Astrocytic GDNF ameliorates anesthesia and surgery-induced cognitive impairment by promoting hippocampal synaptic plasticity in aged mice.

BACKGROUND: Perioperative neurocognitive disorders (PND) are common complications after surgery in older patients. However, the specific mechanism of this condition remains unclear. Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophin that abundantly expressed throughout the brain. It can enhance synaptic plasticity and alleviate learning and memory impairments. Thus, the purpose of this study was to investigate the role of GDNF in PND and the mechanisms involved. METHODS: The PND animal model was established by performing left tibial fracture surgery on 18-month-old C57BL/6 mice under sevoflurane anesthesia. Recombinant adeno-associated virus (rAAV)-GDNF or empty vectors were injected bilaterally into the hippocampal CA1 region of aged mice 3 weeks before anesthesia/surgery. The open field and fear conditioning test were used to assess the behavior changes. Golgi staining and electrophysiology were utilized to evaluate the morphological and functional alterations of neuronal synaptic plasticity. Western blot analysis was carried out to measure the proteins expression levels and immunofluorescence staining was performed to probe the cellular localization of GDNF. RESULTS: Mice with surgery and anesthesia showed a significant decrease in hippocampus-dependent learning and memory, accompanied by a decline in hippocampal synaptic plasticity. Anesthesia/surgery induced a reduction of GDNF, which was colocalized with astrocytes. Overexpression of GDNF in astrocytes could ameliorate the decline in cognitive function by improving hippocampal synaptic plasticity, meanwhile astrocytic GDNF rescued the anesthesia/surgery-induced decrease in GFRα1 and NCAM. CONCLUSION: The study concludes that astrocytic GDNF may improve anesthesia/surgery-induced cognitive impairment by promoting hippocampal synaptic plasticity in aged mice via the GFRα1/NCAM pathway.

Toxicity and fate of cadmium in hydroponically cultivated lettuce (Lactuca sativa L.) influenced by microplastics.

Although more attention has been paid to microplastics (MPs) pollution in environment, research on the synthetic influence of microplastic and heavy metals remains limited. To help fill this information gap, we investigated the adsorption behavior of virgin polyvinyl chloride microplastics (PVCMPs) (≤450 µm white spherical powder) on cadmium (II). The effects on seed germination, seedling growth, photosynthetic system, oxidative stress indicators of lettuce, and changes in Cd bioavailability were evaluated under Cd2+ (25 µmol/L), PVCMPs (200 mg/L), and PVCMP-Cd combined (200 mg/L + 25 µmol/L) exposures in hydroponic system. The results demonstrated that the PVCMPs effectively adsorbed Cd ions, which validated by the pseudo-second-order kinetic and the Langmuir isotherm models, indicating the sorption of Cd2+ on the PVCMPs was primary chemisorption and approximates monomolecular layer sorption. Compared to MPs, Cd significantly inhibits plant seed germination and seedling growth and development. However, Surprising improvement in seed germination under PVCMPs-Cd exposure was observed. Moreover, Cd2+ and MPs alone or combined stress caused oxidative stress with reactive oxygen species (ROS) including H2O2, O2- and Malondialdehyde (MDA) accumulation in plants, and substantially damaged to photosynthesis. With the addition of PVCMPs, the content of Cd in the leaves significantly (P<0.01) decreased by 1.76-fold, and the translocation factor and Cd2+removal rate in the water substantially (P<0.01) decreased by 6.73-fold and 1.67-fold, respectively in contrast to Cd2+ stress alone. Therefore, it is concluded the PVCMP was capable of reducing Cd contents in leaves, alleviating Cd toxicity in lettuce. Notably, this study provides a scientific foundation and reference for comprehending the toxicological interactions between microplastics and heavy metals in the environment.

New advances in the treatment of chondrosarcoma under the PD-1/PD-L1 pathway.

ABSTRACT: Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.

Efficacy and Perioperative Safety of Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer.

