Objective To investigate the efficacy and safety of the Corheart 6 left ventricular assist system in patients with end-stage heart failure. Methods A retrospective study was conducted on patients with end-stage heart failure who were treated with Corheart 6 left ventricular assist system from March 2022 to June 2024 in 4 hospitals in Jiangsu Province. The efficacy of the device was evaluated by comparing changes in clinical indicators at preoperative, discharge, 3-month postoperative, and 6-month postoperative timepoints, including the New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic diameter (LVEDD). The safety of the device was assessed by analyzing the intraoperative position and orientation of the blood pump inlet cannula, as well as the incidence of adverse events. Results In this study, 39 patients were collected, including 34 males and 5 females with a mean age of (56.4±12.5) years, ranging from 20 to 75 years. There was no operative death. There was no death in postoperative 3 months with a survival rate of 100.0%. There were 3 deaths in 6 months postoperatively, with a survival rate of 92.3%. All patients had a preoperative NYHA cardiac function classification of class Ⅳ. The NYHA cardiac function class of the patients improved (P<0.05) at discharge, 3 and 6 months after surgery when compared to the preoperative period. LVEF was significantly higher at 3 months after surgery than that during the preoperative period (P<0.05). LVEDD was significantly smaller at discharge, 3 and 6 months after surgery than that during the preoperative period (P<0.05). The safety evaluation's findings demonstrated that all 39 patients' intraoperative blood pump inlet tubes were oriented correctly, the artificial blood vessel suture sites were appropriate, there were no instances of device malfunction or pump thrombosis, or instances of bleeding or hemolysis, and the rate of the remaining adverse events was low. Conclusion With a low rate of adverse events and an excellent safety profile, the Corheart 6 left ventricular assist system can efficiently enhance cardiac function in patients with end-stage heart failure. It also has considerable clinical uses.

Three soil conditioners were prepared from granulated food waste and decomposed cattle manure combined with desulfurization gypsum, coal gangue, and maifanite, respectively. Field trials were conducted in the saline field growing Cabernet Sauvignon. The effects of soil conditioners on rhizospheric bacterial communities were studied, with the aim of providing a scientific basis for soil amelioration and restoration. Five treatments were designed, including the control (T1), conventional fertilization (T2), reduced chemical fertilization+organic matter-based soil conditioner with calcium additives (T3), reduced chemical fertilization+organic matter-based soil conditioner with silica additives (T4), and reduced chemical fertilization+organic matter-based soil conditioner with magnesium additives (T5), each with three replications. The results indicated that soil conditioners improved the rhizospheric nutrients, yield, and quality of grape (P<0.05), increased relative abundance of Proteobacteria by 17.32%-23.37%, decreased relative abundance of unidentified_Bacteria and Acidobacteriota by 4.22%-28.42% and 20.88%-35.81%, respectively. The bacterial community composition and diversity were different between treatments. Function analysis showed that the expression levels of the genes involved in chromosome and protein synthesis, mRNA biosynthesis, and glyoxylate and dicarboxylate metabolism were up-regulated in the treatments with soil conditioners. The correlation analysis revealed that multiple environmental factors affected the alpha diversity of rhizospheric bacterial communities, and some bacterial taxa were closely related to the grape yield and quality. It is concluded that soil conditioners can effectively alter rhizosphere nutrient levels and bacterial community structures and functions. T5 treatment outperforms other treatments in improving the physico-chemical and biological characteristics of rhizosphere, and the yield, and quality of grape. It has potential for application, and provides an important basis for development of new-type soil conditioners.
Soil Microbiology ; Rhizosphere ; Soil/chemistry* ; Vitis/microbiology* ; Fertilizers ; Bacteria/growth & development* ; Cattle ; Manure ; Animals

Objective To explore the analgesic role of esketamine combined with ultrasound-guided nerve block after thoracoscopic radical operation for non-small cell lung cancer(NSCLC).Methods 130 NSCLC patients who were scheduled to undergo thoracoscopic radical resection of lung cancer in this hospital from February 2022 to December 2023 were selected and randomly divided into a conventional group and an observation group,with 65 cases in each group.The conventional group received postoperative conventional analgesia and ultrasound-guided nerve block,while the observation group added esketamine on this basis.The visual analogue scale(VAS)scores,pain mediators[dopamine(DA),substance P(SP),and 5-hydroxytryptamine(5-HT)],stress response indicators[norepinephrine(NE),cortisol(Cor),and prostaglandin E2(PGE2)]and adverse reactions of the two groups of patients were compared.Results There were statistically significant differences in the intergroup and time effects of the VAS scores after surgery between the two groups of patients(P<0.05),but there was no statistically significant difference in the interaction effect(P>0.05).When the time factor was controlled for comparison,the VAS scores of the observation group at 6,12 and 24 h after the operation were significantly lower than those of the control group,and the differences were statistically significant(P<0.05).When controlling for the group factors,the VAS scores of both groups of patients showed a trend of first increasing and then decreasing over time,and the differences at each time point were statistically significant(P<0.05).The comparisons of the intergroup and time effects of DA,5-HT,SP,NE,Cor and PGE2 levels between the two groups of patients showed statistically significant differences(P<0.05),but the comparison of the interaction effect showed no statistically significant difference(P>0.05).When the time factor was controlled for comparison,the levels of DA,5-HT,SP,NE,Cor and PGE2 in the observation group 24 h after the operation were significantly lower than those in the control group,and the differences were statistically significant(P<0.05).When controlling for the group factors,the levels of DA,5-HT,SP,NE,Cor and PGE2 in the two groups showed a trend of first increasing and then decreasing over time,and the differences at each time point were statistically significant(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups of patients(P>0.05).Conclusion The application of esketamine combined with ultrasound-guided nerve block for postoperative analgesia after thoracoscopic radical resection of NSCLC can effectively alleviate postoperative pain and stress response,and does not increase the risk of adverse reactions.It is worth applying in clinical practice.

