Boosting Monolayer Transition Metal Dichalcogenides Growth by Hydrogen-Free Ramping during Chemical Vapor Deposition.

The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H2) in their synthesis. Using CVD growth of MoSe2 as an example, this study illustrates the role of a H2-free environment during temperature ramping in suppressing the reduction of MoO3, which promotes effective vaporization and selenization of the Mo precursor to form MoSe2 monolayers with excellent crystal quality. As-synthesized MoSe2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm2/(V·s) with an on-off ratio of 7 × 107. This approach can be extended to other TMDs, such as WSe2, MoTe2, and MoSe2/WSe2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Consistent efficacy of hepatic artery infusion chemotherapy irrespective of PD­L1 positivity in unresectable hepatocellular carcinoma.

Atezolizumab/bevacizumab is the first line of treatment for unresectable hepatocellular carcinoma (HCC), combining immune checkpoint inhibitor and anti-VEGF monoclonal antibodies. Hepatic arterial infusion chemotherapy (HAIC) is administered when the above-described combination fails to confer sufficient clinical benefit. The present study aimed to explore the association between tumor programmed cell death-ligand 1 (PD-L1) positivity and HAIC response. A total of 40 patients with HCC who had undergone HAIC with available biopsy samples obtained between January 2020 and May 2023 were retrospectively enrolled. Tumor response, progression-free survival (PFS), disease control rate (DCR) and overall survival (OS) were evaluated. PD-L1 expression in tumor samples was assessed using a combined positivity score. The response rates of HAIC-treated patients with advanced HCC after failure of atezolizumab/bevacizumab combination therapy were recorded. OS (P=0.9717) and PFS (P=0.4194) did not differ between patients with and without PD-L1 positivity. The objective response rate (P=0.7830) and DCR (P=0.7020) also did not differ based on PD-L1 status. In conclusion, the current findings highlight the consistent efficacy of HAIC, regardless of PD-L1 positivity.

Compact Solid Electrolyte Interface Realization Employing Surface-Modified Fillers for Long-Lasting, High-Performance All-Solid-State Li-Metal Batteries.

The implementation of polymer-based Li-metal batteries is hindered by their low coulombic efficiency and poor cycling stability attributed to continuous electrolyte decomposition. Enhancement of the solid electrolyte interface (SEI) stability is key to mitigating electrolyte decomposition. This study proposes surface-functionalized silica mesoball fillers to fabricate a composite polymer electrolyte (MSBM-CPE). As a result of surface modification, the polyethylene oxide matrix benefits from the uniform distribution of the filler, which provides a large surface area and Lewis acid sites. Molecular dynamics simulations reveal that the dissociation energy of lithium bis(trifluoromethanesulfonyl)imide in the filler is fourfold higher (-1.95 eV) than that of the filler-free electrolyte. Consequently, the MSMB-CPE diffusivity is 30 times higher than its filler-free counterpart. The MSMB-CPE of ionic conductivity of 1.16 × 10-2 S cm-1 @60 °C and a venerable Li-ion transference number of 0.81. The excellent compatibility of MSMB-CPE with the Li anode is demonstrated by its stable symmetric cell performance under high current density (200 µA cm-2 @60 °C) for over 5000 h. Approximately 85.60% retention capacity of the [Li/MSMB-CPE/LiFePO4] full cell after 700 cycles. Furthermore, compositional analysis reveals that the SEI layer in MSMB-CPE is smooth with fewer by-products at the electrolyte/Li interface.

Effect of endocrine-disrupting chemicals on the expression of a calcium ion channel receptor (ryanodine receptor) in the mud crab (Macrophthalmus japonicus).

