Chronic pancreatitis-associated metabolic bone diseases: epidemiology, mechanisms, and clinical advances.

Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.

CircPCNXL2 promotes tumor growth and metastasis by interacting with STRAP to regulate ERK signaling in intrahepatic cholangiocarcinoma.

BACKGROUND: circular RNAs (circRNAs) have been reported to exert important effects in the progression of numerous cancers. However, the functions of circRNAs in intrahepatic cholangiocarcinoma (ICC) are still unclear. METHODS: circPCNXL2 (has_circ_0016956) were identified in paired ICC by circRNA microarray. Then, we assessed the biological functions of circPCNXL2 by CCK8, EdU, clone formation, transwell, wound healing assays, and xenograft models. RNA pull-down, mass spectrometry, and RNA immunoprecipitation (RIP) were applied to explore the interaction between cirrcPCNXL2 and serine-threonine kinase receptor-associated protein (STRAP). RNA pull-down, RIP and luciferase reporter assays were used to investigate the sponge functions of circPCNXL2. In the end, we explore the effects of circPCNXL2 and trametinib (a MEK1/2 inhibitor) in vivo. RESULTS: circPCNXL2 was upregulated in ICC tissues and cell lines, which promoted the proliferation and metastasis of ICC in vitro and in vivo. In terms of the mechanisms, circPCNXL2 could directly bind to STRAP and induce the interaction between STRAP and MEK1/2, resulting in the tumor promotion in ICC by activation of ERK/MAPK pathways. Besides, circPCNXL2 could regulate the expression of SRSF1 by sponging miR-766-3p and subsequently facilitated the growth of ICC. Finally, circPCNXL2 could partially inhibit the anti-tumor activity of trametinib in vivo. CONCLUSION: circPCNXL2 played a crucial role in the progression of ICC by interacting with STRAP to activate the ERK signaling pathway, as well as by modulating the miR-766-3p/SRSF1 axis. These findings suggest that circPCNXL2 may be a promising biomarker and therapeutic target for ICC.

Trade-off between Endocrine-Disrupting Compound Removal and Water Permeance of the Polyamide Nanofiltration Membrane: Phenomenon and Molecular Insights.

The polyamide (PA) nanofiltration (NF) membrane has the potential to remove endocrine-disrupting compounds (EDCs) from water and wastewater to prevent risks to both the aquatic ecosystem and human health. However, our understanding of the EDC removal-water permeance trade-off by the PA NF membrane is still limited, although the salt selectivity-water permeance trade-off has been well illustrated. This constrains the precise design of a high-performance membrane for removing EDCs. In this study, we manipulated the PA nanostructures of NF membranes by altering piperazine (PIP) monomer concentrations during the interfacial polymerization (IP) process. The upper bound coefficient for EDC selectivity-water permeance was demonstrated to be more than two magnitudes lower than that for salt selectivity-water permeance. Such variations were derived from the different membrane-solute interactions, in which the water/EDC selectivity was determined by the combined effects of steric exclusion and the hydrophobic interaction, while the electrostatic interaction and steric exclusion played crucial roles in water/salt selectivity. We further highlighted the role of the pore number and residual groups during the transport of EDC molecules across the PA membrane via molecular dynamics (MD) simulations. Fewer pores decreased the transport channels, and the existence of residual groups might cause steric hindrance and dynamic disturbance to EDC transport inside the membrane. This study elucidated the trade-off phenomenon and mechanisms between EDC selectivity and water permeance, providing a theoretical reference for the precise design of PA NF membranes for effective removal of EDCs in water reuse.

Development of a physiologically based pharmacokinetic model for levetiracetam in patients with renal impairment to guide dose adjustment based on steady-state peak/trough concentrations.

Levetiracetam may cause acute renal failure and myoclonic encephalopathy at high plasma levels, particularly in patients with renal impairment. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict levetiracetam pharmacokinetics in Chinese adults with epilepsy and renal impairment and define appropriate levetiracetam dosing regimen.PBPK models for healthy subjects and epilepsy patients with renal impairment were developed, validated, and adapted. Furthermore, we predicted the steady-state trough and peak concentrations of levetiracetam in patients with renal impairment using the final PBPK model, thereby recommending appropriate levetiracetam dosing regimens for different renal function stages. The predicted maximum plasma concentration (Cmax), time to maximum concentration (Tmax), area under the plasma concentration-time curve (AUC) were in agreement (0.8 ≤ fold error ≤ 1.2) with the observed, and the fold error of the trough concentrations in end-stage renal disease (ESRD) was 0.77 - 1.22. The prediction simulations indicated that the recommended doses of 1000, 750, 500, and 500 mg twice daily for epilepsy patients with mild, moderate, severe renal impairment, and ESRD, respectively, were sufficient to achieve the target plasma concentration of levetiracetam.

