Monitoring Of Therapeutic Effects Research Articles

Transcranial Cortex-Wide Imaging of Murine Ischemic Perfusion With Large-Field Multifocal Illumination Microscopy.

Ischemic stroke is a common cause of death worldwide and a main cause of morbidity. Presently, laser speckle contrast imaging, x-ray computed tomography, and magnetic resonance imaging are the mainstay for stroke diagnosis and therapeutic monitoring in preclinical studies. These modalities are often limited in terms of their ability to map brain perfusion with sufficient spatial and temporal resolution, thus calling for development of new brain perfusion techniques featuring rapid imaging speed, cost-effectiveness, and ease of use. We report on a new preclinical high-resolution angiography technique for murine ischemic stroke imaging based on large-field high-speed multifocal illumination fluorescence microscopy. We subsequently showcase the proposed method by monitoring therapeutic effects of thrombolysis in stroke (n=6), further performing cross-strain comparison of perfusion dynamics (n=6) and monitoring the therapeutic effects of sensory stimulation-based treatment (n=11). Quantitative readings of hemodynamic and structural changes in cerebral vascular network and pial vessels were attained with 14.4-µm spatial resolution at 80-Hz frame rate fully transcranially. The in vivo perfusion maps accurately delineated the ischemic core and penumbra, further exhibiting a strong correlation (86.1±4.5%) with ex vivo triphenyl tetrazolium chloride staining, significantly higher than for the conventional laser speckle contrast imaging method. Monitoring of therapeutic effects of thrombolysis confirmed that early recanalization could effectively save the penumbra while reducing the infarct area. Cross-strain comparison of perfusion dynamics affirmed that C57BL/6 mice feature a larger penumbra and smaller infarct core as compared with BALB/c mice, which have few or no collaterals. Sensory stimulation-based treatment could effectively enhance blood flow and abolish perfusion deficits in the ischemic core and penumbra regions. A high-speed fluorescence-based angiography method for transcranial stroke imaging in mice is introduced, which is capable of localizing brain perfusion changes and accurately assessing the ischemic penumbra. Compared with the whole-brain x-ray computed tomography and magnetic resonance imaging methods, which are conventionally used for stroke diagnosis and therapeutic monitoring, the new approach is simple and cost-effective, further offering high resolution and speed for in vivo studies. It thus opens new venues for brain perfusion research under various disease conditions such as stroke, neurodegeneration, or epileptic seizures.

Ultralow limit human IgG detection with 2H-MoS2/L-cysteine based plasmonic fiber-optic spectral combs

The detection of human immunoglobulin G (human IgG) provides crucial evidence in diagnosis of infectious diseases and monitoring of therapeutic effects. Here, we propose a plasmonic fiber-optical surface plasmon resonance (SPR) based sensor to realize the ultralow limit human IgG detection. The proposed sensor is fabricated by attaching a mixture of 2H-MoS2 nanosheets with L-cysteine on a gold-coated tilted fiber Bragg grating. The 2H-MoS2 possesses a large specific surface area, where the L-cysteine can enhance the stability of antibody modification. The composite membrane of 2H-MoS2 and L-cysteine can adsorb more probe rabbit anti-human IgG, which can improve sensitivity of the proposed sensor. The experimental results show that the proposed sensor exhibits a response time of approximately 220 s and a sensitivity of 0.11 dB/(ng/ml). The limit of detection of 0.87 ng/ml of the proposed sensor is one order of magnitude lower than those of other fiber-optic SPR human IgG sensors.

Research progress on platelets in glioma.

Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.