Background: Esophageal cancer (EC) remains a significant global health concern. Minimally invasive surgical techniques, including robot-assisted approaches, have emerged as promising options for improving outcomes and patient recovery in EC management. Objective: This study aims to evaluate the clinical utility of robot-assisted minimally invasive esophagectomy (RAMIE) in the treatment of EC. Methods: A total of 160 EC patients undergoing treatment at our hospital were included in this study. Patients were randomly assigned to either the research group, receiving RAMIE, or the control group, undergoing thoracoscopic minimally invasive esophagectomy (MIE). Surgical outcomes, postoperative recovery, complication rates, and changes in inflammatory factors (IFs) such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were compared between the two groups. Additionally, prognostic survival and EC recurrence rates were assessed at a 1-year follow-up. Results: The research group demonstrated longer operative times, a higher number of dissected lymph nodes, reduced intraoperative bleeding, and quicker postoperative recovery compared to the control group, with significantly fewer complications (P < .05). Furthermore, the research group exhibited lower levels of postoperative IFs and MDA, along with higher levels of SOD and GSH-Px, compared to the control group (P < .05). There was no significant difference between the two groups in terms of prognostic survival and EC recurrence rates (P > .05). Conclusion: RAMIE demonstrates superior efficacy in enhancing therapeutic outcomes and accelerating postoperative recovery in patients with EC, thus establishing its value in EC treatment protocols. RAMIE is suggested as a valuable therapeutic option and warrants clinical adoption for EC management.

Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives. METHODS: Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites. RESULTS: High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites. CONCLUSIONS: Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.

Automatic measurement of lower limb alignment in portable devices based on deep learning for knee osteoarthritis.

BACKGROUND: For knee osteoarthritis patients, analyzing alignment of lower limbs is essential for therapy, which is currently measured from standing long-leg radiographs of anteroposterior X-ray (LLR) manually. To address the time wasting, poor reproducibility and inconvenience of use caused by existing methods, we present an automated measurement model in portable devices for assessing knee alignment from LLRs. METHOD: We created a model and trained it with 837 conforming LLRs, and tested it using 204 LLRs without duplicates in a portable device. Both manual and model measurements were conducted independently, then we recorded knee alignment parameters such as Hip knee ankle angle (HKA), Joint line convergence angle (JCLA), Anatomical mechanical angle (AMA), mechanical Lateral distal femoral angle (mLDFA), mechanical Medial proximal tibial angle (mMPTA), and the time required. We evaluated the model's performance compared with manual results in various metrics. RESULT: In both the validation and test sets, the average mean radial errors were 2.778 and 2.447 (P<0.05). The test results for native knee joints showed that 92.22%, 79.38%, 87.94%, 79.82%, and 80.16% of the joints reached angle deviation<1° for HKA, JCLA, AMA, mLDFA, and mMPTA. Additionally, for joints with prostheses, 90.14%, 93.66%, 86.62%, 83.80%, and 85.92% of the joints reached that. The Chi-square test did not reveal any significant differences between the manual and model measurements in subgroups (P>0.05). Furthermore, the Bland-Altman 95% limits of agreement were less than ± 2° for HKA, JCLA, AMA, and mLDFA, and slightly more than ± 2 degrees for mMPTA. CONCLUSION: The automatic measurement tool can assess the alignment of lower limbs in portable devices for knee osteoarthritis patients. The results are reliable, reproducible, and time-saving.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

[Corrigendum] Upregulation of centromere protein M promotes tumorigenesis: A potential predictive target for cancer in humans.

Subsequently to the publication of this paper, the authors' have realized that Fig. 2A on p. 3927 was published featuring an error; specifically, there was an unintentional duplication of one of the representative images chosen for the figure (the same image was selected to represent the 'BRCA/Normal' and 'Tumor/LUSC' experiments). Additionally, the sample numbers in Fig. 2A were also incorrect. The correct sample numbers are as follows: 3 samples of breast tissue, 12 samples of breast cancer tissue, 3 samples of normal cervical tissue, 9 samples of CESC, 7 samples of LIHC, 3 samples of normal lung tissue and 6 samples of LUSC. These errors were due to negligence during the storage of HPA database images.  The revised version of Fig. 2, showing the correct data for the 'Tumor/LUSC' experiment in Fig. 2A (where the error occurred), is shown on the next page. Note that this error did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to the corrigendum. The authors do stress the importance of a larger sample size to ascertain statistically significant differences in CENPM protein expression, predominantly localized in the cell nucleus. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 3922­3934, 2020; DOI: 10.3892/mmr.2020.11461].

