Membrane-camouflaged biomimetic nanoplatform with arsenic complex for synergistic reinforcement of liver cancer therapy.

Aim: Arsenic has excellent anti-advanced liver cancer effects through a variety of pathways, but its severe systemic toxicity forces the need for a safe and effective delivery strategy.Methods: Based on the chelating metal ion properties of polydopamine (PDA), arsenic was immobilized on an organic carrier, and a M1-like macrophage cell membrane (MM)-camouflaged manganese-arsenic complex mesoporous polydopamine (MnAsOx@MP@M) nanoplatform was successfully constructed. MnAsOx@MP@M was evaluated at the cellular level for tumor inhibition and tumor localization, and in vivo for its anti-liver cancer effect in a Hepa1-6 tumor-bearing mouse model.Results: The nanoplatform targeted the tumor site through the natural homing property of MM, completely degraded and released drugs to kill tumor cells in an acidic environment, while playing an immunomodulatory role in promoting tumor-associated macrophages (TAMs) repolarization.Conclusion: MnAsOx@MP@M has synergistically enhanced the targeted therapeutics against liver cancer via nanotechnology and immunotherapy, and it is expected to become a safe and multifunctional treatment platform in clinical oncology.

[Box: see text].

Posterior Biportal Endoscopic Discectomy for the Treatment of Central Cervical Disc Herniation: Technical Note and Preliminary Results.

OBJECTIVE: To evaluate the preliminary outcomes and clinical efficacy of a novel posterior biportal endoscopic technique in the treatment of central cervical disc herniation (CCDH). METHODS: A total of 11 patients with symptomatic CCDH who met the inclusion criteria underwent posterior biportal endoscopic discectomy between December 2021 and May 2023. The surgical procedure involved flavectomy, foraminotomy, pediculoplasty, and discectomy using 30° and 45° arthroscopes and specialized minimally invasive tools. Functional outcomes were assessed using the Japanese Orthopedic Association scoring system, Neck Disability Index, and visual analog scale for axial neck pain. Clinical efficacy was evaluated at the final follow-up using the modified Macnab criteria. RESULTS: All 11 patients successfully underwent posterior biportal endoscopic discectomy with a mean operative time of 82.7 ± 10.1 minutes and mean estimated blood loss of 31.8 ± 9.8 ml. The mean hospital stay was 5.2 ± 1.1 days, and the mean follow-up period was 13.8 ± 2.4 months. Significant improvements were observed in Neck Disability Index, Japanese Orthopedic Association, and visual analog scale scores. Clinical efficacy was rated as excellent in 3 patients, good in 6 patients, and fair in 2 patients according to the modified Macnab criteria. No cases of cervical instability or kyphosis were observed during postoperative follow-up. CONCLUSIONS: The novel posterior biportal endoscopic technique demonstrated significant clinical efficacy and safety in treating CCDH, with marked improvements in clinical outcomes, rapid postoperative recovery, and a low incidence of complications.

Gui Qi Zhuang Jin Decoction ameliorates mitochondrial dysfunction in sarcopenia mice via AMPK/PGC-1α/Nrf2 axis revealed by a metabolomics approach.