Inhalable explosive nanosensor for real-time visual monitoring of therapeutic effects of lung cancer

Lung cancer, as one of the major diseases that endanger human health, has a very high fatality rate. Consequently, effective evaluation of clinical treatment outcomes for lung cancer is crucial for the formulation of subsequent treatment plans for patients. In this work, we utilized amorphous calcium carbonate nanoparticles (CaCO3 NPs) as sources of calcium ions (Ca2+) to develop CPs (CaCO3@PDA) core–shell nanoprobes. Concurrently, we functionalized the surface of gold nanoparticles with Cy5.5-peptide, AS1411, and (4-aminosulfonylphenyl) boronic acid (4-APBA) to produce APAAs (Au NPs@pep-AS1411-(4-APBA)), which were further assembled with CPs using PEG to construct an innovative explosive nanosensor, CPAs (CaCO3@PDA-APAAs). The CPs component of the nanosensor could cause the release of a substantial amount of Ca2+ in response to the tumor microenvironment (TME), which in turn induced cellular Ca2+ overload and subsequent apoptosis. This event triggers caspase-3 activation, causing the cleavage of a specific peptide sequence (DEVD), resulting in the fluorescence signal being reinstated. Additionally, the 4-APBA moiety on the probe interacted with H2O2 resulting in alterations in surface-enhanced Raman spectroscopy (SERS) signals, which aided in the detection of reactive oxygen species (ROS) during the physiological processes. By utilizing atomization, the nanoprobes were strategically deposited in the affected lung regions to enhance the fluorescence imaging capabilities and effectively mirror the therapeutic outcomes. Overall, the CPAs explosive nanosensor has a potential in advancing the non-invasive visual monitoring of lung cancer prognosis and can be a valuable tool in ongoing efforts to improve the management of this challenging disease.

A novel microRNA miR-4433a-3p as a potential diagnostic biomarker for lung adenocarcinoma

BackgroundLung adenocarcinoma is one of the leading causes of cancer-related deaths because of the lack of early specific clinical indicators. MicroRNAs (miRNAs) have become the focus in lung cancer diagnosis. Further studies are required to explore miRNA expression in the serum of lung adenocarcinoma patients and their correlation with therapy and analyse specific messenger RNA targets to improve the specificity and sensitivity of early diagnosis. MethodsThe Toray 3D-Gene miRNA array was used to compare the expression levels of various miRNAs in the sera of patients with lung adenocarcinoma and healthy volunteers. Highly expressed miRNAs were selected for further analysis. To verify the screening results, serum and pleural fluid samples were analysed using qRT-PCR. Serum levels of the miRNAs and their correlation with the clinical information of patients with lung adenocarcinoma were analysed. The functions of miRNAs were further analysed using the Kyoto Encyclopedia of Gene and Genomes and Gene Ontology databases. ResultsMicroarray analysis identified 60 and 50 miRNAs with upregulated and downregulated expressions, respectively, in the serum of patients with lung adenocarcinoma compared to those in healthy individuals. Using qRT-qPCR to detection of miRNAs expression in the serum or pleural effusion of patients with early and advanced lung adenocarcinoma, we found that miR-4433a-3p could be used as a diagnostic marker and therapeutic evaluation indicator for lung adenocarcinoma. Serum of miR-4433a-3p levels significantly correlated with the clinical stage. miR-4433a-3p may be more suitable than other tumour markers for the early diagnosis and evaluation of therapeutic effects in lung adenocarcinoma. miR-4433a-3p may affect tumour growth and metastasis by acting on target genes (PIK3CD, UBE2J2, ICMT, PRDM16 and others) and regulating tumour-related signalling pathways (MAPK signal pathway, Ras signalling pathway and others). ConclusionmiR-4433a-3p may serve as a biomarker for the early diagnosis of lung adenocarcinoma and monitoring of therapeutic effects.

Brain-Derived Neurotrophic Factor in Pediatric Acquired Brain Injury and Recovery.

We review emerging preclinical and clinical evidence regarding brain-derived neurotrophic factor (BDNF) protein, genotype, and DNA methylation (DNAm) as biomarkers of outcomes in three important etiologies of pediatric acquired brain injury (ABI), traumatic brain injury, global cerebral ischemia, and stroke. We also summarize evidence suggesting that BDNF is (1) involved in the biological embedding of the psychosocial environment, (2) responsive to rehabilitative therapies, and (3) potentially modifiable. BDNF's unique potential as a biomarker of neuroplasticity and neural repair that is reflective of and responsive to both pre- and post-injury environmental influences separates it from traditional protein biomarkers of structural brain injury with exciting potential to advance pediatric ABI management by increasing the accuracy of prognostic tools and informing clinical decision making through the monitoring of therapeutic effects.

