Evaluation Of Therapeutic Effects Research Articles

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.

A miniaturized wash-free microfluidic assay for electrical impedance-based assessment of red blood cell-mediated microvascular occlusion

The production of HbS — an abnormal hemoglobin (Hb) — in sickle cell disease (SCD) results in poorly deformable red blood cells (RBCs) that are prone to microcapillary occlusion, causing tissue ischemia and organ damage. Novel treatments, including gene therapy, may reduce SCD morbidity, but methods to functionally evaluate RBCs remain limited. Previously, we presented the microfluidic impedance red cell assay (MIRCA) for rapid assessment of RBC deformability, employing electrical impedance-based readout to measure RBC occlusion of progressively narrowing micropillar openings. We describe herein the design, development, validation, and clinical utility of the next-generation MIRCA assay, featuring enhanced portability, rapidity, and usability. It incorporates a miniaturized impedance analyzer and features a simplified wash-free operation that yields an occlusion index (OI) within 15 min as a new metric for RBC occlusion. We show a correlation between OI and percent fetal hemoglobin (%HbF), other laboratory biomarkers of RBC hemolysis, and SCD severity. To demonstrate the assay’s versatility, we tested RBC samples from treatment-naïve SCD patients in Uganda that yielded OI levels similar to those from hydroxyurea (HU)-treated patients in the U.S., highlighting the role of %HbF in protecting against microcapillary occlusion independent of other pharmacological effects. The MIRCA assay could also identify a subset of HU-treated patients with high occlusion risks, suggesting that they may require treatment adjustments including a second-line therapy to improve their outcomes. This work demonstrates the potential of the MIRCA assay for accelerated evaluation of RBC health, function, and therapeutic effect in an ex vivo model of the microcapillary networks.

Customized Lanthanide Nanobiohybrids for Noninvasive Precise Phototheranostics of Pulmonary Biofilm Infection.

A noninvasive strategy for in situ diagnosis and precise treatment of bacterial biofilm infections is highly anticipated but still a great challenge. Currently, no in vivo biofilm-targeted theranostic agent is available. Herein, we fabricated intelligent theranostic alginate lyase (Aly)-NaNdF4 nanohybrids with a 220 nm sunflower-like structure (NaNdF4@DMS-Aly) through an enrichment-encapsulating strategy, which exhibited excellent photothermal conversion efficiency and the second near-infrared (NIR-II) luminescence. Benefiting from the site-specific targeting and biofilm-responsive Aly release from NaNdF4@DMS-Aly, we not only enabled noninvasive diagnosis but also realized Aly-photothermal synergistic therapy and real-time evaluation of therapeutic effect in mice models with Pseudomonas aeruginosa biofilm-induced pulmonary infection. Furthermore, such nanobiohybrids with a sheddable siliceous shell are capable of delaying the NaNdF4 dissolution and biodegradation upon accomplishing the therapy, which is highly beneficial for the biosafety of theranostic agents.

Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic, Omalizumab, in Severe Asthma in Adults: Results of the SoMOSA Study.

The anti-IgE monoclonal, omalizumab, is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during one year of omalizumab treatment. 1-year, open-label, Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 severe (GINA step 4/5) uncontrolled atopic asthmatics (≥2 severe exacerbations in previous year) on high-dose inhaled corticosteroids, long-acting β-agonists, ± mOCS. It had two phases: 0-16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE), and 16-52 weeks, to assess late responses by ≥50% reduction in exacerbations or dose of maintenance oral corticosteroids (mOCS). All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ≥50%, while 57% (37/65) on mOCS reduced their dose by ≥50%. The primary outcome 2, 3-dinor-11-β-PGF2α, GETE and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five breathomics (GC-MS) and 5 plasma lipid biomarkers strongly predicted the ≥50% reduction in exacerbations (receiver operating characteristic area under the curve (AUC): 0.780 and 0.922, respectively) and early responses (AUC:0.835 and 0.949, respectively). In independent cohorts, the GC-MS biomarkers differentiated between severe and mild asthma. Conclusions This is the first discovery of omics biomarkers that predict improvement to a biologic for asthma. Their prospective validation and development for clinical use is justified.

