Objective To compare the midterm outcomes of the Bentall procedure versus isolated aortic valve replacement(AVR)in patients with bicuspid aortic valve(BAV)complicated with severe stenosis and ascending aortic dilation in order to assess the therapeutic value of these surgical approaches for this complex cardiac condition.Methods A retrospective cohort study was conducted on 96 eligible patients who underwent surgical treatment in our institute between January 2018 and December 2022.According to surgical approaches,they were divided into an AVR group(65 cases)and a Bentall group(31 cases).Demographic features,comorbidities,preoperative status,and echocardiographic parameters were collected in all patients.Propensity score matching(PSM)was applied in a 1:1 ratio to balance baseline characteristics.Perioperative indicators and follow-up data were compared and analyzed between matched cohorts after control of cofounding factors.Results After PSM,25 matched pairs were screened out and analyzed with comparable baseline data(all P>0.05).The Bentall group demonstrated significantly more superior intraoperative effective orifice area(EOA,2.69±0.47 vs 2.35±0.47 cm2,P=0.013)and EOA index(EOAI,1.69±0.30 vs 1.47±0.29 cm2/m2,P=0.010),and obviously longer cardiopulmonary bypass time[190.00(147.00,257.00)vs 101.00(88.50,124.50)min,P<0.01]and aortic cross-clamp time[141.00(120.00,166.00)vs 66.00(55.00,81.50)min,P<0.01]when compared with the AVR group.During a median follow-up of 28 months,the AVR group had notably larger aortic sinus diameter[32.00(30.00,34.00)vs 26.80(26.00,28.00)mm,P<0.01]and ascending aortic diameter[38.00(34.50,42.00)mm vs 26.00(26.00,28.00)mm,P<0.01],with ongoing dilation in the ascending aorta,while the Bentall group maintained stable dimensions.The Bentall group also showed statistically lower peak aortic valve pressure gradients[21.00(15.50,27.00)vs 25.00(19.50,31.00)mmHg,P=0.049].Conclusion Both Bentall procedure and AVR are effective in treatment of BAV complicated with severe stenosis and ascending aortic dilation.But,Bentall procedure offers advantages in hemodynamic optimization and aortic stability.

Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique that demonstrates great potential in treatment of neurological disorders due to its high spatial resolution and focused penetration ability, enabling millimetre-level precision modulation of specific brain regions with ultrasound to achieve neuromodulation of targeted areas. At present, numerous animal experiments and human studies have been carried out on the regulation of Alzheimer′s disease by TUS. In this review, the regulation effects of TUS on Alzheimer′s disease were introduced from the perspective of targeting different brain regions, including the hippocampus, frontal lobe and whole brain.

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.
Humans ; Neoplasms/metabolism* ; Cyclin-Dependent Kinases/antagonists & inhibitors* ; Cyclins/metabolism* ; Proteolysis ; Antineoplastic Agents/pharmacology* ; Molecular Targeted Therapy ; Proteasome Endopeptidase Complex/metabolism* ; Animals

To promote convergence education among national and international students, Nanjing Medical University designed an optional curriculum Two Sides of the Same Coin in Parasitic Diseases among international students for the Bachelor of Medicine and Bachelor of Surgery (MBBS) program, and a research-based teaching method was employed to teach 31 international students. This curriculum contained three parts, including parasitology-related knowledge, basic knowledge and skills of scientific research, and frontier topics in scientific research advances, and the assessment contents included course sign-in, classroom activity participation and scientific research presentation. Curriculum evaluation showed 100.0% (8/8) of students in batch 2018—2021, 81.8% (9/11) in batch 2022, and 83.3% (10/12) in batch 2023 with a total score of 80 points and higher, with median scores (interquartile range) of 91.1 (7.0), 90.8 (5.7) points and 90.8 (5.7) points, respectively (H = 0.04, P > 0.05). In addition, a questionnaire survey was performed with a Likert scale to assess the interests in curriculum learning, and the curriculum practicality and importance among 31 international students, and a total of 27 valid questionnaires were recovered, with a recovery rate of 87.1%. Questionnaire survey showed that the median total scores (interquartile range) were 7.0 (0.8) points among batch 2018—2021 students, 6.4 (1.4) points among batch 2022 students and 6.0 (1.1) points among batch 2023 students (H = 2.64, P > 0.05). Collectively, these data demonstrate that this optional curriculum improves the interests in parasitology learning of the international students for MBBS program, as well as their capability of self-directed learning, teamwork and innovative.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Colorectal cancer is one of the most common malignant tumors, which is a great threat to human life and health. The change of bile acid homeostasis can activate their corresponding receptors to regulate the immune functions, which is closely related to the occurrence of colorectal cancer. In addition, some bile acids can directly induce colorectal cancer and play an important role in the development of colorectal cancer. In this paper, the metabolic process of bile acids in vivo and the immunomodulatory role of bile acid receptors were reviewed, and the evidence of associations between bile acids and colorectal cancer were summarized, which showed the rebalancing the bile acid levels might play a role in the prevention or treatment of colorectal cancer.