Increased Cerebrospinal Fluid Adenosine 5'-Triphosphate Levels in Patients with Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyneuropathy.

Extracellular adenosine 5'-triphosphate (ATP) acts as a signaling molecule in the peripheral nerves, regulating myelination after nerve injury. The present study examined whether the cerebrospinal fluid (CSF) ATP levels in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are related to disease severity. CSF ATP levels in 13 patients with GBS and 18 patients with CIDP were compared with those in a control group of 16 patients with other neurological diseases (ONDs). In patients with CIDP, CSF ATP levels were compared before and after treatment. The correlations between CSF ATP levels and other factors, including clinical data and CSF protein levels, were also evaluated. Median CSF ATP levels were significantly higher in patients with GBS and CIDP than in those with ONDs. When patients with CIDP were classified into two groups depending on their responsiveness to immunotherapy, median CSF ATP levels were significantly higher in good responders than in ONDs. CSF ATP levels tended to decrease after treatment in patients with CIDP. In patients with CIDP, there is a negative correlation between CSF ATP and CSF protein levels. CSF ATP levels were increased in patients with GBS and CIDP. In particular, CSF ATP levels tended to decrease following treatment in patients with CIDP. CSF ATP levels may be useful biomarkers for the diagnosis or monitoring of therapeutic effects in patients with GBS and CIDP.

Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy

Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently. Based on the strategy of “fluorescence turn on-controllable release”, a novel bifunctional candidate was constructed based on previous developed vascular normalization inducer QDAU5, which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles (FEIRQ NPs). Subsequently, biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis, endoplasmic reticulum stress, and antigen preconditioning and maturation of dendritic cells and CD8+ T cells, leading to excellent antitumor efficacy in the absence of cytotoxic drugs. Additionally, FEIRQ NPs show high fluorescence intensity upon exposure to the β-galactosidase (β-Gal) enzyme expressed in ovarian cancer, enabling real-time monitoring of therapeutic effects. Overall, our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.

Chemometric-empowered spectroscopic techniques in pharmaceutical fields: A bibliometric analysis and updated review

Undeniable increase in pharmaceutical demand has encouraged researchers to develop analytical techniques to analyze drugs and monitor their effects. Chemometrics enabled simple spectroscopic approaches (such as infrared or UV spectroscopy) to analyze complex samples, including drug formulations, excreted fluids and tissues of living organisms. The aim of this study was to evaluate the research trend of this combinatorial technique utilized for pharmaceutical-related sample analysis using a bibliometric analysis. Bibliometric data of published literature from the Scopus database on March 14, 2023 were retrieved using the keyword combinations of "multivariate", "chemometrics", "pattern recognition", "drug", "pharmaceutical" and "spectroscopy". Network visualization analysis was performed using VOSviewer on the co-occurring keywords and authorships, presenting data such as top cited papers (n=10). The literature review was performed based on the research trend revealed by the clusters that emerged in the network visualization. The analysis revealed that the first paper was published in 1973 (n=1) and a total of 3544 records have been published as of March 14, 2023, comprising original research articles (n=3144, 88.71%) and review articles (n=232, 6.55%). The keyword “chemometrics” with Total Link Strength (TLS) of 826 emerged as the most abundant, followed by “metabolomics” (TLS=388), “Raman spectroscopy” (TLS=280), “metabonomics” (TLS=272), “nuclear magnetic resonance” or “NMR” (TLS=271), and “multivariate analysis” (TLS=254). Network visualization revealed that the research falls into two general categories: (1) drug toxicity and efficacy monitoring and (2) quality control of drug manufacturing. The top cited paper (n=3269) was a review article published in 1999 describing the utility of nuclear magnetic resonance combined with multivariate statistics for metabolite profiling of biological samples. The chemometric-empowered spectroscopy techniques were expected to provide objective measurement during clinical studies and monitoring of therapeutic effects.

