The evaluation of synchronous and asynchronous online learning: student experience, learning outcomes, and cognitive load.

BACKGROUND: The abrupt onset of the COVID-19 pandemic compelled universities to swiftly establish online teaching and learning environments that were not only immediately deployable but also conducive to high-quality education. This study aimed to compare the effectiveness of the online synchronous and asynchronous teaching formats in the dermatology lecture for undergraduate medical students, including academic performance, self-efficacy, and cognitive load. METHODS: A total of 170 fourth-year undergraduate medical students attending the dermatology lecture were included. The lecture was delivered using both the synchronous method (live online lecture via Webex meeting) and the asynchronous method (lecture videos shared on YouTube). The students had the freedom to choose their preferred method of attending the online lecture. The study assessed three main aspects: (1) learning outcomes measured through pretest, posttest, and retention test scores; (2) cognitive load experienced by students, including mental load and mental effort measured using eight items; and (3) satisfaction levels with each online teaching format. RESULTS: In this study, 70 students opted for the synchronous online lecture, while 100 students chose the asynchronous online lecture. Both synchronous and asynchronous teaching methods exhibited significant improvements in post and retention test scores compared to the pretest. Satisfaction levels, rated on a scale of 0-5, were generally high for both teaching methods, with no significant differences observed (4.6 for synchronous, 4.53 for asynchronous; p =.350). Regarding cognitive load, the synchronous method showed a significantly lower level than the asynchronous method (p =.0001). Subgroup analysis revealed no difference in mental effort (p =.0662), but the level of mental load was lower in the synchronous method (p =.0005). CONCLUSIONS: Both synchronous and asynchronous online teaching methods demonstrated improvements in learning outcomes and high levels of student satisfaction. However, the cognitive load experienced by students was lower in the synchronous setting compared to the asynchronous setting. These findings remind health professions educators that they would consider the students' cognitive load when designing online curricula.

Influence of confirmed viral infection on adult acute fulminant myocarditis supported with extracorporeal membrane oxygenation.

BACKGROUND: The impact of etiologies of acute fulminant myocarditis (AFM), which requires extracorporeal membrane oxygenation (ECMO), on clinical outcomes remains unknown. This study aimed to investigate the risk factors for ECMO weaning and mortality among patients with AFM due to viral etiologies in a tertiary referral medical center. METHODS: We included 33 adults with AFM who received ECMO and were admitted between January 2002 and January 2021. General demographics, laboratory data, echocardiography findings, and long-term outcomes were analyzed for confirmed viral etiology and unconfirmed etiology groups. RESULTS: The overall hospital survival rate was 54.5%. The age, sex, severity of the hemodynamic condition, and cardiac rhythm were similar between the two groups. Multivariate Cox regression analysis revealed that a confirmed viral etiology (HR 4.201, 95% CI 1.061-16.666), peri-ECMO renal replacement therapy (RRT) (HR 9.804, 1.140-83.333) and a high positive end-expiratory pressure (PEEP) in the ventilator settings at 24 h after ECMO (HR 1.479, 1.020-2.143) were significant prognostic factors for in-hospital mortality. Peri-ECMO RRT was also a significant negative prognostic factor for successful ECMO weaning (OR 0.061, 0.006-0.600) in the multivariate logistic model. CONCLUSIONS: Among AFM patients receiving ECMO support, RRT use was associated with a decreased chance of survival to ECMO weaning. Multiple organ dysfunction and a high PEEP were also predictive of a lower chance of hospital survival. Those with a confirmed diagnosis of viral myocarditis may require more medical attention due to the higher risk of hospital mortality than those without a definite diagnosis.

Ferroptosis promotes anti-tumor immune response by inducing immunogenic exposure in HNSCC.

