Changing patterns of infectious diseases in children during the COVID-19 pandemic.

Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the "off-season," "see-saw," and "upsurge" patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.

A Rare Complication During Transcatheter Closure of Double Atrial Septal Defects With Incomplete Cor Triatriatum Dexter: A Case Report.

The cor triatiatum dexter is an embryologic remnant derived from the right atrium and totally separate from the right atrium. An incomplete cor triatiatum dexter (iCTD) means a partially obstructive remnant at the right atrium. It is usually formed by a remnant of the Eustachian valve (EV), Thebesian valve (ThV), or Chiari network (CN). This anatomic variant is usually asymptomatic but is often associated with other heart abnormalities including atrial septal defects (ASDs), and has the potential to hamper percutaneous heart procedures such as electrophysiological study or ASD closure. Herein, we report a rare complication, transient heart ischemia, in transcatheter closure of double ASDs in a 55-year-old woman with EV. This rare complication was thought to be caused by coronary sinus obstruction during device placement. The ischemic change was resolved spontaneously after we withdrew the device. For a second attempt, we adjusted the position of the device to avoid coronary sinus obstruction under transesophageal echocardiogram guidance and the device was smoothly deployed in a good position with a minimal residual shunt. This case suggests that anatomy details in percutaneous heart procedures are important, and this rare and dangerous complication, heart ischemia, should be identified immediately during the procedure.

Structural characterization and anti-inflammatory activity evaluation of chemical constituents in the extract of Trifolium repens L.

The chemical constituents in Trifolium repens L. were comprehensively studied by UPLC in this work, and a total number of 308 compounds were detected with 169 ones identified. The possible fragmentation pathways were proposed and fragmentation rules were summarized. On the basis of the concluded strategies, the characterized compounds could be classified into organic acids and their derivatives, alkaloids, amino acids, peptides, flavonoids, oligosaccharides, coumarins, and other types of compounds. This approach provided a rapid way for the identification of constituents in T. repens L., and even in other complex analytes. Among the separation and identification of the constituents, three compounds of great amount were isolated and characterized by NMR. The expression of iNOS and COX-2 in LPS-induced RAW 264.7 cells was suppressed by the pretreatment with three isolated constituents. The results implied they may potentially serve as a remedy for the therapy of inflammation. PRACTICAL APPLICATIONS: This work provided a rapid method for the identification of the complex analyte, which could be used in TCM, natural food and so on. The summarized fragmentation rule could be applied for the analysis of several types of compounds, such as organic acids and their derivatives, alkaloids, amino acids and peptides, flavonoids, oligosaccharides, coumarins, and so on. Most of natural plants contain these kinds of compounds, so these rules could have wide applications. Except the phytochemical investigation, T. repens L. displayed anti-inflammation activity according to the reported literature, and the three isolated constituents may potentially serve as a remedy for the therapy of inflammation referring to the result of this research.

[Determination of 53 pesticide residues in tea by gas chromatography-tandem mass spectrometry and double internal standard method].

A gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) method with tandem double columns was established for the determination of 53 pesticide residues in tea. The sample was extracted by acetonitrile with buffering salts of QuEChERS method, cleaned up with an ENVI-Carb/NH2 solid-phase extractant, and determined by GC-MS/MS. To reduce the matrix effect in GC-MS/MS, gulonic acid lactone and sorbitol were added to the standard solutions as protectants; additionally, anthraquione-D8 and triphenyl phosphate were used as double internal standards. The linear ranges were from 20 to 500 µg/L for 52 pesticides, and from 40 to 1000 µg/L for cypermethrin, with correlation coefficients higher than 0.99. The limits of quantification (LOQs) of 28 pesticides were less than 10 µg/kg, and the LOQs of the other 25 pesticides ranged from 10 to 20 µg/kg. The recoveries were in the range 72.5%-130.9%, and the relative standard deviations (RSDs) were in the range 0.4%-19.4%. This method is simple, rapid, sensitive, and reliable for the simultaneous identification and quantification of multiple residues in tea.

