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BACKGROUND: Brain metastases (BM) are very rare in gastric adenocarcinoma (GaC), and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness. However, its pathogenesis remains unclear. Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor (MET) amplification. Therefore, treatment with savolitinib, a small molecule inhibitor of c-Met, was selected. CASE SUMMARY: A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain. Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy. The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department. Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification. After discussing treatment options with the patient, savolitinib tablets were administered. After a month of treatment, the intracranial lesions shrank considerably. CONCLUSION: BM is very rare in advanced GaC, especially in meningeal cancer, that is characterized by rapid disease deterioration. There are very few effective treatment options available; however, technological breakthroughs in genomics have provided a basis for personalized treatment. Furthermore, MET amplification may be a key driver of BM in gastric cancer; however, this conclusion requires further investigation.
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BACKGROUND AND PURPOSE: White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. EXPERIMENTAL APPROACH: WAT status of healthy and adjuvant-induced arthritis (AIA) rats were compared. The contribution of WAT to RA pathology was evaluated by pre-adipocyte transplant experiments and by dissecting perirenal fat pads of AIA rats. The impact of RA on WAT was investigated by culturing pre-adipocytes. Proteins differentially expressed in WAT of healthy and AIA rats were identified by the UPLC/MS2 method. These together with PPARγ siRNA and agonist were used to treat pre-adipocytes in vitro. The medium was used for THP-1 monocyte culture. KEY RESULTS: Compared with healthy controls, AIA WAT was smaller but secreted more leptin, eNAMPT, MCP-1, TNF-α, and IL-6. AIA rat pre-adipocytes increased the levels of these adipokines in healthy recipients. RA patients' serum induced a similar secretion change and impaired differentiation of pre-adipocytes. Adipectomy eased AIA-related immune abnormalities and arthritic manifestations. Hepatokines PON1, IGFBP4, and GPIHBP1 were among the differential proteins in high levels in RA blood, and induced inflammatory secretions by pre-adipocytes. GPIHBP1 inhibited PPARγ expression and caused differentiation impairment and inflammatory secretion by pre-adipocytes, a similar outcome to PPARγ-silencing. This endowed the cells with an ability to activate monocytes, which can be abrogated by rosiglitazone. CONCLUSION AND IMPLICATIONS: Certain hepatokines potentiate inflammatory secretions by pre-adipocytes and expedite RA progression by inhibiting PPARγ. Targeting this signalling or abnormal WAT secretion by various approaches may reduce RA severity.
Subject(s)
Adipose Tissue, White , Arthritis, Experimental , Arthritis, Rheumatoid , PPAR gamma , Animals , Adipose Tissue, White/metabolism , Adipose Tissue, White/drug effects , Humans , Rats , Arthritis, Experimental/metabolism , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Male , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/drug therapy , PPAR gamma/metabolism , PPAR gamma/agonists , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Female , Rats, Inbred Lew , Adipocytes/metabolism , Adipocytes/drug effects , Adipokines/metabolismABSTRACT
The transformation of solid wastes from industrial production into effective adsorbents could significantly contribute to wastewater treatment. In this study, after acidizing and burning soft scale (SS) from coal gasification system, two magnetic adsorbents (mag-ASS and mag-BASS) were prepared via the combination of magnetite with ultrasonic, respectively. The treatment effects of mag-ASS and mag-BASS were then investigated for simulated wastewater containing macromolecular organic matter [i.e., methylene blue (MB)] and Ca2+. The results indicated that the pseudo second order kinetic, Elovich, Freundlich, Langmuir and Temkin model could well describe the adsorption behavior of MB and Ca2+ onto mag-ASS and mag-BASS. The maximum adsorption capacities of mag-ASS for MB and mag-BASS for Ca2+ were 600.53 mg/g and 102.54 mg/g, respectively. Surprisingly, the adsorption abilities of mag-ASS for MB and mag-BASS for Ca2+ show significantly higher than the others. The adsorption mechanisms of MB mainly included electrostatic interaction, π-π conjugate interaction and cation exchange, while those of Ca2+ were mainly electrostatic interaction and cation exchange. The diffusion of MB and Ca2+ onto the magnetic adsorbents might be controlled by the combined effects of intraparticle and liquid film diffusion. There was no significant reduction in adsorption capacity after 8 cycles of adsorption and desorption, indicating that SS-based magnetic adsorbents had good recyclability and stability. Moreover, the removal efficiency of mag-BASS for total hardness and total organic carbon in real coal gasification gray water (CGGW) was 82.60 and 64.10%, respectively. The treatment of CGGW and the resource of wastes would significantly promote the reasonable disposal of coal gasification scales.