OBJECTIVE: Sarcopenia, as a condition of muscle mass loss and functional decline typically diagnosed in elderly individuals, severely affects human physical activity, metabolic homeostasis, and quality of life. Gui Qi Zhuang Jin Decoction (GQZJD), an approved hospital-based prescription with years of clinical application, has been demonstrated to have a notable therapeutic effect on sarcopenia. However, its potential mechanism of action in the treatment of sarcopenia remains uncertain. METHODS: Ultra-performance liquid chromatography paired with Q Exactive™ HF-X mass spectrometry (UPLC-QE-MS) was used to identify the ingredients of GQZJD. Subsequently, GQZJD observed the basic growth and muscles of the sarcopenia mouse, while the behavioral indicators were also tested. Muscle histopathology and serum oxidative stress biochemicals were also detected, and mitochondrial function and energy metabolism-related indicators in the gastrocnemius muscle were examined. Then, a metabolomics strategy was applied to predict possible pathways involving mitochondria by which GQZJD could improve sarcopenia. Finally, quantitative real-time polymerase chain reaction and western blot analyses were carried out to validate the effects of GQZJD on sarcopenia-induced mitochondrial dysfunction, together with uncovering the associated mechanisms. RESULTS: Twenty-seven ingredients absorbed into the blood (IAIBs) of GQZJD were identified using UPLC-QE-MS, which were regarded as the main active ingredients behind its sarcopenia treatment effects. GQZJD administration increased the body weight, gastrocnemius muscle mass, and autonomic activity, mitigated muscle tissue morphology and pathology; and alleviated the oxidative stress levels in sarcopenia mice. Treatment with GQZJD also decreased the mitochondrial reactive oxygen species level and serum lipid peroxide Malonaldehyde concentration. and increased the mitochondrial membrane potential, adenosine triphosphate level, 8­hydroxy-2-deoxyguanosine content, mitochondrial DNA copy number, and the mitochondrial fission factor dynamin-related protein 1. Non-targeted metabolomics suggested that the sarcopenia therapeutic effect of GQZJD on sarcopenia may occur through the glycerophospholipid metabolism, choline metabolism in cancer, phenylalanine metabolism and tyrosine metabolism pathways, implying an association with AMP-activated protein kinase (AMPK) and related signals. Further, the molecular docking results hinted that AMPK performed well in terms of binding energy with the 27 IAIBs of GQZJD (average binding energy, -7.5 kcal/mol). Finally, we determined that GQZJD significantly activated the key targets of the AMPK/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis.. CONCLUSIONS: Our results demonstrated that GQZJD ameliorated d-galactose-induced sarcopenia by promoting the animal behaviours, facilitating mitochondrial function and restoring mitochondrial energy metabolism. with its effects mediated by the AMPK/PGC-1α/Nrf2 axis. Over all, GQZJD represents a promising therapeutic candidate that ameliorated sarcopenia in aging mice.

Precise Identification of Glioblastoma Micro-Infiltration at Cellular Resolution by Raman Spectroscopy.

Precise identification of glioblastoma (GBM) microinfiltration, which is essential for achieving complete resection, remains an enormous challenge in clinical practice. Here, the study demonstrates that Raman spectroscopy effectively identifies GBM microinfiltration with cellular resolution in clinical specimens. The spectral differences between infiltrative lesions and normal brain tissues are attributed to phospholipids, nucleic acids, amino acids, and unsaturated fatty acids. These biochemical metabolites identified by Raman spectroscopy are further confirmed by spatial metabolomics. Based on differential spectra, Raman imaging resolves important morphological information relevant to GBM lesions in a label-free manner. The area under the receiver operating characteristic curve (AUC) for Raman spectroscopy combined with machine learning in detecting infiltrative lesions exceeds 95%. Most importantly, the cancer cell threshold identified by Raman spectroscopy is as low as 3 human GBM cells per 0.01 mm2. Raman spectroscopy enables the detection of previously undetectable diffusely infiltrative cancer cells, which holds potential value in guiding complete tumor resection in GBM patients.

Safety and Efficiency of Anlotinib in Patients with Recurrent Grade 4 Glioma: A Single-Center Retrospective Analysis.

PURPOSE: Anlotinib is a multi-target TKI which has been used in different advanced tumors. However, its efficiency and safety in patients with glioblastoma are still not well discussed. This retrospective study aimed to discover the safety and efficiency of anlotinib in recurrent grade 4 glioma. METHODS: The clinical data of patients with recurrent grade 4 glioma treated with anlotinib in our center were collected and analyzed. The progression-free survival (PFS), overall survival (OS), and OS after recurrence were calculated by Kaplan-Meier method and compared by log-rank test. Sub-group analysis was used to find possible variables that affect survival. RESULTS: From October 2017 to December 2020, seventeen patients with recurrent grade 4 glioma treated with anlotinib were enrolled. The median age was 50 with 13 males. The median KPS was 70. All patients received standard STUPP mode treatment before recurrence. The median PFS was 7 months [95% confidence interval (CI) 5.3-8.6]. The median OS after first diagnosis was 17 months (95% CI 15.7-18.3). The median OS after recurrence was 10 months (95% CI 7.6-12.4). The objective response rate was 33.33% (5/15), and the disease control rate was 60% (9/15). The existence of target genes was identified as a variable affecting the survival after recurrence. The median OS after recurrence in patients with target genes was 12 months (95% CI 6.9-17.1), whereas for patients without targets, the median OS was 4 months (95% CI 1.9-6.1) and for patients with an unknown status, the median OS was 10 months (95% CI 8.4-11.6) (P = 0.013). CONCLUSION: For recurrent grade 4 glioma, anlotinib can be considered as a supplement to the standard STUPP treatment, especially for the patient with anlotinib target genes.

