Analysis of Caregiver Burden and Influencing Factors in Autologous Hematopoietic Stem Cell Transplantation Patients with Bendamustine Preconditioning.

This paper comprehensively analyzes the caregiver burden and its influencing factors on primary caregivers in autologous hematopoietic stem cell transplantation (Auto-HSCT) with bendamustine preconditioning. Auto-HSCT refers to the transplantation of cells back to the patient, aiming to eliminate tumor cells and prolong the patient's life. Bendamustine, while enhancing the success rate of transplantation, has drawn considerable attention to the primary caregivers of patients. Due to the complex nature of the transplantation process, patients have diverse caregiving needs, which caregivers must address to support the entire treatment journey. The caregiver burden of primary caregivers is influenced by various factors, including the patient's disease condition, various aspects of the caregiver as an individual, and psychological factors. The article emphasizes the need for personalized care plans and psychological support to minimize caregiver burden and improve overall quality of life. This study has positive implications for optimizing the implementation of Auto-HSCT therapy.

First Report of Apiospora arundinis Causing Wet Root Rot of Pseudostellaria heterophylla in China.

Pseudostellaria heterophylla is one of the traditional medicines in China. From 2020 to 2022, postharvest wet root rot disease was observed with an incidence of 2~5% on the tuberous roots of the harvested P. heterophylla in Zherong county, Fujian province, China, which usually occurs under damp and unventilated conditions. The symptoms of the disease were as follows: white mycelia grew on the surface of tuberous root initially and gradually wrapped around the roots, the internal root tissue turned yellow and became wet decay finally. To identify the causal agent, a total of 20 samples with symptomatic tuberous roots were collected. Small pieces (3 mm2) were treated by surface disinfection with 75% ethanol and 1% NaOCl, then rinsed 3 times with sterile water. These treated pieces were transferred onto potato dextrose agar (PDA) and incubated at 25°C in the dark for 7 d. Ten pure cultures were obtained using single-spore isolation method. The fungus colonies initially produced white aerial mycelium, subsequently exhibited yellow pigmentation. Mycelia were consisted of smooth, hyaline, branched, and septate hyphae. The conidia were solitary or clustered, brown or dark brown, smooth, ellipsoidal to spherical, 6.66 (5.50-7.81)×5.65 (4.17-7.22) µm (n=50) in size. The conidiophores were hyaline or pale brown and produced conidiogenous cells, which were pale brown, smooth, ampulliform, and 10.14 (8.82-15.30) um long (n=50). Based on these morphological characteristics, the fungus was identified as the genus Apiospora (Arthrinium). The rDNA-ITS region and partial ß-tubulin gene (BenA) were amplified using the primers ITS1/ITS4 (White et al. 1990) and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. The sequences of isolates FJAT-32563 and FJAT-32564 were deposited in GenBank (ITS, OM920984 and OM920985; BenA, OM953823 and OM953824). All sequences had more than 99% similarity with those of A. arundinis strain CBS:106.12 (ITS, KF144883; BenA, KF144973). In the multilocus phylogenetic analysis (ITS + BenA), the two isolates clustered together with other strains of A. arundinis with 100% bootstrap support. The isolates were therefore identified as A. arundinis based on both morphological and molecular characteristics. To confirm the pathogenicity, fresh tuberous roots were selected and surface disinfected, then the roots were immersed with a quarter length in the conidial suspension (106/mL) for 30 min, whereas the control roots were immersed with sterile water (n=30). They were placed in petri dish with wet filter paper at 25±2℃, maintaining 80% relative humidity in the dark. The white aerial mycelium appeared at 5 days after inoculation, and wet root rot decaying occurred after inoculation for 21 days. The symptoms were similar to those described above, whereas the control roots were asymptomatic. The same fungus was re-isolated from the infected roots, showing similar morphological characteristics and molecular traits. Koch's postulates were completed and the pathogenicity test for the isolates has been repeated thrice. Previously, A. arundinis was reported to infect peach and sugarcane (Ji et al. 2020; Liao et al. 2022). To our knowledge, this is the first report of A. arundinis causing wet root rot of P. heterophylla in China. The disease would be a potentially new threat to this medicinal plant.