Subject(s)
Calcium , Coal , Methylene Blue , Methylene Blue/chemistry , Adsorption , Calcium/chemistry , Wastewater/chemistry , Kinetics , Water Pollutants, Chemical/chemistry , Water Purification/methodsABSTRACT
BACKGROUND: This study aimed to uncover the diagnostic value of circRNA (Circ)_0051386 in acute ST-segment elevation myocardial infarction (STEMI) and its predictive value for the occurrence of adverse major adverse cardiovascular events (MACEs). METHODS: This study included 166 patients with STEMI and 83 health donors. The expression levels of serum Circ_0051386 in these participants were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Additionally, the incidence of MACEs during a 6-month follow-up period after percutaneous coronary intervention (PCI) was collected in the STEMI patient cohort. RESULTS: Before and after propensity score matching (PSM), Circ_0051386 all had higher expression levels in the patients with STEMI than the normal subjects (all p < .001)and robust diagnosis values for the STEMI (AUC = 0.766, 0.779). Kaplan-Meier curves showed the high expression Circ_0051386 group had a higher occurrence rate of MACEs during a 6-month follow-up after PCI in patients with STEMI and this phenomenon was confirmed by internal validation (all p < .05). In addition, the multivariate COX regression showed gensini score (HR = 1.020, 95% CI = 1.002 - 1.038, p = .028) and Circ_0051386 (HR = 2.468, 95% CI =1.548-3.935, p < .001)were independent risk factors of the occurrence of MACEs in patients with STEMI after PCI. Pearson analysis presented that Circ_0051386 was positively correlated with gensini scores (r = 0.33), IL-1ß (r = 0.55)and TNF-α(r = 0.41). CONCLUSION: Our study indicated that Circ_0051386 is a biomarker of the diagnostic for STEMI and the predictor of the MACEs in STEMI patients after PCI. Its potential role in STEMI may be the regulation of inflammation in the vascular endothelial.
Subject(s)
Anterior Wall Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/genetics , ST Elevation Myocardial Infarction/surgery , Percutaneous Coronary Intervention/adverse effects , RNA, Circular/genetics , Arrhythmias, Cardiac/etiologyABSTRACT
Long-term occupation of coal gangue dumping sites (CGDS) may destroy ecological environment of nearby area. However, how the CGDS affects the distribution pattern of soil seed banks and vegetation in the nearby area is not clear. In this study, we investigated soil seed bank and vegetation at different distances from the second CGDS of Yangchangwan in Ningdong mining area, Lingwu, Ningxia. The results showed that soil seed bank was mainly distributed in 0-10 cm layer and decreased with increasing soil depth. Species richness of soil seed bank and vegetation first increased and then tended to be stable with increasing distance to the CGDS. The influence range of CGDS on soil seed banks was 300-500 m and was 100-300 m on aboveground vegetation. The CGDS did not affect the vertical distribution pattern of soil seed bank, but significantly affected the horizontal distribution pattern of soil seed banks and aboveground vegetation. The key area of vegetation restoration around the CGDS was between 100 m and 300 m.