ALKBH5 facilitates the progression of infantile hemangioma by increasing FOXF1 expression in a m6A-YTHDF2 dependent manner to activate HK-2 signaling.

Alkylation repair homolog protein 5 (ALKBH5) is reported to participate in infantile hemangioma (IH) progression. However, the underlying mechanism of ALKBH5 in IH remains unclear. Using qRT-PCR and Western blotting, ALKBH5, forkhead box F1 (FOXF1) and hexokinase 2 (HK-2) expressions in IH tissues and IH-derived endothelial cells XPTS-1 were assessed. The Me-RIP assay was used to analyze FOXF1 m6A level. CCK8, colony formation, flow cytometry and transwell assays were employed to determine IH cell viability, proliferation, apoptosis, migration and invasion. The interactions between YTH (YT521-B homology) domain 2 (YTHDF2), FOXF1 and HK-2 were analyzed by RIP, dual luciferase reporter gene assay and/or ChIP assay. The in vivo IH growth was evaluated in immunocompromised mice. FOXF1 was overexpressed in IH tissues, and its silencing inhibited IH cell proliferation, migration and invasion whereas promoting cell apoptosis in vitro. ALKBH5 upregulation facilitated FOXF1 mRNA stability and expression in IH cells in a m6A-YTHDF2-dependent manner. FOXF1 downregulation reversed the impact of ALKBH5 upregulation on IH cellular phenotypes. It also turned out that FOXF1 positively regulated HK-2 expression in IH cells through interacting with the HK-2 promoter. HK-2 upregulation abolished FOXF1 knockdown's inhibition on IH cell aggressive behaviors. ALKBH5 or FOXF1 silencing suppressed IH tumor development via HK-2 signaling in immunocompromised mice. ALKBH5 promoted FOXF1 expression m6A-YTHDF2 dependently, which in turn elevated HK-2 expression, thereby accelerating IH development.

ANP32B promotes colorectal cancer cell progression and reduces cell sensitivity to PRAP1 inhibitor through up-regulating HPF1.

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 family member B, is aberrantly expressed in various cancers, including colorectal cancer. However, the function and mechanism of action of ANP32B in colorectal cancer remain unclear. The present study therefore analyzed the expression of ANP32B and its activity in colorectal cancer patient samples and colorectal cancer cell lines. ANP32B expression was found to be significantly upregulated in colorectal cancer patient samples and cell lines. Upregulation of ANP32B enhanced colorectal cancer cell proliferation and migration, whereas downregulation of ANP32B suppressed colorectal cancer cell proliferation. RNA sequencing analysis of differentially expressed genes in ANP32B silenced colorectal cancer cells showed that histone PARylation factor 1 (HPF1), which protects against DNA damage by interacting with the anti-tumor target PARP1, was significantly downregulated. Luciferase promoter assays testing the regulatory association between ANP32B and HPF1 showed that ANP32B interacted with the HPF1 promoter. Analysis of colorectal cancer samples from The Cancer Genome Atlas showed that ANP32B and HPF1 expression were positively correlated, and recovery assays showed that ANP32B promoted colorectal cancer progression by up-regulating HPF1. Overexpression of ANP32B also reduced the sensitivity of colorectal cancer cells to PARP1 inhibitor, consistent with the oncogenic role of ANP32B. ANP32B may alter the sensitivity of colorectal cancer cells to PARP1 inhibitor via a mechanism associated with the HPF1 gene. In summary, these findings showed that ANP32B acted as a tumor promoter, potentiating both colorectal cancer malignancy and drug resistance. Targeting the ANP32B/HPF1 axis may have benefit for patients with colorectal cancer.

Dual-Targeted Metal Ion Network Hydrogel Scaffold for Promoting the Integrated Repair of Tendon-Bone Interfaces.