Accumulated evidence indicates that immune cell populations play pivotal roles in the process of tumor initiation, progression, recurrence, metastasis, and immune escape. Ferroptosis is a form of regulating cell death in the nexus between metabolism, redox biology, and human health. Ferroptosis is considered as a vital important event in HNSCC, but the underling mechanism of regulating immune cell populations remains poorly understood. Our tissue microarray study showed that patients with high expression of GPX4 were related to poor survival. Moreover, the expression of GPX4 has been negatively associated with immunogenic cell death-related protein calreticulin in HNSCC tissue cohort. Further, RSL3 was used to induce ferroptosis in HNSCC xenograft of C3H/He mouse. We found that the occurrence of ferroptosis had significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and tumor-associated M2-like macrophages (M2 TAMs) in tumor microenvironment. Meanwhile, the tumor-infiltrating CD4+ and CD8+ T cells were increased. And the calreticulin and HMGB1 may be potential candidate proteins improving the immunosuppressive tumor microenvironment. Taken together, our project suggests that ferroptosis can promote anti-tumor immune response by reversing immunosuppressive microenvironment, indicating that ferroptosis inducer is a promising therapeutic strategy in HNSCC.

[An experimental study of acute toxicity and pharmacology of fermented Platycodonis Radix].

This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 µL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.

CD24 blockade promotes anti-tumor immunity in oral squamous cell carcinoma.

OBJECTIVES: Our study elucidates the prognostic role of cluster of differentiation (CD) 24 expression in oral squamous cell carcinoma (OSCC) and determines whether targeting CD24 enhances the anti-tumor immune response by inhibiting tumor-associated macrophages (TAMs). MATERIALS AND METHODS: The expression of CD24 and CD68 was analyzed immunohistochemically via tissue microarrays constructed using 56 cohorts of patients with OSCC and 20 control specimens. Further, CD24 was inhibited in an allograft squamous cell carcinoma (SCC) related mouse model with CD24mAb to determine the tumor volume and weight. Changes in immune cells such as TAMs and T cells in the tumor microenvironment (TME) were analyzed by Flow cytometry. The expression of CD4, CD8, and Ki67 was analyzed via immunohistochemistry. The inhibition of CD24 was confirmed by Western blot and immunohistochemistry. RESULTS: CD24 was overexpressed in OSCC. High expression of CD24 indicated poor survival in patients with OSCC (p = 0.0334). CD24 expression was significantly correlated with CD68 (p = 0.0424). The inhibition of CD24 delayed tumor growth in vivo. A decrease in TAMs number and an increase in T cell number were confirmed, while the ability of tumor proliferation was impaired. CONCLUSION: Targeting CD24 could enhance anti-tumor immune response by inhibiting TAMs.

Taiwanese dermatological association consensus for the definition, classification, diagnosis, and management of urticaria: A 2021 update.

Urticaria is a prevalent disease with substantial physical, psychological, and economic impacts. With the advent of understandings of the disease and the emerging evidence of treatments, the international guidelines for treating urticaria have been updated in recent years. In order to update the 2014 edition of the Taiwanese Dermatological Association (TDA) consensus of urticaria, a total of 17 dermatologists with extensive experience in urticaria management were invited to and attended the TDA consensus meetings. All the specific aspects of the content were approved by at least 75% of the experts in attendance. Comparing to the former edition, several substantial modifications were made. For diagnosis, D-dimer was added as the recommended routine test in patients with chronic spontaneous urticaria. For pharmacological management, treatment suggestions were simplified. The approved-dosed, the up-dosed second-generation antihistamines, omalizumab, and cyclosporine were listed as the first-line to the fourth-line treatment, respectively. In addition, the management for patients of special considerations, such as the elderly, children, and pregnant women, were all discussed and mentioned in the consensus. We hope the updated TDA consensus can serve as a reference for all physicians and can help the physicians providing up-to-dated managements for these patients.

Biomechanical comparison between various screw fixation angles for Latarjet procedure: a cadaveric biomechanical study.

BACKGROUND: The Latarjet procedure is a reliable treatment for the management of anterior glenohumeral instability with glenoid bone loss. However, the biomechanical properties of different fixation angles between screw and glenoid surface (α angle) have rarely been studied. The aim of the study was to investigate and compare the fixation stability, failure load, and failure mechanism between different α angles for Latarjet procedures, which were performed on cadaver specimens. METHODS: Twenty-four shoulder specimens (8 in each of 3 groups) were dissected free of all soft tissue, and a 25% glenoid defect was created. The coracoid process was osteomized and fixed with 2 screws at 3 different α angles: 0° (group A), 15° (group B), and 30° (group C). Specimens were mounted to a testing apparatus, and cyclic loading (100 cycles at 1 Hz) was applied with a staircase protocol (50, 100, 150, and 200 N). Gross graft displacement and interface displacement were measured. The ultimate failure loads and failure mechanisms were recorded. RESULTS: There was no significant difference in gross displacement under any cyclic load between 3 groups. However, a significant larger interface displacement was noted in group C than in group A in 150-N cyclic loading (P = .017). Under failure strength testing, all 24 specimens failed because of screw cutout from the glenoid, and the ultimate failure load was similar among the three groups. CONCLUSION: Compared with the 0° α angle, the displacement after cyclic loading did not significantly increase when the α angle was increased to 15° but significantly increased at 30° for Latarjet procedures, which were performed on cadaver specimens. The results suggest that surgeons should apply the screws as parallel as possible to the glenoid surface when performing the Latarjet procedure. Although mild deviation may not reduce fixation stability, α angles greater than 30° should be avoided.

