SERS Platform for Integrated Enrichment, Isolation, and Identification of Multiple Respiratory Viruses in a Single Assay Using 3D Stereoscopic SERS Tags and Flocked Swabs.

Influenza (flu) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit similar clinical symptoms, complicating the diagnosis and clinical management of these critical respiratory infections. Thus, there is an urgent need for rapid on-site detection technologies that can simultaneously detect SARS-CoV-2 and influenza A viruses. Here, we have developed the first platform that combines in situ sampling with immune swabs and multichannel surface-enhanced Raman spectroscopy (SERS) for simultaneous screening of these two respiratory viruses in a single assay. A seed-mediated growth method was used to assemble a number of silver spheres on the surface of Fe3O4@SiO2 spheres, which not only creates extensive Raman hotspots but also provides numerous sites for Raman signaling molecules, enhancing the sensing sensitivity. Integrating two specific Raman signaling molecules into the nanospheres allows for the parallel detection of both viruses, improving the efficiency of SERS signal read-out. Rapid quantitative screening of both SARS-CoV-2 and H1N1 is achievable within 15 min, with detection limits of 7.76, and 8.13 pg·mL-1 for their respective target proteins. The platform demonstrated excellent performance in testing and analyzing 98 clinical samples (SARS-CoV-2:50; influenza A:48), achieving sensitivities of 88.00, and 95.83% for SARS-CoV-2 and influenza A, respectively. Pearson's correlation analysis revealed a significant correlation with the clinical CT values (P < 0.0001), underscoring the great potential of this platform for the early, rapid, and simultaneous diagnostic discrimination of multiple pathogens.

A Directed Content Analysis for Greatest Problems Among People With and Without Traumatic Brain Injury.

OBJECTIVE: To characterize the greatest problem or need among individuals with a history of traumatic brain injury (TBI), as compared to individuals with a history of other neurological conditions, mental health conditions, and no history of neurological or mental health conditions. DESIGN: A directed content analysis of open-text responses to a single online survey question using a framework guided by the Mayo-Portland Adaptability Inventory-4. SETTING: Community. PARTICIPANTS: 2,861 community-dwelling adults (n = 274 with TBI; n = 289 with other neurological conditions besides TBI; n = 454 with mental health conditions but no neurological conditions; n = 1,844 controls). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Open-text responses to the survey prompt: "What was your greatest problem or need over the past 2 weeks?" RESULTS: The Participation index comprised the greatest proportion of responses across all four participant groups. A quarter (25.4%) of controls reported None (no problem/need), whereas only 7.9 -10.7% of participants in all other groups reported None. Among all groups, individuals with TBI reported the greatest proportion of problems in the Adjustment and Ability indices. Among people with TBI, Money Management (19.7%), None (10.6%), and Anxiety (7.7%) were the three most frequently reported problems. Compared to individuals with mild TBI (mTBI), individuals with moderate-to-severe TBI (msTBI) reported a higher proportion of problems in the Ability and Adjustment indices. Among individuals with msTBI, the Adjustment index accounted for the greatest proportion of problems. CONCLUSIONS: This study employed a person-centered approach to understanding the greatest needs among individuals with TBI. Qualitative differences were observed between individuals with and without a TBI, between people with mTBI and msTBI, and across genders among people with TBI. These findings can help guide research and policy towards addressing challenges perceived as highly important by people living in the community with TBI.

Associations between type 2 diabetes mellitus and risk of falls among community-dwelling elderly people in Guangzhou, China: a prospective cohort study.

