MDM2 accelerated renal senescence via ubiquitination and degradation of HDAC1.

Senescence, an intricate and inevitable biological process, characterized by the gradual loss of homeostasis and declining organ functions. The pathological features of cellular senescence, including cell cycle arrest, metabolic disruptions, and the emergence of senescence-associated secretory phenotypes (SASP), collectively contribute to the intricate and multifaceted nature of senescence. Beyond its classical interaction with p53, murine double minute gene 2 (MDM2), traditionally known as an E3 ubiquitin ligase involved in protein degradation, plays a pivotal role in cellular processes governing senescence. Histone deacetylase (HDAC), a class of histone deacetylases mainly expressed in the nucleus, has emerged as a critical contributor to renal tissues senescence. In this study we investigated the interplay between MDM2 and HDAC1 in renal senescence. We established a natural aging model in mice over a 2-year period that was verified by SA-ß-GAL staining and increased expression of senescence-associated markers such as p21, p16, and TNF-α in the kidneys. Furthermore, we showed that the expression of MDM2 was markedly increased, while HDAC1 expression underwent downregulation during renal senescence. This phenomenon was confirmed in H2O2-stimulated HK2 cells in vitro. Knockout of renal tubular MDM2 alleviated renal senescence in aged mice and in H2O2-stimulated HK2 cells. Moreover, we demonstrated that MDM2 promoted renal senescence by orchestrating the ubiquitination and subsequent degradation of HDAC1. These mechanisms synergistically accelerate the aging process in renal tissues, highlighting the intricate interplay between MDM2 and HDAC1, underpinning the age-related organ function decline.

Analysis of the efficacy of separation surgery for severe neurological compression in multiple myeloma: a retrospective analysis of 35 cases.

PURPOSE: To investigate the effectiveness and safety of separation surgery for Epidural Spinal Cord Compression (ESCC) graded ≥ 2 in patients with Multiple Myeloma (MM), analyze factors influencing surgical outcomes, and develop a preliminary treatment decision framework for these patients. METHODS: A retrospective analysis was conducted on clinical data from 35 MM patients who underwent separation surgery for ESCC graded ≥ 2 between 2013 and 2018. Patient data, including baseline information, surgical details, complications, and pre-operative as well as one-month post-operative efficacy evaluation indicators were recorded. Statistical analysis was performed on pre-operative and post-operative efficacy indicators to determine if there were significant improvements (p < 0.05). Ordered logistic regression was utilized to assess factors associated with an unfavorable post-operative quality of life outcome. RESULTS: Compared to pre-operative values, at one-month post-surgery, patients showed significant improvements in Frankel Score Classification (4 vs 5, p < 0.05), Karnofsky Performance Score (30 vs 70, p < 0.05), and Visual Analogue Scale (8 vs 3, p < 0.05). Complications occurred in 7 cases (20%). The number of segments with ESCC (OR = 0.171, p < 0.05) and pre-operative chemotherapy (OR = 5.202, p = 0.05) were identified as independent factors influencing patient outcomes. Patients with more than two vertebral segments with ESCC exhibited significantly worse post-operative conditions. CONCLUSIONS: Separation surgery effectively alleviates pain, improves neurological function, and enhances the quality of life in patients with ESCC graded ≥ 2 due to MM.

Which factors are associated with adverse prognosis in multiple myeloma patients after surgery? - preliminary establishment and validation of the nomogram.

BACKGROUND: To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram. METHODS: Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated. RESULTS: Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%. CONCLUSION: This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.

Learning curve of tibial cortex transverse transport: a cumulative sum analysis.

OBJECTIVE: This study aimed to describe the learning curve of surgeons performing tibial cortex transverse transport (TTT) and explore its safety and effectiveness during the initial stages of surgeon's learning. METHODS: The clinical data of patients with diabetic foot ulcers classified as Wagner grade ≥ 2, who underwent TTT at our hospital from January 2020 to July 2021, were included in this retrospective analysis. The same physician performed all procedures. Patients were numbered according to the chronological order of their surgery dates. The cumulative sum and piecewise linear regression were used to evaluate the surgeon's learning curve, identify the cut-off point, and divide the patients into learning and mastery groups. A minimum follow-up period of 3 months was ensured for all patients. Baseline data, perioperative parameters, complications, and efficacy evaluation indicators were recorded and compared between the two groups. RESULTS: Sixty patients were included in this study based on the inclusion and exclusion criteria. After completing 20 TTT surgeries, the surgeon reached the cut-off point of the learning curve. Compared to the learning group, the mastery group demonstrated a significant reduction in the average duration of the surgical procedure (34.88 min vs. 54.20 min, P < 0.05) along with a notable decrease in intraoperative fluoroscopy (9.75 times vs. 16.9 times, P < 0.05) frequency, while no significant difference was found regarding intraoperative blood loss (P = 0.318). Of the patients, seven (11.7%) experienced complications, with three (15%) and four cases (10%) occurring during the learning phase and the mastery phase, respectively. The postoperative ulcer area was significantly reduced, and the overall healing rate was 94.8%. Significant improvements were observed in postoperative VAS, ABI, and WIFI classification (P < 0.05). There were no significant differences in the occurrence of complications or efficacy indicators between the learning and mastery groups (P > 0.05). CONCLUSION: Surgeons can master TTT after completing approximately 20 procedures. TTT is easy, secure, and highly efficient for treating foot ulcers. Furthermore, TTT's application by surgeons can achieve almost consistent clinical outcomes in the initial implementation stages, comparable to the mastery phase.

Case report: Giant atypical granular cell tumor of the median nerve.