Endocrine-disrupting chemicals (EDCs) are toxic pollutants generated by artificial activities. Moreover, their hormone-like structure induces disturbances, such as mimicking or blocking metabolic activity. Previous studies on EDCs have focused on the adverse effect of the endocrine system in vertebrates, with limited investigations conducted on ion channels in invertebrates. Thus, in this study, we investigated the potential adverse effects of exposure to bisphenol-A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) at the molecular level on the ryanodine receptor (RyR), a calcium ion channel receptor in Macrophthalmus japonicus. In the phylogenetic analysis, the RyR amino acid sequences in M. japonicus clustered with those in the Crustacean and formed separated branches for RyR in insects and mammals. When exposed to 1 µg L-1 BPA, a significant increase in RyR mRNA expression was observed in the gills on day 1, although a similar level to the control group was observed from day 4 to day 7. However, the RyR expression due to DEHP exposure decreased on days 1 and 4, although it increased on day 7 following exposure to 10 µg L-1. The RyR expression pattern in the hepatopancreas increased for up to 4 days, depending on the BPA concentration. However, there was a tendency for the expression to decrease gradually after the statistical significance increased during the early stage of DEHP exposure (D1). Hence, the transcriptional alterations in the M. japonicus RyR gene observed in the study suggest that exposure toxicities to EDCs, such as BPA and DEHP, have the potential to disrupt calcium ion channel signaling in the gills and hepatopancreas of M. japonicus crabs.

Computational analysis of electrode structure and configuration for efficient and localized neural stimulation.

Neuromodulation technique using electric stimulation is widely applied in neural prosthesis, therapy, and neuroscience research. Various stimulation techniques have been developed to enhance stimulation efficiency and to precisely target the specific area of the brain which involves optimizing the geometry and the configuration of the electrode, stimulation pulse type and shapes, and electrode materials. Although the effects of electrode shape, size, and configuration on the performance of neural stimulation have individually been characterized, to date, there is no integrative investigation of how this factor affects neural stimulation. In this study, we computationally modeled the various types of electrodes with varying shapes, sizes, and configurations and simulated the electric field to calculate the activation function. The electrode geometry is then integratively assessed in terms of stimulation efficiency and stimulation focality. We found that stimulation efficiency is enhanced by making the electrode sharper and smaller. A center-to-vertex distance exceeding 100 µm shows enhanced stimulation efficiency in the bipolar configuration. Additionally, the separation distance of less than 1 mm between the reference and stimulation electrodes exhibits higher stimulation efficiency compared to the monopolar configuration. The region of neurons to be stimulated can also be modified. We found that sharper electrodes can locally activate the neuron. In most cases, except for the rectangular electrode shape with a center-to-vertex distance smaller than 100 µm, the bipolar electrode configuration can locally stimulate neurons as opposed to the monopolar configuration. These findings shed light on the optimal selection of neural electrodes depending on the target applications.

Targeting of CYP2E1 by miRNAs in alcohol-induced intestine injury.

Although binge alcohol-induced gut leakage has been studied extensively in the context of reactive oxygen species-mediated signaling, it was recently revealed that post-transcriptional regulation plays an essential role as well. Ethanol (EtOH)-inducible cytochrome P450-2E1 (CYP2E1), a key enzyme in EtOH metabolism, promotes alcohol-induced hepatic steatosis and inflammatory liver disease, at least in part by mediating changes in intestinal permeability. For instance, gut leakage and elevated intestinal permeability to endotoxins have been shown to be regulated by enhancing CYP2E1 mRNA and CYP2E1 protein levels. Although it is understood that EtOH promotes CYP2E1 induction and activation, the mechanisms that regulate CYP2E1 expression in the context of intestinal damage remain poorly defined. Specific miRNAs, including miR-132, miR-212, miR-378, and miR-552, have been shown to repress the expression of CYP2E1, suggesting that these miRNAs contribute to EtOH-induced intestinal injury. Here, we have shown that CYP2E1 expression is regulated post-transcriptionally through miRNA-mediated degradation, as follows: (1) the RNA-binding protein AU-binding factor 1 (AUF1) binds mature miRNAs, including CYP2E1-targeting miRNAs, and this binding modulates the degradation of corresponding target mRNAs upon EtOH treatment; (2) the serine/threonine kinase mammalian Ste20-like kinase 1 (MST1) mediates oxidative stress-induced phosphorylation of AUF1. Those findings suggest that reactive oxygen species-mediated signaling modulates AUF1/miRNA interaction through MST1-mediated phosphorylation. Thus, our study demonstrates the critical functions of AUF1 phosphorylation by MST1 in the decay of miRNAs targeting CYP2E1, the stabilization of CYP2E1 mRNA in the presence of EtOH, and the relationship of this pathway to subsequent intestinal injury.

Automatic Sleep Stage Classification Using Nasal Pressure Decoding Based on a Multi-Kernel Convolutional BiLSTM Network.

