Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Purpose To explore the feasibility of prenatal MRI as a supplementary imaging examination of fetal multicystic dysplastic kidney(MCDK),and to improve the accuracy of imaging diagnosis.Materials and Methods The MR images of 104 fetuses diagnosed as MCDK by prenatal fetal MRI in Hubei Maternal and Children's Hospital from January 2018 to December 2021 were retrospectively analyzed.The results of fetal MRI were compared with those of autopsy or postnatal surgery,ultrasound and MRI,and the diagnostic accuracy of MRI and ultrasound was compared,respectively,the advantages of MRI combined with ultrasound in the diagnosis of MCDK was also analyzed.Results Among 104 fetuses diagnosed as MCDK by MRI,there were 102 cases with MCDK and 2 cases with misdiagnoses.Amniotic fluid was obviously reduced or absent in 4 cases.Among the 102 cases of MCDK,58 cases(56.9％)were correctly diagnosed as MCDK by ultrasound,40 cases(39.1％)were identified with polycystic alterations,without diagnosed as MCDK,and 4 cases(3.9％)were misdiagnosed as other diseases(1 case with adult polycystic kidney,1 case with multiple renal cyst and 2 cases with renal absence).Conclusion Compared with prenatal ultrasound,prenatal MRI can obtain more information,especially in oligohydramnios and maternal obesity affecting the quality of ultrasound image.MRI can be used as a reliable supplementary method of prenatal ultrasound.

This study summarized the nursing experience of 2 pediatric heart transplant surgeries.Perioperative care included preoperative maintenance of cardiac function,volume management,infection prevention measures,and psychological preparation.Early postoperative care involved circulatory monitoring,management of right heart dysfunction,use of immunosuppressants,observation of rejection reactions,control of postoperative infections,nutritional support,psychological care,and home continuity care.The postoperative rehabilitation effect of the children is satisfactory after multi-team special treatment and nursing care.The postoperative hospitalization time for the 2 patients were 20 and 30 days.After discharge,2 patients showed good recovery during follow-up.

Objective:To explore the effectiveness of applying the ADDIE (analysis, design, develop, implement, evaluate) Model in clinical teaching for nursing interns in spine surgery department.Methods:Using a convenience sampling method, 44 nursing interns in the Department of Orthopedics at Peking Union Medical College Hospital were selected as the control group from July 2021 to May 2022, and were taught using traditional methods. From July 2022 to May 2023, 45 nursing interns were selected as the observation group, and a teaching team was formed to design a training program based on the five stages of the ADDIE instructional design model. This program was tailored to improve the overall clinical competence of the spinal surgery nursing interns. After training, the teaching effects were evaluated based on knowledge test scores, skills test scores, overall clinical competence, and teaching satisfaction.Results:After the training, the skills test scores in specialized nursing for the observation group were (94.87±1.10) points, higher than the control group's (93.98±1.41) points, with a statistically significant difference ( P<0.01). The observation group also scored higher than the control group in clinical judgment, organizational effectiveness, overall performance, and total score in the Mini-Clinical Evaluation Exercise, with statistically significant differences ( P<0.01). Additionally, the observation group reported higher satisfaction with the teaching plan and methods compared to the control group ( P<0.05) . Conclusions:Clinical teaching for spinal surgery nursing interns based on the ADDIE instructional design model can improve their specialized practical skills and overall clinical competence. The interns also expressed a high level of acceptance for this teaching design model.

Chemical constituents of n-butanol part of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied.Eight glycosides were separated and purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography.Based on the physicochemical properties and spectral data, these compounds were 3-ethyl-4-methyl-pentyl ester-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (1), juglanoside E (2), (4S)-α-terpineol-8-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (3), (4S)-α-terpineol-8-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (4), eugenyl-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucuronopyranosyl methylester (6), kaempferol-3-O-β-D-glucuronopyranoside (7), and quercetin-3-O-β-D-glucuronopyranoside (8).Among them, compound 1 was a new compound, and compounds 2-6 were isolated from the genus Cyclocarya for the first time.

Objective:To assess the clinical significance of next-generation sequencing (NGS)-based IGH/ IGK gene rearrangement analysis versus flow cytometry (FCM) in diagnosing minimal residual disease (MRD) of children with acute B-cell lymphoblastic leukemia (B-ALL). Methods:Clinical data, NGS-MRD and FCM-MRD findings at the initial diagnosis and after induction chemotherapy of 85 children diagnosed as B-ALL in Children′s Hospital of Nanjing Medical University from July 2019 to July 2021, were retrospectively analyzed.The sensitivity of the two methods, and the positive rate were compared by χ2 test or Fisher′ s test.The correlation was identified by Spearman correlation analysis. Results:Dominant clone sequences were detected in all children at the initial diagnosis by NGS, while selection markers were identified by FCM in 75(88.2%) patients.Positive MRD rate detected by NGS-MRD was significantly higher than that of FCM-MRD at the same time point after induction chemotherapy[31.8%(27/85) vs.9.4%(8/85), P<0.001]. Compared with those of FCM-MRD, NGS-MRD had good sensitivity (100.0%), specificity (75.3%) and negative predictive value (100.0%), and the positive predictive value was 29.6%.MRD results detected by NGS were consistent with that of FCM ( r=0.569, P<0.001). By July 27, 2022, 2 patients with NGS-MRD (+ )FCM-MRD (-)relapsed during maintenance chemotherapy. Conclusions:NGS is highly consistent with FCM in the detection of MRD in children with B-ALL, which is more sensitive.The combination of NGS-MRD and FCM-MRD benefits more in monitoring MRD in children with B-ALL after induction chemotherapy.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.

Objective:To explore the detection and segmentation of ischemic core infarct volume of the acute stroke in diffusion weighted imaging (DWI) images using cascaded VB-Net.Methods:MRI data of 1 500 patients (2 456 lesions) with acute ischemic stroke in Henan Provincial People′s Hospital from December 2016 to December 2018 were retrospectively analyzed. Firstly, manual segmentation of ischemic core was performed on DWI images (b=1 000 s/mm 2), and then all data were divided into training set, validation set and independent test set by 8∶1∶1. Then, the cascaded VB-Net was constructed, and the core infarct was automatically detected and segmented in the test set. Interclass correlation coefficient (ICC) was used to evaluate the consistency of volume size measured by manual segmentation and cascaded VB-Net. The patients were divided into large ischemic core lesion group (ischemic core volume ≥10 ml) and small ischemic core lesion group (ischemic core volume<10 ml), and the Dice coefficient difference between the two groups was compared using Mann-Whitney U test. Results:In independent test set, cascaded model had the detection rate of 94.6% (243/257) with Dice coefficient of 0.76 (0.68, 0.84). The agreement of cacade VB-Net segmented [4.19(1.21,14.13)ml] and manual segmented ischemic core infarct volume [4.08(1.19,17.92)ml] was high (ICC=0.97, P<0.001). There was no significant difference in Dice coefficient between large and small lesion groups [0.76 (0.69, 0.85), 0.76 (0.67, 0.84), Z=-0.44, P=0.657]. Conclusions:The cascaded VB-Net model provided a tool to realize automatic detection, segmentation, and calculation of ischemic core infarct volume. It has good segmentation accuracy and high consistency with manual segmentation, which can provide an auxiliary decision-making tool for the selection of treatment plans.