Dipeptidyl Peptidase-4 Inhibitor-Related Bullous Pemphigoid: Clinical, Laboratory, and Histological Features, and Possible Pathogenesis.

Dipeptidyl peptidase-4 inhibitor (DPP4i) is a widely used antidiabetic agent. Emerging cases of DPP4i-associated bullous pemphigoid (DBP), whose pathogenesis remains unclear, have been reported. Thus, a retrospective study was conducted from January 2016 to June 2021 to determine the clinical, laboratory, and histopathological features of DBP and idiopathic bullous pemphigoid (IBP). We set up in vitro experiments using vildagliptin-treated HaCaT keratinocytes to validate what we found by analyzing published RNA sequencing data about the genes related to the dermal-epidermal junction. We also observed IL-6 expression by HaCaT cells treated with vildagliptin. We enrolled 20 patients with DBP and 40 patients with IBP. The total Bullous Pemphigoid Disease Area Index (BPDAI) score was similar in both groups. However, the BPDAI score of erosions and blisters in DBP was significantly higher than that in IBP (24.6 vs. 16.68, p = 0.0189), and the score for urticaria and erythema was lower in DBP (12 vs. 19.05, p = 0.0183). The pathological features showed that the mean infiltrating eosinophil number per high-power field was significantly lower in DBP than in IBP (16.7 vs. 27.08, p = 0.023). The expression of LAMA3, LAMB3, LAMC2, DST, and COL17A1 decreased significantly in vildagliptin-treated human keratinocytes. On the other hand, IL-6, the hallmark cytokine of bullous pemphigoid (BP) severity, was found to be upregulated in HaCaT cells by vildagliptin. These experimental findings imply less of a requirement for eosinophil infiltration to drive the inflammatory cascades in DBP blistering. Both immunologic and non-immunologic pathways could be employed for the development of DBP. Our findings may help explain the higher incidence of non-inflammatory BP that was observed in DBP.

[Therapeutic material basis of Daqinglong Decoction: based on serum pharmacochemistry and network pharmacology].

Based on the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology, the components of Daqinglong Decoction absorbed in serum were analyzed and identified, and the therapeutic material basis of the prescription was revealed via network pharmacology. UPLC conditions are as follows: Waters Acquity UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), mobile phase of 0.1% formic acid aqueous solution(A)-0.1% formic acid in acetonitrile(B), gradient elution. Peakview 2.0 and MetabolitePilot 1.5 were employed for the comparison of Daqinglong Decoction, blank serum, and serum after the administration of the decoction, and the components of Daqinglong Decoction absorbed in serum were analyzed based on MS/MS profiles in related database and literature. The targets of the components absorbed in serum were retrieved from SwissTargetPrediction, DrugBank, and Batman-TCM. With the search terms of common cold, influenza, flu, bronchitis, bronchiolitis, asthma, allergic rhinitis, rhinallergosis, allergic coryza, rheumatic arthritis, and nephritis, the related disease targets were screened out. Then the absorbed component-potential target gene network and absorbed component target-disease target network were constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the core targets. iGEMDOCK was employed for molecular docking of the absorbed components and core targets. In the serum after the administration of the decoction, 28 components were preliminarily identified, with 21 prototypes and 7 metabolites. Among them, 5 core components of ephedrine, demethylephedrine, glycyrrhetinic acid, p-hydroxybenzoic acid, and 2-methoxybenzoic acid were screened out, and 9 core targets, such as JUN, tumor protein 53(TP53), and protein kinase B(AKT1), were identified. Molecular docking showed high binding affinity of core components and core targets. Therefore, Daqinglong Decoction may exert therapeutic effect by regulating mitogen-activated protein kinase(MAPK), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG) signaling pathways and further improving and regulating inflammatory response and other physiological and pathological processes. This study clarifies the components of Daqinglong Decoction absorbed in serum and explores the therapeutic material basis of the prescription, which provides a reference for further elucidating the mechanism of Daqinglong Decoction and its clinical application.

