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 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 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.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

Objective To study the clinical significance of globus pallidus signal intensity and the intensity ratio of globus pallidus and putamen (G/P ratio) on magnetic resonance T1WI for the early recognition of neonatal bilirubin encephalopathy.Method From January to December 2017,full-term neonates with hyperbilirubinemia admitted to the neonatology department of our hospital were enrolled in the case group,and full-term neonates without hyperbilirubinemia in the control group.The clinical data,globus pallidus T1WI signal intensity,G/P ratio and the follow-up data were collected.According to the level of hyperbilirubinemia,the neonates in the case group were further assigned into mild hyperbilirubinemia group (serum bilirubin:222 to ＜256 μmol/L),moderate hyperbilirubinemia group (serum bilirubin:256 to ＜342 μmol/L),and severe hyperbilirubinemia group (serum bilirubin:≥ 342 μmol/L).According to the injury score of ABE,the neonates with ABE were assigned into mild ABE group,moderate ABE group and severe ABE group.The correlation of globus pallidus T1WI and T2WI signal values,G/P ratio and the serum bilirubin level and ABE degree were analyzed;receiver operating characteristic (ROC) curve was drawn to explore the predictive value of the T1WI signal value and G/P ratio for the diagnosis of ABE;the changes of globus pallidus T1WI and T2WI signal values during the first 6 months after birth and the results of follow-up to 1 year after discharge were also analyzed.Result A total of 175 neonates were included in the case group (65 in the mild hyperbilirubinemia group,71 in the moderate hyperbilirubinemia group and 39 in the severe hyperbilirubinemia group) and 43 neonates in the control group.39 neonates were diagnosed as ABE (21 mild ABE,12 moderate ABE,and 6 severe ABE).The first T1WI signal value and G/P ratio of neonates in the severe hyperbilirubinemia group was higher than the moderate hyperbilirubinemia group,the mild hyperbilirubinemia group and the control group;the T1WI signal value and G/P ratio in the moderate hyperbilirubinemia group was higher than the mild hyperbilirubinemia group and the control group (P ＜ 0.05).No significant difference existed between the mild group and the control group(P ＞ 0.05).T2WI values showed no differences among neonates with different bilirubin levels (P ＞ 0.05).The first T1WI signal value and G/P ratio in the severe ABE group were significantly higher than the moderate and mild ABE group,and the moderate ABE group higher than the mild ABE group (P ＜ 0.05).The ROC curve indicated the optimal cut-off value of T1WI signal and G/P ratio were 628 and 1.38,respectively.Among all the 175 neonates,9 had a decrease in T1WI signal value and an increase in T2WI signal value at 6 months after birth.After 1 year of follow-up visits,7 children were finally diagnosed as chronic bilirubin encephalopathy.All these children had increased signal intensity on T1WI in the acute phase,plus a decreased T1WI signal and an increased T2WI signal in 1 ～ 6 months after birth.Conclusion The globus pallidus T1WI signal and G/P ratio are closely related to the serum bilirubin level and ABE severity.If T1WI signal value ＞ 628 or G/P value ＞ 1.38,ABE should be considered.The T1WI signal value and G/P ratio play important roles as indicators for the early recognition of neonatal bilirubin encephalopathy.

