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 classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.

【Objective】 To study the blood group serology and molecular biology of patients with RhD--, so as to guide clinical blood use. 【Methods】 The EDTA-K2 anticoagulant blood of the patient was detected for Rh antigens and antibodies. Meanwhile, DNA was extracted, and the 1-10 exon of RHCE and RHAG gene was sequenced by Sanger sequencing. 【Results】 The serological test showed O type RhD--, and all spectral cells were positive. RHCE gene sequencing showed RHCE^*02/RHCE^*02, RHAG gene sequencing showed mutations at site 808 G > A and site 861 G > A of exon 6. 【Conclusion】 When patients were with RhD--, and related immune conditions such as pregnancy and/or transfusion history were present, autologous blood transfusion or plasma exchange could be an option for emergency blood use.

Objective:To investigate the postoperative complications and in-hospital mortality of reoperative cardiac surgery, and to explore the feasibility and safety of reoperative cardiac surgery.Methods:The baseline data and clinical information of patients undergoing cardiac surgery in Nanjing First Hospital from November 2012 to November 2021 were retrospectively conducted, and they were divided into the reoperative cardiac surgery group and the primary surgery group according to whether they underwent reoperative cardiac surgery using a propensity score analysis. The intraoperative indicators, postoperative complications and in-hospital mortality were compared between the two groups after matching.Results:After propensity score analysis, 146 cases were included in each of the group. In terms of intraoperative indicators, the cardiopulmonary bypass time [(141.48±47.88)min vs.(105.31±33.56)min], aortic occlusion time [87.0(70.5, 113.3)min vs. 71.5(53.0, 92.0)min], ICU stay time[2( 1, 4)days vs. 2(1, 2)days], postoperative drainage volume [750(460, 1300)ml vs. 610(410, 840)ml], postoperative transfusion of red blood cells [0(0, 3.5)U vs. 0(0, 2)U], the reoperative cardiac surgery group increased with statistically significant differences( P<0.05). Postoperative complications, the two groups had postoperative hypoxemia [15(10.3%) vs. 6(4.1%)], acute kidney injury [10(6.8%) vs. 0(0)], postoperative infection [24(16.4%) vs. 4(2.7%)], cerebral complications [7(4.8%) vs. 1(0.7%)] )], the incidence rate in the reoperative cardiac surgery group was higher with statistically significant differences( P<0.05). There was no significant difference in in-hospital mortality[7(4.8%) vs. 4(2.8%)]( P>0.05). Conclusion:The time of reoperative cardiac surgeryis is longer, postoperative recovery is slower, and postoperative complication rate is higher, but does not increase in-hospital mortality.

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.

Mice ; Animals ; Humans ; Disease Models, Animal

Cerebral hyperperfusion syndrome is a rare but potentially serious complication of cerebral revascularization,which occurs as a result of postoperative refractory hypertension and impaired cerebrovascular autoregulation. Cerebral hyperperfusion after balloon dilatation is prone to occur within the blood supply area of the offending vessel,rarely outside the offending vessel's supply area. This article presented a case of cerebral hyperperfusion syndrome outside the area treated with endovascular surgery.

Objective:To study the clinical value of blood neutrophil gelatinase-associated lipocalin (NGAL) in the early diagnosis and prognostic evaluation of late-onset sepsis in very/extremely low birth weight infants (VLBWI/ELBWI).Method:From January 2017 to December 2019, VLBWI/ELBWI older than 3 days admitted to NICU of our hospital were prospectively enrolled in the study. The infants were assigned into suspected-sepsis group and non-infection (control) group according to their clinical symptoms and laboratory indicators. In the suspected-sepsis group, complete blood count, C-reactive protein (CRP), procalcitonin (PCT) and blood culture were examined on the 1st day of disease onset and blood NGAL was examined on the 1st day of disease onset, 3rd day of treatment and 2nd week of treatment. In the control group, blood NGAL was examined at the time of enrollment. The suspected-sepsis group was later assigned into sepsis group and non-sepsis infection group and the sepsis group was further assigned into mild sepsis group and severe sepsis group according to the severity of the disease. Blood NGAL levels between the sepsis group and the non-sepsis infection group on the 1st day of onset and the control group were compared. The dynamic changes of NGAL in the sepsis group and the non-sepsis infection group at different time points were compared and analyzed. ROC curve of NGAL level on the first day of onset predicting sepsis was drawn.Result:(1) On the 1st day of disease, the sepsis group (n=106) had higher level of NGAL compared with non-sepsis infection group (n=121) and the control group (n=84). Non-sepsis infection group had significantly higher level of NGAL compared with the control group ( P<0.05). (2) A gradual decrease of NGAL was found in both sepsis and non-sepsis infection group. Significantly higher level of NGAL in sepsis group was found comparing with non-sepsis infection group at different time points ( P<0.05). (3) For blood culture positive and negative patients in the sepsis group, no statistically significant differences existed in NGAL,CRP, PCT levels on the 1st day of disease onset ( P>0.05).(4) The NGAL level in the severe sepsis group was significantly higher than the mild sepsis group on the 1st day of disease onset ( P<0.05). However,CRP and PCT showed no differences between the two groups. (5) On the 1st day of disease onset, to establish the diagnosis of sepsis, the area under the ROC curve of NGAL level was 0.852. The sensitivity and specificity of cut-off value 205.25 ng/ml were 84.0% and 66.9%, respectively. Conclusion:The serum NGAL level is elevated in VLBWI/ELBWI with late-onset sepsis. The more severe the sepsis,the more elevated the NGAL level. NGAL has certain predictive value for late onset sepsis in VLBWI/ELBWI.

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.