Subject(s)
Seed Bank , Soil , Coal , Mining , Waste Disposal FacilitiesABSTRACT
BACKGROUND: Fluoride (F-), an anion with the smallest ionic radius and highest charge density, plays an important role in biomedical and environmental processes, making the development of accurate F- detection methods of great importance. Fluorometric methods with simplicity and sensitivity have gained considerable attention in F- detection. However, their accuracy faces challenges due to issues like autofluorescence interference during real-time light excitation and limited selectivity. Therefore, it is important to establish a simple, real-time light excitation-free, and highly selective method for the accurate determination of F- in complicated samples. RESULTS: Herein, a novel phosphorescent approach is developed for the selective and accurate detection of F- in complex samples. Phosphorescence emission CDs@SiO2 is fabricated by confining CDs in a silica protective layer. This design retains the favorable water solubility of silica while benefitting from its inertness, making it resistant to most substances. Furthermore, phosphorescent analysis without real-time light excitation eliminates autofluorescence interference, significantly improving the signal-to-noise ratio (SNR) and simplifying sample pretreatment. The specific interaction between F- and the Si-O bond can lead to the degradation of the silica protective layer, exposing the CDs to the solution, resulting in phosphorescence quenching, achieving the highly accurate and sensitive detection of F- with a linear range of 0.001-4 mM and a limit of detection (LOD) of 1 µM. SIGNIFICANCE: This novel F- phosphorescence method based on the metal-free phosphorescent nanomaterial CDs@SiO2 integrates the benefits of no autofluorescence interference, high selectivity, and full aqueous compatibility, and its combination with a smartphone provides a simple, portable, and cost-effective detection platform for accurate and highly sensitive determination of F- in complex samples.
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BACKGROUND: Pulmonary artery (PA) aneurysms are usually diagnosed radiographically and present as small or large lesions resembling inflammation or a neoplasm on chest radiography. It has rarely been reported as an endobronchial mass. CASE SUMMARY: We report the case of a 64-year-old man who presented with recurrent hemoptysis. Bronchoscopy revealed a tumorous protrusion blocking the right middle lobe bronchus, which was confirmed to be a PA aneurysm using endobronchial ultrasound bronchoscopy and computed tomography angiography. CONCLUSION: Although endobronchial PA aneurysms are rare, bronchoscopists need to add this lesion to the list of endobronchial masses for which a biopsy is to be assiduously avoided.
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Mitochondrial miRNAs (mitomiRs) are essential regulators of biological processes by influencing mitochondrial gene expression and function. To comprehensively understand related pathological processes and treatments, simultaneous imaging of multiple mitomiRs is crucial. In this study, we present a technique that enables simultaneous monitoring of multiple mitomiRs in living cells using a near-infrared (NIR) photoactivated controlled detection probe (PD-mFleU) with a fluorescence-encoded error correction module and a nonsupervised machine learning data-processing algorithm. This method allows controlled sensing imaging of mitomiRs with a DNA reporter probe that can be activated by NIR light after targeted mitochondrial localization. Multilayer upconversion nanoparticles (UCNPs) are used for encoding probes and error correction. Additionally, the density-based spatial clustering of applications with the noise (DBSCAN) algorithm is used to process and analyze the image. Using this technique, we achieved rapid in situ imaging of the abnormal expression of three mitomiRs (miR-149, miR-590, and miR-671) related to mt-ND1 in drug-resistant cells. Furthermore, upregulating the three mitomiRs simultaneously efficiently reverted drug-resistant cells to sensitive cells. Our study provides an analytical strategy for multiplex imaging of mitomiRs in living cells with potential clinical applications.