Recyclable Supramolecular Assembly-Induced Emission System for Selective Detection and Efficient Removal of Mercury(II).

An efficient strategy for simultaneously detecting and removing Hg2+ from water is vital to address mercury pollution. Herein a supramolecular assembly G⊂H with photoluminescent properties is facilely constructed through the self-assembly of a functional pillar[5]arene bearing two N,N-dimethyldithiocarbamoyl binding sites (H) and an AIE-active tetraphenylethene derivative (G). Remarkably, the fluorescence of G⊂H can be exclusively quenched by Hg2+ among the 30 cations due to the formation of non-luminous ground state complex and only L-cysteine can restore fluorescence in the common 20 amino acids. Meanwhile, the probe G⊂H has a considerable thermal and pH stability, a good anti-interference property from various cations, and a satisfactory sensitivity. More importantly, G⊂H exhibits a prominent capability of Hg2+ removal with rapid capture rate (within 1 h) and excellent adsorption efficiency (98 %), as well as a highly efficient recyclability without losing any adsorption activity.

The association between economic indicators and the incidence of tetraplegia from traumatic spinal cord injury in Taiwan.

BACKGROUND: Economic performance may affect public health parameters. This study aimed to determine the time trend of incidence of traumatic spinal cord injury (SCI) and its association with income, presented by GDP (gross domestic product) per capita. METHODS: This study was a retrospective observational study in Taiwan. Newly diagnosed SCI patients with moderate to severe disability from 2002 to 2015 were identified from the reimbursement database of the National Health Insurance (NHI) system (1998-2015). CIR16-99 (cumulative incidence rate, aged 16-99 years, per 103 person-years) and CIR16-59 (aged 16-59 years) of SCI from 2002 to 2015 were measured. RESULTS: There were 5048 newly diagnosed SCI patients during the study period. After controlling the factors of sex, urbanization level, literacy, income inequality, and global financial crisis (mixed effects models), the CIR16-99 of SCI, traumatic SCI, motor vehicle (MV)-related SCI, fall-related SCI, tetraplegia, traumatic tetraplegia, MV-related tetraplegia, and fall-related tetraplegia were inversely associated with GDP per capita; the ß coefficients ranged from - 4.85 (95% confidence interval - 7.09 to - 2.6) for total SCI to - 0.8 (- 1.3 to - 0.29) for fall-related tetraplegia. We restricted our comparison to Taipei City and the 4 lowest densely populated counties, which also corroborated with the above results. The income elasticity analysis revealed when GDP per capita increased by 1%, the total SCI decreased by 1.39‰; which was also associated with a decrease of 1.34‰, 1.55‰, 1.36‰, 1.46‰, 1.54‰, 1.54‰, and 1.62‰ for traumatic SCI, MV-related SCI, fall-related SCI, tetraplegia, traumatic tetraplegia, MV-related tetraplegia, and fall-related tetraplegia respectively. The ß coefficients show that the compared areas of urbanization level were also inversely correlated with CIR16-59 in the SCI population. CONCLUSIONS: We conclude that the incidence of tetraplegia of traumatic SCI in Taiwan decreases with good economic performance, which may be resulted from the provision of public goods and services, possibly through improvements in the infrastructure of transportation and construction.

Insertion of Pro-Hyp-Gly provides 2 kcal mol-1 stability but attenuates the specific assembly of ABC heterotrimeric collagen triple helices.