Visual analysis on the study status and trends of acupuncture and moxibustion for Alzheimer's disease.

The research history, hot spots and frontier trends of acupuncture and moxibustion for Alzheimer's disease (AD) were explored using knowledge graph technology. The articles on acupuncture and moxibustion for AD were searched from 6 databases, i.e. CNKI, VIP, Wanfang, SinoMed, Pubmed and Web of Science, from January 1st, 1993 to January 1st, 2023. Using CiteSpace6.2.R2 Advance and VOSviewer V1.6.19 softwares, the knowledge map was graphed and the visual analysis was performed. A total of 1 228 Chinese and 309 English articles were included. The high-frequency keywords were generally divided into the keywords of clinical diseases (AD, dementia), those of therapeutic methods (electroacupuncture, acupuncture-moxibustion and acupuncture) and those of mechanism study (β-amyloid, mice). Thirteen keyword clusters were formed among the articles of Chinese version, e.g. acupuncture-moxibustion, dementia, acupuncture and electroacupuncture; and 8 clusters were obtained among English articles, e.g. electroacupuncture, drug therapy and hippocampus. The high-frequency keywords of acupoints included Baihui (GV 20), Dazhui (GV 14), Yintang (GV 24+), Zusanli (ST 36), Fenglong (ST 40), etc. Six clusters of "acupuncture techniques → acupoints" were obtained for the treatment of AD with acupuncture and moxibustion. The therapeutic methods and modes of AD with acupuncture and moxibustion are constantly progressed, the development of clinical research tends to the evaluation of novel therapeutic mode and clinical effect, and the mechanism of acupuncture and moxibustion for the effect on AD are more deeply explored. Among the various therapeutic methods, acupuncture-moxibustion, acupuncture and electroacupuncture have been early predominant; while, many novel methods are gradually displayed later, such as music electroacupuncture and hydro-acupuncture. In recent 30 years, among Chinese and English articles for the studies of AD treated with acupuncture and moxibustion, the theme of them focuses on the two aspects, the observation of clinical effect and the mechanism research. It is found that the clinical therapeutic methods have been gradually improved and the mechanism exploration been deepened.

Diagnosis and treatment of recurrent patellar dislocation with knee extensor device combined with rearrangement.

This study aimed to investigate the clinical effects of combining knee extension mechanism (EM) with rearrangement in the treatment of recurrent patellar dislocation (RPD). Eighty-four patients with RPD admitted to the First Affiliated Hospital of Kunming Medical University were included. In this work, all patients received routine computed tomography (CT) examinations. In addition, the evaluation factors of EM combined with rearrangement therapy in RPD patients were analyzed using logistic regression. Lysholm and Kujula scores, femoral canal width, patellar canal width, patellar tilt angle (PTA), and lateral patellar displacement (LPD) were significantly increased at 1 and 3 years after treatment (p < 0.05). LPA was significantly decreased, while the tibial tuberosity trochlear groove of the femur (TT-TG) demonstrated no considerable differences (p > 0.05). The good rate of the short-term Insall-Salvati index was 78.6%, and that of the long-term Insall-Salvati index was 76.1%. The combination of the knee extension device and rearrangement therapy has a higher rate of short-term and long-term Insall-Salvati index (ISI) excellence. In addition, the range of motion of the knee joint increased significantly, and the Q Angle decreased significantly (p < 0.05). Logistic regression analysis showed that age and ISI were highly correlated with the evaluation of therapeutic effects in patients with RPD. EM combined with rearrangement in the treatment of RPD had positive short-term and long-term efficacy, high application value, and age, which can be popularized in clinical applications and have positive diagnostic value.