Novel word learning ability in 24-month-olds: The interactive role of mother's work status and education level.

Using both online and offline measures, this study investigates how maternal education and work status (stay-at-home, part-time, full-time) are jointly associated with infants' word learning ability and vocabulary size. One hundred 24-month-old infants completed a lab-based mutual exclusivity task, which assesses infants' novel word learning ability. Caregivers reported infants' productive vocabulary size using the MCDIs. There was no evidence for an association between infants' productive vocabulary size and maternal education, maternal work status, or their interaction. However, infants' novel word learning ability was significantly related to both maternal factors and their interaction. The positive association between maternal education and word learning performance was attenuated for infants of part-time and full-time working mothers compared to infants with at home mothers. These findings suggest that using real-time measures with high task demand may better capture developmental differences in infants and expand our understanding of maternal factors contributing to early language development.

Acoustic cues to phrase and clause boundaries in infant-directed speech: Evidence from LENA recordings.

Infant-directed speech (IDS) produced in laboratory settings contains acoustic cues, such as pauses, pitch changes, and vowel-lengthening that could facilitate breaking speech into smaller units, such as syntactically well-formed utterances, and the noun- and verb-phrases within them. It is unclear whether these cues are present in speech produced in more natural contexts outside the lab. We captured LENA recordings of caregiver speech to 12-month-old infants in daylong interactions (N = 49) to address this question. We found that the final positions of syntactically well-formed utterances contained greater vowel lengthening and pitch changes, and were followed by longer pauses, relative to non-final positions. However, we found no evidence that these cues were present at utterance-internal phrase boundaries. Results suggest that acoustic cues marking the boundaries of well-formed utterances are salient in everyday speech to infants and highlight the importance of characterizing IDS in a large sample of naturally-produced speech to infants.

Cubic Crystal Structure Formation and Optical Properties within the Ag-BII-MIV-X (BII = Sr, Pb; MIV = Si, Ge, Sn; X = S, Se) Family of Semiconductors.

Quaternary chalcogenide semiconductors are promising materials for energy conversion and nonlinear optical applications, with properties tunable primarily by varying the elemental composition and crystal structure. Here, we first analyze the connections among several cubic crystal structure types, as well as the orthorhombic Ag2PbGeS4-type structure, reported for select members within the Ag-BII-MIV-X (BII = Sr, Pb; MIV = Si, Ge, Sn; X = S, Se) compositional space. Focusing on the Ag-Pb-Si-S and Ag-Sr-Sn-S systems, we show that one structure type, with the formulas Ag2Pb3Si2S8 and Ag2Sr3Sn2S8, is favored. We have prepared powder and single-crystal samples of Ag2Pb3Si2S8 and Ag2Sr3Sn2S8, showing that each takes on the noncentrosymmetric cubic space group I4̅3d and is isostructural to the previously reported compound Ag2Sr3Ge2Se8. Through hybrid density functional theory calculations, these cubic compounds are demonstrated to be (quasi-)direct band gap semiconductors with high densities of states at the band maxima. The band-gap energies are measured by reflectance spectroscopy as 1.95(3) and 2.66(4) eV for Ag2Pb3Si2S8 and Ag2Sr3Sn2S8, respectively. We further measure the optical properties and show the electronic band structures of three other isostructural AI-BII-MIV-X-type materials, i.e., Ag2Sr3Si2S8, Ag2Sr3Ge2S8, and Ag2Sr3Ge2Se8, showing that the band gaps can be predictably tuned by element substitution. Detailed visual analyses of the different structures and of their relationships with other members of the Ag-BII-MIV-X compositional family provide a basis for a broader understanding of the structure formation and optoelectronic properties within the quaternary chalcogenide semiconductor family.

Enhancing Stability of Tannic Acid-FeIII Nanofiltration Membrane for Water Treatment: Intercoordination by Metal-Organic Framework.

