The evolution of parasitism from mutualism in wasps pollinating the fig, Ficus microcarpa, in Yunnan Province, China.

Theory identifies factors that can undermine the evolutionary stability of mutualisms. However, theory's relevance to mutualism stability in nature is controversial. Detailed comparative studies of parasitic species that are embedded within otherwise mutualistic taxa (e.g., fig pollinator wasps) can identify factors that potentially promote or undermine mutualism stability. We describe results from behavioral, morphological, phylogenetic, and experimental studies of two functionally distinct, but closely related, Eupristina wasp species associated with the monoecious host fig, Ficus microcarpa, in Yunnan Province, China. One (Eupristina verticillata) is a competent pollinator exhibiting morphologies and behaviors consistent with observed seed production. The other (Eupristina sp.) lacks these traits, and dramatically reduces both female and male reproductive success of its host. Furthermore, observations and experiments indicate that individuals of this parasitic species exhibit greater relative fitness than the pollinators, in both indirect competition (individual wasps in separate fig inflorescences) and direct competition (wasps of both species within the same fig). Moreover, phylogenetic analyses suggest that these two Eupristina species are sister taxa. By the strictest definition, the nonpollinating species represents a "cheater" that has descended from a beneficial pollinating mutualist. In sharp contrast to all 15 existing studies of actively pollinated figs and their wasps, the local F. microcarpa exhibit no evidence for host sanctions that effectively reduce the relative fitness of wasps that do not pollinate. We suggest that the lack of sanctions in the local hosts promotes the loss of specialized morphologies and behaviors crucial for pollination and, thereby, the evolution of cheating.

East‒West genetic differentiation across the Indo-Burma hotspot: evidence from two closely related dioecious figs.

BACKGROUND: Understanding biodiversity patterns and their underlying mechanisms is of interest to ecologists, biogeographers and conservationists and is critically important for conservation efforts. The Indo-Burma hotspot features high species diversity and endemism, yet it also faces significant threats and biodiversity losses; however, few studies have explored the genetic structure and underlying mechanisms of Indo-Burmese species. Here, we conducted a comparative phylogeographic analysis of two closely related dioecious Ficus species, F. hispida and F. heterostyla, based on wide and intensive population sampling across Indo-Burma ranges, using chloroplast (psbA-trnH, trnS-trnG) and nuclear microsatellite (nSSR) markers, as well as ecological niche modeling. RESULTS: The results indicated large numbers of population-specific cpDNA haplotypes and nSSR alleles in the two species. F. hispida showed slightly higher chloroplast diversity but lower nuclear diversity than F. heterostyla. Low-altitude mountainous areas of northern Indo-Burma were revealed to have high genetic diversity and high habitat suitability, suggesting potential climate refugia and conservation priority areas. Strong phylogeographic structure and a marked east‒west differentiation pattern were observed in both species, due to the interactions between biotic and abiotic factors. Interspecific dissimilarities at fine-scale genetic structure and asynchronized historical dynamics of east‒west differentiation between species were also detected, which were attributed to different species-specific traits. CONCLUSIONS: We confirm hypothesized predictions that interactions between biotic and abiotic factors largely determine the patterns of genetic diversity and phylogeographic structure of Indo-Burmese plants. The east‒west genetic differentiation pattern observed in two targeted figs can be generalized to some other Indo-Burmese plants. The results and findings of this work will contribute to the conservation of Indo-Burmese biodiversity and facilitate targeted conservation efforts for different species.