Biportal Endoscopic Paraspinal Decompression for Epidural Cement Leakage Removal: A Technical Note.

OBJECTIVE: We aimed to preliminarily explore the efficacy and safety of unilateral biportal endoscopy for the treatment of epidural cement leaks. We report a patient who underwent epidural cement leakage removal and achieved endoscopic spinal decompression. METHODS: A 67-year-old female patient underwent biportal endoscopic paraspinal decompression following percutaneous vertebroplasty for an osteoporotic fracture that resulted in neurologic impairment due to epidural cement leakage. A transforaminal biportal endoscopic surgery was performed to remove the leaked cement, and the left L1 and bilateral L2 nerves were decompressed. RESULTS: The patient's postoperative clinical course was uneventful. CONCLUSIONS: A paraspinal approach that avoids a posterior approach reduces the need to remove stabilizing facet bone, is truly minimally invasive and does not involve an instrumented fusion, maybe a helpful addition in the minimally invasive spine surgeon's armamentarium.

Unilateral biportal endoscopy via two different approaches for upper lumbar disc herniation: a technical note.

BACKGROUND: The traditional surgical procedures for upper lumbar disc herniation (ULDH) usually lead to frequent complications. We aim to investigate the clinical efficacy of the unilateral biportal endoscopy (UBE) technique in treating upper lumbar disc herniation (ULDH). METHODS: From January 2020 to December 2021, the clinical data of 28 patients with ULDH treated with the UBE technique were collected and analyzed for surgery time under UBE, postsurgical drainage, postsurgical hospital stay, and complications. The clinical efficacy was evaluated according to the modified MacNab score, Oswestry disability index (ODI), and visual analogue scale (VAS) of low back pain and lower limb pain before the surgery; one week, one month, and three months after the surgery; and at the last follow-up. RESULTS: All patients underwent the UBE surgery successfully. The surgery time under UBE for non-fusion cases was 47.50 ± 11.84 min (monosegment) and 75.00 ± 20.66 min (two segments), while that for fusion cases was 77.50 ± 21.02 min. The postsurgical drainage for non-fusion cases was 25.00 ± 13.94 mL (monosegment) and 38.00 ± 11.83 mL (two segments), while that for fusion cases was 71.25 ± 31.72 mL. The postsurgical hospital stay was 8.28 ± 4.22 days. The follow-up time was 15.82 ± 4.54 months. The VAS score for each time period after the surgery was significantly lower (P < 0.05), while the ODI was significantly higher than that before the surgery (P < 0.05). According to the modified MacNab scoring standard, the ratio of excellent to good was 96.43% at the last follow-up. Two patients experienced transient numbness and pain in their lower limbs and no activity disorder after the surgery, and they recovered after conservative treatment. CONCLUSIONS: The clinical effect of UBE technique in treating ULDH was reliable. According to the needs of the disease, the interlaminar approach or paraspinal approach of the UBE technique was selected. This technique took into account the effect of treatment, achieved the purpose of minimal invasiveness, and did not require special instruments. Therefore, it has the potential for clinical application.

LncRNA taurine upregulated gene 1 in liver disease.

Long non-coding RNAs (lncRNAs) are RNA sequences exceeding 200 nucleotides in length that lack protein-coding capacity and participate in diverse biological processes in the human body, particularly exerting a pivotal role in disease surveillance, diagnosis, and progression. Taurine upregulated gene 1 (TUG1) is a versatile lncRNA, and recent studies have revealed that the aberrant expression or function of TUG1 is intricately linked to the pathogenesis of liver diseases. Consequently, we have summarized the current understanding of the mechanism of TUG1 in liver diseases such as liver fibrosis, fatty liver, cirrhosis, liver injury, hepatitis, and liver cancer. Moreover, mounting evidence suggests that interventions targeting TUG1 or its downstream pathways may hold therapeutic promise for liver diseases. This review elucidates the characteristics, mechanisms, and targets of TUG1 in liver diseases, offering a theoretical basis for the prevention, diagnosis, treatment, and prognostic biomarkers of liver diseases.