Sleep quality is an essential parameter of a healthy human life, while sleep disorders such as sleep apnea are abundant. In the investigation of sleep and its malfunction, the gold-standard is polysomnography, which utilizes an extensive range of variables for sleep stage classification. However, undergoing full polysomnography, which requires many sensors that are directly connected to the heaviness of the setup and the discomfort of sleep, brings a significant burden. In this study, sleep stage classification was performed using the single dimension of nasal pressure, dramatically decreasing the complexity of the process. In turn, such improvements could increase the much needed clinical applicability. Specifically, we propose a deep learning structure consisting of multi-kernel convolutional neural networks and bidirectional long short-term memory for sleep stage classification. Sleep stages of 25 healthy subjects were classified into 3-class (wake, rapid eye movement (REM), and non-REM) and 4-class (wake, REM, light, and deep sleep) based on nasal pressure. Following a leave-one-subject-out cross-validation, in the 3-class the accuracy was 0.704, the F1-score was 0.490, and the kappa value was 0.283 for the overall metrics. In the 4-class, the accuracy was 0.604, the F1-score was 0.349, and the kappa value was 0.217 for the overall metrics. This was higher than the four comparative models, including the class-wise F1-score. This result demonstrates the possibility of a sleep stage classification model only using easily applicable and highly practical nasal pressure recordings. This is also likely to be used with interventions that could help treat sleep-related diseases.

Optimizing the Amino Acid Sequence Enhances the Productivity and Bioefficacy of the RBP-Albumin Fusion Protein.

The significant growth of the global protein drug market, including fusion proteins, emphasizes the crucial role of optimizing amino acid sequences to enhance the productivity and bioefficacy. Among these fusion proteins, RBP-IIIA-IB, comprising retinol-binding protein in conjunction with the albumin domains, IIIA and IB, has displayed efficacy in alleviating liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs). This study aimed to address the issue of the low productivity in RBP-IIIA-IB. To induce structural changes, the linking sequence, EVDD, between domain IIIA and IB in RBP-IIIA-IB was modified to DGPG, AAAA, and GGPA. Among these, RBP-IIIA-AAAA-IB demonstrated an increase in yield (>4-fold) and a heightened inhibition of HSC activation. Furthermore, we identified amino acid residues that could form disulfide bonds when substituted with cysteine. Through the mutation of N453S-V480S in RBP-IIIA-AAAA-IB, the productivity further increased by over 9-fold, accompanied by an increase in anti-fibrotic activity. Overall, there was a more than 30-fold increase in the fusion protein's yield. These findings demonstrate the effectiveness of modifying linker sequences and introducing extra disulfide bonds to improve both the production yield and biological efficacy of fusion proteins.

Correction: Sung et al. Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy. Cancers 2022, 14, 3749.

In the original publication [...].

Clinical features and outcomes of posterior reversible encephalopathy syndrome after heart transplantation: a case series.

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease that may be associated with hypertension, autoregulatory failure, and the use of calcineurin inhibitors following heart transplantation (HT). In this article, we present a case series of PRES, discussing its potential causes and management strategies. Among the 126 HT recipients at our hospital, four were diagnosed with PRES. Three of these patients developed PRES within 7 days after HT. Prior to the onset of PRES, all patients experienced sustained hypertension, and strict blood pressure (BP) control was maintained. Three of the four patients recovered without PRES recurrence, while one patient died of sepsis after an episode of altered consciousness. Hypertension was observed in all patients prior to the onset of PRES, and the majority experienced symptom improvement with BP control. While most cases of PRES were reversible with conservative treatment, including the administration of antiepileptics, one irreversible case resulted in in-hospital mortality. Thus, PRES can have serious outcomes and is not invariably benign.

Effects of Light on the Fruiting Body Color and Differentially Expressed Genes in Flammulina velutipes.