Tannic acid (TA)-FeIII nanofiltration (NF) membrane has been demonstrated to possess more favorable removal of trace organic contaminants (TrOCs) over the conventional polyamide NF membrane. However, the drawback of acid instability severely hinders the practical application of TA-FeIII NF membrane in the treatment of (weak) acidic wastewater containing TrOCs (e.g., pharmaceutical wastewater, surface water, and drinking water). Herein, we introduced the MIL-101(Cr) nanoparticle, a kind of metal-organic framework (MOF), into the TA-FeIII selective layer to enhance the membrane acid stability. The acid-tolerance parameter of MIL-101(Cr)-stabilized TA-FeIII membrane (TA-FeIII-MOF membrane, 12,000 ppm/s-1) was two orders of magnitude larger than that of the TA-FeIII membrane (50 ppm/s-1), and the TA-FeIII-MOF membrane can withstand acid treatment at pH = 4 for more than 30 days. Meanwhile, the TA-FeIII-MOF membrane displayed increased water permeance from 9.5 to 12.7 L/(m2·h·bar) after the MOF addition, without compromising the selectivity. The enhanced acid stability for the TA-FeIII-MOF membrane was ascribed to an intercoordination mechanism, where FeIII centers (from TA-FeIII complex) coordinated with -COOH groups (from terephthalic acid of MOF) and CrIII centers (from MOF) coordinated with -OH groups (from TA of TA-FeIII complex), which was verified by the density functional theory calculation. This study highlights a new approach for the development of a TA-FeIII-based NF membrane with markedly enhanced acid stability, which is important for its real application in wastewater treatment and water reuse.

Green Solvent Cleaning Removes Irrecoverable Foulants from End-of-Life Membranes in Membrane Bioreactors: Efficacy and Mechanisms.

Removal of irrecoverable foulants, which cannot be removed by conventional chemical cleaning, from end-of-life (EOL) membranes remains a substantial challenge due to the strong interaction between the foulants and membrane matrix. Herein, we developed a green solvent cleaning strategy based on Hansen solubility parameters to achieve the removal of irrecoverable foulants from the EOL polyvinylidene fluoride (PVDF) membranes serving for 6 years in a large-scale membrane bioreactor (MBR). We selected methyl-5-(dimethylamino)-2-methyl-5-oxopentanoate (MDMO) as the green solvent due to its strong interaction with the PVDF material, which might enable the substitution of binding sites of irrecoverable foulants. After the MDMO cleaning, the water permeance of the EOL membrane recovered from 47.6 ± 4.7 to 390.9 ± 8.2 L m-2 h-1 bar-1 (with a flux recovery ratio of ∼100%), with its rejection ability and stability maintained. The main components of irrecoverable fouling were humic acid-like substances revealed by spectroscopic characterization. Molecular dynamic simulation further elucidated the cleaning mechanisms: the strong interaction of MDMO-PVDF enabled substitution of binding sites of irrecoverable foulants by MDMO, followed by desorption of the irrecoverable foulants from PVDF and diffusion of the irrecoverable foulants into the bulk phase of MDMO. Evaluation in a lab-scale MBR treating real municipal wastewater verified the reusability of green solvent cleaned-EOL membranes. This study provides a novel, effective, and green cleaning strategy to remove irrecoverable foulants and prolong the service life of membranes in MBRs, facilitating sustainable wastewater treatment using membrane-based processes.

Mechanism of mitigating effect of wheat germ peptides on lead-induced oxidative damage in PC12 cells.

It is well known that lead-induced neurotoxicity is closely related to oxidative stress. According to previous reports, wheat germ peptides (WGPs) isolated from wheat germ have been shown to have potent antioxidant capacity. This study hypothesized that WGPs could protect PC12 cells from lead-induced oxidative stress. Here, the protecting-efficacies of WGPs were investigated in PC12 cells that were pretreated with WGPs (200 µM, 4 h) and exposed to lead (10 µM, 24 h). The antioxidant capacity was assessed by cell viability, ROS, MDA, SOD, CAT, GR, GPx, GSH, and GSSG. The experimental results showed that WGP3, WGP8, and WGP9 could reverse the reduction of cell viability caused by lead exposure. Lead exposure causes oxidative stress by increasing the levels of ROS and MDA. Moreover, the decrease in the levels of SOD, CAT, GPx, GR, and GSH/GSSG could be observed. However, WGP3, WGP8, and WGP9 can protect PC12 cells against lead-induced oxidative stress by reversing these phenomena. The protein expression of TXNIP, Keap1, and Nrf2 was characterized by western blotting, and the results illustrated that lead exposure up-regulated the expression of TXNIP and Keap1 and down-regulated the expression of Nrf2, and WGP3, WGP8, and WGP9 could improve the antioxidant capacity of PC12 cells by reversing this phenomenon. Therefore, the present study demonstrated that WGP3, WGP8, and WGP9 may protect against lead-induced oxidative stress in PC12 cells by regulating the TXNIP/Keap1/Nrf2 pathway.

