Detectability of intracranial vessel wall atherosclerosis using black-blood spectral CT: a phantom and clinical study.

BACKGROUND: Computed tomography (CT) is the usual modality for diagnosing stroke, but conventional CT angiography reconstructions have limitations. METHODS: A phantom with tubes of known diameters and wall thickness was scanned for wall detectability, wall thickness, and contrast-to-noise ratio (CNR) on conventional and spectral black-blood (SBB) images. The clinical study included 34 stroke patients. Diagnostic certainty and conspicuity of normal/abnormal intracranial vessels using SBB were compared to conventional. Sensitivity/specificity/accuracy of SBB and conventional were compared for plaque detectability. CNR of the wall/lumen and quantitative comparison of remodeling index, plaque burden, and eccentricity were obtained for SBB imaging and high-resolution magnetic resonance imaging (hrMRI). RESULTS: The phantom study showed improved detectability of tube walls using SBB (108/108, 100% versus conventional 81/108, 75%, p < 0.001). CNRs were 75.9 ± 62.6 (mean ± standard deviation) for wall/lumen and 22.0 ± 17.1 for wall/water using SBB and 26.4 ± 15.3 and 101.6 ± 62.5 using conventional. Clinical study demonstrated (i) improved certainty and conspicuity of the vessels using SBB versus conventional (certainty, median score 3 versus 0; conspicuity, median score 3 versus 1 (p < 0.001)), (ii) improved sensitivity/specificity/accuracy of plaque (≥ 1.0 mm) detectability (0.944/0.981/0.962 versus 0.239/0.743/0.495) (p < 0.001), (iii) higher wall/lumen CNR of SBB of (78.3 ± 50.4/79.3 ± 96.7) versus hrMRI (18.9 ± 8.4/24.1 ± 14.1) (p < 0.001), and (iv) excellent reproducibility of remodeling index, plaque burden, and eccentricity using SBB versus hrMRI (intraclass correlation coefficient 0.85-0.94). CONCLUSIONS: SBB can enhance the detectability of intracranial plaques with an accuracy similar to that of hrMRI. RELEVANCE STATEMENT: This new spectral black-blood technique for the detection and characterization of intracranial vessel atherosclerotic disease could be a time-saving and cost-effective diagnostic step for clinical stroke patients. It may also facilitate prevention strategies for atherosclerosis. KEY POINTS: • Blooming artifacts can blur vessel wall morphology on conventional CT angiography. • Spectral black-blood (SBB) images are generated from material decomposition from spectral CT. • SBB images reduce blooming artifacts and noise and accurately detect small plaques.

Advances in nano-preparations for improving tetrandrine solubility and bioavailability.

Tetrandrine (TET) is a natural bis-benzylisoquinoline alkaloid isolated from Stephania species with a wide range of biological and pharmacologic activities; it mainly serves as an anti-inflammatory agent or antitumor adjuvant in clinical applications. However, limitations such as prominent hydrophobicity, severe off-target toxicity, and low absorption result in suboptimal therapeutic outcomes preventing its widespread adoption. Nanoparticles have proven to be efficient devices for targeted drug delivery since drug-carrying nanoparticles can be passively transported to the tumor site by the enhanced permeability and retention (EPR) effects, thus securing a niche in cancer therapies. Great progress has been made in nanocarrier construction for TET delivery due to their outstanding advantages such as increased water-solubility, improved biodistribution and blood circulation, reduced off-target irritation, and combinational therapy. Herein, we systematically reviewed the latest advancements in TET-loaded nanoparticles and their respective features with the expectation of providing perspective and guidelines for future research and potential applications of TET.

Stretchable and Transparent Heaters Based on Hydrophobic Ionogels with Superior Moisture Insensitivity.