Changes in Retinal Thickness and Brain Volume during 6.8-Year Escalating Therapy for Multiple Sclerosis

Background. Different disease-modifying therapies (DMT) for multiple sclerosis (MS) have disparate effects on disability outcomes. Sweden has a leading position globally in initiating high-efficacy DMT instead of escalating DMT from 1st-line to high-efficacy DMT. With optical coherence tomography (OCT), retinal changes can be measured at a few micrometer level. OCT has been increasingly applied in diagnosing MS and monitoring disease course and therapeutic effect. Objective. We investigate the effects of 1st-line versus high-efficacy DMT for MS on retinal and brain atrophy and on functional outcomes during 6.8 years of escalating DMT. Materials and Methods. In this prospective longitudinal observational study, 18 MS patients were followed up for 6.8 years. Twelve of the patients were untreated at baseline. All patients underwent 1st-line DMT for median duration of 2.4 years and then switched to high-efficacy DMT for a median duration of 2.9 years. Findings from neurological examinations, MRI, and OCT measures were registered 2-4 times per year. Results. Ganglion cell-inner plexiform layer (GCIPL) thickness was significantly reduced during 1st-line DMT (73.75 μm, p < 0.01 ) compared to baseline (76.38 μm). During high-efficacy DMT, thickness reduction was slower (73.27 μm, p < 0.05 ), and MRI contrast-loading lesions vanished ( p < 0.01 ). However, brain parenchymal fraction (BPF) decreased during high-efficacy DMT compared to 1st-line DMT. Estimated models showed similar results. Conclusion. GCIPL decline was most profound during 1st-line DMT and diminished during high-efficacy DMT. MRI contrast lesions vanished during high-efficacy DMT. However, brain atrophy continued regardless of high-efficacy DMT.

Application value of circulating LncRNA in diagnosis, treatment, and prognosis of breast cancer.

Breast cancer is the malignant tumor with the highest incidence in women worldwide. It is highly heterogeneous, has a high incidence of drug resistance, recurrence, and metastasis, and is one of the malignant tumors with the highest mortality rate. The early diagnosis, treatment monitoring, and prognosis assessment of breast cancer are the key factors affecting the survival of patients. However, due to the lack of specific biomarkers, breast cancer is still an essential factor affecting women's quality of life and physical and mental health. Long non-coding RNA can regulate various genes and different signaling pathways and plays an essential role in the occurrence and development of tumors. Recent studies have found that the abnormal expression of circulating long non-coding RNA in serum, saliva, and other biological body fluids plays a significant role in early diagnosis, pathological classification, stage, therapeutic effect monitoring, and prognosis evaluation of breast cancer. This article will review the potential application value of circulating lncRNA in breast cancer.

Evaluation of Anti-Factor Xa Level Usage for Low Molecular Weight Heparin in a Healthcare System

Background: Low-molecular-weight heparin (LMWH) is a commonly used anticoagulant for treatment of venous thromboembolism (VTE). Routine monitoring of therapeutic effects through anti-Xa levels is not recommended but may be beneficial in patients with altered pharmacokinetics.1,2 Inappropriate monitoring leads to excessive testing and premature dose adjustments, compromising safety and efficacy. The purpose of this project was to assess appropriateness of monitoring LMWH anti-Xa levels and identify opportunities to optimize utilization within a community health system.

Low Molecular Weight Heparin Anti-Factor Xa Level Monitoring in a Healthcare System