PD-1/PD-L1 inhibitor plus chemotherapy versus standard of care in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor plus chemotherapy vs standard of care (SoC) treatment in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M-SCCHN). METHODS: Randomized controlled trials (RCTs) that investigated PD-1/PD-L1 inhibitor plus chemotherapy vs SoC as first-line treatment for R/M-SCCHN were searched from electronic databases (PubMed, Embase and Cochrane Library). The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: In total, three phase 3 RCTs (KEYNOTE-048, CAPTAIN-1st, and JUPITER-02; n = 1120) with three PD-1 inhibitors (pembrolizumab, camrelizumab and toripalimab) were included in the analysis. Compared with SoC, PD-1 inhibitor plus chemotherapy significantly prolonged PFS (hazard ratio [HR] 0.66, 95% CI 0.40-0.93, p < 0.001) and OS (HR 0.73, 95% CI 0.60-0.86, p < 0.001) of patients. There was no statistical differences in ORR (odds ratio [OR] 1.26; 95% CI 0.97-1.64, p = 0.086), grade 3 or higher AEs (OR 0.77, 95% CI 0.50-1.17, p = 0.221), and treatment-related deaths (OR 1.34, 95% CI 0.60-2.98, p = 0.470) between the two groups. CONCLUSION: PD-1 inhibitor plus chemotherapy showed more survival benefit than SoC in the first-line treatment for R/M-SCCHN, with a similar safety profile.

The efficacy and safety of immune checkpoint inhibitor plus chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of immune checkpoint inhibitor (ICI) and chemotherapy (CT) versus CT alone in advanced non-small-cell lung cancer (NSCLC). METHODS: Databases (PubMed, Embase and Cochrane Library) were searched for relevant randomized controlled trials (RCTs). Clinical outcome measures including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3-5 treatment-related adverse events (AEs) were analyzed by Stata 15.0 software; significance level was 0.05. RESULTS: Eight RCTs involving 4227 patients were included. The results showed ICI + CT significantly improved OS (hazard ratio [HR] = 0.74, 95% CI: 0.62-0.85, p < 0.001), PFS (HR = 0.66, 95% CI: 0.57 - 0.75, p < 0.001) and ORR (odds ratio [OR] = 1.89; 95% CI, 1.43-2.49, p < 0.001) compared with CT alone. Subgroup analysis indicated that significantly longer OS was also observed in subgroups including combination regimens (pembrolizumab + CT, atezolizumab + CT, ipilimumab + CT, and nivolumab + ipilimumab + CT) and PD-L1 status [negative (< 1%), positive (≥ 1%), low (1-49%) and high (≥ 50%)]. However, ICI + CT showed signifcantly higher grade 3-5 treatment-related AEs than CT (OR = 1.46, 95% CI: 1.19 - 1.79, p < 0.001). CONCLUSIONS: ICI + CT showed better clinical efficacy than CT alone in patients with advanced NSCLC, with increased treatment-related AEs.

Combination therapy with immune checkpoint inhibitors in advanced renal cell carcinoma: A meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the efficacy and safety of immune checkpoint inhibitor combination therapy in advanced renal cell carcinoma (RCC). METHODS: We searched PubMed/Embase/Cochrane Library for relevant randomized controlled trials (RCTs). Clinical outcome measures including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and adverse events (AEs) were analyzed by Stata 15.1 software. RESULTS: Seven RCTs involving 3461 patients were included. The pooled hazard ratios of OS and PFS for combination therapy were 0.67 (0.53-0.82, p < 0.001) and 0.68 (0.52-0.83, p < 0.001), respectively. Longer OS and PFS for combination therapy was also observed in the PD-L1 expression leve ≥1% group. The pooled odds ratios of ORRs and grade 3 or higher AEs were 2.31 (1.61-3.32, p < 0.001) and 0.94 (0.65-1.37, p = 0.753), respectively. CONCLUSIONS: Immune checkpoint inhibitor combination therapy showed more clinical benefit in the first-line treatment for advanced RCC, with a safety profile.

Gut microbiota protects from triptolide-induced hepatotoxicity: Key role of propionate and its downstream signalling events.

