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

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 investigate the clinical features of patients with congenital atresia of the oval window (CAOW).Methods:A retrospective analysis was conducted on 7 cases (8 ears) of surgically confirmed CAOW treated at our department from July 2018 to July 2024. Among the cases, 1 patient had bilateral CAOW, and 4 patients had unilateral CAOW combined with other types of ossicular chain malformations in the contralateral ear. We collected and analyzed the clinical data, audiological features, and temporal bone HRCT results of all patients.Results:The 7 patients were diagnosed at ages ranging from 8 to 19 years, with a mean age of (13.2±6.9) years. None of the patients exhibited significant auricular deformities. All presented with conductive hearing loss or mixed hearing loss predominantly of the conductive type, with an intact tympanic membrane. The diagnosis of CAOW was confirmed via endoscopic tympanotomy, revealing a concave oval window area on the medial wall of the tympanic cavity, sealed by a bony plate. All 8 ears exhibited additional ossicular chain deformities. Stapes absence was present in all 8 ears. Partial absence of the incus long process was observed in 3 ears, while, abnormal bony connections between the incus long process and the promontory were seen in 4 ears, 1 ear had a short malleolar handle, 1 ear had a smaller than normal malleus volume. In addition, facial nerve deformities were found in 6 ears, with 4 ears showing bifurcation of the facial nerve and 2 ears showing facial nerve obscuration of the oval window. Pure-tone audiometry revealed that 62.5% (5/8 ears) of patients had air conduction (AC) thresholds≥60 dB preoperatively, with a mean pure-tone average (PTA) of (69.0±11.8) dB HL and a mean air-bone gap (ABG) of (52.0±7.0) dB. The mean AC threshold and ABG were higher in the low-frequency (125-1 000 Hz) range compared to the high-frequency (2 000-8 000 Hz) range (both P<0.05). Preoperative HRCT showed abnormalities in all patients, with 7 ears being diagnosable as CAOW. Although the remaining 1 ear could not be diagnosed as CAOW, stapes and incus long process absence were detected. Conclusion:CAOW is rare in clinical, as the patients with non-progressive conductive hearing loss (AC≥60 dB, ABG≥50 dB) since childhood, intact tympanic membrane without malformations of auricle and external auditory canal, and thick bony plate covered the oval window of the HRCT imaging, CAOW should be highly suspected, which could be confirmed by the exploratory tympanotomy.

Objective:To investigate the long-term outcomes of using 3D-printed preformed titanium meshes in repair and reconstruction of orbital region.Methods:A retrospective analysis was conducted on patients with tumors invading the naso-orbito-maxillary region who underwent surgical resection and repair/reconstruction with 3D-printed preformed titanium meshes. The patients were collected at three medical centers (the Third Affiliated Hospital of Sun Yat-sen University, Xijing Hospital of Air Force Military Medical University, and Shenzhen Longgang District Ear, Nose and Throat Hospital) from 2016 to 2023. Tumor extent was evaluated radiologically, and the surgical approaches, reconstruction outcomes, surgical complications, and long-term follow-up results were analyzed.Results:A total of 46 patients from the three centers were included in this study, comprising 27 males and 19 females, with an average age of 51 years (range: from 13 to 86 years). Among them, 4 patients had benign tumors, while the remaining 42 had malignant tumors. The median follow-up duration was 60.7 months (range: from 19.0 to 75.0 months). Postoperatively, symmetrical globe position was achieved in 38 cases without significant diplopia; 4 cases exhibited enophthalmos without diplopia, and 4 cases had enophthalmos with diplopia. Twelve patients received preoperative radiotherapy, and 30 patients received postoperative radiotherapy. Six patients developed enophthalmos, and 6 experienced titanium mesh exposure after radiotherapy. Following treatment completion, 3 patients underwent repair using frontal flaps, 1 using a superficial temporal artery island flap, and 2 using free flaps. All remaining patients showed no postoperative infections, and their wounds healed normally.Conclusion:The application of 3D-printed preformed titanium mesh enables precise repair of postoperative defects in patients with naso-orbital tumors, facilitating reliable reconstruction of the orbital and facial contours with straightforward operation and dependable outcomes.

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 association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

OBJECTIVE To compare the ability of ultra-high-resolution CT(U-HRCT)and multi-slice spiral CT(MSCT)to display key vocal transmission structures in the middle ear.METHODS Subjects with normal middle ear structures who underwent 0.1 mm layer thickness U-HRCT and 0.625 mm layer thickness MSCT scans at the same time in Beijing Friendship Hospital affiliated to Capital Medical University from December 2019 to August 2024 were retrospectively enrolled.Two experienced head and neck radiologists reconstruct standard transsectional,coronal images based on the thinnest layer thickness.According to the 5-point method,16 key sound transmission structures of the middle ear,including malleus,incus and stapes,as well as joints,ligaments and tendons,were evaluated for image quality scoring.The standard deviation(SD)value,signal noise ratio(SNR),and contrast noise ratio(CNR)of bone in the malleus region and intratympanic gas were measured and calculated on the two examination images.RESULTS Thirty patients(47 sides)with normal middle ear structure were included,including 18 males and 12 females.The two physicians compared the results of U-HRCT in showing malleus head,malleus neck,malleus handle,incus body,long process,and short process,5 points accounted for 100%,and the 5-point scores of incudomalleolar joint space,incudostapedial joint space,stapes footplate and annular ligament were 100%,98.29%,75.83%and 77.83%,respectively,which were significantly higher than those of MSCT(P<0.001).In addition,U-HRCT showed higher scores for lenticular process,stapes head,anterior arch of stapes,posterior arch of stapes,annular ligament,stapes muscle,and tendo musculi tensoris tympani than MSCT(P<0.001),and the lenticular process showed a 100%display rate.There was no significant difference in the SNR between the two groups(P>0.05),but the SD value of the malleus in U-HRCT was 161.6±36.4,which was significantly lower than that in MSCT(297.8±128.1),and the difference was statistically significant(P<0.001).CONCLUSION U-HRCT can clearly visualize the key sound transmission structures of the middle ear,and its visualization ability is significantly better than that of MSCT.