The tendon-bone interface has a complex gradient structure vital for stress transmission and pressure buffering during movement. However, injury to the gradient tissue, especially the tendon and cartilage components, often hinders the complete restoration of the original structure. Here, a metal ion network hydrogel scaffold, with the capability of targeting multitissue, was constructed through the photopolymerization of the LHERHLNNN peptide-modified zeolitic imidazolate framework-8 (LZIF-8) and the WYRGRL peptide-modified magnesium metal-organic framework (WMg-MOF) within the hydrogel scaffold, which could facilitate the directional migration of metal ions to form a dynamic gradient, thereby achieving integrated regeneration of gradient tissues. LZIF-8 selectively migrated to the tendon, releasing zinc ions to enhance collagen secretion and promoting tendon repair. Simultaneously, WMg-MOF migrated to cartilage, releasing magnesium ions to induce cell differentiation and facilitating cartilage regeneration. Infrared spectroscopy confirmed successful peptide modification of nano ZIF-8 and Mg-MOF. Fluorescence imaging validated that LZIF-8/WMg-MOF had a longer retention, indirectly confirming their successful targeting of the tendon-bone interface. In summary, this dual-targeted metal ion network hydrogel scaffold has the potential to facilitate synchronized multitissue regeneration at the compromised tendon-bone interface, offering favorable prospects for its application in the integrated reconstruction characterized by the gradient structure.

A Smartphone Application-Based Remote Rehabilitation System for Post-Total Knee Arthroplasty Rehabilitation: A Randomized Controlled Trial.

BACKGROUND: Remote rehabilitation after total knee arthroplasty has gradually gained popularity in recent years. This study aimed to determine whether smartphone application-based remote rehabilitation could outperform home-based rehabilitation and outpatient guidance in terms of 12-week outcomes following primary unilateral total knee arthroplasty. METHODS: Patients who underwent primary unilateral total knee arthroplasty were recruited and randomly divided into a telerehabilitation group and a control group. A total of 100 patients were examined, with 50 each assigned to the telerehabilitation and control groups. In the telerehabilitation group, a telerehabilitation application was installed on the smartphones of the participants to allow postdischarge guidance. The primary outcomes were knee range of motion (ROM) at 12 weeks postoperatively. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Society Score, The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), Five Times Sit-to-Stand Test (5xSST), Single-Leg Stance Test (SLST), satisfaction, rehabilitation costs, complication rate, and 90-day readmission rate. All outcomes were collected at 2, 6, and 12 weeks after surgery. RESULTS: At 12 weeks postoperatively, the telerehabilitation patients significantly outperformed the controls in terms of knee ROM (124 ± 8.7 versus 119 ± 5.5 P = .01), SF-36 (physiological function) (61.5 ± 20.3 versus 45.5 ± 18.1 P = .000), SF-36 (role-physical) (49.3 ± 41.5 versus 27.7 ± 28.9 P = .012), SLST (13.0 ± 9.1 versus 9.1 ± 5.9 P = .026), and 5xSST (17.7 ± 4.3 versus 19.4 ± 3.5 P = .043). No significant differences were found between groups in the Western Ontario and McMaster Universities Osteoarthritis Index score, Knee Society Score, rehabilitation costs, 90-day readmission rate, or incidence of adverse events. CONCLUSION: Our study showed that smartphone app-based remote rehabilitation worked better than home-based rehabilitation with outpatient guidance in terms of short-term results in ROM, SLST, and 5xSST.

USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.

Ubiquitin-specific protease 4 (USP4) represents a potential oncogene involved in various human cancers. Nevertheless, the biological roles and precise mechanism of USP4 in esophageal squamous cell carcinoma (ESCC) progression are not understood. Here, USP4 expression was found to be markedly upregulated in ESCC tumor tissues and cells. Loss- and gain-of-function assays suggested that USP4 silencing inhibited ESCC cell proliferation, migration, and invasion, while USP4 overexpression promoted these behaviors. Consistently, USP4 silencing repressed tumor growth and metastasis in an ESCC nude mouse model in vivo. As a target molecule of USP4, transforming growth factor-ß-activated kinase 1 (TAK1) also showed high expression in ESCC. Moreover, we observed that USP4 specifically interacted with TAK1 and stabilized TAK1 protein levels via deubiquitination in ESCC cells. Importantly, USP4 promotes ESCC proliferation, migration, and invasion via the MEK/ERK signaling pathway and can be inhibited by U0126. Neutral red (NR), an inhibitor of USP4 can suppress ESCC progression in vitro and in vivo. Overall, this study revealed that USP4/TAK1 plays crucial roles in ESCC progression by modulating proliferation, migration, and invasion, and USP4 might be a potential therapeutic target in ESCC.