As a potential drug for treating inflammatory, autoimmune diseases and cancers, triptolide (TP) is greatly limited in clinical practice due to its severe toxicity, particularly for liver injury. Recently, metabolic homeostasis was vitally linked to drug-induced liver injury and gut microbiota was established to play an important role. In this study, we aimed to investigate the functions of gut microbiota on TP-induced hepatotoxicity using metabolomics in mice. Here, predepletion of gut microbiota by antibiotic treatment strikingly aggravated liver injury and caused mortality after treated with a relatively safe dosage of TP at 0.5 mg/kg, which could be reversed by gut microbial transplantation. The loss of gut microbiota prior to TP treatment dramatically elevated long chain fatty acids and bile acids in plasma and liver. Further study suggested that gut microbiota-derived propionate contributed to the protective effect of gut microbiota against TP evidenced by ameliorative inflammatory level (Tnfa, Il6 and Cox2), ATP, malondialdehyde and hepatic histology. Supplementing with propionate significantly decreased the mRNA levels of genes involved in fatty acid biosynthesis (Srebp1c, Fasn and Elovl6), resulting in the decreased long chain fatty acids in liver. Moreover, TP restricted the growth of Firmicutes and led to the deficiency of short chain fatty acids in cecum content. In conclusion, our study warns the risk for TP and its preparations when antibiotics are co-administrated. Intervening by foods, prebiotics and probiotics toward gut microbiota or supplementing with propionate may be a clinical strategy to improve toxicity induced by TP.

Metabolic profiling of coumarins by the combination of UPLC-MS-based metabolomics and multiple mass defect filter.

Coumarins have aroused high interests due to their diverse bioactivities. Understanding of its metabolism contributes to determine the druggability of coumarin in vivo.A sensitive and efficient strategy based on ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) analysis combined with various data-processing techniques including metabolomics and multiple mass defect filter (MMDF) was established for the comprehensive screening and elucidation of potential coumarin metabolites.Total 20 metabolites of scoparone were identified in this study, including 14 undescribed metabolites. The metabolism of two other similar coumarins scopoletin and esculetin also could be determined using this strategy.By the established strategy, this study gives the insights about the major metabolic pathways of scoparone in vivo and in vitro metabolism, including demethylation, hydroxylation, hydration, cysteine conjugation, glucuronide conjugation and sulfate conjugation. Additionally, the metabolic pathways of scopoletin and esculetin were determined as hydroxylation, glucuronidation and sulfation. These results contribute to the understanding of metabolic characterization of coumarins, and demonstrate that the combination of UPLC-MS-based metabolomics and MMDF is a powerful approach to determine the metabolic pathways of coumarin compounds.

Subtypes of masked hypertension and target organ damage in untreated outpatients.

Purpose: Masked hypertension (MHT) is characterised as an office normotension in the presence of out-of-office hypertension, and can be further categorised as isolated daytime (dMHT), night-time (nMHT) or day-night MHT (dnMHT) according to the time when hypertension is present. MHT is associated with adverse cardiovascular outcome. However, no previous studies contrasted these MHT subtypes in their associations with target organ damage (TOD).Materials and methods: Consecutive untreated patients referred for ambulatory blood pressure (BP) monitoring to our Hypertension Clinic were recruited. Office and ambulatory BPs were measured using the Omron 7051 and SpaceLabs 90217 monitors, respectively. The BP thresholds of daytime and night-time hypertension were of ≥135/85 mmHg and ≥120/70 mmHg, respectively. We performed various TOD measurements, including carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), left ventricular mass index (LVMI) and E/E', estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR).Results: The 1808 participants (mean age, 51 years; women, 52%) included 672 (37.2%) MHT subjects, among whom 123 (18.3%) had dMHT, 78 (11.6%) nMHT, and 471 (70.1%) dnMHT. In all participants as well as patients with office normotension (n = 1222), ambulatory daytime and night-time BPs were similarly associated with all TOD measurements (p ≥ 0.20) after multivariate adjustment. Compared to normotensive subjects (p < 0.05), patients with dMHT had faster cfPWV (7.81 vs. 7.58 m/s) and thicker cIMT (637.6 vs. 610.4 µm), patients with nMHT had thicker cIMT (641.8 vs. 610.4 µm) and increased UACR (0.79 vs. 0.59 mg/mmol), and patients with dnMHT had all worse TOD measures mentioned-above plus elevated eGFR (120.7 vs. 116.8 ml/min/1.73m2).Conclusion: MHT was associated with TOD irrespective of subtype, although TOD varied slightly across these subtypes. The study highlights the importance of controlling both daytime and night-time BP in hypertensive patients.