Collagen is a major structural component of the extracellular matrix and connective tissue. The key structural feature of collagen is the collagen triple helix, with a Xaa-Yaa-Gly (glycine) repeating pattern. The most frequently occurring triplet is Pro (proline)-Hyp (hydroxyproline)-Gly. The reversible thermal folding and unfolding of a series of heterotrimeric collagen triple helices with varying number of Pro-Hyp-Gly triplets were monitored by circular dichroism spectroscopy to determine the unfolding thermodynamic parameters Tm (midpoint transition temperature), ΔHTm (unfolding enthalpy), and ΔGunfold (unfolding free energy). The Tm and ΔGunfold of the heterotrimeric collagen triple helices increased with increasing number of Pro-Hyp-Gly triplets. The ΔGunfold increased by 2.0 ± 0.2 kcal mol-1 upon inserting one Pro-Hyp-Gly triplet into all three chains. The Tm difference between the most stable ABC combination and the second most stable BCC combination decreased with increasing number of Pro-Hyp-Gly triplets, even though the ΔGunfold difference remained the same. These results should be useful for tuning the stability of collagen triple helical peptides for hydrogel formation, recognition of denatured collagen triple helices as diagnostics and therapeutics, and targeted drug delivery.

Longer charged amino acids favor ß-strand formation in hairpin peptides.

Interactions between charged amino acids significantly influence the structure and function of proteins. The encoded charged amino acids Asp, Glu, Arg, and Lys have different number of hydrophobic methylenes linking the backbone to the charged functionality. It remains to be fully understood how does this difference in the number of methylenes affect protein structure stability. Protein secondary structures are the fundamental three-dimensional building blocks of protein structures. ß-Sheet structures are particularly interesting, because these structures have been associated with a number of protein misfolding diseases. Herein, we report the effect of charged amino acid side chain length at two ß-strand positions individually on the stability of a ß-hairpin. The charged amino acids include side chains with a carboxylate, an ammonium, or a guanidinium group. The experimental peptides, fully folded reference peptides, and fully unfolded reference peptides were synthesized by solid phase peptide synthesis and analyzed by 2D NMR methods including TOCSY, DQF-COSY, and ROESY. Sequence specific assignments were performed for all peptides. The chemical shift data were used to derive the fraction folded population and the folding free energy for the experimental peptides. Results showed that the fraction folded population increased with increasing charged amino acid side chain length. These results should be useful for developing functional peptides that adopt the ß-conformation.

Savings of loss-of-life expectancy and lifetime medical costs from prevention of spinal cord injuries: analysis of nationwide data followed for 17 years.

BACKGROUND: The objectives of this research were to determine the savings of loss-of-life expectancy (LE) and lifetime medical costs (LMC) from prevention of spinal cord injuries (SCI) in Taiwan. METHODS: From the claims database of Taiwan National Health Insurance, we identified 6164 adult patients with newly diagnosed SCI with permanent functional disability from 2000 to 2015 and followed them until the end of 2016. We estimated survival function through the Kaplan-Meier method and extrapolated it to lifetime. RESULTS: For the SCI cohort, the LE and loss-of-LE were 17.6 and 13.3 years, respectively, while those for SCI with coding of external causes (E-code) were 18.1 and 13.0 years, respectively. For the SCI cohort with E-code, the loss-of-LE of motor vehicle (MV)-related SCI was significantly higher than that of fall-related SCI. In young and middle-aged patients with SCI with E-code, the loss-of-LE of MV-related paraplegia was significantly higher than that of MV-related quadriplegia and fall-related SCI. With a 3% discount rate, the LMC for patients with SCI after diagnosis were US$82 772, while those for patients with SCI with E-code were US$81 473. The LMC and the cost per year for those living with quadriplegia were significantly higher than those for paraplegia in all age groups, possibly related to the higher frequencies of stroke, chronic lung disease and dementia. CONCLUSIONS: We conclude that quadriplegia has a higher impact on medical costs than paraplegia, and MV-related SCI has a higher impact on loss-of-LE than fall-related SCI. We recommend comprehensive SCI prevention be established, including infrastructures of construction and transportation.

[Comparative study on anti-depressant effect of Zhizichi Decoction and its solid fermentation product on CUMS rats].