BACKGROUND: Several studies have demonstrated that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of falls compared to those without T2DM, which may lead to disability and a lower quality of life. While, limited prospective studies have quantified the associations in southern China. We conducted a longitudinal cohort study to quantify the associations between T2DM and falls and investigate the risk factors of falls among community-dwelling elderly people in Guangzhou, China. METHODS: The population-based study included 8800 residents aged 65 and over in 11 counties of Guangzhou at baseline in 2020 and then prospectively followed up through 2022. Of 6169 participants had complete follow-up and were included in the present study. A fall event was identified by self-reported. The Cox regression was applied to quantify the associations between T2DM and falls, and hazard ratios (HRs) were calculated to the factors associated with falls among participants. RESULTS: The median follow-up time for participants was 2.42 years. During the follow-up period, the incidence of falls among all participants was 21.96%. After adjusting for covariates in Cox regression models, T2DM remained a significant risk factor for falls, with HR of 1.781 (95% CI: 1.600-1.983) in the unadjusted covariates model and 1.757 (1.577-1.957) in the adjusted covariates model. Female (1.286, 1.136-1.457), older age (≥ 80: 1.448, 1.214-1.729), single marital status (1.239, 1.039-1.477), lower education level (primary school and below: 1.619, 1.004-1.361), hypertension (1.149, 1.026-1.286) and stroke (1.619, 1.176-2.228) were associated with a higher risk of falls, whereas everyday physical exercise (0.793, 0.686-0.918) was associated with a lower risk of falls. CONCLUSION: Falls are common, with risks between T2DM and falls quantified and several factors investigated in the longitudinal cohort study among community-dwelling elderly people in Guangzhou, China. Targeted action on the risk factors may reduce the burden of falls in elderly people with T2DM in the future.

Mood Tracker: A Randomized Controlled Trial of a Self-Monitoring Intervention for Emotional Distress After Traumatic Brain Injury.

OBJECTIVE: Persons with traumatic brain injury (TBI) frequently experience emotional distress (ED) manifested in anxiety and depression. However, they may not access mental health services due to external (eg, access, transportation, and cost) or internal (eg, stigma and discomfort with traditional counseling) barriers. Based on substantial literature indicating that self-monitoring can ameliorate several health conditions, we conducted a randomized, parallel group, wait-list control (WLC) trial of a self-monitoring intervention to decrease ED after TBI. SETTING: Community in the southwestern United States. PARTICIPANTS: Persons with medically documented complicated mild, moderate, and severe TBI. DESIGN: About 127 participants were randomized in blocks of 6 to an active treatment (AT) group, wherein they completed multiple assessments of ED each week over a 6-week period via a smartphone app, or a WLC group in a parallel group, controlled trial. Participants received weekly support calls to promote self-monitoring of ED using ecological momentary assessment. MAIN MEASURES: ED (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7), Satisfaction with Life Scale, and Participation Assessment with Recombined Tools-Objective. RESULTS: Analysis of the primary study outcome at 6 weeks after initiation of treatment for the AT group did not demonstrate that self-monitoring was effective in decreasing ED as compared to the WLC group. Brief support calls made weekly to promote compliance with self-monitoring were effective in achieving the target number of self-assessments. About 80% of support calls lasted less than 5 minutes. Greater ED was associated with lower life satisfaction and lower participation indicating the importance of addressing ED in persons with TBI. CONCLUSION: Additional work is needed to develop nontraditional interventions to circumvent barriers that prevent persons with TBI from accessing care for ED. Brief support calls may be an effective, low-cost intervention to improve compliance with self-monitoring or self-management interventions.

Association Between Participation and Satisfaction With Life Over Time in Older Adults With Traumatic Brain Injury: A TBI Model Systems Study.

OBJECTIVE: To examine the association between participation and satisfaction with life at 1, 2, 5, and 10 years after traumatic brain injury (TBI) in older adults. SETTING: Community. PARTICIPANTS: Participants ( N = 2362) who sustained complicated mild to severe TBI, requiring inpatient rehabilitation, at age 60 years or older and had follow-up data on participation and satisfaction with life for at least 1 follow-up time point across 1, 2, 5, and 10 years. Age at each time period was categorized as 60 to 64 years, 65 to 75 years, and 75 years or older. DESIGN: Secondary data analysis of a large multicenter database. MAIN MEASURES: Three domains (Productivity, Social Relations, Out and About) of the Participation Assessment With Recombined Tools-Objective (PART-O); Satisfaction With Life Scale (SWLS). RESULTS: SWLS increased over the 10 years after TBI and was significantly associated with greater frequency of participation across all domains. There was a significant interaction between age and PART-O Social Relations such that there was a weaker relationship between Social Relations and SWLS in the oldest group (75 years or older). There was no interaction between Productivity or Out and About and age, but greater participation in both of these domains was associated with greater life satisfaction across age groups. CONCLUSIONS: These findings indicate that greater participation is associated with increased satisfaction with life in older adults, across all participation domains over the first 10 years postinjury, suggesting that rehabilitation should target improving participation even in older adults. The decreased association of social relations with satisfaction with life in the oldest age group suggests that frequency of social relations may not be as important for life satisfaction in the oldest adults, but quality may still be important.