Purpose: Low molecular weight heparin (LMWH) is widely used for the prevention and treatment of deep vein thrombosis and pulmonary embolism. Routine monitoring of therapeutic effects through anti-Xa levels is not recommended but may be beneficial in patients with altered pharmacokinetics including pregnancy, weight extremes, or renal impairment. Levels should be drawn approximately four hours after the third dose to measure peak anti-Xa activity after achieving steady state. Untimely monitoring results in excessive testing, increased laboratory costs, and unwarranted dose adjustments compromising patient safety and efficacy. The purpose of this performance improvement project was to evaluate the appropriateness of monitoring LMWH anti-Xa levels and identify opportunities to optimize ordering within a healthcare system. Methods: A random sample, retrospective chart review of patients at a multi-site hospital system over a 3 year period was conducted. Inclusion criteria were adult inpatients with at least one anti-Xa level ordered. Data collection included the anticoagulant agent, dose, indication, and administration time; indication for anti-Xa level monitoring, and anti-Xa sample collection time relative to the dose of the anticoagulant administered. Data was collected to assess if the dose was appropriately adjusted in patients who received an anticoagulant dose adjustment following anti-Xa level monitoring. Baseline characteristics collected included patient's creatinine clearance (CrCl), weight, and COVID-19 status. Primary outcomes of this study consisted of ordering trends for anti-Xa levels including indication and corresponding dose adjustments. Secondary outcomes included anti-Xa levels ordered at the appropriate time window and incidence of bleeding or thrombosis following inappropriate dose adjustments. Results: A total of 220 patients with anti-Xa level monitoring were reviewed. An appropriate indication for anti-Xa level monitoring was identified in 28% of patients. Of the 49 patients that warranted anticoagulant dose adjustments following anti-Xa levels, 45 patients (92%) received appropriate dose adjustments. Anti-Xa levels were drawn after the third therapeutic dose of LMWH in 146 patients and 84 of these patients had levels drawn 3-5 hours post-dose. Therefore, 54% of levels drawn were within the appropriate time frame. A total of 4 patients had documentation of bleeding and 1 patient had thrombosis following an inappropriate dose adjustment of LMWH. Conclusion: Appropriate anti-Xa level monitoring in patients with altered pharmacokinetics resulted in justified LMWH dose adjustments and ensured therapeutic concentrations were attained. In patients who received appropriate monitoring and subsequent dose adjustments, there were no adverse events noted. The results of this performance improvement project will be reviewed with pertinent stakeholders and a multi-disciplinary approach will be utilized to develop a protocol for LMWH anti-Xa level monitoring.

May Measurement Month 2018-2019: an analysis of blood pressure screening results from Austria.

Arterial hypertension is a global burden leading to over 10.8 million deaths per year worldwide. May Measurement Month (MMM) is a global project initiated by the International Society of Hypertension to raise the awareness of high blood pressure (BP) in the population. Following the MMM protocol 2508 participants ≥18 years had their BP measured in Austria in MMM18 and MMM19. Of those screened, 54.6% were found to be hypertensive, defined as a BP ≥140/90 mmHg and/or being on treatment for hypertension. Among those individuals with hypertension, 56.1% were on medication but only 42.0% of those treated had controlled BP (<140/90 mmHg). Lower BPs were found in those with previous myocardial infarction (MI), probably explained by a medical monitoring system of patients with MI in Austria. Those with hypertension were referred for further medical investigations and were provided lifestyle advice. Among a high number of individuals receiving antihypertensive treatment, BP is still not controlled. Further screening and monitoring of therapeutic effects is urgently required.

Eosinophilic gastrointestinal disorders in childhood

Eosinophilic gastrointestinal disorders are a group of chronic inflammatory conditions characterised by the presence of eosinophilic infiltrates in the gastrointestinal wall. These disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Their incidence is increasing, with eosinophilic esophagitis known to be the most common form. The etiopathogenesis of eosinophilic gastrointestinal disorders is not fully understood, and most likely associated with an abnormal immune response to food and/or inhalant allergen. They are often accompanied by allergies. Clinical symptoms, especially in the youngest children, are non-specific and depend on the gastrointestinal segment involved. These are most often feeding difficulties and regurgitation in infants, and heartburn, chest pain, dysphagia and food bite impaction in adolescents and adults. Except for eosinophilic esophagitis, there are no uniform diagnostic or therapeutic guidelines for eosinophilic gastrointestinal disorders. Diagnosis is challenging and it is based on the coexistence of clinical, endoscopic and histopathological symptoms and the exclusion of secondary causes of gastrointestinal eosinophilic infiltration. Treatment involves the use of proton pump inhibitors, an elimination diet, or glucocorticoid therapy. Endoscopic or surgical treatment may be necessary in some cases. Clinical remission does not correlate with histopathological remission, therefore monitoring of therapeutic effects requires multiple endoscopies with histopathological assessment of specimens. The aim of this paper was to present the current data on the incidence, diagnosis and treatment of eosinophilic gastrointestinal diseases in children.