Granular cell tumors are extremely uncommon soft tissue neoplasms that mostly occur in the head and neck regions. Granular cell tumors are generally benign, asymptomatic, and rarely involve the median nerve. Due to the lack of awareness about granular cell tumors, they are easily misdiagnosed and mistreated in primary hospitals. Here, we report a giant atypical granular cell tumor located on the median nerve, approximately 12 cm in size, with unusual symptoms of median nerve damage. Magnetic resonance imaging revealed a fusiform mass that was hyperintense on T2-weighted images and iso-hypointense on T1-weighted images. The mass was subsequently biopsied and found to be a granular cell tumor. The tumor was resected, and a pathological examination was performed. Pathological examination revealed necrotic foci, abundant eosinophilic granules, pustular ovoid bodies, and multiple mitoses. Immunohistochemical staining revealed that the tumor cells were positive for S-100, CD68, SMA, SOX-10, Calretinin, and TFE3. The integrated diagnosis was an atypical granular cell tumor. To the best of our knowledge, this is the first report of an atypical granular cell tumor involving the median nerve. Furthermore, we comprehensively reviewed the existing literature to provide a concise summary of the diagnostic criteria, imaging findings, and pathological features of granular cell tumors. Given the high recurrence and metastasis rates of this disease, granular cell tumors of the median nerve should be considered when a patient presents with symptoms of median nerve impairment. The diagnosis of atypical granular cell tumors relies on pathological examination. In addition, extensive resection and long-term follow-up are necessary to improve prognosis.

Significance of preoperative peripheral blood neutrophil-lymphocyte ratio in predicting postoperative survival in patients with multiple myeloma bone disease.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is often used to predict a poor prognosis in patients with tumors. This study investigated the preoperative peripheral blood NLR in predicting postoperative survival (POS) in patients with multiple myeloma bone disease (MMBD). AIM: To evaluate whether NLR can be used to predict the prognosis of MMBD patients after surgery. METHODS: The clinical data of 82 MMBD patients who underwent surgical treatments in Beijing Chao-yang Hospital were collected. The NLR was obtained from the absolute number of neutrophils and lymphocytes, calculated by the number of neutrophils and divided by the number of lymphocytes. The peripheral blood lymphocyte percentage was used as the major marker to analyze the change in characteristics of the immune statuses of multiple myeloma patients. RESULTS: The NLR cut-off values of NLR ≥ 3 patients and NLR ≥ 4 patients were significantly correlated with POS. The 3- and 5-year cumulative survival rates of the high NLR group (NLR ≥ 3 patients) were 19.1% and 0.0%, respectively, which were lower than those of the low NLR group (NLR < 3 patients) (67.2% and 48.3%) (P = 0.000). In the high NLR group, POS (14.86 ± 14.28) was significantly shorter than that in the low NLR group (32.68 ± 21.76). Univariate analysis showed that the lymphocyte percentage 1 wk after the operation (19.33 ± 9.08) was significantly lower than that before the operation (25.72 ± 11.02). Survival analysis showed that postoperative chemotherapy, preoperative performance status and preoperative peripheral blood NLR ≥ 3 were independent risk factors for POS. CONCLUSION: The preoperative peripheral blood NLR can predict POS in MMBD patients. MMBD patients with a high preoperative NLR (NLR ≥ 3) showed poor prognosis.

Preliminary establishment of a spinal stability scoring system for multiple myeloma.

BACKGROUND: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, and the Spinal Instability Neoplastic Score scoring system may not be fully applicable to multiple myeloma (MM) patients. AIM: To evaluate the spinal stability of patients with MM spinal involvement to guide their clinical treatment. METHODS: By using the Delphi method, we collected and extracted information through a series of questionnaires and improved it via feedback. We also preliminarily established a spinal stability scoring system for multiple myeloma. RESULTS: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The MM spinal stability scoring system was created by calculating the scores of the six separate components: location, pain, number of segments, physiological curvature, comorbidities, and neurological function. The minimum value was "0", and the maximum value was "24". A score of "0-10" indicated "spine stability", a score of "11-17" indicated "potential instability", and a score of "18-24" indicated "spine instability". Patients with a score of "11-24" need an intervention such as surgery. CONCLUSION: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM.

Comparison of Tension-Band Wiring With the Cable Pin System in Patella Fractures: A Randomized Prospective Study.

OBJECTIVES: To compare the outcome of tension-band wiring (TBW) with the cable pin system (CPS) for transverse fractures of the patella. DESIGN: Randomized prospective study. SETTING: Academic Level I trauma center. PATIENTS/PARTICIPANTS: From February 2008 to December 2011, 73 consecutive patients with transverse fractures of the patella were prospectively enrolled in this study. INTERVENTION: The patients were randomly divided into 2 groups: one group was treated using the CPS, and the other group was treated using the modified TBW. MAIN OUTCOME MEASUREMENTS: The clinical outcome assessment included analyses of the radiographic images, the modified Hospital for Special Surgery scoring system, and complications. RESULTS: The follow-up time ranged from 12 to 29 months. All fractures healed, with a union rate of 100%. The fracture healing time was significantly shorter in the CPS group (8.51 ± 2.59 weeks, n = 34) compared with the TBW group (11.79 ± 3.04 weeks, n = 39). Postoperative complications in the CPS and TBW groups were observed in 1 and 9 patients, respectively, a difference that was statistically significant. The mean Hospital for Special Surgery score for the CPS group (90.53 ± 5.19 points) was significantly higher than that for the TBW group (81.36 ± 12.71 points). CONCLUSIONS: The CPS is a viable option for transverse fractures of the patella and is associated with a shorter healing time, fewer complications, and better function than TBW. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.