Biportal endoscopy-assisted lateral mass screw fixation using a third portal.

BACKGROUND: The technique of spinal decompression under endoscopy has been widely applied, but reports on endoscopic cervical fixation are rare. The unilateral biportal endoscopic (UBE) technique stands out for its lesser muscle intrusion and more flexible surgical approach. METHOD: We applied the UBE approach for cervical fixation and laminectomy. We achieved bilateral lateral mass screw fixation by making an auxiliary UBE portal combined with the Roy-Camille and Magerl techniques. CONCLUSIONS: Our successful implementation of cervical fixation using the UBE technique at the C3/4 level suggests its efficacy. This approach is a valuable and minimally invasive option for cervical fixation.

Artificial intelligence-based classification of breast nodules: a quantitative morphological analysis of ultrasound images.

Background: Accurate classification of breast nodules into benign and malignant types is critical for the successful treatment of breast cancer. Traditional methods rely on subjective interpretation, which can potentially lead to diagnostic errors. Artificial intelligence (AI)-based methods using the quantitative morphological analysis of ultrasound images have been explored for the automated and reliable classification of breast cancer. This study aimed to investigate the effectiveness of AI-based approaches for improving diagnostic accuracy and patient outcomes. Methods: In this study, a quantitative analysis approach was adopted, with a focus on five critical features for evaluation: degree of boundary regularity, clarity of boundaries, echo intensity, and uniformity of echoes. Furthermore, the classification results were assessed using five machine learning methods: logistic regression (LR), support vector machine (SVM), decision tree (DT), naive Bayes, and K-nearest neighbor (KNN). Based on these assessments, a multifeature combined prediction model was established. Results: We evaluated the performance of our classification model by quantifying various features of the ultrasound images and using the area under the receiver operating characteristic (ROC) curve (AUC). The moment of inertia achieved an AUC value of 0.793, while the variance and mean of breast nodule areas achieved AUC values of 0.725 and 0.772, respectively. The convexity and concavity achieved AUC values of 0.988 and 0.987, respectively. Additionally, we conducted a joint analysis of multiple features after normalization, achieving a recall value of 0.98, which surpasses most medical evaluation indexes on the market. To ensure experimental rigor, we conducted cross-validation experiments, which yielded no significant differences among the classifiers under 5-, 8-, and 10-fold cross-validation (P>0.05). Conclusions: The quantitative analysis can accurately differentiate between benign and malignant breast nodules.

[Contralateral endoscopic approach for lumbar foraminal stenosis using unilateral biportal endoscopic surgery].

OBJECTIVE: To assess the feasibility and imaging outcomes of unilateral biportal endoscopic technique in the treatment of lumbar foraminal stenosis through contralateral approach. METHODS: The clinical data of 33 patients with lumbar foraminal stenosis treated with unilateral biportal endoscopic technique from January 2021 to July 2022 were retrospectively analyzed. There were 17 males and 16 females;age ranging from 34 to 72 years old with an average of (56.00±7.89) years old;operation time and perioperative complications were recorded;visual analogue scale (VAS) of pain was recorded, to evaluate the degree of low back pain and lower extremity pain, and Oswestry disability index (ODI) to evaluate the lumbar spine function. At the latest follow-up, the modified Macnab score was used to evaluate the clinical efficacy. RESULTS: All patients successfully completed the operation. The operation time ranged from 47 to 65 minutes, with an average of (56.10±5.19) minutes. The postoperative follow-up ranged from 12 to 18 months, with an average of (14.9±2.3) months. The VAS of low back and lower extermity pain before operation were (7.273±1.442) and (7.697±1.447) scores, ODI was (69.182±9.740)%. Postoperative lumbocrural pain VAS were (3.394±0.966) and (2.818±0.727) scores, ODI was (17.30±4.78) %. At the latest follow-up, VAS of back and lower extermity pain was (2.788±0.650) and (2.394±0.704) scores, ODI was (14.33±350)%. There were significant differences in VAS of low back and lower extremity pain and ODI before and after operation(P<0.05). At the latest follow-up, according to the modified Macnab criteria, 24 patients got excellent result, 5 as good, 2 as fair, and 2 as poor. CONCLUSION: Unilateral biportal endoscopic treatment of lumbar foraminal stenosis through the contralateral approach is a safe and efficient method, with few complications, quick postoperative recovery, and satisfactory clinical outcomes. During the follow-up period, no iatrogenic lumbar instability was observed.