Objective:To observe the clinical effect of subretinal injection and intravitreal injection of conbercept in the treatment of polypoid choroidal vasculopathy (PCV).Methods:A prospective, randomized double-blind controlled study. From June 2022 to January 2023, 35 patients of 35 eyes with PCV diagnosed at Affiliated Eye Hospital of Nanchang University were included in the study. All patients were first-time recipients of treatment. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), and indocyanine green angiography (ICGA) were performed in all affected eyes. BCVA was performed using an international standard visual acuity chart and converted to logarithmic minimum resolved angle (logMAR) visual acuity for statistical purposes. Enhanced depth imaging with OCT instrument was used to measure the macular retinal thickness (MRT), subfoveal choroidal thickness (SFCT), and pigment epithelium detachment (PED) height. Randomized numerical table method was used to divide the patients into subretinal injection group (group A) and vitreous cavity injection group (Group B), 18 cases with 18 eyes and 17 cases with 17 eyes, respectively. Comparison of age ( t=0.090), disease duration ( t=-0.370), logMAR BCVA ( t=?0.190), MRT ( t=0.860), SFCT ( t=0.247), and PED height ( t=?0.520) between the two groups showed no statistically significant difference ( P>0.05). The eyes of group A were given one subretinal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg), and subsequently administered on demand (PRN); eyes in group B were given intravitreal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg). The treatment regimen was 3+PRN. Lesions were categorized into active and quiescent according to the results of post-treatment OCT and BCVA. Active lesions were treated with intravitreal injection of conbercept at the same dose as before; stationary lesions were followed up for observation. BCVA and OCT were performed at 1, 2, 3, 6 and 9 months after treatment; ICGA was performed at 3, 6 and 9 months. BCVA, MRT, SFCT, and PED height changes before and after treatment were compared and observed in the affected eyes of the two groups. Independent sample t-test was used to compare between the two groups. Results:With the prolongation of time after treatment, the BCVA of the affected eyes in groups A and B gradually increased, and the MRT, SFCT, and PED height gradually decreased. Compared with group B, at 2, 3, 6, and 9 months after treatment, the BCVA of group A was significantly improved, and the difference was statistically significant ( t=?2.215, ?2.820, ?2.559, ?4.051; P<0.05); at 1, 2, 3, 6, and 9 months after treatment, the MRT of the affected eyes in group A ( t=?2.439, ?3.091, ?3.099, ?3.665, ?5.494), SFCT ( t=?3.370, ?3.058, ?3.268, ?4.220, ?4.121), and PED height ( t=?3.460, ?4.678, ?4.956, ?5.368, ?6.396) were significantly reduced, and the differences were statistically significant ( P<0.05). No complications such as intraocular inflammation, high intraocular pressure, or vitreous hemorrhage occurred in any of the affected eyes during or after treatment. Conclusion:Compared with the intravitreal injection of conbercept, the subretinal injection of conbercept can more effectively reduce the height of MRT, SFCT, PED height, and improve the visual acuity of the affected eyes with PCV.