Theranostic nanomotors for tumor multimode imaging and photothermal/photodynamic synergistic therapy

Efficient nanotheranostic reagents for cancer has attracted extensive attention. Herein we report nanomotors UCNPs@mSiO2-Au-Cys for tumor multimode imaging and photothermal (PTT)/photodynamic (PDT) combined therapy. Firstly, the photothermal agent Au NPs and photosensitizer Cy-S-Ph-NH2 (Cys) are loaded by upconversion nanoparticles (UCNPs) with the mesoporous silica shell. Nanomotors generate autonomous motion under 808 nm laser irradiation, which can significantly increase their tumor tissue permeability. Meanwhile, Au NPs provide photothermal conversion, photothermal imaging, and act as nanocatalytic enzyme that can enhance the efficacy of oxygen dependent PDT. Cys also can increase the photothermal effect. In addition, the two emission of UCNPs at 659 and 800 nm under 980 nm excitation are offered respectively the possibility to realize real-time online monitoring of therapeutic effect and the tumor fluorescence imaging. This nano-therapeutics platform based on the optical properties of UCNPs and nano-motor technology will provide potential methods for tumor treatment.

Evaluation of fecal SYPL1 as a diagnostic biomarker in colorectal cancer

BackgroundAt present, there is still no ideal non-invasive biomarker for colorectal cancer (CRC) screening. Previously, we foundserum synaptophysin like 1 (SYPL1) served as a potential biomarker for CRC diagnosis. However, whether fecal SYPL1 (fSYPL1) are more sensitive and specific for CRC remains unclear. MethodsWe analyzed fSYPL1 in controls (n = 70), adenoma patients (n = 80), CRC patients (n = 150) and postoperative CRC patients (n = 25) by ELISA. ResultsSYPL1 was stable in feces. The fSYPL1 levels were significantly higher in CRC patients than in either controls or adenoma patients (P < 0.0001). ROC curves showed that fSYPL1 performed superbly in distinguishing CRC patients from controls (AUC = 0.947; 95% CI: 0.920–0.974, P < 0.0001, sensitivity: 80.67%, specificity: 100.00%), which showed much stronger performance than the traditional biomarkers (FOBT, CEA and CA19-9). Meanwhile, the fSYPL1 level positively correlated with tumor size, tumor invasion, lymph node invasion and clinical stage (P < 0.05). In addition, the detection rate of fSYPL1 was high in early CRC (75.00% in stage I and II). The fSYPL1 levels in CRC patients declined substantially after surgery (P = 0.0002). By means of a lower cut off level, 73.58% of high-risk adenomas were detected. The combination of fSYPL1 and FOBT performed better than the combination of plasma SYPL1, CEA and CA199 in distinguishing CRC patients from controls. ConclusionThe fSYPL1 might be a potential biomarker for CRC screening, early diagnosis, prognosis prediction and therapeutic effect monitoring.

Metabolomics Strategy Assisted by Transcriptomics Analysis to Identify Potential Biomarkers Associated with Tuberculosis.