Role of SPRY4 in health and disease.

SPRY4 is a protein encoding gene that belongs to the Spry family. It inhibits the mitogen-activated protein kinase (MAPK) signaling pathway and plays a role in various biological functions under normal and pathological conditions. The SPRY4 protein has a specific structure and interacts with other molecules to regulate cellular behavior. It serves as a negative feedback inhibitor of the receptor protein tyrosine kinases (RTK) signaling pathway and interferes with cell proliferation and migration. SPRY4 also influences inflammation, oxidative stress, and cell apoptosis. In different types of tumors, SPRY4 can act as a tumor suppressor or an oncogene. Its dysregulation is associated with the development and progression of various cancers, including colorectal cancer, glioblastoma, hepatocellular carcinoma, perihilar cholangiocarcinoma, gastric cancer, breast cancer, and lung cancer. SPRY4 is also involved in organ development and is associated with ischemic diseases. Further research is ongoing to understand the expression and function of SPRY4 in specific tumor microenvironments and its potential as a therapeutic target.

Electrosprayed Eudragit RL100 nanoparticles with Janus polyvinylpyrrolidone patches for multiphase release of paracetamol.

Advanced nanotechniques and the corresponding complex nanostructures they produce represent some of the most powerful tools for developing novel drug delivery systems (DDSs). In this study, a side-by-side electrospraying process was developed for creating double-chamber nanoparticles in which Janus soluble polyvinylpyrrolidone (PVP) patches were added to the sides of Eudragit RL100 (RL100) particles. Both sides were loaded with the poorly water-soluble drug paracetamol (PAR). Scanning electron microscope results demonstrated that the electrosprayed nanoparticles had an integrated Janus nanostructure. Combined with observations of the working processes, the microformation mechanism for creating the Janus PVP patches was proposed. XRD, DSC, and ATR-FTIR experiments verified that the PAR drug was present in the Janus particles in an amorphous state due to its fine compatibility with the polymeric matrices. In vitro dissolution tests verified that the Janus nanoparticles were able to provide a typical biphasic drug release profile, with the PVP patches providing 43.8 ± 5.4% drug release in the first phase in a pulsatile manner. In vivo animal experiments indicated that the Janus particles, on one hand, could provide a faster therapeutic effect than the electrosprayed sustained-release RL100 nanoparticles. On the other hand, they could maintain a therapeutic blood drug concentration for a longer period. The controlled release mechanism of the drug was proposed. The protocols reported here pioneer a new process-structure-performance relationship for developing Janus-structure-based advanced nano-DDSs.

A Retrospective Study to Compare Patient Outcomes from Standard Total Knee Arthroplasty (TKA) versus Navigation-Guided Arthroplasty Using the Brainlab Software-Guided Surgical System at a Center in Hebei Province January 2021 to July 2023.

BACKGROUND This retrospective study aimed to compare patient outcomes from standard total knee arthroplasty (TKA) vs navigation-guided arthroplasty using the Brainlab software-guided surgical system at Cangzhou Hospital of Integrated TCM-WM, Hebei, Hebei Province, China from January 2021 to July 2023. MATERIAL AND METHODS A total of 239 patients who underwent total knee arthroplasty in Cangzhou Hospital of Integrated TCM-WM, Hebei from January 2021 to July 2023 were retrospectively analyzed. According to the inclusion criteria, 212 eligible patients were selected for analysis and divided into a Navigation Group (NG) (n=105) and a Traditional Group (TG) (n=107) according to surgical method used. Outcomes measured included duration of disease, operative time, intraoperative blood loss volume, postoperative length of hospital stay, and pain measured by the hospital for special surgery knee score (HSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and forgotten joint score (FJS). RESULTS The comparison of perioperative results between the 2 groups showed that the incision length in the NG was significantly longer than that in the TG (P<0.001, 95% Cl 2.59-3.35). At 3 months after surgery, the HSS score of the NG was statistically higher than that of the TG (P=0.002, 95% Cl 3.42-4.46); the WOMAC score of the NG was lower than that of the TG (P<0.001, 95% Cl -4.41-2.87); and the FJS score of the NG was significantly higher than that of the TG (P=0.003, 95% Cl 2.39-3.67). CONCLUSIONS Compared with conventional TKA, use of the Brainlab navigation system is associated with a longer incision, more accurate implantation position of the prosthesis, faster recovery of knee joint function, and helps patients to "forget" about their knee prosthesis in the short term.