Objective:To investigate the correlation between pre- and post-treatment changing trends in peripheral blood inflammatory markers and efficacy and their predictive value for prognosis in non-small cell lung cancer (NSCLC) patients treated with the first-line immunotherapy plus chemotherapy.Methods:The clinical data of NSCLC patients admitted to the Department of Radiation and Chemotherapy for Lung Oncology, Zhongnan Hospital of Wuhan University from October 2018 to May 2023 were retrospectively analyzed. The χ2 test was used to analyze the correlation between the changing trend of peripheral blood inflammatory markers and the efficacy of immunotherapy plus chemotherapy. The influencing factors of objective response rate (ORR) were assessed using binary logistic regression analysis. Kaplan-Meier survival curve and Cox proportional hazards model were used to analyze the prognostic value of the changing trend of peripheral blood inflammation markers on patients' prognosis. Results:A total of 102 NSCLC patients treated with first-line immunotherapy plus chemotherapy were included. The proportion of patients with bone metastases was higher in the lymphocyte to monocyte ratio (LMR) decreased group ( n=50) than that in the increased group ( n=52) ( χ2=4.28, P=0.039), whereas the pathological type of patients in the platelet to lymphocyte ratio (PLR) decreased group ( n=51) was more common in squamous carcinoma compared to patients in the increased group ( n=51) ( χ2=18.99, P<0.001), and a higher proportion of patients in the prognostic nutritional index (PNI) decreased group ( n=46) was female than that in the increased group ( n=56) ( χ2=4.29, P=0.038), with statistically significant differences. The 2-cycle objective response rate (ORR) of patients in the LMR increased and decreased groups was 63.5% (33/52) and 44.0% (22/50) ( χ2=3.89, P=0.049), the 2-cycle ORR of patients in the neutrophil to lymphocyte ratio (NLR) increased ( n=24) and decreased ( n=78) groups was 29.2% (7/24) and 61.5% (48/78) ( χ2=7.74, P=0.005), and the 2-cycle ORR for patients in the systemic immune inflammatory index (SII) increased group ( n=27) and decreased group ( n=75) was 33.3% (9/27) and 61.3% (46/75) ( χ2=6.26, P=0.012), with statistically significant differences. Multivariate analysis showed that the changing trend of inflammatory markers in peripheral blood were not related to ORR. The Kaplan-Meier survival curve indicated that patients in the group with SII decreased had longer median progression-free survival (PFS) (not reached vs. 7.1 months, χ2=9.35, P=0.002) and median overall survival (OS) (not reached vs. 16.6 months, χ2=11.08, P<0.001) than those in the SII increased group, and patients in the NLR decreased group had longer median OS (not reached vs. 22.2 months, χ2=4.56, P=0.033) than that in the NLR increased group. Univariate analysis suggested that both brain and bone metastasis ( HR=4.04, 95% CI: 1.23-13.35, P=0.022), increased SII ( HR=2.83, 95% CI: 1.41-5.66, P=0.003) were found to be significant factors affecting the PFS of NSCLC patients, both brain and bone metastasis ( HR=3.47, 95% CI: 1.05-11.45, P=0.041), increased NLR ( HR=2.17, 95% CI: 1.05-4.51, P=0.037) and increased SII ( HR=3.12, 95% CI: 1.54-6.30, P=0.002) were found to be significant factors affecting the OS of NSCLC patients. Multivariate analysis demonstrated that both brain and bone metastasis ( HR=4.32, 95% CI: 1.30-14.40, P=0.017) and increased SII ( HR=2.89, 95% CI: 1.44-5.81, P=0.003) were independent risk factors for PFS in NSCLC patients, both brain and bone metastasis ( HR=3.76, 95% CI: 1.13-12.50, P=0.031) and increased SII ( HR=3.47, 95% CI: 1.28-9.41, P=0.014) remained independent risk factors for OS in patients with NSCLC. Conclusion:The changing trend of peripheral blood inflammatory markers of NSCLC patients cannot independently predict the efficacy of 2-cycle immunotherapy plus chemotherapy. Both brain and bone metastasis, as well as the changing trend of SII can be used as important indicators to predict PFS and OS in advanced NSCLC patients treated with first-line immunotherapy plus chemotherapy. The simultaneous occurrence of brain and bone metastasis and SII increased suggest poor prognosis of NSCLC patients.

Purpose/Significance To probe into the role and the realization path of hospital library in proof-of-concept,and to provide references for proof-of-concept service of library and improving the effectiveness of proof-of-concept.Method/Process Through literature research,the influencing factors,process steps,potential problems and impact of proof-of-concept on the transfor-mation of results are expounded.The proof-of-concept model is constructed according to the logic of"cause and effect",the main role and derivative role of library are discussed in combination with resource and service elements,and the corresponding library functions in the derivative role are explored and the realization path of library in the proof-of-concept is expounded.Result/Conclusion Proof-of-concept is an important means to accelerate the transformation of scientific and technological achievements.Hospital library mainly plays four roles in proof-of-concept,such as activation of driving factors,and can promote the implementation of proof-of-concept around six functions,such as collection construction,cultural construction,collaborative management,etc.

Objective To analyze the safety and efficacy of neuroendoscopic minimally invasive surgery and traditional extraventricular drainage in the treatment of severe hypertensive intraventricular hemorrhage.Methods The clinical data of 50 cases with neuroendoscopic ventricular hematoma evacuation(endoscopy group)and 44 cases with traditional ventricles external puncture drainage(drainage group)from July 2020 to July 2023 were retrospectively analyzed,and the hematoma clearance rates,classification of activities of daily living(ADL)scale,incidence of hydrocephalus,secondary bleeding,intracranial infection,and pulmonary infection were observed between the two groups of patients.Results After surgery,the proportion of patients with hematoma clearance rate>60％and ADL grades Ⅰ,Ⅱ,and Ⅲ in the endoscopy group were significantly higher than those in the drainage group[the proportion of patients with hematoma clearance rate>60％:88.0％(44/50)vs.47.7％(21/44),χ2=17.794,P<0.001;the proportion of individuals with ADL grades Ⅰ,Ⅱ,and Ⅲ:94.0％(47/50)vs.77.3％(33/44),respectively,χ2=5.459,P=0.019],the incidence of complications in endoscopy group was significantly lower in the drainage group[8.0％(4/50)vs.34.1％(15/44),χ2=9.879,P=0.002].Conclusion Compared with traditional ventricular puncture drainage surgery,neuroendoscopic minimally invasive surgery for the treatment of severe hypertensive intracerebral hemorrhage with ventricular casting can achieve better treatment outcomes,a higher hematoma clearance rate,and fewer postoperative complications.