To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective:To investigate the clinical features and risk factors of second asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL).Methods:In this case-control study, the clinical data of ALL children who were diagnosed with pancreatitis and received asparaginase chemotherapy at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from November 2013 to November 2023 were retrospectively analyzed.Multivariate Logistic regression was used to determine independent risk factors for the occurrence of second AAP.Results:A total of 78 children with AAP were included, of whom 32 were re-exposed to asparaginase.Ten of the 32 cases (31.25%) suffered second AAP, and they were rated at intermediate risk, with an age of (8.26±0.87) years.The number of asparaginase re-exposures before second AAP was (2.10±0.99) times.Second AAP developed during the intensification period in 2 cases and during the re-induction period in 8 cases.There were 3 cases (30.00%) of Grade 1 pancreatitis and 7 cases (70.00%) of Grade 2 pancreatitis.No patient died of second AAP.Two patients (20.00%) experienced AAP-related long-term complications, including chronic pancreatitis and insulin-dependent diabetes mellitus.After 2 children with no clinical data related to the first AAP were excluded, 30 re-exposed children were divided into a control group (22 cases) and a case group (8 cases) according to the presence or absence of second AAP.The univariate analysis showed that there were significant differences in activated partial thromboplastin time (APTT)[(29.80±5.25) s vs.(38.47±1.42) s, t=-0.45, P=0.023] and total bilirubin (TBIL)[18.40 (11.00, 25.53) μmol/L vs.24.30 (19.93, 46.48) μmol/L, Z=-0.32, P=0.020] between the 2 groups.The further multivariate Logistic regression analysis showed that after adjusting for age and immunophenotype, TBIL ( HR=1.115, P=0.048) was an independent risk factor for second AAP.Comparisons of the prognosis revealed that there were no significant differences in long-term complications ( P=0.168) and final survival ( P=0.716) between children with only once AAP (68 cases) and those with second AAP (10 cases). Conclusions:Second AAP mostly occurs after the second dose of asparaginase, and the re-induction period is the peak period of incidence of second AAP.Hyperbilirubinemia may be a risk factor of second AAP.Compared with once AAP, second AAP does not increase the mortality and the incidence of AAP-related long-term complications.

BACKGROUND:Hemivertebra deformity should be treated surgically at an early age,but the risk factors for progression of deformity after hemivertebral resection have not been established.OBJECTIVE:To investigate the curative effect of one-stage posterior hemivertebrae resection and pedicle screw fixation in the treatment of congenital scoliosis,and to further explore the risk factors causing the progression of postoperative deformity.METHODS:The medical records of patients who underwent pedicle screw-rod fixation for unilateral hemivertebral deformity from January 2012 to February 2020 and were followed up for at least 2 years were retrospectively analyzed,and a total of 116 patients met the inclusion criteria.All patients were treated with standing anterior and lateral spinal radiographs taken before,after and at each follow-up time point.The segment Cobb angle,the total scoliosis Cobb angle,the proximal complementary Cobb angle,the distal complementary Cobb angle,and the coronal balance distance,apical vertebra distance,upper instrumented vertebra tilt,upper instrumented vertebra disc angle,lower instrumented vertebra tilt,lower instrumented vertebra disc angle,segmental kyphosis/lordosis,thoracic kyphosis,lumbar lordosis and sagittal vertical axis were measured.The progression of deformity and complications were also recorded.RESULTS AND CONCLUSION:(1)Segment Cobb,total scoliosis Cobb,segmental kyphosis,proximal complementary Cobb,and distal complementary Cobb were significantly corrected after operation(P＜0.05),and remained corrected at the last follow-up.Thoracic kyphosis,lumbar lordosis,coronal balance distance,and sagittal vertical axis were all in the normal range pre-operation,after operation and at the last follow-up.(2)During follow-up,10 patients developed coronary decompensation,which was characterized by abnormal progression.(3)Independent sample t-test showed that preoperative total scoliosis Cobb,preoperative apical vertebra distance,age,Risser sign,postoperative upper instrument vertebra tilt and postoperative lowest instrumented vertebra tilt were correlated with postoperative malformation progression(P＜0.05).(4)Multivariate Logistic regression analysis showed that postoperative lowest instrumented vertebra tilt was an independent risk factor for postoperative malformation progression(P=0.002,OR=1.526).(5)Receiver operating characteristic curve analysis showed that a postoperative lowest instrumented vertebra tilt of 8.14° was the optimal threshold for deformity progression after hemivertebrae resection and pedicle rod fixation(sensitivity 0.900,specificity 0.906,area under curve:0.926).(6)It is indicated that the treatment of congenital scoliosis with one-stage posterior hemivertebrae resection and pedicle nail fixation can achieve satisfactory orthopedic effect.Postoperative lowest instrumented vertebra tilt greater than 8.14° was an independent risk factor for postoperative coronal decompensation.