Fusion expression of bifunctional enzyme complex for luciferin-recycling to enhance the luminescence imaging.

Firefly luciferase (Fluc) has been widely used as a bioluminescent monitor. The ATP linear correlation and exogenous luciferin requirement make it useful in most of current imaging systems. However, the utility of this reporter was still limited by the intensity and decay of the luminescent signal, and the active site and structure of enzyme including the relevant substrate channeling region. This study demonstrated a novel construction of bifunctional enzyme system to improve the luminescence generation of firefly luciferase, by bringing in a luciferin-regenerating enzyme (LRE) fusion expressed to the C terminal of luciferase, between which were connected with peptide linker. The fusion protein constructed with typical type of linker, rigid linker (EAAAK) and flexible linker (GGGGS), were analyzed comparing with the unlinked free enzyme. In vivo and in vitro assessment of the bioluminescence intensity and decaying rate to the series of Fluc-LRE enzyme complex were assayed. The fInding demonstrated that the presence of LRE remarkably enhance the generation of luminescence and remained significant stronger signal than that of the control, and the peptide-linked dual enzyme present more stability and continuation on the signal generation and lower decaying rate on signal recession, especially at low dose of Fluc injection. With the advantage of luminescence intensity and reaction period, the peptide mediated fusion expressed LRE may expand the application of Firefly luciferase on bioluminescence imaging.

Study on Chemical Profile and Neuroprotective Activity of Myrica rubra Leaf Extract.

The chemical profile of Myrica rubra (a native species in China) leaf extract was investigated by UPLC-PDA-HRMS, and the neuroprotective activity of two characteristic constituents, myricanol and myricetrin, was evaluated with N2a cells using H2O2-inducedoxidative challenge through a series of methods, e.g., MTT assay, ROS assay and [Ca2+]i assay. Among the 188 constituents detected in the extract of Myrica rubra leaf, 116 were identified definitely or tentatively by the comprehensive utilization of precise molecular weight and abundant multistage fragmentation information obtained by quadrupole orbitrap mass spectrometry. In addition, 14 potential new compounds were reported for the first time. This work established an example for the research of microconstituents in a complex analyte and revealed that suppression of H2O2-induced cytotoxicity in N2a cells was achieved by the pretreatment with myricanol. The evidence suggested myricanol may potentially serve as a remedy for prevention and therapy of neurodegenerative diseases induced by oxidative stress.

Enantioselective Copper-Catalyzed Intermolecular Amino- and Azidocyanation of Alkenes in a Radical Process.

Asymmetric copper-catalyzed intermolecular amino- and azidocyanation reactions of alkenes have been developed that proceed via a radical process in which a key benzylic radical intermediate is enantioselectively trapped by a chiral Box/CuII cyanide complex. A variety of enantiomerically enriched ß-amino/azido alkylnitriles were efficiently synthesized. The ß-azido alkylnitriles could be converted into a series of highly valuable optically active amine-based building blocks and bioactive compounds.

Comparison of the anti-inflammatory active constituents and hepatotoxic pyrrolizidine alkaloids in two Senecio plants and their preparations by LC-UV and LC-MS.

