Effects of vitamin D supplementation on diabetic foot ulcer healing: a meta-analysis.

PURPOSE: To systematically review the effect of vitamin D supplementation on diabetic foot ulcer (DFU) healing. METHODS: The PubMed, Web of Science, Science direct, Ebsco host, CNKI, WanFang, VIP, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the impact of vitamin D supplementation on DFUs from inception to 19 November 2022. Two researchers independently screened the literature, extracted the data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. RESULTS: A total of seven studies involving 580 patients were included. The results of meta-analysis showed that compared with control group, the wound healing efficiency rate (RR = 1.42, 95%CI 1.03 to 1.95, P = 0.03) and wound reduction rate (MD = 13.11, 95%CI 4.65 to 21.56, P < 0.01) of the experimental group were higher; the change values of the wound area (MD = -3.29, 95%CI -4.89 to 1.70, P < 0.01) and 25 (OH) D (MD = 9.63, 95%CI 6.96 to 12.31, P < 0.01) were larger. Supplementation of vitamin D on DFU patients can improve glucose metabolism and insulin indexes: hemoglobin A1c (MD = -0.44, 95%CI -0.62 to -0.26, P < 0.01), fasting insulin (MD = -3.75, 95%CI -5.83 to -1.67, P < 0.01), HOMA - ß (MD = -5.14, 95%CI -8.74 to -1.54, P < 0.01), and quantitative insulin sensitivity check index (MD = 0.02, 95%CI 0.01 to 0.02, P < 0.01). It can also improve inflammation and oxidative stress markers: high sensitivity C-reactive protein (MD = -0.83, 95%CI -1.06 to -0.59, P < 0.01), erythrocyte sedimentation rate (MD = -15.74, 95%CI -21.78 to -9.71, P<0.01), nitric oxide (MD = 1.81, 95%CI 0.07 to 3.55, P = 0.04), and malondialdehyde (MD = -0.43, 95%CI -0.61 to -0.24, P<0.01). There was no statistically significant difference in changes of fasting plasma glucose, homeostasis model of assessment-insulin resistance, total antioxidant capacity, glutathione, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol (P>0.05). CONCLUSION: The current evidence suggests that vitamin D supplementation can significantly promote DFU healing by lowering blood sugar and alleviating inflammation and oxidative stress. Key messages What is already known on this topic  Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, with high morbidity, mortality and resource utilization. Vitamin D has the effect of lowering blood sugar, improving insulin sensitivity, and increasing anti-inflammatory response. Clinical research on vitamin D supplementation for the treatment of DFU is increasing, but due to the lack of combing and integration, the actual efficacy of vitamin D in patients is unclear. What this study adds  This meta-analysis has shown that vitamin D supplementation can significantly promote DFU healing by lowering blood glucose and alleviating inflammation and oxidative stress. How this study might affect research, practice or policy  This study preliminarily found the effectiveness of vitamin D supplementation on the healing of DFU, which can provide a reference for the treatment of DFU by medical staff.

METTL3 facilitates multiple myeloma tumorigenesis by enhancing YY1 stability and pri-microRNA-27 maturation in m6A-dependent manner.

Multiple myeloma (MM) is a pernicious plasma cell disorder and has a poor prognosis. N6-methyladenosine (m6A) is an abundant epigenetic RNA modification and is important in cancer progression. Nevertheless, the function of m6A and its regulator METTL3 in MM are rarely reported. Here, we identified the m6A "writers", METTL3, was enhanced in MM and found that Yin Yang 1 (YY1) and primary-miR-27a-3p were the potential target for METTL3. METTL3 promoted primary-miR-27a-3p maturation and YY1 mRNA stability in an m6A manner. YY1 also was found to facilitate miR-27a-3p transcription. METTL3 affected the growth, apoptosis, and stemness of MM cells through accelerating the stability of YY1 mRNA and the maturation of primary-miR-27a-3p in vitro and in vivo. Our results reveal the key function of the METTL3/YY1/miR-27a-3p axis in MM and may provide fresh insights into MM therapy.

Evaluation of herb-drug interaction of ambrisentan with shikonin based on UPLC-MS/MS.