Eudragit S100 coated nanodiamond-based nanoparticles as an oral chemo-photothermal delivery system for local treatment of colon cancer.

Oral colonic nano-drug delivery system has received more and more attention in the treatment of colon cancer due to local precision treatment and reduction of drug system distribution. However, the complex and harsh gastrointestinal environment and the retention of nanoparticles in the colon limit its development. To this end, we designed Eudragit S100 (ES) coated nanoparticles (ES@PND-PEG-TPP/DOX). Polydopamine coated nanodiamond (PND) was modified with amino-functionalized polyethylene glycol (NH2-PEG-NH2) and triphenylphosphine (TPP) successively. Due to the high specific surface area of PND, it can efficiently load the model drug doxorubicin hydrochloride (DOX). In addition, PND also has high photothermal conversion efficiency, generating heat to kill cancer cells under near infrared (NIR) laser, realizing the combination of chemotherapy and photothermal therapy (CT-PTT). TPP modification enhanced nanoparticle uptake by colon cancer cells and prolonged preparations retention time at the colon. ES shell protected the drug from being destroyed and prevented the nanoparticles from sticking to the small intestine. Ex vitro fluorescence imaging showed that TPP modification can enhance the residence time of nanoparticles in the colon. In vivo pharmacodynamics demonstrated that CT-PTT group has the greatest inhibitory effect on tumor growth, which means that the nanocarrier has potential clinical value in the in-situ treatment of colon cancer.

Biportal endoscopic-assisted cortical bone trajectory screw placement and lumbar interbody fusion.

BACKGROUND: Endoscopically assisted screw fixation with lumbar interbody fusion is rarely performed. We succeeded in implanting the cortical bone trajectory (CBT) screws under the guidance of unilateral biportal endoscopy (UBE). METHOD: We attempted endoscopically assisted screw fixation in a patient with degenerative spondylolisthesis. Through a third portal, ipsilateral CBT screws were implanted without complications. CONCLUSIONS: We successfully performed unilateral biportal endoscopic lumbar interbody fusion (ULIF) with CBT and reversed CBT screws. Compared with percutaneous pedicle screw (PPS) placement, this procedure is a minimally invasive, endoscopic alternative that allows precise screw placement.

Geraniin restricts inflammasome activation and macrophage pyroptosis by preventing the interaction between ASC and NLRP3 to exert anti-inflammatory effects.

Geraniin, a chemical component of the traditional Chinese medicine geranii herba, possesses anti-inflammatory and anti-oxidative activities. However, its anti-inflammatory role in managing NLRP3 inflammasome and pyroptosis remains to be elucidated. To investigate the anti-inflammation mechanism of geraniin, LPS-primed macrophages were incubated with classical activators of NLRP3 inflammasome (such as ATP, Nigericin, or MSU crystals), and MSU crystals were injected into the ankle joints of mice to establish an acute gouty arthritis model. The propidium iodide (PI) staining results showed that geraniin could restrain cell death in the ATP- or nigericin-stimulated bone marrow-derived macrophages (BMDMs). Geraniin decreased the release of lactate dehydrogenase (LDH) and interleukin (IL)-1ß from cytoplasm to cell supernatant. Geraniin also inhibited the expression of caspase-1 p20, IL-1ß in cell supernatant and N-terminal of gasdermin D (GSDMD-NT) while blocking the oligomerization of ASC to form speck. The inhibitory effects of geraniin on caspase-1 p20, IL-1ß, GSDMD-NT, and ASC speck were not observed in NLRP3 knockout (NLRP3-/-) BMDMs. Hence, the resistance of geraniin to inflammasome and pyroptosis was contingent upon NLRP3 presence. Geraniin reduced reactive oxygen species (ROS) production and maintained mitochondrial membrane potential while preventing interaction between ASC and NLRP3 protein. Additionally, geraniin diminished MSU crystal-induced mouse ankle joint swelling and IL-1ß expression. Geraniin blocked the recruitment of neutrophils and macrophages to the synovium of joints. Our results demonstrate that geraniin prevents the assembly of ASC and NLRP3 through its antioxidant effect, thereby inhibiting inflammasome activation, pyroptosis, and IL-1ß release to provide potential insights for gouty arthritis targeted therapy.

