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 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 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 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.

Objective To discover 5-HT2A receptor antagonist molecules with novel structures and explore their structure-activity relationship through structure-and mechanism-based drug design,synthesis and activity evaluation.Methods The way in which pimovanserin interacted with 5-HT2A receptor was analyzed via molecular docking,molecular dynamics simulation and binding free energy calculations.Based on the results of this study,the 5-HT2A receptor antagonist target compounds with novel structures were designed using pimovanserin as the lead molecule.According to the structures of target compounds,corresponding synthetic routes were designed.The heterocyclic methylamine intermediates were obtained by reductive amination or reduction reaction from heterocyclic formaldehyde or heterocyclic methanonitrile before being reacted with 4-(4-fluorobenzylamino)-1-methylpiperidine to obtain the target compounds using CDI urea synthesis method.The inhibitory activity of the target compounds against 5-HT2A receptor was tested at the cellular level,and the anti-hallucinogenic effects of the target compounds were tested in the mouse head twitch response model.Results Twelvenovel compounds were synthesized and their structures were confirmed by HR-MS,1H-NMR and 13C-NMR.The results of the activity assay showed that compounds 6a,6c and 6d exhibited better 5-HT2Areceptor inhibitoryactivity with IC50 values of 120,152 and 285 nmol/L,respectively while compounds 6c and 6d exhibited better anti-hallucinogenic activity in mice with inhibition rates of 97.0％and 82.9％(10 mg/kg),respectively.Conclusion The novel compound 6c and 6d have shown strong 5-HT2A receptor inhibitoryactivity and anti-hallucinogenic activity and deserve more research.Structure-activity relationship analyses of target compounds indicate that the repulsion of the heterocyclic ring with basic N atoms and the accommodation of the heterocyclic ring without basic N atoms by the side extended pocket of the 5-HT2A receptor could significantly affect the ex vivo and in vivo effects of antagonists.

Objective To establish a mice model of atopic dermatitis with acute itching and investigate the antipruritic effect and its mechanism of Xiaofeng Zhiyang granules(XFZYG).Methods A mice model of atopic dermatitis was prepared by induction method.Mice were sensitized by calcipotriol and ovalbumin(OVA)applying to the right ear daily for 10 days,and then stimulated by OVA injected intradermally into the right cheek to resulting in acute itching.These mice were divided into 5 groups:blank control group,model group,low dose(7.2 g/kg)and high dose(14.4 g/kg)of XFZYG,and positive control group(montelukast 5 mg/kg).Drugs were administered by gavage at 12 h and 30 min before stimulation.The leukotriene levels in the serum of the mice were measured by Elisa and the basophil ratio and activation status in the blood were measured by flow cytometry.Results The mean number of scratches in the model group was 56 between 30 min and 60 min after stimulation,while the mean number of scratches in the low and high dose of XFZYG groups were 42 and 23 respectively,which were significantly lower than those in the model group(P<0.05).The serum leukotriene levels and the proportion of basophils in the low and high dose of XFZYG groups were significantly lower than those in the model group(P<0.05).Conclusion XFZYG had certain therapeutic effect on acute itching of atopic dermatitis in mice,and the mechanism of its action was related to the reduction of leukotriene level and basophil ratio in serum of mice with atopic dermatitis.

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 investigate the effects of upadacitinib on the polarization and inflammation of BV2 microglia after oxygen glucose deprivation/recovery (OGD/R) and to explore its mechanism of action. Methods The experiment was divided into 3 groups: control group, OGD group and upadacitinib treatment group. After BV2 cells were treated with OGD/R, MTT was used to detect cell survival rate. Wound scratch assay was used to detect the cell migration ability. qPCR was used to detect mRNA levels of M1-type polarization markers (CD11b, CD32, iNOS) and M2-type polarization markers (Arg-1, IL-10, CD206) of BV2 cells. ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in the culture medium. Western blot was used to detect the expression levels of JAK1/STAT6 pathway-related proteins. Results Upadacitinib increased the survival of BV2 cells after OGD/R (P<0.05), reduced the polarization of BV2 cells to M1 type (P<0.05). Upadacitinib significantly decreased the migration ability of BV2 cells induced by OGD/R (P<0.05), reduced the inflammatory factors secreted by BV2 cells induced by OGD/R: IL-1β, IL-6, TNF-α (P<0.05). Upadacitinib increased the survival rate of co-cultured PC12 cells (P<0.05). Upadacitinib significantly inhibited the expression levels of p-JAK1 and p-STAT6 proteins in BV2 cells activated by OGD/R induction (P<0.05). Conclusion Upadacitinib decreases polarization of BV2 induced by OGD/R to M1 type and reduces inflammation, which is related to JAK1/STAT6 pathway.