Chronic unpredicted mild stress(CUMS) combined with isolated feeding was used to induce depressed rat model. The anti-depressant effects of Zhizichi Decoction(ZZCD) and its solid fermented product(ZZC) were analyzed by behavioral test and comparison of pathological tissues of hippocampus and liver, metabolic characteristics of intestinal flora, and relative abundance of species. The results showed that ZZC could increase sucrose preference, shorten the immobility time in the forced swim test and tail suspension test(P<0.05), and repair damaged hippocampus and liver tissues, and the effect was superior to that of ZZCD. The results of Biolog ECO plates showed that the average well color development(AWCD) of intestinal flora in the model group significantly decreased and the metabolic levels of sugar and amino acids were reduced, while the AWCD of the treatment groups increased. The metabolic levels of the two carbon sources were improved in the ZZC group, while only sugar metabolic level was elevated in the ZZCD group. Metagenomic analysis of intestinal flora showed that the ratio of Firmicutes/Bacteroidetes was 3.87 in the control group, 21.77 in the model group, 5.91 in the ZZC group, and 18.48 in the ZZCD group. Lactobacillus increased by 3.28 times, and Prevotella and Bacteroidetes decreased by 75.59% and 76.39%, respectively in the model group as compared with that in the control group. Lactobacillus decreased by 31.13%, and Prevotella and Bacteroidetes increased by more than three times in the ZZC group as compared with that in the model group, while the corresponding changes in the ZZCD group were not significant. ZZC could improve depression-like beha-viors by regulating the structure of intestinal flora and metabolic functions and repairing damaged hippocampus and liver tissues in depressed rats, showing an anti-depressant effect superior to that of ZZCD. This study is expected to provide a basis for the development of new anti-depressant food products.

[Analysis of chemical constituents of Ginseng-Douchi compound fermentation products based on UPLC-Q-TOF-MS].

In this experiment, ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze and identify chemical constituents of Ginseng-Douchi(GD) compound fermentation, and explore the conversion rules of ginsenosides and soybean isoflavones after compound fermentation. Waters Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was adopted, with 0.1% formic acid aqueous solution(A)-0.1% formic acid acetonitrile solution(B) as mobile phase for gradient elution; electrospray ion source(ESI) was used to collect data in positive and negative ion modes; according to the exact mass number, the secondary spectrum comparison of the database and the existing literature reports, Peakview 2.0/masterview 1.0 software was used to determine the common ion structure formula. Finally, a total of 133 chemical constituents were analyzed and identified from the GD. Ginseng saponins and isoflavone glycosides were significantly converted after fermentation. Among them, peak areas of prototype ginsenosides Rk_3, Rh_1, Rh_2, Rh_3, daidzin, glycitin and genistin decreased significantly; whereas peak areas of se-condary ginsenoside Rb_1, Rb_2, Rk_1, glycitein, genistein and daidzein increased significantly. In this experiment, liquid-mass spectrometry technique was used to investigate the conversion of active ingredients of GD compound fermented products after co-fermentation, so as to provide a scientific basis for elucidating pharmacodynamics material basis and quality control.

[Efficacy of probiotics in preventing late-onset sepsis in very low birth weight infants: a Meta analysis].

OBJECTIVE: To study the efficacy of probiotics in preventing late-onset sepsis (LOS) in very low birth weight (VLBW) infants. METHODS: Databases including PubMed, Web of Science, Cochrane Library, Wanfang Data, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched for randomized controlled trials (RCTs) of probiotics in preventing LOS in VLBW infants. LOS was classified as clinical LOS and confirmed LOS. RevMan 5.4 was used to perform the Meta analysis. RESULTS: A total of 31 RCTs were included, with 3 490 VLBW infants in the probiotics group and 3 376 VLBW infants in the control group. The Meta analysis showed that compared with the control group, the probiotics group had significantly lower risks of clinical LOS (RR=0.79, 95%CI:0.66-0.94, P=0.009) and clinical/confirmed LOS (RR=0.79, 95% CI:0.67-0.94, P=0.007). In the probiotics group, the infants receiving exclusive breastfeeding had a significantly lower risk of confirmed LOS (RR=0.77, 95%CI:0.62-0.96, P=0.02). CONCLUSIONS: Current evidence indicates that probiotics may reduce the risk of clinical LOS and clinical/confirmed LOS in VLBW infants, and the risk of confirmed LOS in VLBW infants who are exclusively breastfed.

Quantifying the impact of temperature variation on birnavirus transmission dynamics in hard clams Meretrix lusoria.