CONTEXT: Ambrisentan is an oral endothelin-receptor antagonist (ERA). However, there is no report on the interaction between ambrisentan and shikonin. OBJECTIVE: To investigate the effect of shikonin on ambrisentan metabolism in vivo and in vitro. MATERIALS AND METHODS: This study developed an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of ambrisentan and (S)-4-hydroxymethyl ambrisentan in rat plasma. Twelve male Sprague-Dawley (SD) rats were divided into two groups (n = 6): the control group and shikonin (20 mg/kg) group. The pharmacokinetics of ambrisentan (2.5 mg/kg) were investigated after 30 min. Additionally, human and rat liver microsomes were used to investigate the herb-drug interaction. RESULTS: The UPLC-MS/MS method was shown to be accurate, precise and reliable, and was successfully applied to the herb-drug interaction study of ambrisentan with shikonin. When co-administrated with 20 mg/kg shikonin, the Cmax and AUC(0-∞) of ambrisentan were significantly increased by 44.96 and 16.65%, respectively (p < 0.05). In addition, there were modest decreases in (S)-4-hydroxymethyl ambrisentan Cmax and AUC(0-∞) in the presence of shikonin (p < 0.05), which indicated that these results were in accordance with the inhibition of shikonin on ambrisentan metabolism. Moreover, enzyme kinetic study indicated that shikonin had an inhibitory effect on human and rat microsomes where the IC50 values of shikonin were 5.865 and 6.358 µM, respectively. CONCLUSIONS: Our study indicated that shikonin could inhibit ambrisentan metabolism. Further studies need to be carried out to verify whether similar interaction truly apply in humans and whether this interaction has clinical significance.

Simultaneous determination of five essential amino acids in plasma of Hyperlipidemic subjects by UPLC-MS/MS.

BACKGROUND: Millions of adults have been reported with hyperlipemia in the world. It is still unclear whether the plasma level of essential amino acids (AAs) will be influenced by the hyperlipemia. This study was aimed to investigate the AAs levels and the underlying metabolic relationship in hyperlipidemic subjects. METHODS: An ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination of phenylalanine (Phe), valine (Val), histidine (His), tryptophan (Trp), and methionine (Met). Plasma samples (100 µL) were precipitated by acetonitrile (300 µL) and analyzed on a BEH C18 (2.1 mm × 100 mm, 1.7 µm) column at 40 °C by gradient elution. The mobile phase composed of 0.1% formic acid and acetonitrile was used with flow rate at 0.2-0.4 ml/0-3 min. Five AAs were determined at positive electrospray ionization (ESI+) at m/z 118.1/72.1 (Val), 150.12/104.02(Met), 156.06/110.05(His), 166.1/120.1(Phe), and 205.2/188.02 (Trp). A total of 75 healthy subjects and 83 hyperlipidemic subjects, who had blood routine test and plasma lipid test were determined by developed UPLC-MS/MS. RESULTS: It was shown that there was good linearity for Val, Met, His, Phe, and Trp within 1-100 µg/mL. The relative standard deviations of precision and accuracy were all within 15%. The level of Val, Phe, Trp, His, and Met were 35.34 ± 15.64, 22.72 ± 9.13, 17.23 ± 4.94, 16.78 ± 13.64, and 6.24 ± 1.97 µg/mL in healthy subjects, while they were 38.04 ± 16.70, 22.41 ± 8.45, 15.62 ± 5.77, 18.35 ± 14.49, and 6.21 ± 1.97 µg/mL in hyperlipidemic subjects respectively. The Spearman's correlations analysis showed that there were high correlations between Val, Phe, Trp, His, Met and triglyceride in healthy subjects. While, those correlations decreased in hyperlipemia cases. CONCLUSION: A convenient and sensitive method for simultaneous determination of Val, Phe, Trp, His, and Met in human plasma was developed. There was a high correlation between Val, Phe, Trp, His, Met and triglyceride. Hyperlipemia influences the metabolic balance of His, Phe, Trp, Met and Val.

The spin-dependent Seebeck effect and the charge and spin figure of merit in a hybrid structure of single-walled carbon nanotubes and zigzag-edge graphene nanoribbons.