Evaluation of Therapeutic Effect of Spirulina in Patients with Geographic Tongue: A Randomized Double Blind Controlled Clinical Trial

Evaluation of Therapeutic Effect of Spirulina in Patients with Geographic Tongue: A Randomized Double Blind Controlled Clinical Trial

Advancements and controversies in conversion therapy for biliary tract malignant tumors with insufficient future liver remnant

Due to the unique location and aggressive tumor biology,hilar cholangiocarcinoma,intrahepatic cholangiocarcinoma,and gallbladder cancer often present with obstructive jaundice and require extensive liver resection,also exhibit high rates of recurrence and metastasis after radical excision. Therefore,surgeons should make treatment decisions based on the biliary anatomy of patients and the biological characteristics of tumors as it significantly affects patient's prognosis. Treatment strategy should be made to ensure the successful implementation of radical resection for biliary tract malignant tumors while maximizing the survival benefits of patients. Firstly,conversion of liver function by relieving jaundice technology and conversion of tumor biological characteristics through systematic therapy,followed by the conversion of future liver remnant. Currently,there are still controversies surrounding indications,methods,standards of relieving jaundice,and treatment plans,cycles,evaluation of therapeutic effects for systematic conversion therapy,and the standards and techniques of conversion therapy for future liver remnant.This article discusses these issues through literature analysis and the author's experience in the hope of resonating with colleagues.

Value of constructing a non-invasive diagnostic model based on serum heme oxygenase-1 and glucose regulatory protein 78 for non-alcoholic fatty liver disease

Objective: To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value. Methods: A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ(2) test. Results: Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients (P < 0.05). Binary logistic analysis results showed that AST, TG, LDL-C, serum HO-1, and GRP78 were independent risk factors for NAFLD (P < 0.05). A nomogram clinical predictive model HGATL was established using HO-1 (H), GRP78 (G) combined with AST (A), TG (T), and LDL-C (L), with the formula P=-21.469+3.621×HO-1+0.116 ×GRP78+0.674×AST+6.250×TG+4.122 ×LDL-C. The results confirmed that the area under the ROC curve of the HGATL model was 0.965 8, with an optimal cutoff value of 81.69, a sensitivity of 87.06%, a specificity of 92.82%, a P < 0.05, and the diagnostic effectiveness significantly higher than that of a single indicator. The calibration curve and DCA both showed that the model had good diagnostic performance. Conclusion: The HGATL model can be used as a novel, non-invasive diagnosis model for NAFLD and has a positive application value in NAFLD diagnosis and therapeutic effect evaluation. Therefore, it should be explored and promoted in clinical applications.

Long-term Outcome of Isobar TTL System for the Treatment of Lumbar Degenerative Disc Diseases.

The Isobar TTL dynamic fixation system has demonstrated favorable outcomes in the short-term treatment of lumbar degenerative disc diseases (LDDs). However, there is a paucity of extensive research on the long-term effects of this system on LDDs. This study aimed to evaluate the long-term clinical and radiological outcomes of patients with LDDs who underwent treatment utilizing the Isobar TTL dynamic fixation system. The study analyzed the outcomes of 40 patients with LDDs who underwent posterior lumbar decompression and received single-segment Isobar TTL dynamic internal fixation at our hospital between June 2010 and December 2016. The evaluation of clinical therapeutic effect involved assessing postoperative pain levels using the visual analogue scale (VAS) and Oswestry disability index (ODI), both before surgery, 3 months after, and the final follow-up. To determine the preservation of functional motion in dynamically stable segments, we measured the range of motion (ROM) and disc height of stabilized and adjacent segments preoperatively and during the final follow-up. Additionally, we investigated the occurrence of adjacent segment degeneration (ASD). Forty patients were evaluated, with an average age of 44.65 years and an average follow-up period of 79.37 months. Fourteen patients belonged to the spondylolisthesis group, while the remaining 26 were categorized under the stenosis or herniated disc group. The preoperative ROM of the stabilized segment exhibited a significant reduction from 8.15° ± 2.77° to 5.00° ± 1.82° at the final follow-up (p < 0.001). In contrast, there was a slight elevation in the ROM of the adjacent segment during the final follow-up, increasing from 7.68° ± 2.25° before surgery to 9.36° ± 1.98° (p < 0.001). The intervertebral space height (IH) in the stabilized segment exhibited a significant increase from 10.56 ± 1.99 mm before surgery to 11.39 ± 1.90 mm at the one-week postoperative follow-up (p < 0.001). Conversely, there was a notable decrease in the IH of the adjacent segment from 11.09 ± 1.82 mm preoperatively to 10.86 ± 1.79 mm at the one-week follow-up after surgery (p < 0.001). The incidence of ASD was 15% (6/40) after an average follow-up period of 79.37 months, with a rate of 15.38% (4/26) in the stenosis or herniated disc group and 14.29% (2/14) in the spondylolisthesis group; however, no statistically significant difference was observed in the occurrence of ASD among these groups (p > 0.05). The Isobar TTL dynamic fixation system is an effective treatment for LDDs, improving pain relief, quality of life (QoL) and maintaining stabilized segmental motion. It has demonstrated excellent long-term clinical and radiographic results.