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 design and synthesize dual-target antidepressant compounds possessing high-affinity binding to the serotonin 1A receptor(5-HT1A)and dual-site synergistic inhibition of the serotonin transporter(SERT).Methods Based on a dual-target synergistic mechanism,benzodioxolane derivatives were designed via scaffold hopping strategy before being synthesized.Their binding affinities to both targets were determined via competitive radioligand binding assays,and their binding modes were investigated using molecular docking.Results Eleven structurally novel target compounds were synthesized and structurally characterized by electrospray ionization mass spectrometry(ESI-MS)and nuclear magnetic resonance(NMR)spectroscopy.Compound 18b demonstrated dual nanomolar affinity for both the 5-HT1A receptor(Ki=2.72 nmol/L)and SERT(Ki=8.85 nmol/L).Molecular docking revealed that its inhibitory effect on SERT resulted from simultaneous occupation of the orthosteric site S1(Asp98 salt bridge)and the allosteric site S2(Arg104 rr-cation interaction),while its high affinity for 5-HT1A depended on the Asp116332 salt bridge anchor and π-π stacking with Phe362652.Conclusion The benzodioxolane-scaffold compounds designed and synthesized in this study exhibited functional synergy between simultaneous occupation of both the S1 and S2 sites of SERT and high-affinity binding to the 5-HT1Areceptor.Among them,compound 18b demonstrates superior activity and promises to be a lead compound for more investigation.

Objective To explore the analgesic role of esketamine combined with ultrasound-guided nerve block after thoracoscopic radical operation for non-small cell lung cancer(NSCLC).Methods 130 NSCLC patients who were scheduled to undergo thoracoscopic radical resection of lung cancer in this hospital from February 2022 to December 2023 were selected and randomly divided into a conventional group and an observation group,with 65 cases in each group.The conventional group received postoperative conventional analgesia and ultrasound-guided nerve block,while the observation group added esketamine on this basis.The visual analogue scale(VAS)scores,pain mediators[dopamine(DA),substance P(SP),and 5-hydroxytryptamine(5-HT)],stress response indicators[norepinephrine(NE),cortisol(Cor),and prostaglandin E2(PGE2)]and adverse reactions of the two groups of patients were compared.Results There were statistically significant differences in the intergroup and time effects of the VAS scores after surgery between the two groups of patients(P<0.05),but there was no statistically significant difference in the interaction effect(P>0.05).When the time factor was controlled for comparison,the VAS scores of the observation group at 6,12 and 24 h after the operation were significantly lower than those of the control group,and the differences were statistically significant(P<0.05).When controlling for the group factors,the VAS scores of both groups of patients showed a trend of first increasing and then decreasing over time,and the differences at each time point were statistically significant(P<0.05).The comparisons of the intergroup and time effects of DA,5-HT,SP,NE,Cor and PGE2 levels between the two groups of patients showed statistically significant differences(P<0.05),but the comparison of the interaction effect showed no statistically significant difference(P>0.05).When the time factor was controlled for comparison,the levels of DA,5-HT,SP,NE,Cor and PGE2 in the observation group 24 h after the operation were significantly lower than those in the control group,and the differences were statistically significant(P<0.05).When controlling for the group factors,the levels of DA,5-HT,SP,NE,Cor and PGE2 in the two groups showed a trend of first increasing and then decreasing over time,and the differences at each time point were statistically significant(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups of patients(P>0.05).Conclusion The application of esketamine combined with ultrasound-guided nerve block for postoperative analgesia after thoracoscopic radical resection of NSCLC can effectively alleviate postoperative pain and stress response,and does not increase the risk of adverse reactions.It is worth applying in clinical practice.

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.

In the view of conventional Chinese medicine,Parkinson's disease(PD)is usually caused by yin deficiency of the liver and kidney,hyperactivity of yang stirring up wind.Nevertheless,in modern clinic of Chinese medicine,the patients with PD may also have the manifestations of motor symptoms such as static tremor,rigidity and bradykinesia,and suffer non-motor symptoms such as constipation,insomnia,olfactory disorders and apathia,probably accompanied by cold body and limbs,puffiness of face and dropsy of limbs,soreness and coldness of the lumbar and knee,and may also exert tongue manifestations of pale and swollen tongue with tooth marks,white coating,and pulse condition of a late,feeble and slow pulse.Under these conditions,the pathogenesis of PD can be considered as the insufficiency and uneven distribution of yang qi,treatment of PD can be performed from the perspective of yang deficiency,and the therapy of warming yang to transform qi can be adopted.This paper discusses the application of therapy of warming yang to transform qi in the treatment of PD,and expands the approach to the treatment of PD with Chinese medicine.

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 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.