A hybrid structure of carbon nanotubes and graphene nanoribbons was predicted and synthesized (Y. Li et al., Nat. Nanotechnol., 2012, 7, 394-400; P. Lou, J. Phys. Chem. C, 2014, 118, 4475-4482). Herein, using the non-equilibrium Green's function (NEGF) combined with density functional theory (DFT), the thermal spin transport properties and the figure of merit (a material constant proportional to the efficiency of a thermoelectric couple made with the material) of a composite of single-walled carbon nanotubes and zigzag-edge graphene nanoribbons, labeled (6,6)SWCNT/n-ZGNR, are investigated for n = 1, 2, 3, and 8. The results manifest that spin-dependent currents with opposite flow directions were generated when a temperature gradient was applied between two electrodes, indicating the occurrence of the spin-dependent Seebeck effect (SDSE). Remarkably, when n = 3, the charge current is equal to zero, meaning that a perfect SDSE is observed. Moreover, a pure spin-dependent Seebeck diode (SDSD) effect can be observed. Finally, we notice that the device presents an n-type characteristic when n = 1, while the device has a p-type feature when n = 2. In particular, the spin-up thermopower is equal to the spin-down thermopower when n = 3; as a consequence, the charge thermopower is equal to zero, further demonstrating that a perfect SDSE is generated. These discoveries indicate that the (6,6)SWCNT/n-ZGNR is a promising candidate for spin caloritronics devices.

Protein interaction module-assisted function X (PIMAX) approach to producing challenging proteins including hyperphosphorylated tau and active CDK5/p25 kinase complex.

Many biomedically critical proteins are underrepresented in proteomics and biochemical studies because of the difficulty of their production in Escherichia coli. These proteins might possess posttranslational modifications vital to their functions, tend to misfold and be partitioned into bacterial inclusion bodies, or act only in a stoichiometric dimeric complex. Successful production of these proteins requires efficient interaction between these proteins and a specific "facilitator," such as a protein-modifying enzyme, a molecular chaperone, or a natural physical partner within the dimeric complex. Here we report the design and application of a protein interaction module-assisted function X (PIMAX) system that effectively overcomes these hurdles. By fusing two proteins of interest to a pair of well-studied protein-protein interaction modules, we were able to potentiate the association of these two proteins, resulting in successful production of an enzymatically active cyclin-dependent kinase complex and hyperphosphorylated tau protein, which is intimately linked to Alzheimer disease. Furthermore, using tau isoforms quantitatively phosphorylated by GSK-3ß and CDK5 kinases via PIMAX, we demonstrated the hyperphosphorylation-stimulated tau oligomerization in vitro, paving the way for new Alzheimer disease drug discoveries. Vectors for PIMAX can be easily modified to meet the needs of different applications. This approach thus provides a convenient and modular suite with broad implications for proteomics and biomedical research.

The Efficacy of Rituximab Combined with 131I for Ophthalmic Outcomes of Graves' Ophthalmopathy Patients.

PURPOSE: The purpose of this study is to examine the effectiveness of introducing both rituximab (RTX) and 131I for active Graves' ophthalmopathy (GO) with hyperthyroidism. METHODS: In total, 217 patients suffering from active GO with hyperthyroidism were included in this research. All subjects were randomly assigned to 3 groups. Patients in group A solely received 131I treatment; group B1 underwent a methylprednisolone treatment in combination with 131I treatment; and group B2 received an RTX in combination with 131I treatment. Hyperthyroidism treatment outcomes, orbital volumetry, ophthalmic assessments, serum cytokine levels, and adverse effects were measured after treatment. RESULTS: The orbital volumetry principle was significantly different from 24 weeks after the start of treatment among all 3 groups, and improvements in most ophthalmic parameters were regarded significantly different among 3 groups (all p < 0.05). The expression levels of miR-146a and most serum cytokines were regarded significantly different from 24 weeks after the start of treatment among 3 groups (all p < 0.05). CONCLUSIONS: In comparison with other therapies, RTX treatment in combination with 131I treatment is considered to be more effective for hyperthyroidism with active GO.