Consumption of Coffee and Tea Is Associated with Macular Retinal Nerve Fiber Layer Thickness: Results from the UK Biobank.

Coffee and tea drinking are thought to be protective for the development and progression of neurodegenerative disorders. This study aims to investigate associations between coffee and tea consumption with macular retinal nerve fiber layer (mRNFL) thickness, a marker of neurodegeneration. After quality control and eligibility screening, 35,557 out of 67,321 United Kingdom (UK) Biobank participants from six assessment centers were included in this cross-sectional study. In the touchscreen questionnaire, participants were asked how many cups of coffee and tea were consumed daily on average over the last year. Self-reported coffee and tea consumption were divided into four categories including 0 cup/day, 0.5-1 cups/day, 2-3 cups/day, and ≥4 cups/day, respectively. The mRNFL thickness was measured by the optical coherence tomography (Topcon 3D OCT-1000 Mark II) and automatically analyzed by segmentation algorithms. After adjusting for covariates, coffee consumption was significantly associated with an increased mRNFL thickness (ß = 0.13, 95% CI = 0.01~0.25), which was more prominent in those who drank 2~3 cups coffee per day (ß = 0.16, 95% CI = 0.03~0.30). The mRNFL thickness was also significantly increased in tea drinkers (ß = 0.13, 95% CI = 0.01~0.26), especially for those who drank more than 4 cups of tea per day (ß = 0.15, 95% CI = 0.01~0.29). The positive associations with mRNFL thickness, indicating that both coffee and tea consumptions had likely neuroprotective potentials. Causal links and underlying mechanisms for these associations should be explored further.

Axial Shortening in Myopic Children after Repeated Low-Level Red-Light Therapy: Post Hoc Analysis of a Randomized Trial.

INTRODUCTION: Axial length (AL) elongation in myopia is considered irreversible. We aimed to systemically report unexpected AL shortening observed in a randomized clinical trial (RCT) after repeated low-level red-light (RLRL) therapy. METHODS: This is a post hoc analysis of a multicenter, single-masked RCT. Two hundred sixty-four myopic children aged 8-13 years allocated to RLRL treatment (intervention group) or a single vision spectacle (SVS, control group) were included. AL was measured using an IOL-master 500 at baseline, 1-, 3-, 6-, and 12-month follow-up visits. AL shortening was defined as AL reduction from baseline to follow-up visits at three cutoffs: > 0.05 mm, > 0.10 mm, and > 0.20 mm. Frequency of AL shortening at different cutoffs was calculated. Analysis was done with intent to treat (ITT). RESULTS: At 12-months follow up, frequency of AL shortening > 0.05 mm was 26/119 (21.85%) and 2/145 (1.38%) for the RLRL group versus the control group, respectively. The frequency was 18/119 (15.13%) versus 0/145 (0%) for AL shortening > 0.10 mm, and 7/119 (5.88%) versus 0/145 (0%), for AL shortening > 0.20 mm, respectively (p < 0.001). Mean AL shortening after 12 months (SD) was -0.156 (0.086) mm in the RLRL group and -0.06 mm in the control group. Age was significantly associated with AL shortening in the multivariable analysis. For the RLRL group that exhibited AL shortening (n = 56), choroidal thickness (ChT) thickening (0.056 mm) could only explain 28.3% of AL shortening (-0.20 mm). CONCLUSION: Nearly a quarter of children had > 0.05 mm AL shortening following 12 months of RLRL therapy, whereas AL shortening rarely occurred among controls. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04073238).

Clinically Significant Axial Shortening in Myopic Children After Repeated Low-Level Red Light Therapy: A Retrospective Multicenter Analysis.

