Rapid nanomolar detection of cocaine in biofluids by electrochemical aptamer-based sensor with low-temperature effect for drugged driving screening.

Cocaine is one of the most abused illicit drugs, and its abuse damages the central nervous system and can even lead directly to death. Therefore, the development of simple, rapid and highly sensitive detection methods is crucial for the prevention and control of drug abuse, traffic accidents and crime. In this work, an electrochemical aptamer-based (EAB) sensor based on the low-temperature enhancement effect was developed for the direct determination of cocaine in bio-samples. The signal gain of the sensor at 10 °C was greatly improved compared to room temperature, owing to the improved affinity between the aptamer and the target. Additionally, the electroactive area of the gold electrode used to fabricate the EAB sensor was increased 20 times by a simple electrochemical roughening method. The porous electrode possesses more efficient electron transfer and better antifouling properties after roughening. These improvements enabled the sensor to achieve rapid detection of cocaine in complex bio-samples. The low detection limits (LOD) of cocaine in undiluted urine, 50% serum and 50% saliva were 70 nM, 30 nM and 10 nM, respectively, which are below the concentration threshold in drugged driving screening. The aptasensor was simple to construct and reusable, which offers potential for drugged driving screening in the real world.

Music Therapy and Music Intervention for NSCLC Patients Undergoing PET with Fear of Cancer Recurrence.

Background: Cancer and psychiatric symptoms are associated. Fear of cancer recurrence (FCR) is the most common psychological problem for cancer survivors. Pharmacological interventions can help, but also have major drawbacks. Music therapy and music interventions have been shown to be a safe and practical complementary treatment. Objective: This randomized, controlled trial aimed to investigate the effects of music therapy and music intervention in attenuating non-small cell lung cancer (NSCLC) patients' anxiety related to FCR. Methods: NSCLC patients with FCR were randomly allocated to a music therapy and intervention group (G1) and Control group (G2). Patients' anxiety was measured using the State-Trait Anxiety Inventory scores and heart rates. Primary outcome measure were PET scans. Secondary measures were salivary cortisol, salivary α-amylase levels and heart rate. Findings: Patients in G1 showed higher glucose metabolism of 18F-FDG in the superior frontal gyrus, anterior cingulate, superior temporal gyrus, and parahippocampal gyrus, compared to those in G2 (all P < .001). Heart rates and salivary α-amylase area under the curve (AUC) and relative variation (VAR) in G1 were significantly lower than those in G2 (all P < .05). State-Trait Anxiety Inventory scores and cortisol AUC in G1 were significantly lower than those in G2 (all P < .05). Conclusions: Music therapy and interventions can reduce anxiety and endocrinological responses and change glucose metabolism of 18F-FDG in fear-related brain regions.Trial registration: Registered retrospectively, ISRCTN Registry, www.isrctn.com, ISRCTN23276302Clinical Implications: Cancer treatment centers and physical examination centers should consider providing music therapy and intervention to the appropriate patients as a routine component of a comprehensive clinical care during medical examinations.

Cold-hot Janus electrochemical aptamer-based sensor for calibration-free determination of biomolecules.

Real-time, high-frequency measurements of pharmaceuticals, metabolites, exogenous antigens, and other biomolecules in biological samples can provide critical information for health management and clinical diagnosis. Electrochemical aptamer-based (EAB) sensor is a promising analytical technique capable of achieving these goals. However, the issues of insufficient sensitivity, frequent calibration and lack of adapted portable electrochemical device limit its practical application in immediate detection. In response we have fabricated an on-chip-integrated, cold-hot Janus EAB (J-EAB) sensor based on the thermoelectric coolers (TECs). Attributed to the Peltier effect, the enhanced/suppressed current response can be generated simultaneously on cold/hot sides of the J-EAB sensor. The ratio of the current responses on the cold and hot sides was used as the detection signal, enabling rapid on-site, calibration-free determination of small molecules (procaine) as well as macromolecules (SARS-CoV-2 spike protein) in single step, with detection limits of 1 µM and 10 nM, respectively. We have further demonstrated that the J-EAB sensor is effective in improving the ease and usability of the actual detection process, and is expected to provide a universal, low-cost, fast and easy potential analytical tool for other clinically important biomarkers, drugs or pharmaceutical small molecules.