Light plays vital roles in fungal growth, development, reproduction, and pigmentation. In Flammulina velutipes, the color of the fruiting body exhibits distinct changes in response to light; however, the underlying molecular mechanisms remain unknown. Therefore, in this study, we aimed to analyze the F. velutipes transcriptome under red, green, and blue light-emitting diode (LED) lights to identify the key genes affecting the light response and fruiting body color in this fungus. Additionally, we conducted protein-protein interaction (PPI) network analysis of the previously reported fruiting body color-related gene, Fvpal1, to identify the hub genes. Phenotypic analysis revealed that fruiting bodies exposed to green and blue lights were darker than those untreated or exposed to red light, with the color intensifying more after 48 h of exposure to blue light compared to that after 24 h of exposure. Differentially expressed gene (DEG) analyses of all light treatments for 24 h revealed that the numbers of DEGs were 17, 74, and 257 under red, green, and blue lights, respectively. Subsequently, functional enrichment analysis was conducted of the DEGs identified under green and blue lights, which influenced the color of F. velutipes. In total, 103 of 168 downregulated DEGs under blue and green lights were included in the enrichment analysis. Among the DEGs enriched under both green and blue light treatments, four genes were related to monooxygenases, with three genes annotated as cytochrome P450s that are crucial for various metabolic processes in fungi. PPI network analysis of Fvpal1 revealed associations with 11 genes, among which the expression of one gene, pyridoxal-dependent decarboxylase, was upregulated in F. velutipes exposed to blue light. These findings contribute to our understanding of the molecular mechanisms involved in the fruiting body color changes in response to light and offer potential molecular markers for further exploration of light-mediated regulatory pathways.

Automated Scoring of Alzheimer's Disease Atrophy Scale with Subtype Classification Using Deep Learning-Based T1-Weighted Magnetic Resonance Image Segmentation.

Background: Application of visual scoring scales for regional atrophy in Alzheimer's disease (AD) in clinical settings is limited by their high time cost and low intra/inter-rater agreement. Objective: To provide automated atrophy scoring using objective volume driven from deep-learning segmentation methods for AD subtype classification using magnetic resonance imaging (MRI). Methods: We enrolled 3,959 participants (1,732 cognitively normal [CN], 1594 with mild cognitive impairment [MCI], and 633 with AD). The occupancy indices for each regional volume were calculated by dividing each volume by the size of the lateral and inferior ventricular volumes. MR images from 355 participants (119 CN, 119 MCI, and 117 AD) from three different centers were used for validation. Two neuroradiologists performed visual assessments of the medial temporal, posterior, and global cortical atrophy scores in the frontal lobe using T1-weighted MR images. Images were also analyzed using the deep learning-based segmentation software, Neurophet AQUA. Cutoff values for the three scores were determined using the data distribution according to age. The scoring results were compared for consistency and reliability. Results: Four volumetric-driven scoring results showed a high correlation with the visual scoring results for AD, MCI, and CN. The overall agreement with human raters was weak-to-moderate for atrophy scoring in CN participants, and good-to-almost perfect in AD and MCI participants. AD subtyping by automated scores also showed usefulness as a research tool. Conclusions: Determining AD subtypes using automated atrophy scoring for late-MCI and AD could be useful in clinical settings or multicenter studies with large datasets.

Comparison of the transcranial approach and transsphenoidal approach based on the anatomical location of origin in pediatric craniopharyngiomas.

BACKGROUND: Various clinical classifications of craniopharyngiomas (CRPs) have been proposed to suggest optimal surgical planning. We aimed to evaluate the clinical outcomes of pediatric CRPs and the clinical significance of anatomical classification in relation to the diaphragm sellae. METHODS: A retrospective review was conducted on patients under 18 years of age who underwent surgery for CRPs from July 1998 to August 2022. The patients were divided into transcranial approach (TCA), and transsphenoidal approach (TSA) groups, which included microscopic TSA and endoscopic endonasal approach (EEA) groups. EEA has been adopted at our institute since 2011. CRPs were classified by their origin and relationship with the diaphragm sellae. RESULTS: A total of 132 pediatric CRP patients were included in this study, 117 of whom underwent surgery for primary CRP and 15 for recurrent CRP. Among them, 89 (67.4%) underwent TCA, 9 (6.8%) had microscopic TSA, and 34 (25.8%) had EEA. In subdiaphragmatic CRPs with competent diaphragm sellae, TSA tended to yield better outcomes than did TCA in terms of stalk preservation and ophthalmological outcomes. After the introduction of EEA, the proportion of supradiaphragmatic CRPs treated via the TSA increased from 0% to 50% (p < 0.001). Gross total resection (HR=0.194; 95% CI=0.102-0.367, p < 0.001) and adjuvant therapy (HR=0.208; 95% CI=0.048-0.897, p = 0.035) were found to be positive prognostic factors for long-term tumor control. CONCLUSIONS: Over time, with the adoption of EEA at our institute, the impact of anatomical classification on the surgical apprpoach has decreased. Nevertheless, an individualized surgical approach should be employed to improve long-term outcomes and minimize complications for pediatric CRPs.