Tumor and metastatic lymph nodes metabolic activity on 18F-FDG-PET/CT to predict progression-free survival in locally advanced cervical cancer.

OBJECTIVE: The present study investigated the predictive diseases progression value of preoperative fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with local advanced cervical cancer (LACC). METHODS: In total, 267 patients [median age 58 (range: 27-85) years old] with LACC underwent 18F-FDG PET/CT prior to any treatment. The maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesion and metastatic lymph nodes were measured on PET/CT and correlated with clinicopathological features and progression-free survival (PFS). RESULTS: The median follow-up was 36.52 (range: 3.09-61.29) months. During the observation period, 80 (30.0%) patients exhibited disease progression. Univariate analysis showed that FIGO stage, concurrent chemoradiotherapy (CRT), serum level of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag), primary tumor MTV (pMTV) and TLG (pTLG), lymph nodes SUVmax (nSUVmax) and TLG (nTLG), and total metabolic activity (sMTV, sTLG) were associated with PFS. nSUVmax ≥ 5.29, CEA ≥ 7.11 ng/ml and deficiency of concurrent CRT were independent risk factor for PFS (p = 0.006, p = 0.008, p = 0.014). The 3-year PFS for patients with high nSUVmax were 42.2% compared to 56.3% for low nSUVmax values. CONCLUSION: Pretreatment cervical and lymph nodes metabolic parameters were associated with PFS in patients with LACC.

Stigma and self-esteem in facial burn patients: A correlation study.

BACKGROUND: A considerable number of burn patients have greater psychological stress due to the special trauma site. In clinical practice, it is found that medical staff pay more attention to the rehabilitation of physical function, while the mental health status of patients is greatly neglected. In contact with patients, we found that attention should be paid to the levels of stigma and self-esteem. However, there are few studies on stigma and self-esteem in patients with facial burns. Therefore, this study aimed to describe the stigma and self-esteem levels of facial burns, investigate the relationship between these two variables, and explore the influencing factors of stigma in patients with facial burns, in order to provide evidence for follow-up interventions to improve this population. METHODS: From August 2020 to June 2021, we recruited patients with facial burns who met the inclusion criteria in one burn specialist clinic and three burn units of a tertiary A hospital in Guangzhou, China. The survey tools of this study include sociodemographic and disease-related information questionnaires, the Chinese version of the Social Impact Scale, and the self-esteem scale (these scales were validated). SPSS 25.0 software was used for data analysis through t test, analysis of variance, correlation analysis, multiple linear regression method for data statistics. RESULTS: The total stigma score of facial burn patients was (58.01 ± 7.57), which was at a medium level; the self-esteem score was (19.72 ± 2.43), which was at a low level. Correlation analysis showed that there was a positive correlation between the self-esteem score and the total score of stigma (r = 0.286, P < 0.01). The family per capita monthly income, education level, way of medical expenses expenditure, and self-esteem of facial burn patients were the influencing factors of their stigma, and these factors explained 33.7% of the variation in stigma (F=8.659, P＜0.01). CONCLUSIONS: Patients with facial burns have low levels of stigma and self-esteem, which requires our efforts. In particular, there is a positive correlation between stigma and self-esteem, and self-esteem is an independent risk factor affecting stigma. Our findings suggest that interventions aimed at enhancing self-esteem have the potential to positively impact the reduction of stigma in this patient population.

Progression of radio-labeled molecular imaging probes targeting chemokine receptors.

Chemokine receptors are significantly expressed in the surface of most inflammatory cells and tumor cells. Guided by chemokines, inflammatory cells which express the relevant chemokine receptors migrate to inflammatory lesions and participate in the evolution of inflammation diseases. Similarly, driven by chemokines, immune cells infiltrate into tumor lesions not only induces alterations in the tumor microenvironment, disrupting the efficacy of tumor therapies, but also has the potential to selectively target tumoral cells and diminish tumor progression. Chemokine receptors, which are significantly expressed on the surface of tumor cell membranes, are regulated by chemokines and initiate tumor-associated signaling pathways within tumor cells, playing a complex role in tumor progression. Based on the antagonists targeting chemokine receptors, radionuclide-labeled molecular imaging probes have been developed for the emerging application of molecular imaging in diseases such as tumors and inflammation. The value and limitations of molecular probes in disease imaging are worth reviewing.