INTRODUCTION: Myopia is recognized as a progressive eye disease. The aim of this study was to evaluate the frequency and associated factors of clinically significant axial length (AL) shortening among myopic children following repeated low-level red light (RLRL) therapy. METHODS: The clinical data that were collected for the myopic children aged 3-17 years who received an RLRL therapy delivered by home-use desktop light device that emitted light at 650 nm for at least 1 year, were reviewed. The clinical data included AL, spherical equivalent refraction (SER), and visual acuity measured at baseline and follow-up. The primary outcomes were frequency of AL shortening of > 0.05 mm, > 0.10 mm, and > 0.20 mm per year, and associated factors of AL shortening per year. RESULTS: A total of 434 myopic children with at least 12 months of follow-up data were included. The mean age of participants was 9.7 (2.6) years with SER of -3.74 (2.60) diopters. There were 115 (26.50%), 76 (17.51%), and 20 (4.61%) children with AL shortening based on cutoffs of 0.05 mm/year, 0.10 mm/year, and 0.20 mm/year, respectively. In the multivariable model, AL shortening was significantly associated with older baseline age, female gender, and longer baseline AL or greater spherical equivalent refraction (all P < 0.05). Among AL shortened eyes, the mean AL difference (standard deviation, SD) was -0.142 (0.094) mm/year. Greater AL shortening was observed among children who were younger and had longer baseline AL (all P < 0.05). CONCLUSIONS: More than a quarter of children had AL shortening > 0.05 mm following RLRL therapy, and the overall mean AL change was -0.142 mm/year. Further studies should explore the mechanisms underlying AL shortening.

Longitudinal Changes and Predictive Value of Choroidal Thickness for Myopia Control after Repeated Low-Level Red-Light Therapy.

PURPOSE: To evaluate longitudinal changes in macular choroidal thickness (mCT) in myopic children treated for 1 year with repeated low-level red-light (RLRL) therapy and their predictive value for treatment efficacy on myopia control. DESIGN: A secondary analysis of data from a multicenter, randomized controlled trial (RCT; NCT04073238). PARTICIPANTS: Myopic children aged 8-13 years who participated in the RCT at 2 of 5 sites where mCT measurements were available. METHODS: Repeated low-level red-light therapy was delivered using a home-use desktop light device that emitted red-light at 650 nm. Choroidal thickness was measured by SS-OCT at baseline and 1-, 3-, 6-, and 12-month follow-ups. Visual acuity, axial length (AL), cycloplegic spherical equivalent refraction (SER), and treatment compliance were measured. MAIN OUTCOME MEASURES: Changes in mCT at 1, 3, 6, and 12 months relative to baseline, and their associations with myopia control. RESULTS: A total of 120 children were included in the analysis (RLRL group: n = 60; single-vision spectacle [SVS] group: n = 60). Baseline characteristics were well balanced between the 2 groups. In the RLRL group, changes in mCT from baseline remained positive over 1 year, with a maximal increase of 14.755 µm at 1 month and gradually decreasing from 5.286 µm at 3 months to 1.543 µm at 6 months, finally reaching 9.089 µm at 12 months. In the SVS group, mCT thinning was observed, with changes from baseline of -1.111, -8.212, -10.190, and -10.407 µm at 1, 3, 6, and 12 months, respectively. Satisfactory myopia control was defined as annual progression rates of less than 0, 0.05, or 0.10 mm for AL and less than 0, 0.25, or 0.50 diopters for SER. Models that included mCT changes at 3 months alone had acceptable predictive discrimination of satisfactory myopia control over 12 months, with areas under the curve of 0.710-0.786. The predictive performance of the models did not significantly improve after adding age, gender, and baseline AL or SER. CONCLUSIONS: This analysis from a multicenter RCT found RLRL induced sustained choroidal thickening over the full course of treatment. Macular choroidal thickness changes at 3 months alone can predict 12-month myopia control efficacy with reasonable accuracy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

First Report of Green Mold Disease Caused by Penicillium ochrochloron on Medicinal Plant Pseudostellaria heterophylla in China.