Corn peptides attenuate non-alcoholic fatty liver disease via PINK1/Parkin-mediated mitochondrial autophagy.

Background: Corn peptides, a novel food prepared from corn gluten meal (CGM) by enzymatic hydrolysis or microbial fermentation, have attracted considerable interest owing to their various bioactive properties. However, the underlying mechanism of corn peptides attenuate non-alcoholic fatty liver disease (NAFLD) remains unclear. Objective: This study aimed to investigate the effect of corn peptides in NAFLD and to decipher the underlying mechanisms. Design: NAFLD was induced by a high-fat diet (HFD) for 10 weeks. Corn peptides were administered during the period. Human hepatocellular carcinomas (HepG2) cells induced by free fatty acids were used for this mechanism study. Results: Corn peptides alleviated HFD-induced histopathological changes, disorders of lipid metabolism, and mitochondrial damage. Moreover, corn peptides blocked mitophagy suppression by HFD based on the increased LC3, ATG7 expressions, as well as decreased P62 levels. Corn peptides increased the expression of proteins involved in fatty acid ß-oxidation, such as PPARα and PGC-1α. Corn peptides also improved the Ser/Thr kinase PINK1 (PINK1) and the E3 ubiquitin ligase Parkin (Parkin) translocation to mitochondria, which is confirmed by immunofluorescence. Furthermore, stable knockdown of PINK1 by PINK1 SiRNA in HepG2 inhibited PINK1-Parkin-associated mitophagy and resulted in lipid accumulation. Conclusion: Corn peptides improved cell injury and ameliorated mitochondrial dysfunction and lipid accumulation via PINK1/Parkin-mediated autophagy in NAFLD. Thus, corn peptides could be a promising nutritional molecule with natural functions for preventing NAFLD.

Unilateral biportal endoscopic transforaminal lumbar interbody fusion versus conventional interbody fusion for the treatment of degenerative lumbar spine disease: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis compares the efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) to conventional interbody fusion in lumbar degenerative diseases (LDD). METHODS: An extensive literature search was conducted in PubMed, Web of Science, and the Cochrane Library. Research related to UBE-TLIF published up to November 2022 was reviewed. The relevant articles were selected based on inclusion and exclusion criteria, as well as an evaluation of the quality of the data extraction literature. Meta-analysis was performed using Review Manager 5.3 software. RESULTS: This meta-analysis included six high-quality case-control trials (CCTs) involving 621 subjects. The clinical outcomes assessment showed no statistical differences in complication rates, fusion rates, leg pain VAS scores, or ODI scores. After UBE-TLIF, low back pain VAS scores were significantly improved with less intraoperative blood loss and a shorter hospital stay. A longer time was required for UBE-TLIF, however. CONCLUSION: Despite the lack of sufficient high quality randomized controlled trials (RCTs) in this study, the results of this meta-analysis suggest that UBE-TLIF is more effective than open surgery in terms of length of stay, blood loss reduction during surgery, and improved low back pain after surgery. Nevertheless, the evidence will be supplemented in the future by more and better quality multicenter randomized controlled trials.

The accordion technique enhances bone regeneration via angiogenesis factor in a rat distraction osteogenesis model.