Comprehensive study of clinicopathological and immune cell infiltration and lactate dehydrogenase expression in patients with thymic epithelial tumours.

BACKGROUND: Lactate dehydrogenase (LDH) has emerged as a promising biomarker for cancer. However, the current understanding of LDH and circulating LDH expression in thymic epithelial tumour (TET) is lacking. METHODS: A comprehensive literature review and meta-analysis were performed to evaluate the clinical significance of circulating LDH levels in patients with TET. Circulating LDH levels were measured using a laboratory analyser (Cobas8000, Roche, Basel, Switzerland). The maximum standardised uptake value (SUVmax) was determined in patients who underwent whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Multiplex immunohistochemistry (IHC) was performed using a commercially available kit (Opal 6-plex Detection Kit, Akoya Biosciences, Marlborough, MA, USA) and slide scanner (Slideview VS200, Olympus, Tokyo, Japan). All statistical analyses were performed using SPSS (IBM Corp., Armonk, NY, USA) and Prism version 9.0 (GraphPad Inc., San Diego, CA, USA). Differences with p < 0.05 were considered to be statistically significant. RESULTS: Meta-analysis revealed that elevated circulating serum levels of LDH predicted poor prognosis in patients with TET. Circulating levels of LDH were analysed in the serum of 313 patients with TET and 87 with benign mediastinal mass. The mean circulating LDH level in patients with thymic carcinoma (TC) was significantly higher than that in those with thymoma (TM) and the benign group (p < 0.001). Expression levels of circulating LDH were significantly reduced in postoperative samples compared with that in preoperative samples (p < 0.05). Receiver operating characteristic (ROC) curve analysis for diagnosing TC yielded an area under the curve of 0.74, with a sensitivity of 54 % and specificity of 86 %. Furthermore, patients with TC exhibited higher 18F-FDG PET/CT SUVmax values compared to those with TM. Correlation analysis demonstrated a positive association between SUVmax values and circulating LDH levels. In addition, the percentages of LDH-positive cells in TC and type B1 TM tissues were higher than those in other subtypes of TM, and a significant positive correlation between the percentages of LDH-positive and CD20-positive cells was detected in patients with TET (p < 0.05). CONCLUSION: Circulating serum LDH level may serve as a non-invasive biomarker for the diagnosis and prognosis of TET. The relationship between LDH expression and immune cell infiltration merits further regarding its application in companion diagnosis for immunotherapy.

Haploidentical hematopoietic stem cell transplantation for hematologic malignancies: a novel conditioning regimen with anti-T lymphocyte immunoglobulin instead of anti-thymocyte globulin for in vivo T cell depletion.

We evaluated the safety and efficacy of a novel protocol for haploidentical stem cell transplantation (haplo-SCT) in 312 patients with hematologic malignancies. The protocol evolved from the Beijing platform replacing ATG with ATLG; adding Fludarabine and removing cytarabine and Simustine. GVHD prophylaxis combined Basiliximab and low-dose cyclophosphamide post-transplant; overall, the conditioning duration was shortened. Median times to neutrophil and platelet recovery were both 11 days. Graft rejection occurred in 0.96% of patients. Cumulative incidences of grades II-IV and III-IV acute GVHD by day 200 were 35.3% and 8.9%, respectively. Probabilities of total and extensive chronic GVHD at 2 years were 40.7% and 14.7%. CMV viremia was observed in 35.6% of patients, with a 1.9% 100-day CMV pneumonia incidence and no CMV-related mortality. Cumulative incidences of non-relapse mortality at 100 days, 1 year, and 2 years were 2.9, 4.4, and 6.6%. The 4-year OS, RFS, and GRFS rates were 78.9, 70.7, and 47.3%. Older recipient age was associated with higher NRM, while positive pre-transplant MRD predicted worse OS, RFS, and higher relapse incidence. Our novel protocol for haplo-SCT is associated with low infection rates and acceptable risks of graft failure, severe GVHD, and mortality, representing a safe and effective haploidentical transplantation strategy.