Evaluation of therapeutic effect and prognostic value of 18F-FDG PET/CT in different treatment nodes of DLBCL patients.

In the present study, we aimed to investigate the role of baseline (B), interim (I) and end-of-treatment (Eot) 18F-FDG PET/CT in assessing the prognosis of diffuse large B cell lymphoma (DLBCL), so as to identify patients who need intensive treatment at an early stage. A total of 127 DLBCL patients (62 men; 65 women; median age 62years) were retrospectively analyzed in this study. Baseline (n = 127), interim (n = 127, after 3-4 cycles) and end-of-treatment (n = 53, after 6-8 cycles) PET/CT images were re-evaluated; semi-quantitative parameters such as maximum standardized uptake value of lesion-to-liver ratio (SUVmax(LLR)) and lesion-to-mediastinum ratio (SUVmax(LMR)), total metabolic tumor volume (TMTV) and total metabolic tumor volume (TLG) were recorded. ΔTLG1 was the change of interim relative to baseline TLG (I to B), ΔTLG2 (Eot to B). ΔSUVmax and ΔTMTV were the same algorithm. The visual Deauville 5-point scale (D-5PS) has been adopted as the major criterion for PET evaluation. Visual analysis (VA) and semi-quantitative parameters were assessed for the ability to predict progression-free survival (PFS) and overall survival (OS) by using Kaplan-Meier method, cox regression and logistic regression analysis. When visual and semi-quantitative analysis are combined, the result is only positive if both are positive. At a median follow-up of 34months, the median PFS and OS were 20 and 32months. The survival curve analysis showed that advanced stage and IPI score with poor prognosis, ΔSUVmax(LLR)1 < 89.2%, ΔTMTV1 < 91.8% and ΔTLG1 < 98.8%, ΔSUVmax(LLR)2 < 86.4% were significantly related to the shortening of PFS in patient (p < 0.05). ΔSUVmax(LLR)1 < 83.2% and ΔTLG1 < 97.6% were significantly correlated with the shortening of OS in patients (p < 0.05). Visual analysis showed that incomplete metabolic remission at I-PET and Eot-PET increased the risk of progress and death. In terms of predicting recurrence by I-PET, the combination of visual and semi-quantitative parameters showed higher positive predictive value (PPV) and specificity than a single index. Three to four cycles of R-CHOP treatment may be a time point for early prediction of early recurrence/refractory (R/R) patients and active preemptive treatment. Combined visual analysis with semi-quantitative parameters of 18F-FDG PET/CT at interim can improve prognostic accuracy and may allow for more precise screening of patients requiring early intensive therapy.

Experimental Animal Models for Influenza/Flu Virus Vaccine Development

Objectives: The objective of this review is to explore the different animal models used in the development of Influenza / Flu Virus Vaccine as well as some important guidelines adhered to it.&#x0D; Methods: Laboratory animal models are widely used in the preclinical evaluation of potential vaccines and antiviral compounds to investigate the safety and efficacy of the vaccine or compound in preventing or moderating infection, disease, or secondary transmission. Animal models must also represent humans in terms of similarity of clinical signs, histopathological changes, virus growth kinetics, or transmission. Common animal models for influenza virus vaccine testing include mice, ferrets, and non-human primates. These models help researchers assess vaccine efficacy, immune response, and potential side effects before advancing to human trials. Animal models play a crucial role in the development and testing of influenza vaccines, as they help researchers examine potential side effects and adverse reactions, evaluate the efficacy of vaccines, study the immune response elicited by vaccines, understand the pathogenesis of influenza virus infection, and predict the potential impact of emerging strains. They also help test various vaccine platforms and delivery methods, and compare the effectiveness of different vaccine formulations in animals to identify promising candidates for further human trials.&#x0D; Results: We have discussed in detail the various animal models such as Chick embryo model for the development of influenza virus vaccine and mice, ferrets, guinea pig and non-human primates etc. used for the evaluation of safety and therapeutic effectiveness.&#x0D; Conclusion: As we have discussed various animal models, their merits, demerits etc. for the evaluation of safety and effectiveness of influenza virus vaccine and expect that these will help for the young researchers to carry out their vaccine research using suitable animal models.&#x0D; Keywords: influenza virus, vaccine development, mouse models, ferret model, guinea pig model, cotton rat model