The nature of interspecific interactions and co-diversification patterns, as illustrated by the fig microcosm.

Interactions between mutualists, competitors, and antagonists have contrasting ecological effects that, sustained over generations, can influence micro- and macroevolution. Dissimilar benefits and costs for these interactions should cause contrasting co-diversification patterns between interacting clades, with prevalent co-speciation by mutualists, association loss by competitors, and host switching by antagonists. We assessed these expectations for a local assemblage of 26 fig species (Moraceae: Ficus), 26 species of mutualistic (pollinating), and 33 species of parasitic (galling) wasps (Chalcidoidea). Using newly acquired gene sequences, we inferred the phylogenies for all three clades. We then compared the three possible pairs of phylogenies to assess phylogenetic congruence and the relative frequencies of co-speciation, association duplication, switching, and loss. The paired phylogenies of pollinators with their mutualists and competitors were significantly congruent, unlike that of figs and their parasites. The distributions of macroevolutionary events largely agreed with expectations for mutualists and antagonists. By contrast, that for competitors involved relatively frequent association switching, as expected, but also unexpectedly frequent co-speciation. The latter result likely reflects the heterogeneous nature of competition among fig wasps. These results illustrate the influence of different interspecific interactions on co-diversification, while also revealing its dependence on specific characteristics of those interactions.

Pre-TACE kurtosis of ADCtotal derived from histogram analysis for diffusion-weighted imaging is the best independent predictor of prognosis in hepatocellular carcinoma.

PURPOSE: To determine the feasibility of pre-TACE IVIM imaging based on histogram analysis for predicting prognosis in the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-five patients prospectively underwent 1.5T MRI 1 week before TACE. Histogram metrics for IVIM parameters and ADCs maps between responders and non-responders with mRECIST assessment were compared. Kaplan-Meier, log-rank tests and Cox proportional hazard regression model were used to correlate variables with time to progression (TTP). RESULTS: Mean (p = 0.022), median (p = 0.043), and 25th percentile (p < 0.001) of perfusion fraction (PF), mean (p < 0.001), median (p < 0.001), 25th percentile (p < 0.001) and 75th percentile (p = 0.001) of ADC(0,500), mean (p = 0.005), median (p = 0.008) and 25th percentile (p = 0.039) of ADCtotal were higher, while skewness and kurtosis of PF (p = 0.001, p = 0.005, respectively), kurtosis of ADC(0,500) and ADCtotal (p = 0.005, p = 0.001, respectively) were lower in responders compared to non-responders. Multivariable analysis demonstrated that mRECIST was associated with TTP independently, and kurtosis of ADCtotal had the best predictive performance for disease progression. CONCLUSION: Pre-TACE kurtosis of ADCtotal is the best independent predictor for TTP. KEY POINTS: • mRECIST was associated with TTP independently. • Lower kurtosis and higher mean for ADCs tend to have good response. • Pre-TACE kurtosis of ADC total is the best independent predictor for TTP.

PPARα Mediates the Hepatoprotective Effects of Nutmeg.