A high throughput method for Monitoring of Sorafenib, regorafenib, cabozantinib and their metabolites with UPLC-MS/MS in rat plasma.

As multi-targeted tyrosine kinase inhibitors, sorafenib, regorafenib and cabozantinib are widely used in hepatocellular carcinoma (HCC) for systemic therapies with anti-proliferative and anti-angiogenic effects. Nevertheless, adverse effects or insufficient efficacy appear frequently due to the plasma concentration with individual variability of these drugs. To ensure the curative effect and safety by therapeutic drug monitoring (TDM), this study developed a high throughput method to quantify sorafenib, regorafenib, cabozantinib and their active metabolites in plasma simultaneously. The chromatographic separation analysis achievement was performed on a Waters-ACQUITY UPLC BEH C18 column by UPLC-MS/MS system using a gradient elution of solvent A (acetonitrile) and solvent B (water with 0.1% formic acid) in 3.0 min. This method presented satisfactory results of specificity, precision (the intra-day coefficient of variation was between 2.5% and 6.6%, and the inter-day coefficient of variation was between 4.0% and 11.1%) and accuracy (within ±15% for intra-day and inter-day), as well as the stability under certain conditions, the matrix effect in plasma, and extraction recovery (75.6%-94.4%). The linearity of each analyte in the proper concentration scope indicated excellent. This study strictly complied with the performance rules of assay validation in biological medium proposed by FDA and was successfully applied to the pharmacokinetic study in rats. Thus, it would be an advantageous option to research the relationship between concentration-efficacy and concentration-toxic in HCC patients who were supposed to take these medications.

The Pid Family Has Been Diverged into Xian and Geng Type Resistance Genes against Rice Blast Disease.

Rice blast (the causative agent the fungus Magnaporthe oryzae) represents a major constraint on the productivity of one of the world's most important staple food crops. Genes encoding resistance have been identified in both the Xian and Geng subspecies genepools, and combining these within new cultivars represents a rational means of combating the pathogen. In this research, deeper allele mining was carried out on Pid2, Pid3, and Pid4 via each comprehensive FNP marker set in three panels consisting of 70 Xian and 58 Geng cultivars. Within Pid2, three functional and one non-functional alleles were identified; the former were only identified in Xian type entries. At Pid3, four functional and one non-functional alleles were identified; once again, all of the former were present in Xian type entries. However, the pattern of variation at Pid4 was rather different: here, the five functional alleles uncovered were dispersed across the Geng type germplasm. Among all the twelve candidate functional alleles, both Pid2-ZS and Pid3-ZS were predominant. Furthermore, the resistance functions of both Pid2-ZS and Pid3-ZS were assured by transformation test. Profiting from the merits of three comprehensive FNP marker sets, the study has validated all three members of the Pid family as having been strictly diverged into Xian and Geng subspecies: Pid2 and Pid3 were defined as Xian type resistance genes, and Pid4 as Geng type. Rather limited genotypes of the Pid family have been effective in both Xian and Geng rice groups, of which Pid2-ZS_Pid3-ZS has been central to the Chinese rice population.

The Symptoms and Factors Associated With Posttraumatic Stress Disorder for Burns Nurses: A Cross-Sectional Study From Guangdong Province in China.

The symptoms of posttraumatic stress disorder (PTSD) among medical staff have become a significant issue. Environments related to burns are highly stressful for nurses and can lead to PTSD, thus affecting their mental health. It is vital to consider that the quality of burns care, and the outcomes of such treatments, may be threatened if nurses experience PTSD. We evaluated PTSD symptoms in burns nurses and explored the correlations between demographic characteristics, work-related characteristics, professional identity, turnover intention, and PTSD symptoms. This was a cross-sectional study involving 273 nurses working in the burns unit from Guangdong, China, between July and August 2019. Nurses were recruited from 30 hospitals and completed three validated psychological questionnaires: Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Professional Identity Scale (PIS) for nurses, and Turnover Intention Questionnaire (TIQ). We also collated information relating to sociodemographic and work-related characteristics. The cutoff point for the PCL-C was defined as 38 points; 17.22% (n = 47) of participants scored higher than or equal to 38. The PCL-C score was negatively correlated with professional identity level (P < .01) and positively correlated with turnover intention (P < .01). The workplace, mean monthly income, experience of workplace violence, and professional identity level were important factors and all associated with the severity of PTSD. PTSD symptoms were common in burns nurses. Attention should be paid to the mental well-being of these staff. Screening processes need to be initiated to identify individuals suffering from PTSD and take appropriate early interventional action.