The efficacy-associated biomarkers for immune checkpoint inhibitors in gastrointestinal cancer: a literature review.

Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer. The literature on ICI treatment in GI cancers was searched in the PubMed, Embase, and Cochrane Library databases for publications up to April 2023. Clinical practice and research has gradually revealed some biomarkers related to the treatment of GI cancers with ICIs, which can be roughly divided into three types: biomarkers that predict the effectiveness of ICIs treatment, biomarkers associated with resistance to ICIs, and biomarkers associated with immune related adverse events (irAEs). This review article provides a literature review on biomarkers related to the efficacy of ICIs in the treatment of GI cancers. According to existing clinical research results, there are multiple biomarkers that can be used for predicting and monitoring the efficacy and risk of adverse events of ICIs in the treatment of digestive system malignant tumors.

Efficient Sequential Co-Delivery Nanosystem for Inhibition of Tumor and Tumor-Associated Fibroblast-Induced Resistance and Metastasis.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them. Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier's inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model. In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of sequential release, co-loading of tretinoin and betulinic acid, and folic acid-mediated active targeting. As expected, the nano-formulation exhibited enhanced cytotoxicity in different cellular models and effectively increased drug accumulation at the tumor site by disrupting the cellular barrier composed of CAFs by tretinoin. Notably, the co-loaded nano-formulations proved to be more potent in inhibiting tumor growth in mice and also showed better anti-metastatic effects in lung metastasis models compared to the formulations with either drug alone. This novel drug delivery system has the potential to be used to develop more effective cancer therapies. Targeting CAFs with celastrol sensitizes tumor cells to chemotherapy, increasing the efficacy of betulinic acid. The combination of drugs targeting tumor cells and CAFs may lead to more effective therapies against various cancers.

A Smart Responsive Nanotheranostic System for MRI of Tumor Response to Immunotherapy and Enhanced Synergism of Thermo‐Immunotherapy

AbstractThe challenges associated with the assessment of immune checkpoint inhibitor (ICI) therapy and low immunotherapy response observed in patients with poorly immunogenic tumors are addressed. A smart‐responsive nanoprobe MZF@Gd is synthetized based on magnetic resonance tuning (MRET). The nanoprobe is designed to be targeted and cleaved by granzyme B, a marker of cytotoxic T‐cell activation. MZF@Gd consisted of superparamagnetic Mn‐ and Zn‐doped ferrite magnetic nanoparticles (MZF‐MNPs) with a magnetocaloric effect and a paramagnetic contrast agent gadolinium‐diethylenetriamine penta‐acetic acid (Gd‐DTPA). These components are connected by the granzyme B substrate peptides. The activation of the T1WI signal through MRET, following the cleavage of the probe by granzyme B, enabled the accurate evaluation of the ICI therapeutic effect. Subsequently, an active‐targeting magnetothermally responsive nanotheranostic agent FA‐P(MZF@Gd/JQ1) is fabricated. This agent incorporated the MRET probe MZF@Gd, JQ‐1 (an inhibitor of PD‐L1), the thermosensitive copolymer PCL‐b‐P(MEO2MA‐co‐OEGMA), and folic acid on the surface. Nanotheranostic agents killed tumor cells through magnetocaloric effects, stimulated antitumor immunity, and regulated the drug release, thereby achieving a synergistic effect between hyperthermia and immunotherapy. Moreover, MZF@Gd released from the agent sensitively detected the presence of granzyme B at the tumor site, thereby enabling an effective assessment of therapeutic efficacy.

Central and Peripheral Motor Conduction Studies by Single-Pulse Magnetic Stimulation.