Susceptibility of hard clams Meretrix lusoria to birnavirus (BV) infections caused by temperature variations, from a mechanistic perspective, has rarely been explored. We used a deterministic susceptible-infectious-mortality (SIM) model to derive temperature-dependent key epidemiologic parameters based on data sets of viral infections in hard clams subjected to acute temperature changes. To parameterize seasonal pattern dependence, we estimated monthly based cumulative mortality and basic reproduction numbers (R0 ) between 1997 and 2017 by way of statistical analysis. Two alternative disease control models were also proposed to assess status of controlled temperature-mediated BV infection by using, respectively, control reproduction number (RC )-control line criterion and removal strategy-based control measure. We showed that based on RC -control strategy, when temperatures ranged from 15 to 26.8°C, proportion of susceptible hard clams removed should be at least 0.22%. Based on removal-control strategy, we found that by limiting pond water temperature to 25-30°C, together with increased removal rates and periods to remove hard clams, it is better to remove hard clams from June and August to reduce both mortality rate and spread of BV. Our results can be used to monitor BV transmission potential in hard clams that will contribute to government control strategy to eradicate future BV epidemics.

[Effect of baicalin on expression of fibrogenic factors TGF-ß1, mmp2 and timp2 in tissue of mice with pulmonary fibrosis].

To investigate the effect of baicalin extracted from Qinbai Qingfei Concentrated Pills on the expressions of TGF-ß1, mmp2 and timp2 in mice with pulmonary fibrosis induced by bleomycin. The Biacore technique was used to detect the specific binding between Qinbai Qingfei Concentrated Pills and TGF-ß1, and the affinity components were enriched, regenerated and recovered by Biacore fishing. Then ultra-performance liquid chromatography and quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) were used to determine whether the monomer was baicalin. Biacore was used to verify the affinity kinetics of baicalin, which was validated by pharmacodynamics in vivo. Totally 30 BALB/C mice were randomly divided into three groups: baicalin group, blank group and model group. The blank group was given sodium chloride injection(0.08 mL·kg~(-1)), while the model group and the baicalin group were injected with 4 mg·kg~(-1) bleomycin. The localization of TGF-ß1, mmp2 and timp2 protein in the cells and the mRNA expressions of TGF-ß1, mmp2 and timp2 were detected by RT-PCR 14 days later. The results of Biacore affinity analysis showed that the peak of binding response between Qinbai Qingfei Concentrated Pills and TGF-ß1 protein reached 1 524.0 RU, with specific binding. The affinity constant K_D of baicalin and TGF-ß1 was 1.620 06 µmol·L~(-1), which was determined by SPR kinetic analysis, suggesting a stable binding between baicalin and TGF-ß1, which verified the results of angulation. The results of immunohistochemistry showed that the deposition of cellulose in baicalin group was significantly less than that in model group, the mRNA expressions of TGF-ß1, mmp2 and timp2 were decreased in baicalin solution compared with the model group. Baicalin combined with TGF-ß1 could inhibit the expressions of mmp2 and timp2 and delay the progress of pulmonary fibrosis.

Lymphotoxin-α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3-dependent manner.

Tumor angiogenesis is critical for tumor progression as the new blood vessels supply nutrients and facilitate metastasis. Previous studies indicate tumor associated lymphocytes, including B cells and T cells, contribute to tumor angiogenesis and tumor progression. The present study aims to identify the function of Lymphotoxin-α (LT-α), which is secreted by the activated lymphocytes, in the tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). The coculture system between HNSCC cell line Cal27 and primary lymphocytes revealed that tumor cells promoted the LT-α secretion in the cocultured lymphocytes. In vitro data further demonstrated that LT-α promoted the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) by enhancing the PFKFB3-mediated glycolytic flux. Genetic and pharmacological inhibition of PFKFB3 suppressed the enhanced proliferation and migration of HUVECs. We further identified that LT-α induced PFKFB3 expression was dependent on the TNFR/NF-κB signaling pathway. In addition, we proved that PFKFB3 blockade decreased the density of CD31 positive blood vessels in HNSCC xenografts. Finally, the results from the human HNSCC tissue array revealed that the expression of LT-α in HNSCC samples positively correlated with microvessel density, lymphocytes infiltration and endothelial PFKFB3 expression. In conclusion, infiltrated lymphocyte secreted LT-α enhances the glycolysis of ECs in a PFKFB3-dependent manner through the classical NF-κB pathway and promotes the proliferation and migration of ECs, which may contribute to the aberrant angiogenesis in HNSCCs. Our study suggests that PFKFB3 blockade is a promising therapeutic approach for HNSCCs by targeting tumor angiogenesis.