Pseudostellaria heterophylla is one of the Chinese herbal medicines with high medicinal and economic values. From 2019 to 2021, postharvest green mold disease was observed with an incidence of 2~5% on the tuberous roots of the harvested P. heterophylla at eight locations in Zherong county, Fujian Province, China. The symptoms were as follows: white mycelial growth on the tuberous roots surface initially, then green mold layers forming, and the tuberous roots decaying finally. To identify the causal agent, a total of 20 symptomatic tuberous roots were collected. Small pieces (5 mm×5 mm) were treated by surface disinfestion with 75% ethanol and 1% NaOCl, then rinsed 3 times with sterile distilled water. These treated pieces were transferred onto potato dextrose agar (PDA) and incubated at 25°C in the dark for 7 days. Twenty pure cultures were obtained by single-spore isolation method. Colonies on PDA medium initially appeared as white mycelium that developed grayish-green conidia with white margins. Mycelium was septate and colorless. Conidiophores were predominantly monoverticillate, occasionally biverticillate. Stipes was long and slender. Phialides were ampulliform to almost cylindrical with collula, 11.25 (7.80-23.50) µm long (n=50). Conidia were smooth walled and pale green, with globose to ellipsoidal shape, 2.75 (2.37-3.27)× 2.47 (2.18-3.13) µm (n=50). Based on these morphological characteristics, the isolates matched the description of the genus Penicillium. Genomic DNAs from two representative isolates (FJAT-32578 and FJAT-32579) were extracted with a fungal genomic DNA extraction kit. The rDNA ITS region and partial ß-tubulin gene (BenA) were amplified using the primers ITS1/ITS4 (White et al. 1990) and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. The sequences of isolate FJAT-32578 and FJAT-32579 were deposited in GenBank (ITS, OM920986 and OM920987; BenA, OM953825 and OM953826). All sequences showed above 99% similarity to P. ochrochloron type strain CBS357.48 (ITS, NR111509; BenA, GU981672). In multilocus phylogenetic analysis (ITS + BenA), the two isolates from this study clustered together with other strains of P. ochrochloron with 100% bootstrap support. The two isolates were thus identified as P. ochrochloron based on both morphological and molecular characteristics. Pathogenicity tests were conducted in triplicate by inoculating the aseptic wounds with 10 µl of conidial suspension (1×106 conidia/ml) of the two isolates in the each healthy tuberous root (cv. Zheshen No.1). The experiment was conducted twice. All the inoculated tuberous roots were placed in sterilized Petri dishes with moistened filter paper, and incubated at 25 ± 2 °C. Fifteen days after inoculation, all inoculated tuberous roots demonstrated the same symptoms as those observed in the field conditions. The re-isolated fungi from the artificially infected tuberous roots were confirmed as P. ochrochloron using the method described above, while the control tuberous roots treated with sterile water did not develop symptoms, fulfilling Koch's postulates. To our knowledge, this is the first report of P. ochrochloron causing green mold disease on P. heterophylla in China, which would be a potentially new threat to the medicinal plant.

Fast and Non-Destructive Profiling of Commercial Coffee Aroma under Three Conditions (Beans, Powder, and Brews) Using GC-IMS.

The flavor of coffee can be affected by the preparation parameters. In this investigation, the flavor profiles of three coffee brands under three conditions (bean, powder, and brew) were analyzed by gas chromatography-ion mobility spectrometry (GC-IMS) and the electronic nose (E-nose). The flavor results were further studied using multiple factor analysis (MFA). A total of 117 peaks were identified in all coffee samples by GC-IMS, and the principal component analysis (PCA) showed these coffee samples could be grouped and separated. A total of 37 volatile organic compounds (VOCs) were selected as biomarkers to distinguish coffee samples, including 5 aldehydes, 10 ketones, 8 alcohols, 2 acids, 4 esters, 5 furans, and 3 other compounds. The comparison between E-nose and GC-IMS data using partial least squares regression (PLSR) and MFA showed GC-IMS could present very close sample spaces. Compared with E-nose, GC-IMS could not only be used to classify coffee samples in a very short time but also provide VOC bio-markers to discriminate coffee samples.

Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study.

BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.

Targeting Multiple End Organs in Lupus and Other Systemic Rheumatic Diseases by Inhibiting Bruton's Tyrosine Kinase.