Subject(s)
MicroRNAs , Nanoparticles , MicroRNAs/genetics , MicroRNAs/metabolism , Mitochondria/metabolism , Gene Expression , Fluorescence , Drug ResistanceABSTRACT
Acid phosphatase (ACP) as a clinical diagnostic biomarker for several pathophysiological diseases has aroused widespread interest. Compared to commonly developed single-mode ACP detection technology, the multi-mode detection method with self-validation can provide more reliable results. Herein, we proposed a triple-mode phosphorescence, fluorescence, and colorimetric method for ACP detection in combination with CDs@SiO2. HAuCl4 with oxidase-like activity can catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to the blue oxide TMB (TMBox), offering absorption signals and quenching the phosphorescence and fluorescence of CDs@SiO2 based on the internal filtration effect (IFE). ACP can hydrolyze ascorbic acid 2-phosphate (AAP) to yield ascorbic acid (AA), thereby reducing TMBox to TMB, triggering solution fading and restoring phosphorescence and fluorescence signals. When the ACP inhibitor malathion is present, the reduction of TMBox is hindered, which successively led to the suppression of CDs@SiO2 phosphorescence and fluorescence signal recovery. According to these principles, triple-mode ACP (LOD = 0.0026 mU mL-1) and malathion detections (LOD = 0.039 µg mL-1) with favorable accuracy and sensitivity are realized. With simplicity, robustness, and versatility, the triple-mode sensor can be extended to the detection of the AAP hydrolase family and the screening of corresponding inhibitors.
Subject(s)
Acid Phosphatase , Colorimetry , Acid Phosphatase/metabolism , Colorimetry/methods , Malathion , Silicon Dioxide , Oxidation-Reduction , Limit of Detection , Ascorbic Acid , CarbonABSTRACT
Background: Increased post-prandial glycemic excursions contribute to the development of diabetes and have been observed in women with recent gestational diabetes mellitus (GDM) and with normal glucose tolerance at post-partum. As a convenient meal replacement, low-GI biscuits are helpful for improving glycemic excursions in patients with type 2 diabetes. However, it is unknown whether low-GI biscuits as pre-loads or mid-meal snacks have a better effect in diminishing post-prandial glycemic excursions from the individual level in women with recent GDM. Therefore, the aim of this trial is to tailor a better dietary strategy utilizing low-GI biscuits (Fitmeal) to improve post-prandial glycemic excursions through within-subject comparison in such a population and observe the long-term effect of a tailored dietary approach in glycemic control. Methods: We have designed a two-phase trial including a randomized, crossover, non-blinded trial in the first phase, followed by a 4-week tailored intervention in the second phase. A total of 52 post-partum women with recent GDM will be allocated into four meal plans: (1) Fitmeal pre-load 30 min before standard lunch meal (P+L), (2) Fitmeal as a mid-meal snack 2 h before standard lunch meal (S+L), (3) isocaloric standard control with co-ingestion of Fitmeal and standard lunch meal (CL) at the same time, and (4) placebo control with 200 ml of water taken 30 min before standard lunch meal (W + L), on four consecutive days. Acute post-prandial glycemic response (PGR) measured by continuous glucose monitoring (CGM) will be compared among the four meals. In the second phase, all participants will receive a 4-week tailored intervention using Fitmeal as pre-loads or mid-meal snacks based on within-subject PGR results from the first phase. Glycemic metrics, dietary behaviors, and psychosocial factors (e.g., quality of life, self-efficacy, perceived stress, and depression) will be examined at baseline and end-point. Discussion: This trial is expected to optimize the use of low-GI biscuits as pre-loads or mid-meal snacks in improving individual post-prandial glycemic excursions among women with recent GDM. Furthermore, the findings of this study will provide novel information on how to deliver an effective dietary intervention at the individual level and guide future clinical practice of medical nutrition therapy for diabetes prevention. Trial registration number: Chinese clinical trial registry, ChiCTR2200060923.