Adverse effect of smoking on surgical site infection following ankle and calcaneal fracture fixation: a meta-analysis.

Purpose: Studies have reported conflicting findings on the relationship between smoking and surgical site infection (SSI) post fixation for ankle and calcaneal fractures. This meta-analysis explored the effect of smoking on SSI incidence following open reduction and internal fixation (ORIF) of these fractures. Methods: Full-text studies on smoking's influence on post-ORIF SSI rates for closed ankle and calcaneal fractures were sourced from the PubMed, Embase, and Cochrane databases, with no consideration given to language or publication date. Study quality was appraised using the Newcastle-Ottawa Scale. Odds ratios (OR) and the corresponding 95% CIs were determined using random-effects models. This meta-analysis adhered to the PRISMA guidelines and was registered with PROSPERO (CRD42023429372). Results: The analysis incorporated data from 16 cohort and case-control studies, totaling 41 944 subjects, 9984 of whom were smokers, with 956 SSI cases. Results indicated smokers faced a higher SSI risk (OR: 1.62; 95% CI: 1.32-1.97, P < 0.0001) post ORIF, with low heterogeneity (I 2 = 26%). Smoking was identified as a significant deep SSI risk factor (OR: 2.09; 95% CI: 1.42-3.09; P = 0.0002; I 2 = 31%). However, the subgroup analysis revealed no association between smoking and superficial SSI (OR: 1.05; 95% CI: 0.82-1.33; P = 0.70; I 2 = 0%). Conclusion: Smoking is associated with increased SSI risk after ORIF for closed ankle and calcaneus fractures. Although no clear link was found between superficial SSI and smoking, the data underscore the negative influence of smoking on deep SSI incidence.

Is smoking a risk factor for complications following total ankle arthroplasty? A meta-analysis.

BACKGROUND: Smoking has long been recognized as a risk factor for impaired wound and bone healing, particularly in the context of ankle and foot surgery. Despite numerous studies exploring the association between smoking and complications following ankle replacement, there remains significant inconsistency in their findings. Therefore, this meta-analysis study aims to elucidate whether smoking increases the rate of complications after total ankle arthroplasty (TAA), providing valuable insights for clinical management. METHODS: A comprehensive systematic search was conducted in the PubMed, Embase, and Wiley databases to identify relevant English studies on the influence of smoking on postoperative complications following ankle replacement without any restrictions on publication dates. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Random-effect models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI). This study adhered to PRISMA guidelines for transparent reporting and was registered with PROSPERO. RESULTS: The analysis incorporated data from 12 retrospective cohort studies, totaling 17331 subjects, 2580 of whom were smokers and 791 complications following TAA. The findings revealed a statistically significant disparity in wound-related complications (OR: 2.26; 95 % CI: 1.13-4.50; P = .02), particularly evident in current smokers with an OR of 3.30 (95 % CI: 2.12-5.14; P < .00001). However, we lacked sufficient evidence to substantiate an association between smoking and complications related to the prosthesis (OR: 1.09; 95 % CI: 0.77-1.53; P = .64) or systemic complications (OR: 1.18; 95 % CI: 0.10-14.13; P = .90) following TAA. CONCLUSIONS: Smoking, especially current smoking, is associated with increased wound complication risk post-operation for total ankle arthroplasty. Despite a lack of definitive evidence on the optimal timeframe for smoking cessation before surgery, discontinuing smoking appears to be a prudent measure to mitigate these complications.

Clinical diagnostic value of targeted next­generation sequencing for infectious diseases (Review).