Nutmeg is a Traditional Chinese Medicine used to treat gastrointestinal diseases. Some reports have indicated that nutmeg has hepatoprotective activity. In this study, a thioacetamide (TAA)-induced acute liver injury model in mice was used to explore the mechanism of the protective effects of nutmeg extract (NME), including its major bioactive component myrislignan. The results indicated that NME could effectively protect TAA-induced liver damage as assessed by recovery of increased serumtransaminases, decrease in hepatic oxidative stress, and lower hepatic inflammation. Metabolomics analysis further revealed that treatment with NME led to the recovery of a series of lipids including lysophosphatidylcholines that were decreased and a lowering of acylcarnitines that were increased in mouse plasma and liver after TAA exposure. Gene expression analysis demonstrated that the hepatoprotective effect of NME was achieved by modulation of the peroxisome proliferator-activated receptor alpha (PPARα) as well as the decrease in oxidative stress. NME could not protect from TAA-induced liver injury in Ppara-null mice, suggesting that its protective effect was dependent on PPARα. Myrislignan, a representative neolignan in nutmeg, showed potent protective activity against TAA-induced liver toxicity. These data demonstrate that nutmeg alleviates TAA-induced liver injury through the modulation of PPARα and that the lignan compounds in nutmeg such as myrislignan partly contributed to this action.

Metabolic engineering of Escherichia coli for microbial production of L-methionine.

L-methionine has attracted a great deal of attention for its nutritional, pharmaceutical, and clinical applications. In this study, Escherichia coli W3110 was engineered via deletion of a negative transcriptional regulator MetJ and over-expression of homoserine O-succinyltransferase MetA together with efflux transporter YjeH, resulting in L-methionine overproduction which is up to 413.16 mg/L. The partial inactivation of the L-methionine import system MetD via disruption of metI made the engineered E. coli ΔmetJ ΔmetI/pTrcA*H more tolerant to high L-ethionine concentration and accumulated L-methionine to a level 43.65% higher than that of E. coli W3110 ΔmetJ/pTrcA*H. Furthermore, deletion of lysA, which blocks the lysine biosynthesis pathway, led to a further 8.5-fold increase in L-methionine titer of E. coli ΔmetJ ΔmetI ΔlysA/pTrcA*H. Finally, addition of Na2 S2 O3 to the media led to an increase of fermentation titer of 11.45%. After optimization, constructed E. coli ΔmetJ ΔmetI ΔlysA/pTrcA*H was able to produce 9.75 g/L L-methionine with productivity of 0.20 g/L/h in a 5 L bioreactor. This novel metabolically tailored strain of E. coli provides an efficient platform for microbial production of L-methionine. Biotechnol. Bioeng. 2017;114: 843-851. © 2016 Wiley Periodicals, Inc.

Origins and evolution of cinnamon and camphor: A phylogenetic and historical biogeographical analysis of the Cinnamomum group (Lauraceae).

Tropical and subtropical amphi-Pacific disjunction is among the most fascinating distribution patterns, but received little attention. Here we use the fossil-rich Cinnamomum group, a primarily tropical and subtropical Asian lineage with some species distributed in Neotropics, Australasia and Africa to shed light upon this disjunction pattern. Phylogenetic and biogeographic analyses were carried out using sequences of three nuclear loci from 94 Cinnamomum group and 13 outgroup samples. Results show that although there are three clades within a monophyletic Cinnamomum group, Cinnamomum and previously recognized subdivisions within this genus were all rejected as natural groups. The Cinnamomum group appears to have originated in the widespread boreotropical paleoflora of Laurasia during the early Eocene (ca. 55Ma). The formation and breakup of the boreotropics seems to have then played a key role in the formation of intercontinental disjunctions within the Cinnamomum group. The first cooling interval (50-48Ma) in the late early Eocene resulted in a floristic discontinuity between Eurasia and North America causing the tropical and subtropical amphi-Pacific disjunction. The second cooling interval in the mid-Eocene (42-38Ma) resulted in the fragmentation of the boreotropics within Eurasia, leading to an African-Asian disjunction. Multiple dispersal events from North into South America occurred from the early Eocene to late Miocene and a single migration event from Asia into Australia appears to have occurred in the early Miocene.

Improvement and characterization of a hyperthermophilic glucose isomerase from Thermoanaerobacter ethanolicus and its application in production of high fructose corn syrup.