PurposeTo investigate the dysregulated pathways and identify reliable diagnostic biomarkers for tuberculosis using integrated analysis of metabolomics and transcriptomics.MethodsThree groups of samples, untargeted metabolomics analysis of healthy controls (HC), latent tuberculosis infection patients (LTBI), and active tuberculosis patients (TB), were analyzed using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and ultra-high performance liquid chromatography-quantitative mass spectrometry (UHPLC-QE-MS). Both univariate and multivariate and statistical analyses were used to select differential metabolites (DMs) among group comparison, and LASSO regression analysis was employed to discover potential diagnostic biomarkers. Metabolite set enrichment analysis was performed to identify the altered metabolic pathways specifically in patients with TB. Meanwhile, a transcriptomic dataset GSEG4992 was downloaded from the GEO database to explore the differentially expressed genes (DEGs) between TB and HC identified in significantly enriched pathways. Finally, an integrative analysis of DMs and DEGs was performed to investigate the possible molecular mechanisms of TB.ResultsThirty-three specific metabolites were significantly different between TB and HC, of which 7 (5-hydroxyindoleacetic acid, isoleucyl-isoleucine, heptadecanoic acid, indole acetaldehyde, 5-ethyl-2,4-dimethyloxazole, and 2-hydroxycaproic acid, unknown 71) were chosen as combinational potential biomarkers for TB. The area under the curve (AUC) value of these biomarkers was 0.97 (95% CI: 0.92–1.00). Metabolites set enrichment analysis (MSEA) displayed that there were 3 significantly enriched pathways among all. The genes in 3 significantly enriched pathways were further analyzed, of which 9(ALDH3B1, BCAT1, BCAT2, GLYAT, GOT1, IL4I1, MIF, SDS, SDSL) were expressed differentially. The area under the curve (AUC) values of these DEGs enriched in pathways mostly were greater than 0.8. As a result, a connected network of metabolites and genes in the pathways were established, which provides insights into the credibility of selected metabolites.ConclusionThe newly identified metabolic biomarkers display a high potential to be developed into a promising tool for TB screening, diagnosis, and therapeutic effect monitoring.

Intraoperative findings of abnormal muscle response for hemifacial spasm following botulinum neurotoxin treatment.

This study aimed to investigate the effect of preoperative botulinum toxin (BTX) injection on intraoperative abnormal muscle response (AMR) in patients with hemifacial spasm (HFS). A total of 104 patients (32 men, 72 women) who underwent microvascular decompression (MVD) for HFS were included in this study. A total of 62 patients without and 42 patients with preoperative BTX treatments were assigned to group A and group B, respectively. AMR recordings were obtained from the orbicularis oculi and mentalis muscles by stimulation of the marginal mandibular branch and zygomatic branch of the facial nerve, respectively. The intraoperative AMR monitoring findings and therapeutic effects were compared between groups A and B. The rates of the patients with unavailable AMRs recorded from the orbicularis oculi muscles in group B (38.1%) were significantly higher than those in group A (14.5%, p = 0.006). Moreover, in cases with over 4 times BTX injection, the recordings of AMR from the orbicularis oculi muscles were poorer than the cases with less BTX injection (p = 0.001). There were no significant differences in the rates of the patients with unavailable AMRs recorded from the mentalis muscles between the two groups. There were no significant differences in the surgical results obtained between the two groups. Preoperative BTX injections should be less than 4 times to ensure effective AMR monitoring. MVD using AMR monitoring is useful for patients with HFS who were previously treated by BTX as well as those who were not treated.

Structural Transformative Antioxidants for Dual-Responsive Anti-Inflammatory Delivery and Photoacoustic Inflammation Imaging.

We have synthesized a PEGylated, phenylboronic acid modified L-DOPA pro-antioxidant (pPAD) that can self-assemble into nanoparticles (pPADN) for the loading of a model glucocorticoid dexamethasone (Dex) through 1,3-diol/phenylboronic acid chemistry and hydrophobic interactions for more effective treatment of inflammation. Upon exposure to ROS, pPADN convert into the active form of L-DOPA, and a cascade of oxidative reactions transform it into antioxidative melanin-like materials. Concomitantly, the structural transformation of pPADN triggers the specific release of Dex, along with the acidic pH of inflammatory tissue. In a rat model of osteoarthritis, Dex-loaded pPADN markedly mitigate synovial inflammation, suppress joint destruction and cartilage matrix degradation, with negligible in vivo toxicity. Moreover, in situ structural transformation makes pPADN suitable for noninvasive monitoring of therapeutic effects as a photoacoustic imaging contrast agent.