Lnc NEAT1/miR-29b-3p/Sp1 form a positive feedback loop and modulate bortezomib resistance in human multiple myeloma cells.

The overall survival of multiple myeloma (MM) patients significantly improved with the use of proteasome inhibitor such as bortezomib. However, resistance to sorafenib limits its use. Bortezomib-resistant MM cells were generated and their bortezomib-resistant properties were confirmed by cell viability and apoptosis assays. To explore functions and underlying mechanisms of long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) on bortezomib resistance in MM, MTT assays, flow cytometry analyses, dual luciferase report gene assays, RNA pulldown assays and chromatin immunoprecipitation assays were carried out. NEAT1 and specific protein 1 (Sp1) was upregulated while miR-29b-3p was down regulated in bortezomib-resistant MM cells. NEAT1 promoted Sp1 expression by sponging miR-29b-3p and then enhanced the tolerance of MM cells to bortezomib. Sp1 targeted to NEAT1 promoter region promoting NEAT1 transcription and formed a positive feedback loop. NEAT1 and Sp1 levels were higher and miR-29b-3p was levels were lower in bortezomib-resistant MM patients. NEAT1/miR-29b-3p/Sp1 feedback loop enhanced the tolerance of MM cells to bortezomib. These results indicate potentially valuable targets for overcoming bortezomib resistance for MM.

UPLC-MS/MS Determination of Linezolid and Heme in Plasma of Infected Patients and Correlation Analysis.

Linezolid can cause serious haematological toxicity, such as thrombocytopenia and aneamia. Heme, composed of iron and porphyrin, is an important component of hemoglobin. In order to investigate the relationship between the concentration of linezolid and heme in the plasma of infected patients, a UPLC-MS/MS method that can determine the concentrations of linezolid and heme simultaneously was developed and validated. A total of 96 healthy subjects and 81 infected patients, who received blood routine blood tests, were included and determined by the UPLC-MS/MS method. The results showed that the concentration of linezolid was 5.08 ± 3.46 µg/mL in infected patients who were treated with linezolid. The heme in healthy subjects was 7.05 ± 8.68 µg/mL, and it was significantly decreased to 0.88 ± 0.79 µg/mL in infected patients (P < 0.01). Spearman correlation analysis showed that linezolid had a high negative correlation with platelet (PLT) (R = -0.309). Heme had a high positive correlation with hemoglobin (Hb) (R = 0.249) in healthy subjects and infected patients. The ROC analysis showed that heme had diagnostic value to distinguish low Hb (110 g/L). In conclusion, there was a positive correlation between heme and Hb, and this correlation was also observed in infected patients. A high concentration of linezolid was inclined to decrease PLT. Monitoring of heme and linezolid helps in the early diagnose of low Hb and PLT.

miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer.