Objective: The purpose of this study was to observe the effect of the accordion technique (AT) during the distraction phase on chondrogenesis and bone regeneration in a rat femoral distraction osteogenesis (DO) model, and investigate its potential mechanism for reducing the total treatment time of DO. Methods: Fifty-four male Sprague-Dawley (SD) rats that were specific-pathogen-free (SPF) were subjected to DO surgery on the right femur. The distraction rate was 0.5 mm/day for 10 days, following a latency period of 5 days. Rats were randomly divided into Control (no AT, n = 18), Group LA (low amplitude with AT, n = 18), and Group HA (high amplitude with AT, n = 18) according to different AT protocols in the distraction phase. Rats were respectively euthanized by anesthesia overdose at 2, 4 and 6 weeks of the consolidation phase, and the femurs were harvested. Digital radiography, micro-computed tomography (micro-CT), biomechanical tests, and histomorphological analysis were used to assess the quality of regenerated bone in the distraction area. Results: Digital radiographic, micro-CT, biomechanical tests, and histological analysis revealed an increase in early-stage callus formation (p < 0.05) and improved blood supply to the callus tissue in Group LA, as compared to both the Control and Group HA. The enhanced differentiation of fibrous and cartilaginous tissue into bone tissue was also observed in Group LA, leading to improved strength and stiffness (p < 0.05) of the regenerated bone at 6 weeks of the consolidation phase. The angiogenic (hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), p < 0.05) and osteogenic (runt-related transcription factor 2 (RUNX2), osteocalcin (OCN) and osteopontin (OPN), p < 0.05) biomarkers were higher expressed in Group LA at 2 and 4 weeks of consolidation phase, whereas decreased at 6 weeks of consolidation phase. Conclusion: The application of AT with low amplitude during the distraction phase can enhance chondrogenesis and bone regeneration by activating the angiogenesis factor pathway and upregulating the expression of osteogenic-related biomarkers such as HIF-1α, VEGF, RUNX2, OCN, and OPN.

Parental presence during induction of anesthesia in children undergoing tonsillectomy and adenoidectomy.

OBJECTIVE: To investigate the effect of parental presence during induction of anesthesia (PPIA) in relieving preoperative anxiety of children undergoing tonsillectomy and adenoidectomy. METHODS: One hundred and sixty children undergoing tonsillectomy and adenoidectomy were divided into the control group and the trial group. The control group received routine nursing in the operation room, while anesthesia was induced in the trial group children in the presence of their parents as part of the routine nursing. The differences in heart rate and mean dynamic pressure during pre-operative visit and anesthesia induction between the two groups were observed and recorded. The Modified Yale Preoperative Anxiety Scale (m-YPAS) and the Induction Compliance Checklist (ICC) were scored. The anxiety status of the children and their family members in the two groups was scored at different times, and the psychological stress of anesthesiologists during anesthesia induction was scored by a visual analogue scale. The differences in each index between the two groups were compared. Operation time and costs in-hospital were also compared. RESULTS: Compared with the control group, the heart rate and blood pressure scores as well as the ICC in the trial group were lower than those in the control group (P < 0.01). On comparing the scores of m-YPAS between the two groups, we observed that the scores of the children in the trial group were lower than those in the control group before entering the induction room and anesthesia induction (P < 0.01). There was no statistical difference between the scores of the children in the trial group and the control group on the day of operation and on the way to the operating room (P > 0.05). The nursing satisfaction scores of the family members in the trial group were significantly superior to those in the control group (P < 0.01). The scores of the visual analogue scale for psychological pressure of anesthesiologists during anesthesia induction were higher in the trial group than in the control group (P < 0.05). The operation time and costs in study group were both significantly higher than those of control group (P < 0.05). CONCLUSION: PPIA can significantly reduce preoperative anxiety and surgical physiological stress response in children undergoing tonsillectomy and adenoidectomy, and it is worth being encouraged.

TIMELESS promotes the proliferation and migration of lung adenocarcinoma cells by activating EGFR through AMPK and SPHK1 regulation.