Synthesis of a cerium-based nanomaterial with superior oxidase-like activity for colorimetric determination of glutathione in food samples.

Enzyme-like nanomaterials have received significant attention for their high stability and low cost. However, most nanomaterials require complicated synthesis processes, limiting the range of their potential applications. In this study, a novel cerium-based nanomaterial was fabricated in a facile manner from a mixture of dipicolinic acid (DPA), guanosine 5'-monophosphate (GMP), and cerium acetate under ambient conditions. The obtained nanomaterial, designated as DPA-Ce-GMP, exhibited superior oxidase-like activity owing to the mixed valence (Ce3+/Ce4+) of cerium ions. DPA-Ce-GMP efficiently catalyzed the oxidation of 3,3,5,5-tetramethylbenzidine (TMB), achieving a color reaction without requiring hydrogen peroxide. Thus, DPA-Ce-GMP was incorporated into a simple, rapid, and sensitive colorimetric sensor for glutathione (GSH) detection. Within this sensor, TMB oxidation is inhibited by the reducibility of GSH. The sensor exhibits a linear response over two concentration ranges (0.05-10 and 10-40 µM), and its detection limit is 17.1 nM (3σ/slope). The proposed sensor was successfully applied to GSH quantification in food samples. The developed sensor provides an efficient biomimic oxidase for GSH detection in real samples. Facile approach to prepare cerium-based nanomaterial with superior oxidase-like activity for colorimetric detection of glutathione in food samples.

Iron-Catalyzed Regiodivergent Hydrostannation of Alkynes: Intermediacy of Fe(IV)-H versus Fe(II)-Vinylidene.

We report an iron system, Cp*Fe(1,2-R2PC6H4X), which controls the Markovnikov and anti-Markovnikov hydrostannation of alkynes by tuning the ionic metal-heteroatom bonds (Fe-X) reactivity. The sequential addition of nBu3SnH to the iron-amido catalyst (1, X = HN-, R = Ph) affords a distannyl Fe(IV)-H species responsible for syn-addition of the Sn-H bond across the C≡C bond to produce branched α-vinylstannanes. Activation of the C(sp)-H bond of alkynes by an iron-aryloxide catalyst (2, X = O-, R = Cy) affords an iron(II) vinylidene intermediate, allowing for gem-addition of the Sn-H to the terminal-carbon producing ß-vinylstannanes. These catalytic reactions exhibit excellent regioselectivity and broad functional group compatibility and enable the large-scale synthesis of diverse vinylstannanes. Many new reactions have been established based on such a synthetic Fe-X platform to demonstrate that the initial step of the catalysis is conveniently controlled by the activation of either the tin hydride or the alkyne substrate.

Epidemiological characteristics of four common respiratory viral infections in children.

BACKGROUND: Viruses are the main infectious agents of acute respiratory infections in children. We aim to describe the epidemiological characteristics of viral pathogens of acute respiratory tract infections in outpatient children. METHODS: From April 2018 to March 2019, the results of viral detection using oral pharyngeal swabs from 103,210 children with acute respiratory tract infection in the outpatient department of the Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. Viral antigens, including adenovirus (ADV), influenza A (FLUA), influenza B (FLUB) and respiratory syncytial virus (RSV), were detected by the colloidal gold method. RESULTS: At least one virus was detected in 38,355 cases; the positivity rate was 37.2%. A total of 1910 cases of mixed infection with two or more viruses were detected, and the positivity rate of multiple infection was 1.9%. The ADV positivity rate was highest in the 3-6-year-old group (18.7%), the FLUA positivity rate was highest in the > 6-year-old group (21.6%), the FLUB positivity rate was highest in the > 6-year-old group (6.6%), and the RSV positivity rate was highest in the < 1-year-old group (10.6%). There was a significant difference in the positivity rate of viral infection among different age groups (χ2 = 1280.7, P < 0.001). The rate of positive viral infection was highest in winter (47.1%). The ADV infection rate was highest in spring (18.2%). The rates of FLUA and FLUB positivity were highest in winter (28.8% and 3.6%, respectively). The rate of RSV positivity was highest in autumn (17.4%). The rate of positive viral infection in different seasons was significantly different (χ2 = 6459.1, P < 0.001). CONCLUSIONS: Viral infection rates in children differ for different ages and seasons. The positivity rate of ADV is highest in the preschool period and that of RSV is highest in infants; that of FLU increases with age. The total positive rate of viral infection in different seasons is highest in winter, as is the rate of FLU positivity.

