Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

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.

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.

[Objective]To evaluate the application of prostate-specific membrane antigen(PSMA)PET/CT in prostate biopsy screening,and propose effective strategies for prostate biopsy decision making based on PSMA PET/CT detection.[Methods]A retrospective analysis was conducted on PSMA PET/CT imaging and clinical pathological data from 155 patients with suspected prostate cancer between January 2020 and December 2023.PRIMARY score was used as the standardized evaluation method for PSMA PET/CT in the diagnosis of prostate cancer.And compared the positive prostate biopsy rates,missed diagnosis rates and biopsy reduction rates were compared regarding different PRIMARY scores.Receiver operating characteristic(ROC)curves were used to analyze prostate-specific antigen(PSA)and its derived parameters and identify the most suitable supplementary screening indicators for combined use with the PRIMARY score.[Results]Among patients with PRIMARY scores of 1 to 5,the proportions of patients diagnosed with prostate cancer were 15.8%(3/19),17.1%(7/41),50%(12/24),95.2%(20/21)and 98%(49/50),respectively.Using PRIMARY score of 3-5 as the biopsy screening strategy resulted in a positive prostate biopsy rate of 85.3%and biopsy reduction rate of 38.7%,but a missed diagnosis rate of 11%.PSA density>0.15 ng/(mL·cm3)was selected as a supplementary screening criterion to detect prostate cancer from patients with PRIMARY scores of 1-2.The combined application of the above two screening criteria reduced the missed diagnosis rate to 2.2%.[Conclusion]This study proposes a novel biopsy screening strategy for suspected prostate cancer patients using PSMA PET/CT,that is,a PRIMARY score of 3-5 or a PRIMARY score of 1-2 but PSA density>0.15 ng/(mL·cm3),which can effectively avoid unnecessary biopsies and significantly reduce the missed diagnosis rate.

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.

The knowledge and experience of medical practitioners in the diagnosis and treatment of diseases throughout history are mostly reflected in the description and analysis of relevant clinical events.The diagnosis and treatment thinking and cognitive reasoning process among the knowledge has dynamic and complex characteristics in time and space.However,the current exploration of ancient doctors' diagnosis and treatment experience of diseases and syndromes is mainly focuses on the academic evolution of the entire historical time line,and lacks the exploration of the concept of time and its medical relevance in ancient books.It mainly focuses on entity knowledge,and lacks the presentation of temporal dynamic cognitive logic.Moreover,the research primarily focuses on the study of specific terms in ancient Chinese medicine books,without fully covering ancient medical events.To address this issue,this research proposes to construct the evolution model of diagnosis and treatment experience based on time-series dynamic perspective:according to the time series of diagnosis and treatment events,it covers the time system module,the"coming disease"module,the"already sick"module,and the"after sick"module,which involves the dynamic risk assessment of disease occurrence by ancient medical practitioners,the grasp of the dynamic evolution of the already sick state and the treatment plan,and the dynamic health plan for the after sick state.

OBJECTIVE: To summarize the research progress on knee laxity of biomechanics and prevention and treatment after posterior cruciate ligament (PCL) reconstruction. METHODS: The domestic and international literature on the prevention and treatment of knee laxity after PCL reconstruction in recent years was extensively reviewed and analyzed. RESULTS: Different degrees of knee laxity often occur after PCL reconstruction, which can lead to poor prognosis in patients. The causes are associated with a variety of factors, including abnormal graft remodeling (such as differences in healing time and biomechanics among different types of grafts), tunnel position deviation (such as graft wear caused by the "killer turn" effect), and mechanical factors in postoperative rehabilitation (such as improper early weight-bearing and range of motion). These factors may promote graft elongation, increase early posterior tibial translation, and thereby induce knee laxity. CONCLUSION While PCL reconstruction improves knee stability, it is crucial to focus on and prevent postoperative knee laxity. However, current surgical methods are limited by factors such as graft characteristics, surgical technique flaws, and rehabilitation protocols, and thus can not fully correct the issue of abnormal postoperative laxity. Surgical techniques and treatment strategies still need further improvement and optimization to enhance patients' postoperative outcomes and quality of life.
Humans ; Joint Instability/surgery* ; Posterior Cruciate Ligament Reconstruction/adverse effects* ; Posterior Cruciate Ligament/surgery* ; Knee Joint/physiopathology* ; Biomechanical Phenomena ; Range of Motion, Articular ; Postoperative Complications/prevention & control* ; Knee Injuries/surgery*

OBJECTIVE: To summarize research progress on enhanced recovery after posterior cruciate ligament (PCL) reconstruction, clarify the core contradictions, effective intervention methods, and evaluation shortcomings in current clinical practice, and provide theoretical support for optimizing clinical rehabilitation strategies. METHODS: Relevant domestic and international literature in recent years was systematically searched. The key technologies and challenges for enhanced recovery after PCL reconstruction were analyzed from three aspects: the core issues of enhanced recovery after PCL reconstruction, treatment strategies, and the post-reconstruction effectiveness evaluation system. RESULTS: Enhanced recovery after PCL reconstruction mainly faces two core problems. First, there is a balance dilemma between graft tendon protection and knee joint function recovery: the tensile capacity of the graft tendon is weak in the early postoperative period, so excessive weight-bearing easily leads to relaxation, while overly conservative immobilization causes muscle atrophy and joint adhesion. Second, the return-to-sport rate is significantly affected by injury type and treatment method: patients with combined multiple ligament or meniscus injuries have a much lower return-to-sport rate than those with isolated PCL injury, and the risk of return-to-sport failure is higher. Current research mainly promotes rehabilitation from two aspects: physical therapy and surgical technology. Physical therapy runs through the perioperative period: preoperatively, muscle strength training, swelling control, and maintenance of joint range of motion are used to optimize surgical conditions; postoperatively, phased intervention is implemented. Surgical technology focuses on minimally invasive and anatomical approaches: arthroscopic surgery reduces injury, double-bundle reconstruction and internal tension-relief technology improve stability, and modified tunnel positioning and special surgical methods avoid the risk of "Killer Turn". Postoperative functional evaluation adopts multi-dimensional indicators: subjective evaluation relies on scales such as Lysholm and International Knee Documentation Committee (IKDC); objective evaluation assesses stability through Telos stress test and posterior drawer test; imaging evaluation takes MRI as the core; psychological evaluation is assisted by the Tampa scale of kinesiophobia-11 (TSK-11). However, there are obvious shortcomings, such as the lack of PCL-specific evaluation tools. CONCLUSION Enhanced recovery after PCL reconstruction requires the integration of precise surgery, individualized rehabilitation, and comprehensive subjective and objective evaluation. In the future, biomaterials and digital technologies should be integrated to optimize the full-cycle management of PCL reconstruction, thereby improving functional recovery and the effect of return to sports.
Humans ; Posterior Cruciate Ligament Reconstruction/rehabilitation* ; Posterior Cruciate Ligament/injuries* ; Recovery of Function ; Knee Joint/physiopathology* ; Knee Injuries/rehabilitation* ; Return to Sport ; Enhanced Recovery After Surgery ; Tendons/transplantation* ; Arthroscopy