Two Senecio plants, Senecio cannabifolius Less. and its variety S. cannabifolius Less. var. integrifolius (Kiodz.) Kidam., were both used as the raw material of Feining granule, a traditional Chinese medicine product for treating respiratory diseases. In this study, the chemical profiles of these two plants were investigated and compared by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). A total number of 83 constituents, including 55 organic acids, 11 flavonoids, 4 alkaloids, 3 terpenes and 10 other types of compounds, were characterized. The results indicated that the levels of most flavonoids were higher in S. cannabifolius than in S. cannabifolius var. integrifolius, however, the levels of hepatotoxic pyrrolizidine alkaloids (PAs) were higher in S. cannabifolius var. integrifolius than in S. cannabifolius. Fifteen constituents were evaluated on lipopolysaccharides (LPS) induced RAW 264.7 cells, and eleven of them showed inhibition effect against nitric oxide (NO) production. Finally, the levels of ten major constituents (including seven anti-inflammatory active ones) and two PAs in Feining granule from two Senecio plants were determined and compared by the LC-UV and LC-MS methods, respectively. It was found that one organic acid (homogentisic acid) and two PAs (seneciphylline and senecionine) had higher contents in the preparation of S. cannabifolius var. integrifolius than in that of S. cannabifolius, however, the situations were inverse for the levels of four organic acids and flavonoids (chlorogenic acid, hyperoside, isoquercitrin, and isochlorogenic acid B). Based on the above results, S. cannabifolius might be a better raw material for Feining granule than S. cannabifolius var. integrifolius, because it contained more anti-inflammatory constituents and less hepatotoxic PAs than the latter. However, more pharmacological evaluations should be carried out to support the selection. The results in this study were helpful for the quality control of Feining granule.

Structural characterization of secoiridoid glycosides by high-performance liquid chromatography/electrospray ionization mass spectrometry.

RATIONALE: The fragmentation behavior of seven secoiridoid glycosides (SIGs) isolated from Gentiana triflora Pall., a traditional Chinese medicine, was investigated by electrospray ionization ion trap mass spectrometry (ESI-IT-MS). METHODS: Multistage electrospray ionization mass spectrometry (ESI-MS(n)) experiments both in positive- and negative-ion mode were used to elucidate the main fragmentation pathways of these compounds. RESULTS: In full scan mass spectra, different deprotonated or protonated molecules were observed for compounds with different basic structure. Ring cleavages of the aglycon moiety were observed in MS(2) spectra and the characteristic ions provided valuable information on the basic structural skeletons. Their fragmentation pathways and fragment ion structures were proposed. CONCLUSIONS: The established fragmentation patterns have been successfully used to identify eleven SIGs in the extract of Gentiana triflora Pall.

Fragment ion diagnostic strategies for the comprehensive identification of chemical profile of Gui-Zhi-Tang by integrating high-resolution MS, multiple-stage MS and UV information.

Gui-Zhi-Tang was considered to be the most famous formula in Shang-Han-Lun, treating 32 symptoms of disease after adding up or cutting down crude drugs. The chemical constituents in Gui-Zhi-Tang were comprehensively studied by rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) combined with rapid resolution liquid chromatography - diode array detector - ion trap mass spectrometry (RRLC-DAD-IT-MS) in this work, and a total number of 187 compounds were detected. Systematic diagnostic ion filtering strategies were recommended for flavonoids and oleanane-type triterpenoids, respectively. On the basis of the summarized strategies, compounds in Glycyrrhizae could be easily classified into flavones, isoflavones, flavanones or chalcones with special structures, and triterpene saponins with different sugar moieties. Consequently, among 187 compounds, 144 ones were confirmed or assumed tentatively. In addition, nine potential novel compounds were reported for the first time. This approach provided a rapid method for characterizing the constituents in Gui-Zhi-Tang, and would be also helpful in other TCM formulae analysis.

Identification of the effective constituents for anti-inflammatory activity of Ju-Zhi-Jiang-Tang, an ancient traditional Chinese medicine formula.

The anti-inflammatory constituents of Ju-Zhi-Jiang-Tang (JZJT), a formula used for thousands of years in China, were identified by LC-MS and pharmacological activity evaluation. In this study, the whole extract of formula was separated into multiple components to facilitate the analytical process. To characterize their contributions to pharmacological activity of formula, activity indexes of constituents were proposed and calculated for the first time, which integrated the chemical and pharmacological information of multiple components. Among the 151 constituents detected in JZJT by LC-Q-TOF-MS and LC-IT-MS, a total number of 108 constituents were identified unambiguously or tentatively, including eighteen potential novel compounds. And, the structures of some constituents were confirmed by NMR. According to their activity indexes, polymethoxy flavones were indicated as the major active constituents responsible for the anti-inflammatory activity of JZJT. To verify the feasibility of activity indexes in predicting the active constituents, nine compounds with positive and negative index values were selected to validate their anti-inflammatory activity in vitro. The results showed that two polymethoxy flavones with higher positive index values, i.e., nobiletin and tangeretin can significantly exert anti-inflammatory effects, while other compounds with negative values did not show any activity. In conclusion, our results indicated the proposed approach might be an efficient and rapid way to identify active constituents of TCM formulae.