MOFs@POMs-derived bimetallic oxide Fe2(MoO4)3 nanoparticles for sensitive colorimetric detection of salicylic acid in aspirin.

A colorimetric sensing method for salicylic acid (SA) was developed by designing and fabricating bimetallic oxide nanozymes. Firstly, by calcinating MIL-100(Fe)@PMo12 (MOFs@POMs) at different temperature, Fe2(MoO4)3-Ts (T = 400℃, 500℃, 600℃, 700℃) nanoparticles (NPs) were successfully prepared. Secondly, by evaluating the peroxidase-like activities, Fe2(MoO4)3-600 NPs shows the best peroxidase-like activity attributed to the Fenton-like effect and the synergistic coupling interaction between Mo and Fe. Finally, based on the specific complexation between SA and Fe3+, a sensitive colorimetric sensor for SA was established, which exhibits superior selectivity and interference with a detection limit of 0.11 µM and a linear range of 10 to 100 µM, the lowest LOD for SA to date, to the best of our knowledge.

A highly sensitive point-of-care detection platform for Salmonella typhimurium by integrating magnetic enrichment and fluorescent CsPbBr3@SiO2.

A platform was designed based on Fe3O4 and CsPbBr3@SiO2 for integrated magnetic enrichment-fluorescence detection of Salmonella typhimurium, which significantly simplifies the detection process and enhances the working efficiency. Fe3O4 served as a magnetic enrichment unit for the capture of S. typhimurium. CsPbBr3@SiO2 was employed as a fluorescence-sensing unit for quantitative signal output, where SiO2 was introduced to strengthen the stability of CsPbBr3, improve its biomodificability, and prevent lead leakage. More importantly, the SiO2 shell shows neglectable absorption or scattering towards fluorescence, making the CsPbBr3@SiO2 exhibit a high quantum yield of 74.4%. After magnetic enrichment, the decreasing rate of the fluorescence emission intensity of the CsPbBr3@SiO2 supernatant at 527 nm under excitation light at UV 365 nm showed a strong linear correlation with S. typhimurium concentration of 1 × 102~1 × 108 CFU∙mL-1, and the limit of detection (LOD) reached 12.72 CFU∙mL-1. This platform has demonstrated outstanding stability, reproducibility, and resistance to interference, which provides an alternative for convenient and quantitative detection of S. typhimurium.

Essential Role of Granulosa Cell Glucose and Lipid Metabolism on Oocytes and the Potential Metabolic Imbalance in Polycystic Ovary Syndrome.

Granulosa cells are crucial for the establishment and maintenance of bidirectional communication among oocytes. Various intercellular material exchange modes, including paracrine and gap junction, are used between them to achieve the efficient delivery of granulosa cell structural components, energy substrates, and signaling molecules to oocytes. Glucose metabolism and lipid metabolism are two basic energy metabolism pathways in granulosa cells; these are involved in the normal development of oocytes. Pyruvate, produced by granulosa cell glycolysis, is an important energy substrate for oocyte development. Granulosa cells regulate changes in intrafollicular hormone levels through the processing of steroid hormones to control the development process of oocytes. This article reviews the material exchange between oocytes and granulosa cells and expounds the significance of granulosa cells in the development of oocytes through both glucose metabolism and lipid metabolism. In addition, we discuss the effects of glucose and lipid metabolism on oocytes under pathological conditions and explore its relationship to polycystic ovary syndrome (PCOS). A series of changes were found in the endogenous molecules and ncRNAs that are related to glucose and lipid metabolism in granulosa cells under PCOS conditions. These findings provide a new therapeutic target for patients with PCOS; additionally, there is potential for improving the fertility of patients with PCOS and the clinical outcomes of assisted reproduction.

[Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease].