Contralateral translaminar endoscopic approach for highly down-migrated lumbar disc herniation using percutaneous biportal endoscopic surgery : Original research.

OBJECTIVE: Unilateral biportal endoscopy (UBE)is a minimally invasive spine surgery with reduced traumatization of the posterior lumbar ligament and muscular structures. This study reports contralateral translaminar approach with UBE for highly down-migrated lumbar disc herniation (LDH). METHODS: Data of 32 patients with highly down-migrated LDH treated using UBE at our center from January 2020 to July 2022 were retrospectively analyzed. The operation time and perioperative complications were recorded, and the visual analog scale (VAS) of pain was recorded to evaluate the degree of lower back and extremity pain. The Oswestry disability index (ODI) was used to evaluate lumbar spine function. The modified MacNab score was used to evaluate clinical efficacy. RESULTS: All patients successfully underwent the operation, with a time range from 47 to 65 min and an average operation time of 56.09 ± 5.11 min. Overall, 17 and 15 were males and females, respectively, with ages ranging from 34 to 72 years and an average age of 56 ± 7.89 years. The postoperative follow-up period was 12-18 months, with an average of 14.9 ± 2.3 months. The postoperative lower back VAS pain score and ODI were statistically significant compared with preoperatively (P < 0.05). At the final follow-up, according to the modified Macnab criteria, 90.6% of cases were classified as good or excellent. CONCLUSION: UBE treatment of highly down-migrated LDH through the contralateral translaminar approach is safe and efficient. Therefore, this approach can be an efficient alternative for patients with highly downward-migrating LDH.

Aligned cryogel fibers incorporated 3D printed scaffold effectively facilitates bone regeneration by enhancing cell recruitment and function.

Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration.

Sivelestat in Patients at a High Risk of Postoperative Acute Lung Injury After Scheduled Cardiac Surgery: A Prospective Cohort Study.

Background: Sivelestat, a neutrophil elastase inhibitor, is specifically developed to mitigate the occurrence of acute lung injury (ALI) in individuals who are undergoing cardiovascular surgery. However, its impact on patients who are at a heightened risk of developing ALI after scheduled cardiac surgery has yet to be determined. In order to address this knowledge gap, we undertook a study to assess the efficacy of sivelestat in protecting the lungs of these patients. Methods: We conducted a prospective cohort study involving 718 patients who were at high risk of developing postoperative acute lung injury (ALI) and underwent scheduled cardiac surgery between April 25th, 2022, and September 7th, 2023. Among them, 52 patients received sivelestat (administered at a dosage of 0.2mg/kg/h for 3 days), while 666 patients served as controls, not receiving sivelestat. The control conditions were the same for all patients, including ventilation strategy, extubating time, and fluid management. Subsequently, a propensity-score matched cohort was established, consisting of 40 patients in both the sivelestat and control groups. The primary outcome measure encompassed a composite of adverse outcomes, including 30-day mortality, ALI, acute respiratory distress syndrome (ARDS), and others. Secondary outcomes assessed included pneumonia, ventricular arrhythmias, mechanical ventilation (MV) time, and more. Results: After conducting propensity matching in our study, we observed that there were no significant differences in 30-day mortality between the sivelestat and control groups (0% vs 2.5%, P=0.32). However, the use of sivelestat exhibited a significant reduction in the incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) compared to the control group (0% vs 55%, P<0.01), pneumonia (0 vs 37.5%, P<0.01), MV time (median:8 hours, IQR:4-14.8 hours vs median: 15.2 hours, IQR:14-16.3 hours, P<0.01). Compared to the control group, the sivelestat could significantly decrease white cell count (P<0.01), neutrophile percentage (P<0.01) and C-reactive protein (P<0.01) in the period of postoperative 5 days. Conclusion: The prophylactic administration of sivelestat has shown promising results in reducing the occurrence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with a heightened risk of developing these conditions after elective cardiac surgery. Our study findings indicate that sivelestat may provide protective effects by suppressing inflammation triggered by neutrophil activation, thereby safeguarding pulmonary function. Registration: ChiCTR2200059102, https://www.chictr.org.cn/showproj.html?proj=166643.