Bruton tyrosine kinase (Btk) plays a vital role in activating and differentiating B-cells and regulating signaling in myeloid cells. Indeed, the potential use of Btk inhibitors in preventing lupus has been reported. Here, we extend these observations to 4 additional models of end-organ inflammation: (a) BWF1 lupus nephritis mice, (b) anti-GBM nephritis, (c) bleomycin-induced systemic sclerosis like skin disease, and (d) bleomycin-induced lung disease. In agreement with the previous studies, BTK inhibitor (BTKB66) treatment was effective in treating lupus nephritis in terms of reducing renal damage both functionally and histologically, accompanied by significant decrease in proteinuria. Both low-dose and high-dose BTKB66 profoundly blocked renal disease in the anti-GBM nephritis model, with efficacy that was comparable to that seen with dexamethasone. This study provides the first evidence that BTK inhibition has both therapeutic and preventative effects in bleomycin-induced SSc-like disease, in terms of reducing skin thickness, fibrosis, collagen deposition, and inflammation. Likewise, significantly lower lung inflammatory cell infiltration was observed after treatment with BTKB66. Therapeutic benefit was associated with lower numbers of macrophages, proliferating macrophages and activated T-cells in the respective injured organs. The observation that these immune cells play key roles in driving end organ inflammation in multiple systemic rheumatic diseases have broad implications for the use of BTKB66 in managing patients with systemic rheumatic diseases where multiple end organs are afflicted, including lupus and systemic sclerosis.

Emodin targeting the colonic metabolism via PPARγ alleviates UC by inhibiting facultative anaerobe.

BACKGROUND: Emodin is an active ingredient of traditional Chinese medicine Rheum palmatum L. and Polygonum cuspidatum, which possesses anti-inflammatory and intestinal mucosal protection effects. Our previous study found that emodin significantly alleviated ulcerative colitis induced by sodium dextran sulfate (DSS). In this study, we found the underlying mechanism of emodin on ulcerative colitis (UC). PURPOSE: We aimed to further explore the mechanism of emodin in the treatment of ulcerative colitis from the perspective of metabolism and intestinal flora. METHODS: Ulcerative colitis was induced by 3% sodium dextran sulfate (DSS) on mice, and the mice were respectively treated with mesalazine, rosiglitazone, emodin, and emodin combined with GW9662 (PPARγ inhibitor) simultaneously. Weight changes, the disease activity index (DAI), colonic length, and pathologic changes in colon were used to evaluate the efficacy of emodin. LC-MS/MS was performed for metabolomics analysis of colon. In addition, intestinal flora was assessed using 16S rDNA sequencing. A vector-based short hairpin RNA (shRNA) method was used to silence PPARγ gene expression in Caco-2 cells. RESULTS: Emodin binds to the active site of PPARγ protein and forms hydrogen bond interaction with ARG288 and CYS285 amino acids. Furthermore, Emodin significantly promotes the protein expression of PPARγ, while inhibiting iNOS and NF-kB p65 in UC mice, however, this effect is hardly shown when it is combined with GW9662 (the inhibitor of PPARγ). Meanwhile, emodin suppresses the expression of iNOS in Caco-2 cells induced with IFNγ and IL-22, but has no effect on its expression in shPPARγ-Caco-2 cells. In addition, through activating PPARγ signal pathway, emodin is capable of regulating colonic metabolism including oxidative phosphorylation and citrulline metabolism and effecting luminal availability of oxygen and nitrate. This promotes the recovery of anoxic environment of colon epithelial cells, which strains the growth and expansion of Enterobacteriaceae. CONCLUSION: The mechanism of Emodin in the treatment of ulcerative colitis relies on its regulation of PPARγ signal pathway, which could modulate colonic metabolism and restore intestinal homeostasis.

Adenosine and L-proline can possibly hinder Chinese Sacbrood virus infection in honey bees via immune modulation.