Single-pulse magnetic stimulation is the simplest type of transcranial magnetic stimulation (TMS). Muscle action potentials induced by applying TMS over the primary motor cortex are recorded with surface electromyography electrodes, and they are called motor-evoked potentials (MEPs). The amplitude and latency of MEPs are used for various analyses in clinical practice and research. The most commonly used parameter is the central motor conduction time (CMCT), which is measured using motor cortical and spinal nerve stimulation. In addition, stimulation at the foramen magnum or the conus medullaris can be combined with conventional CMCT measurements to evaluate various conduction parameters in the corticospinal tract more precisely, including the cortical-brainstem conduction time, brainstem-root conduction time, cortical-conus motor conduction time, and cauda equina conduction time. The cortical silent period is also a useful parameter for evaluating cortical excitability. Single-pulse magnetic stimulation is further used to analyze not only the central nervous system but also the peripheral nervous system, such as for detecting lesions in the proximal parts of peripheral nerves. In this review article we introduce four types of single-pulse magnetic stimulation-of the motor cortex, spinal nerve, foramen magnum, and conus medullaris-that are useful for the diagnosis, elucidation of pathophysiology, and evaluation of clinical conditions and therapeutic effects. Single-pulse magnetic stimulation is a clinically useful technique that all neurologists should learn.

Evaluation of therapeutic effects of nanofibrous mat containing mycophenolate mofetil on oral lichen planus: In vitro and clinical trial study

Objectives Recently, topical drug delivery system has gained increasing interest in the treatment of oral lesions. Lichen planus is a chronic inflammatory disease affecting mucous membranes and skin. The current study aimed to fabricate a drug delivery system containing mycophenolate mofetil for the treatment of oral lichen planus lesions. Methods Firstly, a nanofibrous mat containing mycophenolate mofetil, zinc oxide nanoparticles, and aloe vera was designed and fabricated. The antimicrobial, cytocompatibility, anti-inflammatory, and antioxidative characteristics of fabricated scaffolds were evaluated. Then, this nanofibrous mat was applied to 12 patients suffering from bilateral erythematous/erosive Oral Lichen planus (OLP) lesions for 2 weeks. The treatment outcomes, including oral symptoms and lesion size, were compared with the routine topical treatment of these lesions; Triamcinolone ointment. Results The characterization of nanofibrous mat approved the successful fabrication of scaffolds. The fabricated nanofibers showed notable antimicrobial activity. The amounts of TNF 𝛼, IL6, and reactive oxygen species (ROS) of stimulated human gingival fibroblasts were decreased after exposure to NFs/Myco/Alv/ZnO scaffolds. The clinical trial results demonstrated the same therapeutic effects compared to the commercial ointment, while the symptoms of patients were significantly improved in the mats group. Significance. Considering the successful results of this study, the application of nanofibrous mat can be a promising product for improving treatment outcomes of OLP.

Toxicity and anti-diabetic effectiveness of polymeric nanoparticles containing natural compounds

Objective: To develop the nanoparticle formulations, characterization and evaluation of safety and in vivo anti diabetic potential by using experimental animal model.&#x0D; Methods: Different nano formulations such as Cur-nanoparticles, Pip-nanoparticles as well as Cur-Pip dual drug loaded nanoparticles were developed by nano co-precipitation method. The developed formulations were subjected for FT-IR analysis to determine the drug-drug and drug-polymer interaction. The Differential Scanning Colorimetric (DSC) study was carried out to observe the glass transition. Surface topography of nano formulations were carried out by Scanning Electron Microscopy (SEM). X-ray diffraction study was carried out to determine the crystalline properties of different formulations. Particle size of the polymeric nanoparticles was evaluated by Zeta sizer of nanoseries. Toxicity of nanoformulation was evaluated as per OECD guideline-407. For evaluation of therapeutic effectiveness, in-vivo anti-diabetic potential of nano formulations, the Streptozotocin (STZ) induced diabetes model was considered.&#x0D; Results: The developed formulations were spherical in shape and smooth surfaced. There were no interaction between the drugs and polymers. The result of toxicity study revealed that, there were no changes in behavior, food intake; hematology as well as biochemical parameters were observed that indicates the developed formulation is completely safe. The anti-diabetic effect of different formulations was screened against Streptozotocin induced diabetes in experimental animals. All the formulations were proved as effective in restoring blood glucose level however, Cu+Pi NP (184.15) group showed highest anti diabetic activity in comparison to control group (207.93)&#x0D; Conclusions: From this study, it was observed that, Curcumin-Piperine dual drug loaded nanoparticles exhibit better anti diabetic potential in comparison to control and Curcumin-NP treated group.&#x0D; Keywords: Nanoparticles, Streptozotocin, anti-diabetes, toxicity, hematology, biochemical