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The air pollution in China currently is characterized by high fine particulate matter (PM2.5) and ozone (O3) concentrations. Compared with single high pollution events, such double high pollution (DHP) events (both PM2.5 and O3 are above the National Ambient Air Quality Standards (NAAQS)) pose a greater threat to public health and environment. In 2020, the outbreak of COVID-19 provided a special time window to further understand the cross-correlation between PM2.5 and O3. Based on this background, a novel detrended cross-correlation analysis (DCCA) based on maximum time series of variable time scales (VM-DCCA) method is established in this paper to compare the cross-correlation between high PM2.5 and O3 in Beijing-Tianjin-Heibei (BTH) and Pearl River Delta (PRD). At first, the results show that PM2.5 decreased while O3 increased in most cities due to the effect of COVID-19, and the increase in O3 is more significant in PRD than in BTH. Secondly, through DCCA, the results show that the PM2.5-O3 DCCA exponents α decrease by an average of 4.40% and 2.35% in BTH and PRD respectively during COVID-19 period compared with non-COVID-19 period. Further, through VM-DCCA, the results show that the PM2.5-O3 VM-DCCA exponents [Formula: see text] in PRD weaken rapidly with the increase of time scales, with decline range of about 23.53% and 22.90% during the non-COVID-19 period and COVID-19 period respectively at 28-h time scale. BTH is completely different. Without significant tendency, its [Formula: see text] is always higher than that in PRD at different time scales. Finally, we explain the above results with the self-organized criticality (SOC) theory. The impact of meteorological conditions and atmospheric oxidation capacity (AOC) variation during the COVID-19 period on SOC state are further discussed. The results show that the characteristics of cross-correlation between high PM2.5 and O3 are the manifestation of the SOC theory of atmospheric system. Relevant conclusions are important for the establishment of regionally targeted PM2.5-O3 DHP coordinated control strategies.
Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Humans , Beijing , Air Pollutants/analysis , Rivers , Environmental Monitoring/methods , COVID-19/epidemiology , Air Pollution/analysis , Particulate Matter/analysis , China/epidemiologyABSTRACT
In situ visualization of lipid composition diversity in lipid droplets (LDs) is essential for decoding lipid metabolism and function. However, effective probes for simultaneously localizing and reflecting the lipid composition of LDs are currently lacking. Here, we synthesized full-color bifunctional carbon dots (CDs) that can target LDs as well as respond to the nuance in internal lipid compositions with highly sensitive fluorescence signals, due to lipophilicity and surface state luminescence. Combined with microscopic imaging, uniform manifold approximation and projection, and sensor array concept, the capacity of cells to produce and maintain LD subgroups with varying lipid composition was clarified. Moreover, in oxidative stress cells, LDs with characteristic lipid compositions were deployed around mitochondria, and the proportion of LD subgroups changed, which gradually disappeared when treated with oxidative stress therapeutics. The CDs demonstrate great potential for in situ investigation of the LD subgroups and metabolic regulations.
Subject(s)
Lipid Droplets , Mitochondria , Lipid Droplets/metabolism , Mitochondria/metabolism , Lipid Metabolism , LipidsABSTRACT
Non-puerperal mastitis(NPM)is a group of chronic inflammatory diseases with breast pain,lumps,abscesses and sinus tracts/fistulas as the main clinical manifestations,which is easily confused with breast cancer or other benign breast diseases.NPM always leads to a long treatment cycle and high recurrence rate,which may cause a large economic and psychological burden to patients.At present,the etiology and pathogenesis of NPM are still unclear,but it has a certain correlation with immune abnormality,bacterial infection,hormone disorder and other factors.Although several diagnostic methods available,the diagnosis of NPM relies on histopathological examination mainly.The treatment methods of the disease include observation and follow-up,pharmacotherapy,surgical treatment,etc.,but there is still no unified standard for specific treatment timing and treatment selection.In view of the controversy over etiology and treatment selection of NPM,this paper comprehensively summarizes the latest research progress in disease characteristics,clinical diagnosis and treatment of NPM based on domestic and foreign literature,aiming to provide reference and inspiration for the selection of reasonable clinical diagnosis and treatment.
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The canonical transient receptor potential channel(TRPC)proteins form Ca2+-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1-/-mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/-mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1-/-cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factor-kappa B(NF-κB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca2+influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.
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The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC50 = 16.94 μg·mL-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.