Flexible and stretchable transparent heaters (THs) have been widely used in various applications, including deicing and defogging of flexible screens as well as thermotherapy pads. Ionic THs based on ionogels have emerged as a promising alternative to conventional electronic THs due to their unique advantages in terms of transparency-conductance conflict, uniform heating, and interfacial adhesion. However, the commonly used hydrophilic ionogels inevitably introduce a moisture-sensitive issue. In this work, we present a stretchable and transparent hydrophobic ionogel-based heater that utilizes ionic current-induced Joule heating under high-frequency alternating current. This ionogel-based TH exhibits exceptional multifunctional properties with low hysteresis, a fracture strain of 840%, transmittance of 93%, conductivity of 0.062 S m-1, temperature resistance up to 165 °C, voltage resistance up to 120 V, heating rate of 0.1 °C s-1, steady-state temperature at 115 °C, and uniform heating even when bent or stretched (up to 200%). Furthermore, it maintains its heating performance when it is directly exposed to water. This hydrophobic ionogel-based TH expands the range of materials available for ionic THs and paves the way for their practical applications.

Application of Modified Kite Flap in Reconstruction of Facial Wounds After Operation and Case Series.

Our team used a new kite flap preparation method to repair wounds after the removal of a benign facial tumor with satisfactory aesthetic results. Thus, this modified kite flap has significant value in facial trauma repair.

The role of epicardial fat radiomic profiles for atrial fibrillation identification and recurrence risk with coronary CT angiography.

OBJECTIVES: Fat radiomic profile (FRP) was a promising imaging biomarker for identifying increased cardiac risk. We hypothesize FRP can be extended to fat regions around pulmonary veins (PV), left atrium (LA), and left atrial appendage (LAA) to investigate their usefulness in identifying atrial fibrillation (AF) and the risk of AF recurrence. METHODS: We analysed 300 individuals and grouped patients according to the occurrence and types of AF. We used receiver operating characteristic and survival curves analyses to evaluate the value of imaging biomarkers, including fat attenuation index (FAI) and FRP, in distinguishing AF from sinus rhythm and predicting post-ablation recurrence. RESULTS: FRPs from AF-relevant fat regions showed significant performance in distinguishing AF and non-AF with higher AUC values than FAI (peri-PV: FRP = 0.961 vs FAI = 0.579, peri-LA: FRP = 0.923 vs FAI = 0.575, peri-LAA: FRP = 0.900 vs FAI = 0.665). FRPs from peri-PV, peri-LA, and peri-LAA were able to differentiate persistent and paroxysmal AF with AUC values of 0.804, 0.819, and 0.694. FRP from these regions improved AF recurrence prediction with an AUC of 0.929, 0.732, and 0.794. Patients with FRP cut-off values of ≥0.16, 0.38, and 0.26 had a 7.22-, 5.15-, and 4.25-fold higher risk of post-procedure recurrence, respectively. CONCLUSIONS: FRP demonstrated potential in identifying AF, distinguishing AF types, and predicting AF recurrence risk after ablation. FRP from peri-PV fat depot exhibited a strong correlation with AF. Therefore, evaluating epicardial fat using FRP was a promising approach to enhance AF clinical management. ADVANCES IN KNOWLEDGE: The role of epicardial adipose tissue (EAT) in AF had been confirmed, we focussed on the relationship between EAT around pulmonary arteries and LAA in AF which was still unknown. Meanwhile, we used the FRP to excavate more information of EAT in AF.

Increased incidence of napkin-ring sign plaques on cervicocerebral computed tomography angiography associated with the risk of acute ischemic stroke occurrence.