Evaluation of therapeutic effect of oral Ursodeoxycholic Acid on indirect hyperbilirubinemia in term neonates undergoing phototherapy: A randomized controlled clinical trial

Introduction and aims Phototherapy is the most common treatment modality of neonatal hyperbilirubinemia. We aimed to evaluate the therapeutic effect of oral Ursodeoxycholic Acid (UDCA) on indirect hyperbilirubinemia in term neonates undergoing phototherapy. Materials and methods This randomized controlled clinical trial was performed on 106 full-term neonates with jaundice who were admitted to the neonatal ward of 17 Shahrivar Hospital in Rasht, Iran. The neonates were randomly assigned to two groups of intervention (10 mg/kg UDCA+phototherapy) and control (phototherapy alone). Total serum bilirubin (TSB) was measured at the time of admission, during first 12, 24, and 48 hours after admission and at the time of discharge. The duration of hospitalization and side effects were also assessed in both groups. IBM SPSS Statistics for Windows, version 20 was used to analyze the data. Results Results showed that in the intervention group, 28 (52.8%) of neonates were boys with the mean age of 5.1±1.25 days. While, in the control group 29 (54.7%) of them were boys with the mean age of 5.19±2.26 days. Bilirubin levels in both groups decreased significantly after hospitalization (at 12, 24 and 48 hours) (P &lt;0.001). The mean of bilirubin at 12, 24 and 48 hours in the intervention and control groups were 17.1, 13.2, 10.2 mg / dl and 17.1, 14.2 and 11.3 mg / dl, respectively. At the time of discharge, TSB in the former compared to the latter group was significantly reduced (7.74± 1.39 vs. 8.67±1.35) (P = 0.001). In addition, the duration of hospitalization was considerably shorter in the intervention compared to the control group (P = 0.038) and no side effects were observed. Conclusions Administering UDCA plus phototherapy reduced TSB and length of hospital stay with proper safety and efficacy. Therefore, it seems that this combination can be an appropriate treatment modality in neonatal hyperbilirubinemia.

Clinical significance of WT1 in the evaluation of therapeutic effect and prognosis of non-M3 acute myeloid leukemia

ABSTRACT To explore the clinical significance and prognosis of acute myeloid leukemia (AML) patients with WT1 mutations.In total, the clinical data of 269 adult patients with non-M3 AML were considered retrospectively. From these patients, 153 carried WT1 mutation whereas 116 were negative. WT1 mutation positive patients were further divided into WT1 low expression and high expression groups base on the expression level of WT1 by qPCR at diagnosis (cut off: 170500). Survival and therapeutic effect analysis were performed for the above patients with different interfering factors such as co-mutations, the extent of WT1 log reduction and the chemotherapy regimens. Patients with high WT1 expression have higher rate of relapse. We can accurately identify patients with inferior outcomes when we take the following factors into consideration: the WT1 expression level at diagnosis; different prognostic factors including co-mutations (especially NPM1 and FLT3-ITD); the log reduction of WT1 after induction therapy and the risk of stratification. Idarubicin + Cytarabine (IA) regimen could reduce the expression level of WT1 after treatment, and Allo-HSCT played an important role in improving the prognosis of patients with WT1 high expression and patients with WT1 negativity. Among the relapsed patients, there existed a rising trend of WT1-MRD in advance than MFC-MRD and that of patients with continuous complete remission (CR). Different clinical background should be taken into consideration when we judge the prognosis and therapeutic effect of patients with WT1 mutations. In addition, WT1 may be an optional MRD marker, which needs regular monitoring.