Characterization of the chemical constituents in Da-Huang-Gan-Cao-Tang by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and liquid chromatography coupled with ion trap mass spectrometry.

In this work, the chemical constituents in Da-Huang-Gan-Cao-Tang, a traditional Chinese formula, were studied by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and liquid chromatography coupled with ion trap mass spectrometry for the first time. Among the 146 compounds detected in Da-Huang-Gan-Cao-Tang, 104 compounds were identified unambiguously or tentatively based on their accurate molecular weight and multistage MS data, including one potential novel compound and two reported in Glycyrrhiza genus for the first time. The possible fragmentation pathways were proposed and fragmentation rules of the major types of compounds were concluded. This study provided an example to facilitate the tedious identification of chemical composition in traditional Chinese medicine, and maybe a promising reference approach to research the analogous formulae.

A multi-functional electrochemical sensing system using microfluidic technology for the detection of urea and creatinine.

This study presents a new microfluidic system capable of precise measurements of two important biomarkers, urea and creatinine, automatically. In clinical applications, high levels of these two biomarkers are early indicators of nephropathy or renal failure and should be monitored on a regular basis. The microfluidic system is composed of a microfluidic chip, a control circuit system, a compressed air source and several electromagnetic valves to form a handheld system. The microfluidic chip is fabricated by using micro-electromechanical systems and microfluidic techniques comprising electrochemical sensor arrays and polydimethylsiloxane-based microfluidic structures such as micropumps/micromixers, normally closed valves and microchannels. The microfluidic system performs a variety of critical processes including sample pretreatment, mixing, transportation and detection on a single chip. The experimental results show that the entire procedure takes approximately 40 min, which is much faster than the traditional method (more than 6 h). Furthermore, the total sample volume consumed in each operation is only 0.1 mL, which is significantly less than that required in a large system (5 mL). The developed automatic microfluidic system may provide a powerful platform for further clinical applications.

Reversible posterior encephalopathy syndrome as the presentation of late postpartum eclampsia: a case report.

We presented a case of previous healthy postpartum woman suffering from seizure of sudden onset with conscious change and anisocoric pupils. Head magnetic resonance imaging (MRI) revealed multiple high signal-intensity lesions on fluid-attenuated inversion recovery (FLAIR) / T2 weighted image (T2WI) in bilateral subcortical white matters (especially the parieto-occipital areas), brain stem, and bilateral cerebellum, and mild high signal-intensity lesions on diffusion weighted MRI (DWI). These neurological and radiological anomalies recovered completely later. The final diagnosis was the rare presentation of late postpartum eclampsia as reversible posterior encephalopathy syndrome (RPES).

Aurora-A overexpression associates with Ha-ras codon-12 mutation and blackfoot disease endemic area in bladder cancer.

Our data revealed that 59.4% of the bladder cancer specimens showed Aurora-A overexpression, of which 31.8% also had Ha-ras codon-12 mutation; 45.5% were from blackfoot-disease endemic areas in which arsenic exposure is a major environment factor associated with various cancer formation. We further demonstrated that arsenic treatment of the immortalized bladder cell line, E7, increased Aurora-A expression. All together, co-existence of Aurora-A overexpression and Ha-ras mutation suggests a possible additively effect on the tumorigenesis of bladder cancer. In addition, Aurora-A overexpression and up-regulated by arsenic exposure opens a new direction for exploring the occurrence of bladder cancer occurrence in Taiwan.