OBJECTIVES: Carotid atherosclerosis plays an essential role in the occurrence of ischemic stroke. This study aimed to investigate whether a larger burden of napkin-ring sign (NRS) plaques on cervicocerebral computed tomography angiography (CTA) increased the risk of acute ischemic stroke (AIS). METHODS: This retrospective, single-center, cross-sectional study enrolled patients with NRS plaques identified in the subclavian arteries, brachiocephalic trunk, carotid arterial system, and vertebrobasilar circulation on contrast-enhanced cervicocerebral CTA. Patients were divided into AIS and non-AIS groups based on imaging within 12 h of symptom onset. Univariate and multivariate logistic regression analyses were performed to determine the risk factor of AIS occurrence. RESULTS: A total of 202 patients (66.72 years ± 8.97, 157 men) were evaluated. Plaques with NRS in each subject of the AIS group (N = 98) were significantly more prevalent than that in the control group (N = 104) (1.96 ± 1.17 vs 1.41 ± 0.62). In the AIS group, there were substantially more NRS plaques on the ipsilateral side than contralateral side (1.55 ± 0.90 vs. 0.41 ± 0.66). NRS located on the ipsilateral side of the AIS showed an area under the receiver curve (AUC) of 0.86 to identify ischemic stroke. NRS plaque amounts were an independent risk factor for AIS occurrence (odds ratio, 1.86) after adjusting for other factors. CONCLUSIONS: Increased incidence of napkin-ring sign plaques on cervicocerebral CTA was positively associated with AIS occurrence, which could aid in detecting asymptomatic atherosclerotic patients at high risk of AIS in routine screening or emergency settings. CLINICAL RELEVANCE STATEMENT: Napkin-ring sign plaque provides an important imaging target for estimating acute ischemic stroke risk and identifying high-risk patients in routine screening or emergency settings, so that timely anti-atherosclerotic therapy can be used for prevention. KEY POINTS: • This cross-sectional study investigated the association between high-risk carotid artery plaques and acute ischemic stroke. • Increased incidence of napkin-ring sign plaques on cervicocerebral computed tomography angiography is positively associated with acute ischemic stroke occurrence. • Napkin-ring signs help identify risky patients prone to acute ischemic stroke to facilitate prevention.

Research on the correlation between the renal resistive index, renal microvessel density, and fibrosis.

BACKGROUND: This study was designed to investigate the relationship between the renal resistive index (RRI), renal microvessel density (RMD), and fibrosis in patients with chronic kidney disease (CKD). METHODS: A total of 73 CKD patients were included in the study. Prior to kidney biopsy, we recorded the RRI of the interlobar artery and the estimated glomerular filtration rate (eGFR). Immunohistochemical analysis was performed to assess CD34 expression, and Masson staining was used to evaluate histopathological specimens for RMD and the degree of fibrosis. The percentage of the positive area (PPA) was recorded. Subsequently, we investigated the correlation between RRI, RMD, and kidney fibrosis. RESULTS: RMD (CD34 PPA-total and CD34 PPA-peritubular capillary) showed a slight increase in early CKD stages (1-2) and gradually declined from CKD stages 2 to 5. No correlation was observed between the RRI and RMD or between the RRI and fibrosis across CKD stages 1 to 5. However, across CKD stages 2 to 5, RRI negatively correlated with CD34 PPA-glomerulus (r = -0.353, p = 0.022), but no correlation was found with CD34 PPA-total, CD34 PPA-peritubular capillary, or kidney fibrosis. eGFR showed a positive correlation with RMD (CD34 PPA-total, CD34 PPA-peritubular capillary, and CD34 PPA-glomerulus) across CKD stages 2 to 5, while no correlation was found from CKD stages 1 to 5. CONCLUSION: There was no correlation between RRI and RMD or between RRI and fibrosis across CKD stages 1 to 5 (RRI ≤ 0.7).

Effects of oral intake fruit or fruit extract on skin aging in healthy adults: a systematic review and Meta-analysis of randomized controlled trials.