Sacbrood virus (SBV) infects larvae of honey bees, resulting in infected larvae becoming fluid-filled sacs. Our previous studies showed that the extract of herbal medicine, Radix Isatidis, could inhibit Chinese SBV (CSBV) infection in Asian honey bees (Apis cerana). Here, two compounds, adenosine and L-proline, which were previously reported to be associated with immune modulation, were identified in R. Isatidis extract and then selected for an evaluation of their antiviral effect on CSBV infection in A. cerana. Our results revealed that both adenosine and L-proline could significantly mitigate the impact of CSBV on the growth and development of infected larvae and modulate hosts' immune responses by downregulating the expression of immune genes in infected larvae. The results gained from this study suggest that adenosine and L-proline could possibly interfere CSBV infection via immune modulation to avoid exacerbations and nonspecific damage to infected larvae's own tissues.

Effect of Huangqin decoction on regulating intestinal flora in colitis mice characterized as inhibition of the NOD2-dependent pathway.

CONTEXT: Chinese herb Huangqin decoction (HQD) can regulate intestinal flora in ulcerative colitis (UC) mice. OBJECTIVE: Our study clarifies the mechanism of HQD in regulating the intestinal flora of UC mice. MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided into six groups: Control, Model (3% DSS), Sulfasalazine (500 mg/kg), HQD-L (250 mg/kg), HQD-M (500 mg/kg), and HQD-H (1000 mg/kg) groups. Measurement of body weight, colon length, DAI, and haematoxylin-eosin staining were conducted. FISH and 16S rDNA detected colonic bacterial infiltration and intestinal flora changes. The expression of RegIIIγ and PRRs (NOD2, TLR5, TLR4) were detected by FCM and WB, respectively. In addition, WB, qPCR, or IHC were used to detect the expression of NOD2, MyD88, RIP2, and NF-κB p65 in the colon. ELISA was used to determine cytokines. RESULTS: Compared with the model group (DAI score, 2.38 ± 0.05; histological score, 4.08 ± 0.54), HQD treatment significantly reduced the DAI score (L, 2.16 ± 0.09; M, 1.45 ± 0.05; H, 1.18 ± 0.05) and histological score (L, 3.16 ± 0.82; M, 2.50 ± 0.81; H, 1.51 ± 0.76); restored the weight, the colonic length (p < 0.05). 16S rDNA identification showed HQD regulated the balance of intestinal flora. Moreover, HQD suppressed the expression of RegIIIγ (p < 0.05) and prevented colonic bacterial infiltration. Furthermore, WB results showed NOD2, and TLR4 were inhibited by HQD, especially NOD2 (p < 0.01). The data of WB, qPCR, and IHC demonstrated that the NOD2-dependent pathway was inhibited by HQD (p < 0.01). DISCUSSION AND CONCLUSIONS: HQD (1000 mg/kg) regulates the intestinal flora of colitis mice, mainly characterized as inhibition of the NOD2-dependent pathway. These results indicate that HQD has potential.

Maternal gestational diabetes in singleton pregnancies conceived by ART may be modified by periconceptional B vitamins.

Background: The risk of maternal gestational diabetes mellitus (GDM) may be influenced by pregnancies conceived through assisted reproductive technology (ART). However, the influence of the dosage of B vitamins (folate, vitamin B6 and vitamin B12) on GDM weren't considered. Thus, we hypothesized that periconceptional B vitamins could modify maternal GDM in singleton pregnancies conceived by ART. Methods: This study is a prospective cohort study using data from 3,252 women with singleton pregnancies and received a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. We included an interaction term in the multivariable logistic and linear regression models, respectively, to test our hypothesis. Results: Women who underwent ART were significantly associated with the incidence of GDM compared with spontaneous pregnancy women. The adjusted odds ratio (aOR) was 1.59, and the 95% confidence interval (CI) was 1.08-2.34. ART pregnancies also elevated OGTT (oral glucose tolerance test) 1-h blood glucose levels and OGTT 2-h blood glucose levels (P < 0.05). A positive association between dietary vitamin B6 (aOR = 1.60, 95% CI: 1.13-2.27), dietary vitamin B12 (aOR = 1.88, 95% CI: 1.34-2.64) and dietary folate (aOR = 1.66, 95% CI: 1.19-2.32) with GDM risk comparing the highest to the lowest quartile (all P trend < 0.001). The aORs of GDM for inadequate (< 400 µg/day), adequate (400-800 µg/day), and excessive (> 800 µg/day) supplemental folate intake were 1.00, 0.93, and 1.30, respectively (P trend = 0.033). Since only the supplemental folate illustrates a statistically significant interaction with ART (P for interaction < 0.05), the association between ART and GDM and OGTT blood glucose levels stratifying by supplemental folate were further evaluated. These increased risks of GDM (aOR = 1.62, 95% CI: 1.39-3.39) and the regression coefficients (ß) of 1-h blood glucose (ß = 0.76, 95% CI: 0.39-1.13) and 2-h blood glucose (ß = 0.60, 95% CI: 0.29-0.92) in the multiple linear regression model were significant only in the ART group with excessive supplemental folate (> 800 µg/day). Conclusion: The risk of GDM is significantly elevated, particularly among those women who conceived ART with the intake of excessive supplemental folate (> 800 µg/day).