As sequencing technology transitions from research to clinical settings, due to technological maturity and cost reductions, metagenomic next­generation sequencing (mNGS) is increasingly used. This shift underscores the growing need for more cost­effective and universally accessible sequencing assays to improve patient care and public health. Therefore, targeted NGS (tNGS) is gaining prominence. tNGS involves enrichment of target pathogens in patient samples based on multiplex PCR amplification or probe capture with excellent sensitivity. It is increasingly used in clinical diagnostics due to its practicality and efficiency. The present review compares the principles of different enrichment methods. The high positivity rate of tNGS in the detection of pathogens was found in respiratory samples with specific instances. tNGS maintains high sensitivity (70.8­95.0%) in samples with low pathogen loads, including blood and cerebrospinal fluid. Furthermore, tNGS is effective in detecting drug­resistant strains of Mycobacterium tuberculosis, allowing identification of resistance genes and guiding clinical treatment decisions, which is difficult to achieve with mNGS. In the present review, the application of tNGS in clinical settings and its current limitations are assessed. The continued development of tNGS has the potential to refine diagnostic accuracy and treatment efficacy and improving infectious disease management. However, further research to overcome technical challenges such as workflow time and cost is required.

Frailty and all-cause and cancer-related mortality in cancer patients: A prospective cohort study.

PURPOSE: To evaluate the associations between frailty and all-cause and cancer-related mortality. Additionally, the objective is to compare the magnitude of these associations between older adults and younger adults. METHODS: We gathered baseline data from NHANES (1999-2018) and developed a cumulative index consisting of 39 items to evaluate frailty. The National Death Index database was utilized to track the survival status of individuals. The Cox regression model was employed to estimate the associations between frailty status and all-cause and cancer-related mortality. RESULTS: Ultimately, 3398 cancer patients were included in the analysis, comprising 910 younger adults and 2488 older adults. Compared to non-frail patients, the elevated all-cause and cancer-related mortality among pre-frail patients was not statistically significant (HRs = 1.312, 95%CI: 0.956-1.800, P = 0.092; HRs = 1.462, 0.811-2.635, P = 0.207). However, a significant elevation of both all-cause and cancer-related mortality risk was observed among frail patients (HRs = 2.213, 1.617-3.030, P < 0.001; HRs = 2.463, 95%CI = 1.370-4.429, P = 0.003). Frailty individuals demonstrated a more pronounced association with the prediction of all-cause mortality in younger (HRs = 2.230, 1.073-4.634, P = 0.032) than in older adults (HRs = 2.090, 1.475-2.960, P < 0.001). Sensitivity analysis consistently revealed robust results. RCS plots suggested a progressively escalating dose-response correlation between frailty and both all-cause and cancer-related mortality risk. CONCLUSIONS: Pre-frailty did not result in an increase in mortality risks compared to non-frailty. However, frailty caused a higher all-cause and cancer-related mortality risk than non-frailty. Identifying those at risk and implementing targeted interventions may contribute to extending healthy life expectancy, regardless of age.

3D-printed porous titanium suture anchor: a rabbit lateral femoral condyle model.

BACKGROUND: The inclusion of a connecting path in a porous implant can promote nutrient diffusion to cells and enhance bone ingrowth. Consequently, this study aimed to evaluate the biomechanical, radiographic, and histopathological performance of a novel 3D-printed porous suture anchor in a rabbit femur model. METHODS: Three test groups were formed based on the type of suture anchor (SA): Commercial SA (CSA, Group A, n = 20), custom solid SA (CSSA, Group B, n = 20), and custom porous SA (CPSA, Group C, n = 20). The SAs were implanted in the lateral femoral condyle of the right leg in each rabbit. The rabbits (New Zealand white rabbits, male, mean body weight of 2.8 ± 0.5 kg, age 8 months) underwent identical treatment and were randomized into experimental and control groups via computer-generated randomization. Five rabbits (10 femoral condyles) were euthanized at 0, 4, 8, and 12 weeks post-implantation for micro-CT, histological analysis, and biomechanical testing. RESULTS: At 12 weeks, the CPSA showed a higher BV/TV (median 0.7301, IQR 0.7276-0.7315) than the CSSA and CSA. The histological analysis showed mineralized osteocytes near the SA. At 4 weeks, new bone was observed around the CPSA and had penetrated its porous structure. By 12 weeks, there was no significant difference in ultimate failure load between the CSA and CPSA. CONCLUSIONS: We demonstrated that the innovative 3D-printed porous suture anchor exhibited comparable pullout strength to conventional threaded suture anchors at the 12-week postoperative time-point period. Furthermore, our porous anchor design enhanced new bone formation and facilitated bone growth into the implant structure, resulting in improved biomechanical stability.