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Serum L-Carnitine Levels Are Associated With First Stroke in Chinese Adults With Hypertension.

BACKGROUND: This study aimed to evaluate the association of serum L-carnitine with first stroke and explore potential effect modifiers. METHODS: This is a nested, case-control study drawn from the China Stroke Primary Prevention Trial among rural Chinese adults with hypertension, including 557 first stroke cases and 557 age-matched, sex-matched, treatment group-matched, and residence-matched controls. Serum L-carnitine was measured by liquid chromatography with tandem quadrupole mass spectrometry. Multiple conditional logistic regression models were used to evaluate the association between L-carnitine and first stroke. RESULTS: The mean level of serum L-carnitine in the stroke population was 4.7 µg/mL, which was significantly lower than that of the control group (5.7 µg/mL). When L-carnitine was assessed as quintiles, compared with the reference group (quintile 1, <3.3 µg/mL), the odds of stroke were 0.62 (95% CI, 0.39-1.00) in quintile 2, 0.66 (95% CI, 0.40-1.10) in quintile 3, 0.47 (95% CI, 0.28-0.81) in quintile 4, and 0.50 (95% CI, 0.30-0.84) in quintile 5. The trend test was significant (P=0.01). When quintiles 2 to 5 were combined, the adjusted odds ratio of first stroke was 0.58 (95% CI, 0.38-0.87) compared with quintile 1. Similar associations were found for ischemic stroke and hemorrhagic stroke. In subgroup analysis, a significant L-carnitine-stroke association was only observed in the normal folate group (P interaction, 0.039) and in the MTHFR CC genotype group (P interaction, 0.047). CONCLUSIONS: In this study of rural Chinese adults with hypertension, serum L-carnitine had an inverse but nonlinear association with first stroke. Folate status and the MTHFR C677T variant were significant effect modifiers of the association.

Expression of TRIM44 and its correlation with TLR4 in laryngeal squamous cell carcinoma.

Some members of the tripartite motif-containing protein family have been reported as important regulators of carcinogenesis. In the present study, it was investigated whether tripartite motif-containing protein 44 (TRIM44) acts as a pro-oncogene through their over-expression in laryngeal squamous cell carcinoma. Its results showed that TRIM44 was up-regulated in tumor tissues and cell lines of laryngeal squamous cell carcinoma. In vitro, knockdown of TRIM44 significantly inhibited cell growth of laryngeal squamous cell carcinoma. Furthermore, TRIM44 knockdown inhibited tumor growth in nude mice in vivo, further suggesting the oncogenic activity of TRIM44 in laryngeal squamous cell carcinoma. Also, TRIM44 positively correlated with TLR4 at the mRNA and protein levels, and Si-RNA-NF-κB restrained laryngeal squamous cell carcinoma from proliferating. All indicated that TRIM44 might play a key role in tumor invasion through their over-expression and inhibition of TRIM44 is an effective strategy for the treatment of laryngeal squamous cell carcinoma.

Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study.

BACKGROUND AND AIMS: Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. METHODS: Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. RESULTS: There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: ß = - 0.50, P <  0.001; CC: ß = - 0.14, P = 0.087; CT: ß = - 0.20, P = 0.011; TT: ß = - 1.19, P <  0.001). Moreover, the decline in trend in genotype TT participants was stronger than in genotype CC participants (P for difference <  0.001) and genotype CT participants (P for difference <  0.001), while there was no significant difference between genotype CC and genotype CT participants (P for difference = 0.757). CONCLUSIONS: Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

A New Practical Tool for Assessing the Analytical Performance and Designing Risk-Based Statistical Quality Control Procedures in Laboratories.