Synergistic effect of combined treatment with baicalin and emodin on DSS-induced colitis in mouse.

The treatment of combination drugs in complex diseases has been spotlighted. Ulcerative colitis (UC) is a chronic inflammatory disease that has made progress in combination therapy. Baicalin, a flavone from Scutellaria baicalensis Georgi. (Lamiaceae), and emodin, an anthraquinone derivative from Rhei Radix et Rhizoma. (Polygonaceae), both have been reported to possess antiinflammatory activities. Our study investigated whether combined treatment with baicalin and emodin had a synergistic effect in inhibiting colitis inflammation. The results showed that baicalin combined with emodin at a lower dose had the same effect as the two drugs alone significantly alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis mice, involving the prevention of the loss of body weight and colon shortening, the decrease in the disease activity index (DAI), and intestinal damages. The combined treatment decreased the expression of CD14/TLR4/NF-κB pathway proteins and increased the expression of PPAR-γ protein in the colon of colitis mice. Further study in vitro has shown that baicalin decreased the expression of CD14, whereas emodin increased the expression of PPAR-γ, both of which inhibited the activity of NF-κB and exerted antiinflammatory effects. Furthermore, compared to the treatment using the two drugs individually, baicalin combined with emodin had more significant effects on the expression of CD14 and PPAR-γ. Therefore, emodin combined with baicalin had a synergistic effect on DSS-induced colitis.

Antiviral Activities of a Medicinal Plant Extract Against Sacbrood Virus in Honeybees.

BACKGROUND: Sacbrood is an infectious disease of the honey bee caused by Scbrood virus (SBV) which belongs to the family Iflaviridae and is especially lethal for Asian honeybee Apis cerana. Chinese Sacbrood virus (CSBV) is a geographic strain of SBV. Currently, there is a lack of an effective antiviral agent for controlling CSBV infection in honey bees. METHODS: Here, we explored the antiviral effect of a Chinese medicinal herb Radix isatidis on CSBV infection in A. cerana by inoculating the 3rd instar larvae with purified CSBV and treating the infected bee larvae with R. isatidis extract at the same time. The growth, development, and survival of larvae between the control and treatment groups were compared. The CSBV copy number at the 4th instar, 5th instar, and 6th instar larvae was measured by the absolute quantification PCR method. RESULTS: Bioassays revealed that R. isatidis extract significantly inhibited the replication of CSBV, mitigated the impacts of CSBV on larval growth and development, reduced the mortality of CSBV-infected A. cerana larvae, and modulated the expression of immune transcripts in infected bees. CONCLUSION: Although the mechanism underlying the inhibition of CSBV replication by the medicine plant will require further investigation, this study demonstrated the antiviral activity of R. isatidis extract and provides a potential strategy for controlling SBV infection in honey bees.

Association of serum 25-Hydroxyvitamin D with Vitamin D intervention and outdoor activity among children in North China: an observational study.