Objective To evaluate the efficacy of ultrasound guided transversus abdominis plane block for elderly herpetic neuralgia located in anterior abdominal wall.Methods A total of 112 elderly patients aged 65-75 years with less than 30 days of herpes zoster neuralgia located in anterior abdominal wall were enrolled for receiving a treatment of transversus abdominis plane block.Patients were randomly allocated into two groups:the control group (n =56) taking gabapentin and celebrex,and the observation group (n =56)receiving transversus abdominis plane block (three times per week for two weeks) as add on therapy to gabapentin and celebrex.Morphine 10 mg was ready for oral application in breakthrough pain.Pain was evaluated by McGill scores assessed by short-form of Mcgill pain questionnaire(SF-M PQ)and visual analogue scale(VAS)before(T0)and after 1 (T1)and 2 weeks(T2)of transversus abdominis plane block,and 1 (T3)and 8(T4)weeks after end of the treatment.Pain relief(PAR)was calculated by the formula:PAR=(VAS score before block-VAS score after block)/ VAS score before block × 100％.The morphine consumption and sleep quality were observed during the treatment and 1 week after treatment.Analgesic efficacy was graded 8 weeks after end of treatment.The effective rate and good response rate were calculated.Incidences of complications were recorded.Results There was no significant difference in the VAS score between the two groups before treatment(t =0.419,P ＞0.05),while VAS scores after treatment were lower in the observation group than in the control group(t =17.925,19.662,12.580 and 13.987,respectively,P＜0.05).Before treatment,there was no significant difference in the total score of McGill between the two groups(t =0.544,P＞0.05).After treatment,the total scores of McGill were lower in the observation group than in the control group(t =18.612,20.135,13.213 and 12.356,respectively,P ＜0.05).The pre-therapy scores of sleep quality after treatment were decreased in the observation group as compared with the control group(t =7.798,9.545,10.335 and 16.318,respectively,P ＜0.05).Before treatment and at different time points of T1,T2,T3,T4,the morphine consumptions were not significant different between two groups(t =1.939,P＞0.05).While after treatment,the morphine consumptions were decreased in the observation group versus in the control group(t =22.341,16.758,17.827,15.541 respectively,P ＜0.05).No punctures of abdominal cavity,chest cavity,internal organs or blood vessels by mistake occurred.Conclusions Ultrasound-guided transversus abdominis plane block is effective and has less adverse reactions in treating herpetic neuralgia located in anterior abdominal wall.

OBJECTIVE:To evaluate clinical efficacy of Angong niuhuang pill combined with chemical drug in the treatment of severe craniocerebral injury and its effect on the concentration of Mg2+ in peripheral blood,and to provide evidence-based reference in clinic.METHODS:Retrieved from Chinese Journal Full-text Database,China Science and Technology Journal Database,China Bxdxiology Medicine disc,Wanfang Database,Chinese Clinical Trial Registry,PubMed,Excerpta Media Database,The Cochrane Library,Web of Science,Clinical Trials,and related literatures of intemet searched by Google Scholar,randomized controlled trials (RCT) about Angong niuhuang pill combined with chemical drug (trial group) vs.chemical drug (control group) in the treatment of severe craniocerebral injury and its effects on the concentration of Mg2+ in peripheral blood were collected.After literature screening,data extraction,quality evaluation with modified Jadad scale,meta-analysis of Glasgow Coma Scale (GCS) scores and Mg2+ concentration in peripheral blood were conducted by using Rev Man 5.3 statistical software after 7 d of treatment.RESULTS:A total of 6 RCTs were included,involving 773 patients.Results of meta-analysis showed that GCS [MD=2.87,95％CI (1.64,4.10),P＜0.01] and Mg2+ concentration in peripheral blood [MD=0.11,95％CI(0.06,0.16),P＜0.01] of trial group were significantly higher than those of control group,with statistical significance.CONCLUSIONS:Therapeutic efficacy of Angong niuhuang pill combined with chemical drug is better than that of chemical drug alone in the treatment of severe craniocerebral injury,can improve clinical symptom and prognosis.

OBJECTIVE:To provide reference for pharmacy staff to choose different drug label databases according to different needs.METHODS:The information organization mode of the three open access drug label databases that included Drugs@FDA,FDA Online Label Repository and DailyMed had been collected and analyzed comparatively from three aspects:retrieval function settings,search results display,data resources and service targets.RESULTS & CONCLUSIONS:In respect of retrieval function,DailyMed provided the most abundant retrieval functions than others.In respects of search results display,DailyMed provided the highest degree of formatted data,followed by FDA Online Label Repository,while Drugs@FDA provided semi-formatted data.Three databases provided the functions of page replication and printing,among which the interface of DailyMed was friendlier and the content of DailyMed was more open;it provided all the download functions.In respects of data resources and service targets,developers of Drugs@FDA and FDA Online Label Repository were FDA,and that of DailyMed was National Library of Medicine (NLM).The data sources used by Drugs@FDA were the drug labels after strict approval by FDA,and the description of drug information by Drugs@FDA was the most comprehensive.FDA Online Label Repository was the original drug labels submitted by the manufacturer to FDA,which was the latest content,and even included unlisted drugs.The data sources of DailyMed were from the information listed on the drug package,and included the information of drug label which was listed but not approved strictly;it covered most comprehensive drugs.