Charged Black-Hole-Like Electronic Structure Driven by Geometric Potential of 2D Semiconductors.

One of the exotic expectations in the 2D curved spacetime is the geometric potential from the curvature of the 2D space, still possessing unsolved fundamental questions through Dirac quantization. The atomically thin 2D materials are promising for the realization of the geometric potential, but the geometric potential in 2D materials is not identified experimentally. Here, the curvature-induced ring-patterned bound states are observed in structurally deformed 2D semiconductors and formulated the modified geometric potential for the curvature effect, which demonstrates the ring-shape bound states with angular momentum. The formulated modified geometric potential is analogous to the effective potential of a rotating charged black hole. Density functional theory and tight-binding calculations are performed, which quantitatively agree well with the results of the modified geometric potential. The modified geometric potential is described by modified Gaussian and mean curvatures, corresponding to the curvature-induced changes in spin-orbit interaction and band gap, respectively. Even for complex structural deformation, the geometric potential solves the complexity, which aligns well with experimental results. The understanding of the modified geometric potential provides us with an intuitive clue for quantum transport and a key factor for new quantum applications such as valleytronics, spintronics, and straintronics in 2D semiconductors.

Midterm Clinical Outcomes of Endovascular Treatment for Acute Aortic Dissection with Malperfusion Syndrome.

Purpose: There is limited data on the midterm results of endovascular treatment for acute type B aortic dissection (TBAD) with malperfusion syndrome (MS), particularly in Asia. This study aimed to investigate the clinical outcomes of endovascular treatment of acute TBAD with MS. Materials and Methods: We retrospectively analyzed 27 patients who underwent endovascular treatment for acute TBAD with MS. Results: Among the 27 patients with TBAD and MS, malperfusion was observed in the isolated renal (44.4%), visceral (7.4%) and iliofemoral (25.9%) arteries, as well as their combinations (22.2%). The patients underwent thoracic endovascular aortic repair (TEVAR) only (25.9%), selective stenting only in arteries affected by malperfusion (22.2%), or combined treatment with TEVAR and selective stenting (51.9%). Primary technical success was achieved in all the patients. No inhospital mortality or early death within 30 days after operation occurred. The rates of stroke, limb ischemia, acute kidney injury, and reintervention at 30 days were 7.4%, 3.7%, 25.9%, and 3.7%, respectively. The mean follow-up period was 4.3±3.1 years. During the follow-up, the rates of death, stroke, maintenance hemodialysis, aneurysmal change, and reintervention were 0%, 3.7%, 7.4%, 7.4%, and 7.4%, respectively. Two patients required reintervention due to limb ischemia and aneurysmal changes in the distal portion of the stent graft. Computed tomography scans revealed a significant increase in aortic diameters in patients who underwent selective stenting compared to those who underwent TEVAR over a 3-year period, with changes in aortic area measuring 878.9 mm2 vs. 188.4 mm2 at the middle of the lesion (P=0.037), 303.7 mm2 vs. 22.8 mm2 at the level of the celiac trunk (P=0.025), and 442.9 mm2 vs. 37.3 mm2 at the level of the renal artery (P=0.019). Conclusion: The endovascular treatment of acute TBAD with MS demonstrated a high primary technical success rate and promising short- and midterm clinical outcomes.

The effects of various stair-climbing exercises on functional mobility and trunk muscle activation in community-dwelling older adults: A pilot randomized controlled trial.