Background: In recent years, oral various fruits or supplements of fruits natural extracts have been reported to have significant anti-aging effects on the skin (1, 2), However, despite many studies on this topic, there is often no clear evidence to support their efficacy and safety. In this paper, we present a comprehensive review and Meta-analysis of the evidence for the safety and efficacy of oral fruits and fruits extracts in improving skin aging. Methods: Four databases, Pubmed, Embase, Web of Science, and Cochrane Library (CENTRAL), were searched for relevant literature from 2000-01 to 2023-03. Seven randomized controlled trials (RCTs) of fruit intake or fruit extracts associated with anti-skin aging were screened for Meta-analysis. Results: Compared to placebo, oral intake of fruit or fruit extracts showed significant statistical differences in skin hydration and transepidermal water loss (TEWL), with a significant improvement in skin hydration and a significant decrease in TEWL. No significant statistical difference was observed in minimal erythema dose (MED), overall skin elasticity (R2), or wrinkle depth, and no evidence of significant improvement in skin condition was observed. Conclusion: Meta-analysis results suggest that consume administration of fruits or fruit extracts significantly enhances skin hydration and reduces transcutaneous water loss, but there is insufficient evidence to support other outcome recommendations, including minimal erythema dose (MED), overall skin elasticity(R2), and wrinkle depth. Systematic Review Registration: PROSPERO (york.ac.uk), identifier CRD42023410382.

Emerging Trends and Focus in Human Skin Microbiome Over the Last Decade: A Bibliometric Analysis and Literature Review.

Background: Human skin microbiome is the first barrier against exogenous attack and is associated with various skin disease pathogenesis and progression. Advancements in high-throughput sequencing technologies have paved the way for a deeper understanding of this field. Based on the bibliometric analysis, this investigation aimed to identify the hotspots and future research trends associated with human skin microbiomes studied over the past decade. Methods: The published research on skin microbiome from January 2013 to January 2023 was retrieved from the Web of Science Core Collection. Data cleaning processes to ensure robust data and the bibliometrix packages R, CiteSpace, VOSviewer, Origin, and Scimago Graphica for bibliometric and visual analyses were utilized. Results: A total of 1629 published documents were analyzed. The overall publication trend steadily increased, with relatively fast growth in 2017 and 2020. The United States of America has the highest number of publications and citations and shows close collaborations with China and Germany. The University of California, San Diego, indicated a higher number of publications than other institutions and the fastest growth rate. The top three most publishing journals on this topic are Microorganisms, Frontiers in Microbiology, and Experimental dermatology. Gallo RL is the most influential author with the highest h- and g-index and most publications in skin microecology, followed by Grice EA and Kong HH. The top 10 most frequently used keywords in recent years included skin microbiome, microbiome, staphylococcus aureus, diversity, atopic dermatitis, skin, bacteria, infections, gut microbiota, and disease. Conclusion: The skin microbiome is an area of research that requires continuous analysis, and even with much-achieved progress, future research will further be aided as technology develops.

IL1R2 is a Novel Prognostic Biomarker for Lung Adenocarcinoma.

AIMS: The aim of this study is to figure out the role of IL1R2 in LUAD (lung adenocarcinoma). BACKGROUND: IL1R2, a special member of IL-1 receptor family, binds to IL-1 and plays an important role in inhibiting IL-1 pathway, which seems to be involved in tumorigenesis. Emerging studies demonstrated higher IL1R2 expression levels in several malignancies. OBJECTIVE: In the present study, we assessed the expression of IL1R2 in LUAD tissues with immunohistochemistry and explored various databases to determine whether it could be a potential prognostic biomarker and therapeutic target. METHODS: The expression level of IL1R2 in lung adenocarcinoma was analyzed by Immunohistochemistry and UALCAN database. The correlation between IL1R2 expression and the patient prognosis was identified by Kaplan-Meier plotter. The correlation of IL1R2 expression with immune infiltrates was clarified by TIMER database. The protein-protein interaction network and gene functional enrichment analysis were constructed and performed by STRING and Metascape database. RESULTS: Immunohistochemistry showed that the expression of IL1R2 was higher in tumor tissues of LUAD patients and that patients with lower IL1R2 level have a better prognosis than their counterparts. We validated our findings in several online databases and found that IL1R2 gene was also positively correlated with B cells and neutrophils and biomarkers of CD8+ T cells and exhausted T cells. PPI network and gene enrichment analyses showed that expression of IL1R2 was also associated with complex functionspecific networks involving IL-1 signal, NF-KappaB transcription factors. CONCLUSION: According to these findings, we demonstrated that IL1R2 was involved in the progression and prognosis of LUAD and the underlying mechanism needs further investigation.