The expression levels of microRNA (miR)-221-3p and miR-222-3p in thyroid cancer have been found to be upregulated compared with those in normal tissues. The present study aimed to determine the effects and potential underlying mechanisms of miR-221-3p and miR-222-3p on the regulation of radioactive iodine (131I) uptake and radiosensitivity of thyroid cancer cells. The potential regulatory target genes of miR-221-3p and miR-222-3p were predicted by bioinformatics analysis, and reverse transcription-quantitative polymerase chain reaction was used to verify miR-221-3p, miR-222-3p and target gene expression levels in thyroid cancer tissues and cell lines. Overexpression of miR-221-3p or miR-222-3p in cell models was performed using lentivirus infection. Knockdown of miR-221-3p and miR-222-3p in cells was achieved using oligonucleotide inhibitor transfection. Western blotting was used to analyze the expression levels of target proteins. In addition, the effects of miR-221-3p and miR-222-3p on the radiosensitivity of thyroid cancer cells were verified using a colony formation assay. The results of the present study revealed that the expression levels of miR-221-3p and miR-222-3p were significantly upregulated, while the expression levels of suppressor of cytokine signaling 3 (SOCS3) were downregulated in thyroid cancer tissues. Furthermore, miR-221-3p and miR-222-3p overexpression downregulated the expression levels of SOCS3, E-cadherin and solute carrier family 5 member 5 (NIS), and upregulated the expression levels of phosphorylated STAT3 and vimentin. Following the overexpression of miR-221-3p or miR-222-3p in the FTC133 and TPC1 cell lines, their radiosensitivity was suppressed. In conclusion, the findings of the present study suggested that miR-221-3p and miR-222-3p may downregulate the expression levels of NIS and promote radioresistance. The potential mechanism was hypothesized to be associated with the miR-221-3p and miR-222-3p targeting of the SOCS3 gene, which may subsequently activate the STAT3 signaling pathway.

Clinical significance of extra-thyroid 99mTc-pertechnetate uptake before initial radioiodine therapy for differentiated thyroid carcinoma.

OBJECTIVE: To analyse the clinical characteristics of extra-thyroid 99mTc-pertechnetate uptake in order to explore the effect of the phenomenon on radioactive iodine (RAI) therapy for differentiated thyroid carcinoma (DTC) and its clinical significance. METHODS: This study retrospectively selected patients with DTC and extra-thyroid 99mTc-pertechnetate uptake. The clinical features, location, location count and extra-thyroid 99mTc-pertechnetate uptake distribution were analysed, combined with the uptake rate, stimulated thyroglobulin (sTg) level, post-therapy whole-body scan and curative effect. RESULTS: A total of 38 patients were enrolled in the study and 65 extra-thyroid 99mTc-pertechnetate foci were detected. Thirty-four patients showed abnormal 99mTc-pertechnetate uptake in the lymph nodes (26 of 38; 68.4%), lungs (four of 38; 10.5%) and bones (four of 38; 10.5%). The corresponding uptake rates were 0.2%, 0.2% and 0.8%, respectively. The uptake rate and sTg were significantly positively correlated (r = 0.36). 131I uptake was found in 36 patients at the 99mTc-pertechnetate uptake site. The number of iodine uptake foci was significantly higher than that of 99mTc-pertechnetate uptake foci. The sTg value and pathological staging significantly differed between the excellent and nonexcellent response groups (Z = -2.947 and Z = -2.348, respectively). CONCLUSION: Extra-thyroid 99mTc-pertechnetate uptake mostly indicated metastases with specific clinical features, which may have prognostic value for the judgment of iodine uptake function and the RAI therapy plan.

Liquid chromatography-tandem mass spectrometric method for the quantification of eliglustat in rat plasma and the application in a pre-clinical study.

Eliglustat is an oral substrate reduction therapy drug and has been approved as a first-line treatment for adults with Gaucher disease type 1 (GD 1). In the present study, we aimed to develop and establish an accurate and simple ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the measurement of eliglustat concentration in rat plasma. The goal of chromatographic separation of eliglustat and the internal standard (bosutinib) was finished on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 µm) column. Acetonitrile and 0.1% formic acid in water were employed as the mobile phase in a mode of gradient elution with the 0.40 mL/min flow rate. The detection was carried out on a XEVO TQ-S triple quadrupole tandem mass spectrometer coupled with electrospray ionization (ESI) interface in the positive-ion mode. Multiple reaction monitoring (MRM) was used to monitor the precursor-to-product ion transitions of m/z 405.4 → 84.1 for eliglustat and m/z 530.2 → 141.2 for bosutinib (IS), respectively. It was found that the linearity of the method in the range of 1-500 ng/mL was good for eliglustat. The values of intra- and inter-day accuracy and precision were all within the acceptance limits, and no matrix effect was found in this method. The current developed method was further performed to support in vivo pharmacokinetic study of eliglustat after oral treatment with 10 mg/kg eliglustat to rats.