BACKGROUND: Stair-climbing (SC) is an essential daily life skill, and stair-climbing exercise (SCE) serves as a valuable method for promoting physical activity in older adults. This study aimed to compare the impact of SCEs with heel contact (HC) and heel off (HO) during SC on functional mobility and trunk muscle (TM) activation amplitudes in community-dwelling older adults. METHODS: In the pilot randomized controlled trial, participants were randomly allocated to either the HC group (n = 17; mean age 75.9 ± 6.3 years) or the HO group (n = 17; mean age 76.5 ± 4.6 years). The HC participants performed SCE with the heel of the ankle in contact with the ground, while the HO participants performed SCE with the heel of the ankle off the ground during SC. Both groups participated in progressive SCE for one hour per day, three days per week, over four consecutive weeks (totaling 12 sessions) at the community center. We measured timed stair-climbing (TSC), timed up and go (TUG), and electromyography (EMG) amplitudes of the TMs including rectus abdominis (RA), external oblique (EO), transverse abdominus and internal oblique abdominals (TrA-IO), and erector spinae (ES) during SC before and after the intervention. RESULTS: Both groups showed a significant improvement in TSC and TUG after the intervention (P < .01, respectively), with no significant difference between the groups. There was no significant difference in the EMG activity of the TMs between the groups after the intervention. The amplitude of TMs significantly decreased after the intervention in both groups (P < .01, respectively). CONCLUSION: Both SCE methods could improve balance and SC ability in older adults while reducing the recruitment of TMs during SC. Both SCE strategies are effective in improving functional mobility and promoting appropriate posture control during SC in older adults.

Radiofrequency ablation versus intra-articular mesenchymal stem cell injection for knee osteoarthritis: a systematic review and network meta-analysis.

BACKGROUND: Knee osteoarthritis (OA) is a prevalent degenerative disease and causes disability, pain and imposes a substantial burden on patients. Conventional treatments for knee OA show limited effectiveness. Consequently, innovative treatments, such as radiofrequency ablation (RFA) and intra-articular mesenchymal stem cells (IA MSC), have gained attention for addressing these limitations. OBJECTIVE: We compared the efficacy of RFA and IA MSC for knee OA through a network meta-analysis (NMA). EVIDENCE REVIEW: A literature search was conducted using PubMed, MEDLINE, Embase, Cochrane Library, Web of Science and handsearching. Randomized controlled trials (RCTs) comparing RFA or IA MSC to conventional treatments for knee OA were included. The primary outcomes comprised the pain score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The clinical outcomes were compared using a frequentist approach, and the treatments were ranked using the surface under the cumulative ranking curve (SUCRA) values. FINDINGS: We included 34 RCTs (n=2371). Our NMA revealed that RFA and IA MSC were significantly more effective than conventional treatments in managing pain at both 3 and 6 months with moderate certainty. Specifically, RFA demonstrated the highest SUCRA values, indicating its superior efficacy. For WOMAC scores, both RFA and MSC showed significant improvements at 3 months, with RFA maintaining its lead at 6 months, although MSC did not display significant superiority at this stage. CONCLUSIONS: This analysis suggests that RFA and MSC are resilient treatment options in knee OA. Despite some study heterogeneity, these treatments consistently outperformed conventional treatments, particularly in the short to mid-term, although with varying levels of certainty in their efficacy. PROSPERO REGISTRATION NUMBER: CRD42023492299.

Biological and prognostic significance of NDRG2 downregulation in oral squamous cell carcinoma.

OBJECTIVE: Downregulation of N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor gene, has been associated with poor clinical outcomes in various cancers. However, the prognostic significance of NDRG2 in oral squamous cell carcinoma (OSCC) remains unknown. This study aimed to evaluate the prognostic value of NDRG2 downregulation in OSCC and to elucidate the mechanism by which NDRG2 is downregulated and the biological role of NDRG2 in tumor progression. METHODS: Immunohistochemical and in silico analyses of NDRG2 expression were performed, and the correlation between NDRG2 expression and clinicopathological data was analyzed. The effect of NDRG2 knockdown on the biological behavior of OSCC cells was investigated and the effect of 5-aza-2'-deoxycytidine (5-aza-dC) on NDRG2 expression was determined. RESULTS: NDRG2 expression was significantly downregulated and DNA hypermethylation of NDRG2 was frequently found in head and neck SCC, including OSCC. Low NDRG2 expression was significantly correlated with adverse clinicopathological features and worse survival in OSCC. NDRG2 knockdown could enhance the oncogenic properties of OSCC cells. NDRG2 mRNA levels in OSCC cells could be restored by 5-aza-dC. CONCLUSION: Downregulation of NDRG2 promotes tumor progression and predicts poor prognosis in OSCC. Therefore, restoration of NDRG2 expression may be a potential therapeutic strategy in OSCC.