Utility of shear wave-based ultrasound elastography in chronic kidney disease and related pathological quantitative analysis.

OBJECTIVES: The purpose of this study was to investigate the effects of tissue fibrosis and microvessel density on shear wave-based ultrasound elastography (SWUE) of chronic kidney disease (CKD). In addition, we were looking to see whether SWUE could predict stage of CKD, correlating with the histology on kidney biopsy. METHODS: Renal tissue sections from 54 patients diagnosed with suspected CKD were subjected to immunohistochemistry (CD31 and CD34), and the degree of tissue fibrosis was assessed using Masson staining. Before renal puncture, both kidneys were examined using SWUE. Comparative analysis was used to assess the correlation between SWUE and microvessel density, and between SWUE and the degree of fibrosis. RESULTS: Fibrosis area according to Masson staining (p < 0.05) and integrated optical density (IOD) (p < 0.05) were positively correlated with CKD stage. The percentage of positive area (PPA) and IOD for CD31 and CD34 were not correlated with CKD stage (p > 0.05). When stage 1 CKD was removed, PPA and IOD for CD34 were negatively correlated with CKD stage (p < 0.05). Masson staining fibrosis area and IOD were not correlated with SWUE (p > 0.05), PPA and IOD for CD31 and CD34 were not correlated with SWUE (p > 0.05) and, finally, no correlation between SWUE and CKD stage was found (p > 0.05). CONCLUSION: The diagnostic value of SWUE for CKD staging was very low. The utility of SWUE in CKD was affected by many factors and its diagnostic value was limited. KEY POINTS: • There was no correlation between SWUE and the degree of fibrosis, or between SWUE and microvessel density among patients with CKD. • There was no correlation between SWUE and CKD stage and the diagnostic value of SWUE for CKD staging was very low. • The utility of SWUE in CKD is affected by many factors and its value was limited.

Effectiveness of Dietary Supplement for Skin Moisturizing in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The dietary supplement industry offers many oral cosmetics that purportedly assist in skin moisturization often with unclear evidence supporting efficacy and safety. To update the accessible proofs pertaining to the safety and effectiveness of oral dietary supplements to facilitate skin moisturizing via an all-around review and meta-analysis. Methods: Three on-line databases [Pubmed, Embase, and Cochrane Library (CENTRAL)] were retrieved from January 2000 to November 2021. An overall 66 randomized controlled trials (RCTs) of skin care were recognized. Meta-analysis was performed for dietary supplements with four or more available research. Results: Oral collagen or ceramide resulted in a statistically significant increase in skin hydration and a decrease in transepidermal water loss (TEWL) compared to placebo. No benefits regarding the improvement of skin conditions in terms of water content and TEWL were observed for lactic acid bacteria or Lactobacillus fermented foods. A statistically significant and positive effect on skin hydration was observed for both hyaluronan and procyanidin, with an unknown effect on TEWL due to insufficient RCTs. There was a non-significant improvement in the water content of stratum corneum for astaxanthin based on subgroup analyses. Among the dietary supplements trialed in ≤ 3 RCTs, the judgment regarding their effects on skin moisturizing was prevented by inconsistent conclusions as well as insufficient research. All food supplements were safe throughout the research (normally ≤ 24 weeks). Conclusion: Oral dietary supplements, including collagen, ceramides, hyaluronan, and procyanidin, were proven to be effective for skin moisturization. At present, for skin moisturization, the proofs supporting the recommendation of other dietary supplements, such as lactic acid bacteria and astaxanthin, are insufficient. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021290818.

Application of PRP in Chloasma: A Meta-Analysis and Systematic Review.