BACKGROUND: We developed a new practical tool and applied it to assess the performance of 14 biochemical assays and designed risk-based statistical quality control (SQC) procedures. METHODS: Two graphs were combined to develop the new tool. Data points of assays were plotted on the tool to determine their sigma performance and the risk-based SQC procedures. The quality goal index (QGI) was also calculated for quality improvement. RESULTS: Among 14 assays, total bilirubin, direct bilirubin, alanine aminotransferase, creatine kinase, and gammaglutamyl transferase achieved 6-sigma performance, the recommended SQC procedure was 13s rule (n = 2) with a run size of 1,000 patient samples. Triglycerides was 5-sigma quality and could be controlled with 13s/22s/R4s multi-rule procedure (n = 2) with a run size of 450. Uric acid, creatinine, total cholesterol, and aspartate aminotransferase obtained 4-sigma quality and could be controlled using 13s/22s/R4s/41s multi-rule procedure (n = 4) with run size of 200. The performance for urea, alkaline phosphatase, amylase, and lactate dehydrogenase was 3-sigma and 13s/22s/R4s/41s/6X multi-rule procedure (n = 6) with run size of 45 was recommended. The QGI for assays with sigma quality below 6.0 were all less than 0.8. CONCLUSIONS: The developed tool can be used to simplify laboratory practices in assessing analytical performance and designing SQC procedures.

The Optimal Cutoff Value to Predict HIV Infection Using the Architect HIV Ag/Ab Combo.

BACKGROUND: The Architect HIV Ag/Ab Combo has been implemented worldwide as a screening test for more than ten years. However, its high sensitivity may lead to false-positive results in a low-prevalence setting. METHODS: This study was carried out to evaluate the performance of the Architect HIV Ag/Ab Combo based on the sample-to-cutoff (S/CO) ratios, to explore the optimal cutoff value to predict HIV infection and reduce the frequency of false-positive results. A retrospective analysis of clinical samples using the Architect HIV Ag/Ab Combo between July 2011 and February 2020 was performed. The sensitivity, specificity, positive predictive value (PPV), and false-positive rate (FPR) were evaluated and the receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff value to predict HIV infection. RESULTS: During the study period, 531 out of 692,155 samples were repeatedly reactive by the Architect HIV Ag/Ab Combo. The median S/CO value of HIV-positive were significantly higher than that of false-positive. The PPV of males (85.68%) was significantly higher than that of females (47.89%). The optimal cutoff value estimated by ROC analysis was 8.96 with the highest sum of sensitivity (100.00%) and specificity (100.00%) for males. However, for females, the optimal cutoff value was 26.97 with the highest sum of sensitivity (100.00%) and specificity (100.00%). CONCLUSIONS: For the Architect HIV Ag/Ab Combo, the optimal cutoff value needs to be set for the different genders to predict the final status of HIV infection reliably.

MCTS1 promotes laryngeal squamous cell carcinoma cell growth via enhancing LARP7 stability.

MCTS1 Re-Initiation and Release Factor (MCTS1) has been characterised as an oncoprotein in some cancers. In this study, we explored the expression of MCTS1 in laryngeal squamous cell carcinoma (LSCC) and its regulatory effects on the proliferation and cell-cycle progression of tumour cells, as well as the underlying mechanisms. The data from the Cancer Genome Atlas was used to analyse MCTS1 expression and its correlation with survival outcomes in LSCC patients. Subsequent in vitro cellular and molecular studies were performed based on representative LSCC cell lines. Results showed that the upregulation of MCTS1 in LSCC is linked to poor progression-free survival (PFS) and disease-specific survival (DSS). In TU177 and AMC-HN-8 cells, MCTS1 exerted positive regulations on cell viability, colony formation, cell cycle progression, and the expression of CDK1, CDK2, cyclin A2, and cyclin B1. Co-IP assay confirmed mutual interaction between MCTS1 and LARP7, mainly in the cytoplasm. Cycloheximide (CHX) chase and co-IP assay of ubiquitination showed that MCTS1 could increase LARP7 protein half-life and reduce its poly-ubiquitination. LARP7 overexpression enhanced the viability and colony formation of LSCC cells and also elevated the expression of CDK1, CDK2, cyclin A2, and cyclin B1. In addition, its overexpression partly reversed the negative influence of MCTS1 knockdown. In summary, this study confirmed that the expression of MCTS1 might be an indicator of unfavourable prognosis for patients with LSCC. Mechanically, it promotes LSCC cell viability and proliferation via interacting with LARP7 and reducing its proteasomal-mediated degradation.

Structural Characterization of Polysaccharide Derived from Gastrodia elata and Its Immunostimulatory Effect on RAW264.7 Cells.