Repellency, Toxicity, and Chemical Composition of Plant Essential Oils from Myrtaceae against Asian Citrus Psyllid, Diaphorina citri Kuwayama (Hemiptera Liviidae).

Diaphorina citri Kuwayama (D. citri) is one of the major pests in the citrus industry, which spreads Citrus Huanglongbing disease. It has developed resistance to chemical insecticides. Therefore, searching for greener solutions for pest management is critically important. The main aim of this study was to evaluate the repellent and insecticidal efficacy of essential oils (EOs) from four species of Myrtaceae plants: Psidium guajava (PG), Eucalyptus robusta (ER), Eucalyptus tereticornis (ET), and Baeckea frutescens (BF) against D. citri and to analyze their chemical compositions. GC-MS analysis was performed, and the results indicated that the EOs of PG, ER, ET, and BF were rich in terpenoids, ketones, esters, and alcohol compounds. The repellent rate of all four EOs showed that it decreased with exposure time but increased with the concentration of EOs from 80.50% to 100.00% after treating D. citri for 6 h with four EOs at 100% concentration and decreased to 67.71% to 85.49% after 24 h of exposure. Among the compounds from the EOs tested, eucalyptol had the strongest repellent activity, with a 24 h repellency rate of 100%. The contact toxicity bioassay results showed that all EOs have insecticidal toxicity to D. citri; the LC50 for nymphs was 36.47-93.15 mL/L, and for adults, it was 60.72-111.00 mL/L. These results show that when PG is used as the reference material, the ER, ET, and BF EOs have strong biological activity against D. citri, which provides a scientific basis for the further development of plant-derived agrochemicals.

Inhibition of ethanol-induced eNAMPT secretion attenuates liver ferroptosis through BAT-Liver communication.

BACKGROUND & AIMS: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) has long been recognized as an adipokine. However, the exact role of eNAMPT in alcoholic liver disease (ALD) and its relevance to brown adipose tissue (BAT) remain largely unknown. This study aimed to evaluate the impact of eNAMPT on liver function and the underlying mechanisms involved in BAT-Liver communication. METHODS: Serum eNAMPT levels were detected in the serum of both ALD patients and mice. Chronic and binge ethanol feeding was used to induce alcoholic liver injury in mice. An eNAMPT antibody, a coculture model of brown adipocytes and hepatocytes, and BAT-specific Nampt knockdown mice were used to investigate the role of eNAMPT in ALD. RESULTS: Serum eNAMPT levels are elevated in ALD patients and are significantly positively correlated with the liver injury index. In ALD mice, neutralizing eNAMPT reduced the elevated levels of circulating eNAMPT induced by ethanol and attenuated liver injury. In vitro experiments revealed that eNAMPT induced hepatocyte ferroptosis through the TLR4-dependent mitochondrial ROS-induced ferritinophagy pathway. Furthermore, ethanol stimulated eNAMPT secretion from brown adipocytes but not from other adipocytes. In the coculture model, ethanol-induced release of eNAMPT from brown adipocytes promoted hepatocyte ferroptosis. In BAT-specific Nampt-knockdown mice, ethanol-induced eNAMPT secretion was significantly reduced, and alcoholic liver injury were attenuated. These effects can be reversed by intraperitoneal injection of eNAMPT. CONCLUSION: Inhibition of ethanol-induced eNAMPT secretion from BAT attenuates liver injury and ferroptosis. Our study reveals a previously uncharacterized critical role of eNAMPT-mediated BAT-Liver communication in ALD and highlights its potential as a therapeutic target.

Impact of COVID-19 on emotional and behavioral problems among preschool children: a meta-analysis.