Objective To investigate the expression of immunophenotype in gastrointestinal stromal tumors and analyze its clinical value in the diagnosis and prognosis of gastrointestional stromal tumors.Methods Reviewed the clinical data of 323 patients with gastrointestinal stromal tumors in Fuzhou General Hospital of PLA from January 2004 to January 2014.Detected expressions of CD-117,DOG-1,CD-34,alpha-SMA,S-100.Desmin and Ki-67 by immunohistochemical S-P method,frequency statistics,independent sample t test and correlation analysis was carried out with SPSS 20.Results The positive rates of CD-117,DOG-1 and GIST in the group CD-34 were 97％,95.6％ and 86％ respectively,the positive rates of alpha-SMA,S-100 and Desmin were 59.8％,27.7％ and 17％ respectively,the positive expression of CD-117,CD-34,alpha α-SMA and Desmind in intestinal gastrointestinal stromal tumors and gastric gastrointestinal stromal tumors were significantly different,among them (P ＜ 0.05),the positive rates of gastrointestinal stromal tumors and alpha-SMA in intestinal CD-117 were significantly higher than those in gastric gastrointestinal stromal tumors (3.37 vs 2.99,P =0.002;1.59 vs 1.09 P =0.005).The positive expression of CD-34 and Desmin was significantly lower than that of gastric gastrointestinal stromal tumors (1.90 vs 3.02,P =0.000;0.12 vs 0.50,P =0.001).The expression of CD-117 was significantly correlated with location and risk grade (P =0.000,0.002).The expression of DOG-1 was significantly correlated with the risk grade,and the overall survival (P ＜0.05).The expression of CD-34 was significantly correlated with location,size,risk grade,status,and overall survival (P =0.000,0.007,0.016,0.001).There was a significant correlation between the expression of alpha-SMA and location (P =0.036).There was a significant correlation between the expression of S-100 and the overall survival (P =0.036).The expression of Desmin was significantly correlated with the age and location of the first visit (P =0.001).Conclusion In the diagnosis of gastrointestinal stromal tumors,CD-117,DOG 1 and CD-34 combined alpha-SMA and Desmin have good complementation,it is also helpful to judge the location of the intestine and stomach of gastrointestinal stromal tumors,if necessary,it can also be detected by gene mutation,with reference to the level of mitotic figures,which can reduce the misdiagnosis rate and increase the detection rate.

Objective To explore the life quality of postoperative patients after a hypertensive cerebral hem-orrhage in the basal ganglia and the factors influencing it, so as to provide evidence for improving the life quality of such patients. Methods A total of 128 patients were studied retrospectively. Their gender, age, occupation, mari-tal status, education level, place of residence and family size were tabulated, as well as whether or not they were liv-ing with their children, smoking or drinking alcohol. Their household income was recorded along with their clinical condition during surgery ( midline shift, blood loss, operative time, whether a hernia occurred, consciousness, and whether bleeding broke into the ventricles. The SF-36 health measurement scale was used to evaluate the patients′life quality, and the factors influencing it were analyzed. Results Univariate analysis showed that: ( 1) Their physio-logical functioning ( PF) and global health ( GH) were mainly affected by age, marital status, family size, midline shift, quantity of cerebral hemorrhage, occurrence of herniation, consciousness and whether the hemorrhage broke in-to the ventricles. (2) Their physiological role (RP) was influenced by marital status, education background, household monthly income, midline shift, consciousness and whether the hemorrhage broke into the ventricles. (3) Pain (BP) was mainly affected by marital status and family size. (4) Social functioning (SF) was closely related to marital status, family size, consciousness and whether hemorrhage broke into the ventricles. (5) Their mental health (MH) was main-ly affected by the amount of bleeding, whether they were living with their children, the operation′s duration and whether the hemorrhage broke into the ventricles. (6) Their emotions (RE) were influenced by their consciousness and whether bleeding broke into the ventricles. (7) Their vitality (VT) was affected by their marital status, smoking, consciousness and whether the bleeding broke into the ventricles. Multivariate analysis showed that whether the hemorrhage broke into the ventricles was the most influential factor. Family size was also influential. Conclusions Age, number of family members, whether they are living with their children, and whether hemorrhage broke into the ventricles are all influen-tial in predicting the life quality of survivors of hypertensive cerebral hemorrhage in the basal ganglia.