A polysaccharide from Gastrodia elata (named GEP-1) was isolated with a DEAE-52 column and Sephadex G-100 column. The structural characteristics showed that GEP-1 was mainly composed of glucose (92.04%), galactose (4.79%) and arabinose (2.19%) with a molecular weight of 76.444 kDa. The polydispersity (Mw/Mn) of GEP-1 was 1.25, indicating that the distribution of molar mass (Mw) was relatively narrow, which suggested that GEP-1 was a homogeneous polysaccharide. Moreover, the molecular conformation plot of the root mean square (RMS) radius ( 1/2) versus Mw yielded a line with a slope less than 0.33 (0.15 ± 0.02), displaying that GEP-1 is a compact and curly spherical molecule in NaNO3 aqueous solution. NMR and methylation analyses revealed that the main chain structure of GEP-1 was α-(1→4)-glucans. Furthermore, it was proven that GEP-1 possessed cytoproliferative and enhancing phagocytic activities and induced cytokine (TNF-α, IL1-ß) and nitric oxide (NO) release in macrophages by upregulating the related gene expression. In addition, the RNA-seq results suggested that the GEP-1-induced immunomodulatory effect was mainly caused by activation of the NF-κB signaling pathway, which was further verified by NF-κB ELISA and pathway inhibition assays. As a result, GEP-1 exhibits the potential to be developed as a novel cheap immunostimulant without obvious toxicity.

Next-Generation Sequencing of Plasma Cell-Free DNA for Treatment Monitoring in Advanced Head and Neck Cancer Patients.

BACKGROUND: Liquid biopsy, especially circulating tumor DNA (ctDNA), has been reported to provide information on tumor genetic features and possible disseminated disease in many kinds of solid tumors. In this pilot study, we investigated the utilization of ctDNA for monitoring treatment response and progression of the disease in patients with head and neck cancers (HNC) by next-generation sequencing (NGS). METHODS: We sequenced ctDNA from 24 plasma samples collected at different time points from 19 HNC patients undergoing surgery or chemotherapy using a targeted gene panel composed of 61 actionable genes recurrently mutated in human malignancies in Tongren Hospital from November 2016 to February 2018. Also, the presence or absence of the residual ctDNA after chemotherapy in 9 patients was associated with the treatment efficacy evaluated by computed tomography (CT). RESULTS: We found that TP53 (2/6) and PIK3CA (2/6) are the most commonly recurring mutated genes. Out of 7 patients with matched tissue and pre-treatment blood samples, we confirmed concordance of ctDNA mutation in 5 patients. In 4 post-surgery patients with undetectable ctDNA mutation, ctDNA did not reoccur during the follow-up period of over 20 months. CONCLUSIONS: These results suggested that NGS detection of ctDNA may contribute to minimal residual disease (MRD) detection and chemotherapy efficacy prediction in HNC.

Baseline Plasma Zinc and Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study.

Background and Purpose- We aimed to examine the relation of baseline plasma zinc with the risk of first stroke and investigate any possible effect modifiers in hypertensive patients. Methods- The study population was drawn from the CSPPT (China Stroke Primary Prevention Trial), using a nested case-control design, including 599 first stroke cases and 599 matched controls. Results- Compared with participants with baseline plasma zinc <106.9 µg/dL (median), a significantly lower risk of first hemorrhagic stroke was found in those with plasma zinc ≥106.9 µg/dL (multivariate-adjusted odds ratio, 0.45; 95% CI, 0.21-0.94). Furthermore, the inverse plasma zinc-first hemorrhagic stroke association was significantly stronger in participants with body mass index ≥25.0 kg/m2 or plasma copper <100.1 µg/dL at baseline (Pinteraction <0.05 for both variables). However, there was no significant association between plasma zinc and first ischemic stroke (<103.3 versus ≥103.3 µg/dL [median]; multivariate-adjusted odds ratio, 1.16; 95% CI, 0.83-1.61). Conclusions- In this sample of hypertensive patients, we found a significant, inverse association between plasma zinc and first hemorrhagic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

[Study on identification of different producing areas of Gastrodia elata using multivariable selection and two-dimensional correlation spectroscopy of near infrared spectroscopy].