Background: Chloasma is a common skin pigment disorder. Treatment of chloasma has been challenging, often unsatisfactory, and difficult to avoid recurrence. PRP is a new treatment for chloasma, but there is no consensus on its use. Lingyun Zhao's team recently reported a systematic evaluation and meta-analysis of the efficacy and safety of PRP in the treatment of chloasma, which is consistent with our ideas, but we will elaborate on the application of PRP in chloasma from a deeper and more comprehensive perspective. Before we started this study, we had registered with Prospero as CRD42021233721. Methods: The authors searched the public medical network, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, Scopus, and Science Network. The clinical trials registry ClinicalTrials.gov databases were searched for relevant publications to June 2021. The results showed the area and severity of chloasma (MASI) or revised MASI (mMASI) score. Results: Three RCTs, one nonrandomized controlled study, and four were prospective before and after self-controlled studies met the inclusive criteria. Intradermal PRP injections significantly improved chloasma as indicated by the significant decrease MASI (average balance -6.71, 95% CI -8.99 to -4.33) and mMASI scores (average balance -2.94, 95% CI -4.81 to -1.07). The adverse reactions were mild, and there were no significant long-term adverse events. Conclusive. The data can reflect the effectiveness and safety of PRP therapy for chloasma. RCTs are needed to determine effective treatment parameters, and long-term follow-up should be included to better clarify the efficacy and side effects of PRP in treating chloasma.

Topoarchitected polymer networks expand the space of material properties.

Many living tissues achieve functions through architected constituents with strong adhesion. An Achilles tendon, for example, transmits force, elastically and repeatedly, from a muscle to a bone through staggered alignment of stiff collagen fibrils in a soft proteoglycan matrix. The collagen fibrils align orderly and adhere to the proteoglycan strongly. However, synthesizing architected materials with strong adhesion has been challenging. Here we fabricate architected polymer networks by sequential polymerization and photolithography, and attain adherent interface by topological entanglement. We fabricate tendon-inspired hydrogels by embedding hard blocks in topological entanglement with a soft matrix. The staggered architecture and strong adhesion enable high elastic limit strain and high toughness simultaneously. This combination of attributes is commonly desired in applications, but rarely achieved in synthetic materials. We further demonstrate architected polymer networks of various geometric patterns and material combinations to show the potential for expanding the space of material properties.

A Facile Approach for Anisotropic Hydrogel with Light-Regulated Stiffness and Its Application to Achieve Mechanical Toughening.

Many load-bearing tissues in nature obtain high toughness by fabricating anisotropic structures with spatially regulated composition and modulus at the macroscale. This inspires a toughening strategy for hydrogels based on the controlling of modulus heterogeneity. Herein, a facile approach to realize light-regulated spatial modulus heterogeneity with large contrast in hydrogels is proposed. Ferric citric acid complex (Fe3+ /CA-complex) is used as a light-responsive ionic cross-linker, which can first stiffen an alginate/polyacrylamide (Alg/PAAm) hydrogel by coordinating with the Alg to form another network, then realize light-triggered softening through photoreduction of ferric ions (Fe3+ ). Based on this, a stripe-patterned hydrogel with alternating stiff and soft segments can be fabricated through photopatterning. The modulus contrast between the stiff and soft phases can be adjusted by control of several influence factors and the maximum modulus contrast can reach up to 87 times. As a result, the toughness of the stripe-patterned hydrogel is enhanced by 3.5 times comparing to that hydrogel without a pattern. This approach shows great potential in the synthesis of smart hydrogels with light-programmable mechanical performances, and may be widely applicable for the hydrogels with functional groups that can coordinate with metal ions.

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury.