High fructose corn syrup (HFCS) is an alternative of liquid sweetener to sucrose that is isomerized by commercial glucose isomerase (GI). One-step production of 55 % HFCS by thermostable GI has been drawn more and more attentions. In this study, a new hyperthermophilic GI from Thermoanaerobacter ethanolicus CCSD1 (TEGI) was identified by genome mining, and then a 1317 bp fragment encoding the TEGI was synthesized and expressed in Escherichia coli BL21(DE3). To improve the activity of TEGI, two amino acid residues, Trp139 and Val186, around the active site and substrate-binding pocket based on the structural analysis and molecular docking were selected for site-directed mutagenesis. The specific activity of mutant TEGI-W139F/V186T was 2.3-fold and the value of k cat/K m was 1.86-fold as compared to the wild type TEGI, respectively. Thermostability of mutant TEGI-W139F/V186T at 90 °C for 24 h showed 1.21-fold extension than that of wild type TEGI. During the isomerization of glucose to fructose, the yield of fructose could maintain above 55.4 % by mutant TEGI-W139F/V186T as compared to 53.8 % by wild type TEGI at 90 °C. This study paved foundation for the production of 55 % HFCS using the thermostable TEGI.

Enhanced and asymmetric signatures of hybridization at climatic margins: Evidence from closely related dioecious fig species.

Hybridization plays a significant role in biological evolution. However, it is not clear whether ecological contingency differentially influences likelihood of hybridization, particularly at ecological margins where parental species may exhibit reduced fitnesses. Moreover, it is unknown whether future ecosystem change will increase the prevalence of hybridization. Ficus heterostyla and F. squamosa are closely related species co-distributed from southern Thailand to southwest China where hybridization, yielding viable seeds, has been documented. As a robust test of ecological factors driving hybridization, we investigated spatial hybridization signatures based on nuclear microsatellites from extensive population sampling across a widespread contact range. Both species showed high population differentiation and strong patterns of isolation by distance. Admixture estimates exposed asymmetric interspecific gene flow. Signatures of hybridization increase significantly towards higher latitude zones, peaking at the northern climatic margins. Geographic variation in reproductive phenology combined with ecologically challenging marginal habitats may promote this phenomenon. Our work is a first systematic evaluation of such patterns in a comprehensive, latitudinally-based clinal context, and indicates that tendency to hybridize appears strongly influenced by environmental conditions. Moreover, that future climate change scenarios will likely alter and possibly augment cases of hybridization at ecosystem scales.

[Relationship between physical activity and the incidence of metabolic syndrome in Chinese adults: a prospective cohort study].

OBJECTIVE: To investigate the association between physical activity (PA) and the incidence of metabolic syndrome (MS) in Chinese adults. METHODS: Data on PA and other variables were obtained at the baseline examination of China Multi-center study of Cardiovascular Epidemiology in 1998 and of International Collaborative study of Cardiovascular Disease in Asia(InterASIA) during 2000 - 2001. Follow-up study was conducted in 2007 - 2008. A total of 11 512 Chinese adults aged 35 - 74 years (5563 men and 5949 women) were included in the final data analysis. Information on demographics, PA, smoking and alcohol consumption were obtained and components of MS were examined. Participants were divided into four groups according to quartile of total metabolic equivalent (MET) values per day. In addition, subjects were grouped into the following categories according to occupational PA: inactive, light, moderate and vigorous. Binary logistic model was used to examine the association between PA and the incidence of MS. RESULTS: A total of 2527 cases with MS were documented during an average following up of 8.1 years. The annual incidence rate of MS was 2.71% (2527/93 178.68). After multivariate logistic regression analysis, compared with participants with total PA volume < 32.0 MET×h×d(-1) (annual incidence rate was 3.19% (697/21 830.74)), the RR (95%CI) value of participants with total PA volume during 32.00 - 37.85, 37.86 - 52.29, and ≥ 52.30 MET×h×d(-1) was 1.05(0.92 - 1.19), 0.98(0.86 - 1.12), and 0.68(0.59 - 0.80), respectively (χ(2)trend = 34.23, P < 0.05), with corresponding annual incidence rates of 2.82% (690/24 504.25), 2.73% (661/24 179.36) and 2.11% (479/22 664.33). In addition, compared to inactive occupational PA (annual incidence rate was 2.76% (402/14 588.33)), the corresponding RR (95%CI) value was 0.80 (0.69 - 0.92), 0.70 (0.59 - 0.82), and 0.54 (0.45 - 0.65) (χ(2)trend = 42.34, P < 0.05), and the annual incidence rates were 2.86% (648/22 663.41), 2.40% (455/18 956.14) and 1.89% (344/18 173.86) in participants with light, moderate and vigorous occupational PA, respectively. CONCLUSION: Both increased total PA volume and occupational PA intensity are significantly associated with decreased risk of incidence of MS.