The efficacy and quality of Gastrodia elata from different producing areas are significant difference. The identification of producing area is helpful for the scientific and reasonable usage of medicinal material. Application near infrared spectroscopy( NIR) together with variance spectra,principal component analysis( PCA),interval partial least squares( i PLS) and genetic algorithm( GA),the characteristic spectra of G. elata from inside and outside of Yunnan province( except Zhaotong) and Zhaotong were extracted,and the pattern recognition models of i PLS-DA and GA-SVM were built,and the suitability of the models were also validated. The results showed that the prediction accuracy of i PLS-DA model was 96. 15%,the values of R2,RMSECV and RMSEP were 0. 893,0. 224 and0. 321,respectively. The prediction accuracy of GA-SVM model was 100% and RMSECV was 0. 719 4. Both methods could identify G. elata from different producing area preferably. Further,two-dimensional spectroscopy analysis was conducted for the characteristic spectra extracted by i PLS and GA. The results showed that the differential spectra of G. elata from outside and inside Yunnan were mainly located in the absorption areas of the stretch,bending and double frequency of C-H,C-N,O-H and N-H bonds of polysaccharides,aromatic hydrocarbon,amides and starch. The differential spectra of G. elata from outside Yunnan and Zhaotong were mainly located in the absorption areas of the stretch,bending and double frequency of C-H,O-H and N-H bonds of vegetable protein,aromatic hydrocarbon,polysaccharides,and alcohols. The differential spectra of G. elata from inside Yunnan and Zhaotong were mainly located in the absorption areas of the stretch,bending,transformation and double frequency of CHO,N-H,C-H,O-H and HOH bonds of lignin,aromatic hydrocarbon,alcohols,polysaccharides and aliphatics. Effective recognition of different producing areas and exploration the difference of component of G. elata could be conducted through NIR combined with multivariable selection and two-dimensional spectroscopy,which provided the basis for the reasonable development and efficient utilization of G. elata.

Integrating dynamic contrast-enhanced magnetic resonance imaging and diffusion kurtosis imaging for neoadjuvant chemotherapy assessment of nasopharyngeal carcinoma.

BACKGROUND: Since neoadjuvant chemotherapy (NAC) has proven a benefit for locally advanced nasopharyngeal carcinoma (NPC), early response evaluation after chemotherapy is important to implement individualized therapy for NPC in the era of precision medicine. PURPOSE: To determine the combined and independent contribution between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) in the early monitoring of NAC response for NPC. STUDY TYPE: Prospective. POPULATION: Fifty-three locally advanced NPC patients. FIELD STRENGTH/SEQUENCE: Four examinations before and at 4, 20, and 40 days after NAC initiation were performed at 3T MRI including DCE-MRI and DKI (b values = 0, 500, 1000, 1500 s/mm2 ). ASSESSMENT: DCE-MRI parameters (Ktrans [the volume transfer constant of Gd-DTPA], kep [rate constant], νe [the extracellular volume fraction of the imaged tissue], and νp [the blood volume fraction]) and DKI parameters (Dapp [apparent diffusion for non-Gaussian distribution] and Kapp [apparent kurtosis coefficient]) were analyzed using dedicated software. STATISTICAL TESTS: MRI parameters and their corresponding changes were compared between responders and nonresponders after one or two NAC cycles treatment using independent-samples Student's t-test or Mann-Whitney U-test depending on the normality contribution test and then followed by logistic regression and receiver operating characteristic curve (ROC) analyses. RESULTS: The responder group (RG) patients presented significantly higher mean Ktrans and Dapp values at baseline and larger Δ K ( 0 - 4 ) trans , Δvp(0-4) , and ΔDapp(0-4) values after either one or two NAC cycles compared with the nonresponder group (NRG) patients (all P < 0.05). ROC analyses demonstrated the higher diagnostic accuracy of combined DCE-MRI and DKI model to distinguish nonresponders from responders after two NAC cycles than using DCE-MRI (0.987 vs. 0.872, P = 0.033) or DKI (0.987 vs. 0.898, P = 0.047) alone. DATA CONCLUSION: Combined DCE-MRI and DKI models had higher diagnostic accuracy for NAC assessment compared with either model used independently. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1208-1216.