Glioblastoma (GBM) is the most aggressive malignant tumor of the adult central nervous system, with limited treatment options and poor prognosis. Radiotherapy (RT) remains a cornerstone of GBM treatment; however, tumor cell resistance to RT severely limits its efficacy. Recently, metabolic reprogramming (MR) has gained widespread attention as a critical mechanism enabling GBM cells to evade RT‐induced stress. In this review, the central roles of glucose, lipid, and amino acid metabolic reprogramming in GBM's resistance to RT were outlined, highlighting how GBM remodels metabolic pathways to enhance DNA damage repair, antioxidant defenses, and immune evasion after RT. Although combining metabolic inhibitors with RT has shown potential in improving GBM treatment outcomes, challenges such as overcoming the blood‐brain barrier and addressing tumor heterogeneity remain. The integration of nanomedicine‐based delivery systems and immunotherapy offers new hope for GBM treatment. Future research should focus on developing multidimensional, personalized metabolic targeting strategies, combined with immunotherapy and emerging technologies, to further improve therapeutic outcomes and survival rates for GBM patients.

China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.

Atherosclerosis, a chronic inflammatory disease, is markedly influenced by both immune and inflammatory reactions throughout its progression. Dendritic cells, as pivotal antigen-presenting entities, play a crucial role in the initiation of immune responses and the preservation of immunological homeostasis. Accumulating data indicates that dendritic cells are present in healthy arteries and accumulate significantly in atherosclerotic plaques. Novel immunotherapeutic approaches and vaccination protocols have yielded substantial clinical advancements in managing chronic inflammatory diseases, with dendritic cell-centric modalities emerging for atherosclerotic management. In this review, we delineate the essential functions and underlying mechanisms of dendritic cells and their subsets in the modulation of atherosclerotic inflammation and immune responses. We underscore the immense promise of dendritic cell-based immunotherapeutic strategies, including vaccines and innovative combinations with nanotechnological drug delivery platforms for atherosclerosis treatment. We also discuss the challenges associated with dendritic cell immunotherapy and provide perspectives on the future direction of this field.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

This study aimed to identify mutations in the human insulin receptor gene (INSR) and investigate their role in the pathogenesis of severe insulin resistance syndrome. Sanger sequencing of the INSR gene was performed on a patient clinically suspected of having type A insulin resistance syndrome admitted to the Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital. Upon identifying mutations, relevant exons were sequenced in her first-degree relatives. Additionally, control groups consisting of individuals with type 2 diabetes and those with normal glucose tolerance were screened for the mutation detected in the patient. Functional predictions of the INSR protein were made using MutationTaster, SIFT, and PolyPhen2 software. A previously unreported heterozygous missense mutation, c.3652G/A (Asp1218Asn), in exon 20 was identified in both the proband and her father. This mutation was not present in any of the control individuals. Multiple prediction tools indicate that this mutation likely disrupts gene/protein structure or function. The c.3652G/A (Asp1218Asn) heterozygous mutation in INSR is a novel variant that plays a significant role in the pathogenesis of severe insulin resistance in this Chinese family.