BACKGROUND: Lung adenocarcinoma (LUAD) has high morbidity and is prone to recurrence. TIMELESS (TIM), which regulates circadian rhythms in Drosophila, is highly expressed in various tumors. Its role in LUAD has gained attention, but the detailed function and mechanism have not been clarified completely at present. METHODS: Tumor samples from patients with LUAD patient data from public databases were used to confirm the relationship of TIM expression with lung cancer. LUAD cell lines were used and siRNA of TIM was adopted to knock down TIM expression in LUAD cells, and further cell proliferation, migration and colony formation were analyzed. By using Western blot and qPCR, we detected the influence of TIM on epidermal growth factor receptor (EGFR), sphingosine kinase 1 (SPHK1) and AMP-activated protein kinase (AMPK). With proteomics analysis, we comprehensively inspected the different changed proteins influenced by TIM and did global bioinformatic analysis. RESULTS: We found that TIM expression was elevated in LUAD and that this high expression was positively correlated with more advanced tumor pathological stages and shorter overall and disease-free survival. TIM knockdown inhibited EGFR activation and also AKT/mTOR phosphorylation. We also clarified that TIM regulated the activation of SPHK1 in LUAD cells. And with SPHK1 siRNA to knock down the expression level of SPHK1, we found that EGFR activation were inhibited greatly too. Quantitative proteomics techniques combined with bioinformatics analysis clarified the global molecular mechanisms regulated by TIM in LUAD. The results of proteomics suggested that mitochondrial translation elongation and termination were altered, which were closely related to the process of mitochondrial oxidative phosphorylation. We further confirmed that TIM knockdown reduced ATP content and promoted AMPK activation in LUAD cells. CONCLUSIONS: Our study revealed that siTIM could inhibit EGFR activation through activating AMPK and inhibiting SPHK1 expression, as well as influencing mitochondrial function and altering the ATP level; TIM's high expression in LUAD is an important factor and a potential key target in LUAD.

"Early Efficacy and Safety of Unilateral Biportal Endoscopic Lumbar Interbody Fusion Versus Minimal Invasive in the Treatment of Lumbar Degenerative Diseases".

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To compare the early clinical efficacy and radiologic outcomes between unilateral biportal endoscopic lumbar interbody fusion (ULIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). SUMMARY OF BACKGROUND DATA: Along with the continuous development of endoscopic technology, the early safety and effectiveness of ULIF technology are still unknown. MATERIALS AND METHODS: This retrospective study included 61 patients who underwent fusion surgery through ULIF or MIS-TLIF in 2021. Twenty-nine patients underwent ULIF (group A), and 32 underwent MIS-TLIF (group B). Fusion rate, bone graft volume, hidden blood loss (HBL), C-reactive protein level, operative time, Oswestry Disability Index , Visual Analog Scale score, and MacNab criteria were assessed in both groups. RESULTS: The Visual Analog Scale score for back pain in the early postoperative period was significantly lower in group A than in group B ( P <0.05). All other clinical scores showed improvement, with no significant difference between the 2 groups ( P >0.05). There was no statistically significant difference in postoperative C-reactive protein levels and fusion rates between the 2 groups ( P >0.05). However, HBL was higher and operative time was longer in group A than in group B ( P <0.05). Most importantly, there were no statistically significant differences between groups A and B in fusion rate, length of stay and bone graft volume ( P >0.05). No serious surgical complications occurred in our study. CONCLUSIONS: ULIF is a new option for lumbar fusion. Despite the drawbacks of longer operation time and higher HBL, ULIF may be a viable alternative to MIS-TLIF as technology advances.

HOXD-AS2-STAT3 feedback loop attenuates sensitivity to temozolomide in glioblastoma.

AIMS: Glioblastoma multiforme (GBM) is the deadliest glioma and its resistance to temozolomide (TMZ) remains intractable. Long non-coding RNAs (lncRNAs) play crucial roles in that and this study aimed to investigate underlying mechanism of HOXD-AS2-affected temozolomide sensitivity in glioblastoma. METHODS: We analyzed and validated the aberrant HOXD-AS2 expression in glioma specimens. Then we explored the function of HOXD-AS2 in vivo and in vitro and a clinical case was also reviewed to examine our findings. We further performed mechanistic experiments to investigate the mechanism of HOXD-AS2 in regulating TMZ sensitivity. RESULTS: Elevated HOXD-AS2 expression promoted progression and negatively correlated with prognosis of glioma; HOXD-AS2 attenuated temozolomide sensitivity in vitro and in vivo; The clinical case also showed that lower HOXD-AS2 sensitized glioblastoma to temozolomide; STAT3-induced HOXD-AS2 could interact with IGF2BP2 protein to form a complex and sequentially upregulate STAT3 signaling, thus forming a positive feedback loop regulating TMZ sensitivity in glioblastoma. CONCLUSION: Our study elucidated the crucial role of the HOXD-AS2-STAT3 positive feedback loop in regulating TMZ sensitivity, suggesting that this could be provided as a potential therapeutic candidate of glioblastoma.