The impact of the Coronavirus Disease 2019 (COVID-19) on society is continuous, resulting in negative psychological consequences. Given the vulnerability and sensitivity to the environment among preschool children, their emotional and behavioral problems deserve more attention. The current study aimed to explore the impact of the epidemic on preschool children's mental health by determining the pooled prevalence of emotional and behavioral problems amidst the Coronavirus Disease 2019 pandemic and to reveal potential reasons for variations between studies. Published studies were searched in Embase, PubMed, ProQuest, PsycINFO, Web of Science, CNKI, and Wanfang. Based on the inclusion criteria outlined in this study, a total of 10 studies encompassing 38,059 participants were incorporated. Employing a random-effect model for estimating the prevalence of emotional and behavioral problems, the results revealed a pooled prevalence rate of 24.3% (95% CI, 0.15-0.38; I²=99.9%) among preschool children. This rate surpasses the pre-outbreak prevalence observed in different countries, signifying a detrimental influence of the epidemic on the mental well-being of preschoolers. Therefore, mental health care and recovery are essential for the vulnerable group during and after the public health crisis. Specific emotional and behavioral problems among preschool children are expected to be researched in the future to provide more targeted guidance for intervention.

Photothermal driven BMSCs osteogenesis and M2 macrophage polarization on polydopamine-coated Ti3C2 nanosheets/poly(vinylidene fluoride trifluoroethylene) nanocomposite coatings.

Mild thermal stimulation plays an active role in bone tissue repair and regeneration. In this work, a bioactive polydopamine/Ti3C2/poly(vinylidene fluoride trifluoroethylene) (PDA/Ti3C2/P(VDF-TrFE)) nanocomposite coating with excellent near-infrared light (NIR)-triggered photothermal effect was designed to improve the osteogenic ability of implants. By incorporating dopamine (DA)-modified Ti3C2 nanosheets into the P(VDF-TrFE) matrix and combining them with alkali initiated in situ polymerization, the resulting PDA/Ti3C2/P(VDF-TrFE) nanocomposite coating gained high adhesion strength on Ti substrate, excellent tribological and corrosion resistance properties, which was quite important for clinical application of implant coatings. Cell biology experiments showed that NIR-triggered mild thermal stimulation on the coating surface promoted cell spreading and growth of BMSCs, and also greatly upregulated the osteogenic markers, including Runt-Related Transcription Factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN). Simultaneously, the synthesis of heat shock protein 47 (HSP47) was significantly promoted by the mild thermal stimulation, which strengthened the specific interaction between HSP47 and collagen Ⅰ (COL-Ⅰ), thereby activating the integrin-mediated MEK/ERK osteogenic differentiation signaling pathway. In addition, the results also showed that the mild thermal stimulation induced the polarization of macrophages towards M2 phenotype, which can attenuate the inflammatory response of injured bone tissue. Antibacterial results indicated that the coating exhibited an outstanding antibacterial ability against S. aureus and E. coli. Conceivably, the versatile implant bioactive coatings developed in this work will show great application potential for implant osseointegration.

The potential benefits of PGC-1α in treating Alzheimer's disease are dependent on the integrity of the LLKYL L3 motif: Effect of regulating mitochondrial axonal transportation.

Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). The transcriptional coactivator PPARγ coactivator 1 (PGC-1a) has been identified as a key regulator of mitochondrial biogenesis and function. However, the precise structure/function relationship between PGC-1a and mitochondrial quality control remains incompletely understood. In this study, we investigated the impact of PGC-1a on AD pathology and its underlying mechanisms with a specific focus on mitochondrial axonal transport. Additionally, we generated two PGC-1α mutants by substituting leucine residues at positions 148 and 149 within the LKKLL motif or at positions 209 and 210 within the LLKYL motif with alanine. Subsequently, we examined the effects of these mutants on mutAPP-induced abnormalities in anterograde and retrograde axonal transport, disrupted mitochondrial distribution, and impaired mitophagy. Mutagenesis studies revealed that the LLKYL motif at amino acid position 209-210 within PGC-1α plays an essential role in its interaction with estrogen-related receptors (ERRα), which is necessary for restoring normal mitochondrial anterograde axonal transport, maintaining proper mitochondrial distribution, and ultimately preventing neuronal apoptosis. Furthermore, it was found that the Leu-rich motif at amino acids 209-210 within PGC-1α is crucial for rescuing mutAPP-induced impairment in mitophagy and loss of membrane potential by restoring normal mitochondrial retrograde axonal transport. Conversely, mutation of residues 148 and 149 in the LKKLL motif does not compromise the effectiveness of PGC-1α. These findings provide valuable insights into the molecular determinants governing specificity of action for PGC-1α involved in regulating mutAPP-induced deficits in mitochondrial axonal trafficking. Moreover, they suggest a potential therapeutic target for addressing Alzheimer's disease.

