinical stage at initial treatment, presence of bone metastasis, and postoperative adjuvant therapy are independent risk factors for the prognosis of MM patients. Among these, age and clinical stage at initial treatment are common independent risk factors that affect the prognosis of different subtypes of MM patients.

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 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.