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The research and clinical applications of exercise therapy to the treatment of Parkinson's disease (PD) are increasing. Pain is among the important symptoms affecting the daily motor function and quality of life of PD patients. This paper reviewed the progress of research on different exercise therapies for the management of pain caused by PD and described the role and mechanism of exercise therapy for pain relief. Aerobic exercise, strength exercise, and mind-body exercise play an effective role in pain management in PD patients. The pain suffered by PD patients is divided into central neuropathic, peripheral neuropathic, and nociceptive pain. Different types of pain may coexist with different mechanistic backgrounds and treatments. The analgesic mechanisms of exercise intervention in PD-induced pain include altered cortical excitability and synaptic plasticity, the attenuation of neuronal apoptosis, and dopaminergic and non-dopaminergic analgesic pathways, as well as the inhibition of oxidative stress. Current studies related to exercise interventions for PD-induced pain suffer from small sample sizes and inadequate research of analgesic mechanisms. The neurophysiological effects of exercise, such as neuroplasticity, attenuation of neuronal apoptosis, and dopaminergic analgesic pathway provide a sound biological mechanism for using exercise in pain management. However, large, well-designed randomized controlled trials with improved methods and reporting are needed to evaluate the long-term efficacy and cost-effectiveness of exercise therapy for PD pain.
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BACKGROUND: Over the past 20 years, we have gained a deep understanding of the biological heterogeneity of diffuse large B cell lymphoma (DLBCL) and have developed a range of new treatment programs based on the characteristics of the disease, bringing us to the era of immune-chemotherapy. However, the effectiveness and molecular mechanisms of targeted-immunotherapy remain unclear in DLBCL. Targeted-immunotherapy may be beneficial for specific subgroups of patients, thus requiring biomarker assessment. CASE SUMMARY: Here, we report a case of MCD subtype DLBCL with MYD88L265P and CD79B mutations, considered in the initial stage as lymphoplasmic lymphoma (LPL) or Waldenstrom macroglobulinemia (WM). Flow cytometry supported this view; however, the immunohistochemical results of the lymph nodes overturned the above diagnosis, and the patient was eventually diagnosed with MCD subtype DLBCL. The presence of a monoclonal IgM component in the serum and infiltration of small lymphocytes with a phenotype compatible with WM into the bone marrow led us to propose a hypothesis that the case we report may have transformed from LPL/WM. CONCLUSION: This highlights the possible transformation from WM to DLBCL, CD79B mutation may be a potential biomarker for predicting this conversion.
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OBJECTIVE: To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens. METHODS: This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05. RESULTS: There was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria. CONCLUSION: In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.
Subject(s)
Cross Infection , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Cephalosporins , Drug Resistance, Bacterial , Extremities , Humans , Microbial Sensitivity Tests , Retrospective StudiesABSTRACT
OBJECTIVE: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. METHODS: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. RESULTS: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. CONCLUSIONS: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.
Subject(s)
Lymphangioleiomyomatosis , Biomarkers , Humans , Lymphangioleiomyomatosis/diagnosis , ROC Curve , Sensitivity and Specificity , Vascular Endothelial Growth Factor DABSTRACT
Normal embryogenesis requires complex regulation and precision, which depends on multiple mechanistic details. Defective embryogenesis can occur by various mechanisms. Maintaining redox homeostasis is of importance during embryogenesis. NADPH, as produced from the action of glucose-6-phosphate dehydrogenase (G6PD), has an important role in redox homeostasis, serving as a cofactor for glutathione reductase in the recycling of glutathione from oxidized glutathione and for NADPH oxidases and nitric oxide synthases in the generation of reactive oxygen (ROS) and nitrogen species (RNS). Oxidative stress differentially influences cell fate and embryogenesis. While low levels of stress (eustress) by ROS and RNS promote cell growth and differentiation, supra-physiological concentrations of ROS and RNS can lead to cell demise and embryonic lethality. G6PD-deficient cells and organisms have been used as models in embryogenesis for determining the role of redox signaling in regulating cell proliferation, differentiation and migration. Embryogenesis is also modulated by anti-oxidant enzymes, transcription factors, microRNAs, growth factors and signaling pathways, which are dependent on redox regulation. Crosstalk among transcription factors, microRNAs and redox signaling is essential for embryogenesis.