BACKGROUND: Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the association of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. METHODS: In this observational study, a total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention (either prescribed by physicians or given by parents) and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem-mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons. RESULTS: The overall rate of hypovitaminosis D was 65.60%. Of the children's outdoor activity, 35.63, 31.95, and 32.42% were below 30 min/d, 30-60 min/d and over 60 min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48, 32.87, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30-60 min/d], independent of vitamin D intervention. CONCLUSIONS: High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children's vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.

Can supplementary pollen feeding reduce varroa mite and virus levels and improve honey bee colony survival?

Varroa destructor is an ectoparasitic mite of immature and adult honey bees that can transmit several single-stranded RNA viruses to its host. Varroa reproduce in brood cells, and mite populations increase as colonies produce brood in spring and summer. Mite numbers also can sharply rise, particularly in the fall, by the migration of varroa into hives on foragers. Colonies with high levels of varroa and viruses often die over the winter. Feeding colonies pollen might keep virus levels low and improve survival because of the positive effects of pollen on immunity and colony growth. We compared varroa and virus levels and overwinter survival in colonies with (fed) and without (unfed) supplemental pollen. We also measured the frequency of capturing foragers with mites (FWM) at colony entrances to determine its relationship to varroa and virus levels. Colonies fed supplemental pollen were larger than unfed colonies and survived longer. Varroa populations and levels of Deformed wing virus (DWV) rose throughout the season, and were similar between fed and unfed colonies. The growth of varroa populations was correlated with FWM in fed and unfed colonies, and significantly affected DWV levels. Increasing frequencies of FWM and the effects on varroa populations might reduce the positive influence of supplemental pollen on immune function. However, pollen feeding can stimulate colony growth and this can improve colony survival.

Baicalein Restores the Balance of Th17/Treg Cells via Aryl Hydrocarbon Receptor to Attenuate Colitis.

As one of the ligands of aryl hydrocarbon receptor (AhR), baicalein, isolated from Scutellaria baicalensis Georgi, has been proved to exert potential therapeutic effects on ulcerative colitis (UC), but its therapeutic mechanism remains obscure. Authentically, ulcerative colitis can be alleviated by regulating the differentiation of naïve CD4+ T cells via AhR activation. So, our study planned to prove the hypothesis that baicalein protected mice against UC by regulating the balance of Th17/Treg cells via AhR activation. Immunofluorescence and western blot results showed that baicalein could promote AhR activation and induce it to transfer to the nucleus. We further determined the effect of baicalein on naïve CD4+ T cell differentiation in vitro by magnetic cell separation and drug intervention. The results showed that baicalein could promote Treg cell differentiation by activating AhR. In vivo study, UC mice were established by free drinking of dextran sulfate sodium (DSS) for 7 days and then were orally administrated by baicalein (10, 20, and 40 mg/kg), TCDD (AhR agonist), and CH223191 (antagonist). The results demonstrated that baicalein improved the symptoms of UC mice, regulated the balance of Th17/Treg cells, and restored the balance of proinflammatory cytokines such as IL-17, IL-6, and TNF-α; anti-inflammatory cytokines such as IL-10 and TGF-ß; and epithelial protective cytokine IL-22 in UC mice, and these effects were related to AhR. Taken together, our research found that baicalein might be a potential drug for UC via regulating Treg cell differentiation and maintaining immune homeostasis and attempted to shed a light on the pivotal role of AhR in these effects.

Natural Product Medicines for Honey Bees: Perspective and Protocols.

The western honey bee remains the most important pollinator for agricultural crops. Disease and stressors threaten honey bee populations and productivity during winter- and summertime, creating costs for beekeepers and negative impacts on agriculture. To combat diseases and improve overall bee health, researchers are constantly developing honey bee medicines using the tools of microbiology, molecular biology and chemistry. Below, we present a manifesto alongside standardized protocols that outline the development and a systematic approach to test natural products as 'bee medicines.' These will be accomplished in both artificial rearing conditions and in colonies situated in the field. Output will be scored by gene expression data of host immunity, bee survivorship, reduction in pathogen titers, and more subjective merits of the compound in question. Natural products, some of which are already encountered by bees in the form of plant resins and nectar compounds, provide promising low-cost candidates for safe prophylaxis or treatment of bee diseases.