Co-mutation of OsLPR1/3/4/5 provides a promising strategy to minimize Cd contamination in rice grains.

Minimizing cadmium (Cd) contamination in rice grains is crucial for ensuring food security and promoting sustainable agriculture. Utilizing genetic modification to generate rice varieties with low Cd accumulation is a promising strategy due to its cost-effectiveness and operational simplicity. Our study demonstrated that the CRISPR-Cas9-mediated quadruple mutation of the multicopper oxidase genes OsLPR1/3/4/5 in the japonica rice cultivar Tongjing 981 had little effect on yields. However, a notable increase was observed in the cell wall functional groups that bind with Cd. As a result, the quadruple mutation of OsLPR1/3/4/5 enhanced Cd sequestration within the cell wall while reducing Cd concentrations in both xylem and phloem sap, thereby inhibiting Cd transport from roots to shoots. Consequently, Cd concentrations in brown rice and husk in oslpr1/3/4/5 quadruple mutants (qm) decreased by 52% and 55%, respectively, compared to the wild-type. These findings illustrate that the quadruple mutation of OsLPR1/3/4/5 is an effective method for minimizing Cd contamination in rice grains without compromising yields. Therefore, the quadruple mutation of OsLPR1/3/4/5 via biotechnological pathways may represent a valuable strategy for the generation of new rice varieties with low Cd accumulation.

The Buerger's rabbit model: a closer step to unravelling thromboangiitis obliterans?

OBJECTIVE: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. METHODS: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). RESULTS: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. CONCLUSION: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Herpotrichone A Exerts Neuroprotective Effects by Relieving Ferroptosis.

Inhibition of oxidative stress and ferroptosis is currently considered to be a promising therapeutic approach for neurodegenerative diseases. Herpotrichones, a class of compounds derived from insect symbionts, have shown potential for neuroprotective activity with low toxicity. However, the specific mechanisms through which herpotrichones exert their neuroprotective effects remain to be fully elucidated. In this study, the natural [4 + 2] adducts herpotrichone A (He-A) and its new analogues were isolated from the isopod-associated fungus Herpotrichia sp. SF09 and exhibited significantly protective effects in H2O2-, 6-OHDA-, and RSL3-stimulated PC12 cells and LPS-stimulated BV-2 cells. Moreover, He-A was able to relieve ferroptotic cell death in RSL3-stimulated PC12 cells and 6-OHDA-induced zebrafish larvae. Interestingly, He-A can activate antioxidant elements and modulate the SLC7A11 pathway without capturing oxidic free radical and chelating iron. These findings highlight He-A as a novel hit that protects against ferroptosis-like neuronal damage in the treatment of neurodegenerative diseases.

Effects of Tongluo Jiedu prescription on immune function and oxidative stress in patients with oral cancer.

BACKGROUND: Oral cancer, which is caused by mucous membrane variation, represents a prevalent malignant tumor in the oral and maxillofacial region, posing a significant threat to patients' lives and safety. While surgical intervention stands as a cornerstone treatment for oral cancer patients, it carries the risk of incomplete treatment or high rates of postoperative recurrence. Hence, a multifaceted approach incorporating diverse treatment modalities is essential to enhance patient prognosis. AIM: To analyze the application effect of Tongluo Jiedu prescription as adjuvant therapy and its influence on patient prognosis in patients with oral cancer. METHODS: Eighty oral cancer patients in our hospital were selected and divided into the observation group and control group by a random number table. The control group was treated with continuous arterial infusion chemotherapy of cisplatin and 5-fluorouracil. The observation group was additionally given Tongluo Jiadu prescription. The inflammatory stress level, peripheral blood T-cell subsets, and immune function of the two groups were subsequently observed. SPSS 21.0 was used for data analysis. RESULTS: The observation group demonstrated lower levels of interleukin-6 and C-reactive protein, and a higher level of tumor necrosis factor in comparison to the control group. After treatment, the immune function in the observation group was significantly better than in the control group. CONCLUSION: Tongluo Jiedu prescription can improve the immune function and oxidative stress level of patients with oral cancer and accelerate the recovery process.