[Impact factors for efficacy of specific immunotherapy in children with dust mite allergic asthma].

OBJECTIVE: To investigate impact factors for the efficacy of specific immunotherapy (SIT) in children with dust mite allergic asthma. METHODS: Ninety-nine children with house dust mite allergic asthma received standardized SIT, and the level of asthma control was evaluated after 6 months (S1 stage), 12 months (S2 stage), 18 months (S3 stage), and 24 months (S4 stage) of treatment. The age of first visit, course of asthma, level of asthma severity, initial serum specific immunoglobulin E (sIgE) level, combination with allergic rhinitis or atopic dermatitis, use of inhaled corticosteroids, and local or systemic side effects during treatment were recorded, and their impacts on the level of asthma control were analyzed. RESULTS: As the SIT proceeded, the number of clinically controlled cases increased significantly (P<0.01). The level of asthma control was significantly affected by the age of patients at first visit in S1 and S3 stages, and combination with allergic rhinitis or atopic dermatitis in S1 stage (P<0.05). In all stages of SIT, the controlled cases had significantly higher initial serum sIgE levels than the uncontrolled cases (P<0.05). In S1 and S2 stages, there was a significantly higher proportion of controlled cases among children with a high level of asthma severity than among those with a low level of asthma severity (P<0.05). CONCLUSIONS: There is a positive correlation between long-term efficacy of SIT and the course or the total dose of treatment. Patients with higher initial serum sIgE levels achieve clinical control earlier than those with lower initial serum sIgE levels during SIT.

Association between dietary niacin intake and cognitive function in the elderly: Evidence from NHANES 2011-2014.

Recent studies have shown an inconsistent association between dietary niacin and cognitive function. And this remains unclear in the American outpatient population. The aim of this study was to assess whether there is an association between dietary niacin and cognitive performance in an older American population aged ≥60 years. A total of 2523 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were enrolled. Cognitive function was assessed by the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Cognitive impairment that meets one of the four scoring conditions listed above is defined as low cognitive function. Dietary niacin intake was obtained from 2 days of a 24-h recall questionnaire. Based on the quartiles of dietary niacin intake, they were divided into four groups: Q1 (<15.51 mg), Q2 (15.51-20.68 mg), Q3 (20.69-26.90 mg), and Q4 (>26.91 mg). The stability of the results was assessed using multifactorial logistic regression, restricted cubic spline (RCS) models, and sensitivity stratified analysis. More than half of the participants had cognitive impairment (52.52%). In the fully adjusted model, niacin was associated with a significantly reduced risk of cognitive impairment in Q3 and Q4 compared with the Q1 group (OR: 0.610, 95% CI: 0.403, 0.921, p = .022; OR: 0.592, 95% CI: 0.367, 0.954, p = .034). Meanwhile, niacin was negatively associated with poor cognition as assessed by the CERAD-WL test, CERAD test, AFT, and DSST. An L-shaped dose-response relationship between dietary niacin and cognitive function was observed in all participants (nonlinear p < .001). There were also interactions that existed in populations with different carbohydrate intakes and cholesterol intakes (p for interaction = .031, p for interaction = .005). These findings provide new evidence for the potential role of dietary niacin intake on cognitive function in the elderly.