Ischemic heart disease has a high mortality, and the recommended therapy is reperfusion. Nevertheless, the restoration of blood flow to ischemic tissue leads to further damage, namely, myocardial ischemia/reperfusion injury (MIRI). Apoptosis is an essential pathogenic factor in MIRI, and ginsenosides are effective in inhibiting apoptosis and alleviating MIRI. Here, we reviewed published studies on the anti-apoptotic effects of ginsenosides and their mechanisms of action in improving MIRI. Each ginsenoside can regulate multiple pathways to protect the myocardium. Overall, the involved apoptotic pathways include the death receptor signaling pathway, mitochondria signaling pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway, and MAPK signaling pathway. Ginsenosides, with diverse chemical structures, regulate different apoptotic pathways to relieve MIRI. Summarizing the effects and mechanisms of ginsenosides contributes to further mechanism research studies and structure-function relationship research studies, which can help the development of new drugs. Therefore, we expect that this review will highlight the importance of ginsenosides in improving MIRI via anti-apoptosis and provide references and suggestions for further research in this field.

Spontaneous Disappearance of Filar Cysts Diagnosed by Transabdominal Ultrasonography: A Report of Three Cases.

Filar cysts (FCs) can be detected using ultrasound before or after delivery. They usually present as anechoic structures with a clear boundary just caudal to the lower end of the conus medullaris. They are generally considered a physiological variation and do not affect health. Some studies have pointed out that FCs in children can disappear spontaneously, as identified by ultrasound or magnetic resonance imaging. Three cases of FCs diagnosed by prenatal transabdominal ultrasound were reported in this study, and it was observed that FCs could disappear spontaneously in utero. The shortest time of disappearance was 4 weeks.

Basic Pan-Cancer Analysis of the Carcinogenic Effects of Cyclin-Dependent Kinase 4 (CDK4) in Human Surface Tumors.

Although the evidence based on current human, animal, or molecular biology can explain some of the relationships between CDK4 and cancer, there is no pan-cancer analysis of the gene CDK4 in human skin tumors. Therefore, the potential carcinogenic effects of CDK4 in 33 tumors were initially explored in the datasets of the GEO (Gene Expression Omnibus) and the CGA (Cancer Genome Atlas). We found that CDK4 was highly expressed in most cancers and that CDK4 performance levels significantly correlated with the prognosis of cancer patients. These were found in our preliminary exploration. In addition, we used the dataset in tumors such as cutaneous melanoma or lung adenocarcinoma and found increased levels of phosphorylation of r24 l/C/h/s. In addition, fibroblast infiltration associated with CDK4 cancer was observed in head and neck, sarcoma, and melanoma skin. Using this pan-cancer study, our group has provided a comprehensive preliminary demonstration of the oncogenic effects of the CDK4 gene on different human skin tumors.

Induction of notochordal differentiation of bone marrow mesenchymal­derived stem cells via the stimulation of notochordal cell­rich nucleus pulposus tissue.

The degeneration of intervertebral disc (IVD) tissue, initiated following the disappearance of notochordal cells (NCs), is characterized by the decreased number of nucleus pulposus (NP) cells (NPCs) and extracellular matrix. Transplanting proper cells into the IVD may sustain cell numbers, resulting in the synthesis of new matrix; this represents a minimally invasive regenerative therapy. However, the lack of cells with a correct phenotype severely hampers the development of regenerative therapy. The present study aimed to investigate whether porcine NC­rich NP tissue stimulates bone marrow­derived mesenchymal stem cell (BM­MSC) differentiation toward NC­like cells, which possess promising regenerative ability, for the treatment of disc degeneration diseases. BM­MSCs were successfully isolated from porcine femurs and tibiae, which expressed CD90 and CD105 markers and did not express CD45. Differentiation induction experiments revealed that the isolated cells had osteogenic and adipogenic differentiation potential. When co­cultured with NC­rich NP tissue, the BM­MSCs successfully differentiated into NC­like cells. Cell morphological analysis revealed that the cells exhibited an altered morphology, from a shuttle­like to a circular one, and the expression of NC marker genes, including brachyury, keratin­8, and keratin­18, was enhanced, and the cells exhibited the ability to generate aggrecan and collagen II. Taken together, the findings of the present study demonstrated that the primarily isolated and cultured BM­MSCs may be stimulated to differentiate into NC­like cells by porcine NC­rich NP explants, potentially providing an ideal cell source for regenerative therapies for disc degeneration diseases.