Prevalence of anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation in people with autoimmune skin diseases.

BACKGROUND: Autoimmune skin diseases (ASDs) such as psoriasis and vitiligo, in addition to causing visible skin symptoms, are closely associated with psychological health issues. However, a comprehensive understanding of the prevalence of these psychological comorbidities in affected individuals is lacking. This study aims to identify the prevalence of anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation in people with ASDs. METHOD: PubMed, MEDLINE, Web of Science, and Cochrane Library searches were conducted from 1993 to May 2024. Observational studies reporting prevalence data for anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation among people with ASDs were included in the analysis. The Newcastle-Ottawa scale was used to evaluate the quality of studies. RESULTS: The study included 114 studies from 37 countries including 823,975 participants. The estimated pooled prevalence of anxiety in patients with ASDs was 33.3% (95% CI: 27.3-29.3%). The estimated pooled prevalence of depression was 33.7% (95% CI: 29.2-38.1%). The estimated pooled prevalence of sleeping problems was 45.0% (95% CI:31.6-58.4%). The estimated pooled prevalence of cognitive impairment and suicidal ideation was 30.8% (95% CI:15.0-46.7%) and 21.6% (95% CI:13.4-29.8%), respectively. The most common mental disorder in patients with systemic lupus erythematosus and psoriasis was sleeping problems at 55.9% (95% CI: 35.6-76.1%, I2 = 97%) and 39.0% (95% CI: 21.1-56.9%, I2 = 99%). CONCLUSION: Among patients with ASDs, anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation were common. The most prevalent mental disorder among patients with systemic lupus erythematosus and psoriasis was sleeping problems. Those with ASDs may experience considerable psychological burdens, and integrated mental health support is necessary for their treatment.

Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis.

BACKGROUND: Angiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and minimisation of functional deficits following ischaemia. The insulin-like growth factor (IGF) family is crucial for angiogenesis. Insulin-like growth factor-binding protein 5 (IGFBP5), a binding protein of the IGF family, may have places in angiogenesis, but the mechanisms are not yet completely understood. We sought to probe whether IGFBP5 is involved in pathological angiogenesis and uncover the molecular mechanisms behind it. METHODS AND RESULTS: IGFBP5 expression was elevated in the vascular endothelium of gastrocnemius muscle from critical limb ischaemia patients and hindlimb ischaemic (HLI) mice and hypoxic human umbilical vein endothelial cells (HUVECs). In vivo, loss of endothelial IGFBP5 (IGFBP5EKO) facilitated the recovery of blood vessel function and limb necrosis in HLI mice. Moreover, skin damage healing and aortic ring sprouting were faster in IGFBP5EKO mice than in control mice. In vitro, the genetic inhibition of IGFBP5 in HUVECs significantly promoted tube formation, cell proliferation and migration by mediating the phosphorylation of IGF1R, Erk1/2 and Akt. Intriguingly, pharmacological treatment of HUVECs with recombinant human IGFBP5 ensued a contrasting effect on angiogenesis by inhibiting the IGF1 or IGF2 function. Genetic inhibition of IGFBP5 promoted cellular oxygen consumption and extracellular acidification rates via IGF1R-mediated glycolytic adenosine triphosphate (ATP) metabolism. Mechanistically, IGFBP5 exerted its role via E3 ubiquitin ligase Von Hippel-Lindau (VHL)-regulated HIF1α stability. Furthermore, the knockdown of the endothelial IGF1R partially abolished the reformative effect of IGFBP5EKO mice post-HLI. CONCLUSION: Our findings demonstrate that IGFBP5 ablation enhances angiogenesis by promoting ATP metabolism and stabilising HIF1α, implying IGFBP5 is a novel therapeutic target for treating abnormal angiogenesis-related conditions.