A cerium-based fluorescent nanosensor for highly specific detection of glutathione over cysteine and homocysteine.

Ever-increasing attention has been focused on constructing a sensing system for specific detection of glutathione (GSH) over cysteine (Cys) and homocysteine (Hcy), which usually interfere with the GSH detection due to their similar structures and the presence of thiol groups in these amino acids. Here, a novel fluorescence-sensing system is developed for highly specific GSH detection over Cys and Hcy. The sensing system is constructed through facilely mixing dipicolinic acid (DPA) and guanosine 5'-monophosphate (GMP) with cerium acetate at ambient conditions, denoted as DPA-Ce-GMP. The resultant DPA-Ce-GMP possesses fluorescence emission with excellent thermal stability and anti-light bleaching, which can be quenched by copper ions (Cu2+). The GSH, and not Cys or Hcy, can trap Cu2+ from DPA-Ce-GMP, resulting in the restoration of the fluorescence of the sensing system. The limit of detection reaches as low as 7.1 nM. The GSH detection in a real sample of human serum was further explored and exhibits satisfactory recovery. The developed sensing system has the advantages of ease-of-preparation, excellent selectivity and stability, demonstrating its potential application in disease diagnosis in the future.

Structural, Optical, and Electronic Properties of Two Quaternary Chalcogenide Semiconductors: Ag2SrSiS4 and Ag2SrGeS4.

Quaternary chalcogenide materials have long been a source of semiconductors for optoelectronic applications. Recent studies on I2-II-IV-X4 (I = Ag, Cu, Li; II = Ba, Sr, Eu, Pb; IV = Si, Ge, Sn; X = S, Se) materials have shown particular versatility and promise among these compounds. These semiconductors take advantage of a diverse bonding scheme and chemical differences among cations to target a degree of antisite defect resistance. Within this set of compounds, the materials containing both Ag and Sr have not been experimentally studied and leave a gap in the full understanding of the family. Here, we have synthesized powders and single crystals of two Ag- and Sr-containing compounds, Ag2SrSiS4 and Ag2SrGeS4, each found to form in the tetragonal I4̅2m structure of Ag2BaGeS4. During the synthesis targeting the title compounds, two additional materials, Ag2Sr3Si2S8 and Ag2Sr3Ge2S8, have also been identified. These cubic compounds represent impurity phases during the synthesis of Ag2SrSiS4 and Ag2SrGeS4. We show through hybrid density functional theory calculations that Ag2SrSiS4 and Ag2SrGeS4 have highly dispersive band-edge states and indirect band gaps, experimentally measured as 2.08(1) and 1.73(2) eV, respectively. Second-harmonic generation measurements on Ag2SrSiS4 and Ag2SrGeS4 powders show frequency-doubling capabilities in the near-infrared range.

Ratiometric fluorescence nanoplatform integrated with smartphone as readout device for sensing trace water.

In our investigation, a smartphone-integrated ratiometric fluorescent sensing system with lanthanide-based infinite coordination polymers (Ce-GMP-DPA@Tb-DPA) as signal probe has been successfully constructed for sensitive and portable detection of water in organic solvents. The Ce-GMP-DPA presents blue luminescence which is suppressed once the Tb-DPA is integrated to form the complex of Ce-GMP-DPA@Tb-DPA. Due to the energy transfer from Ce to Tb, the as-formed Ce-GMP-DPA@Tb-DPA exhibits green fluorescence of Tb-DPA. The presence of water can decompose the Tb-DPA, which blocks energy transfer from Ce to Tb, resulting in the decrease of green emission of Tb-DPA and the recovery of blue emission of Ce-GMP-DPA. Therefore, a ratiometric fluorescence assay is established for quantitative water detection within a wide linear range from 0.2 to 90.0% in ethanol. The limit of detection (LOD) reaches as low as 0.16% in ethanol, 0.62% in THF, and 0.0076% in acetonitrile, respectively. Furthermore, a smartphone installed with Color Picker APP as signal reader and analyzer is designed to integrate with the detection assay. With white spirit as real sample, water can be on-site detected with high accuracy (RSD < 2.81%). The developed platform presents great potential for portable water detection in practical application with merits of low cost, easy carry, and simple operation.

Value Iteration Networks with Double Estimator for Planetary Rover Path Planning.

Path planning technology is significant for planetary rovers that perform exploration missions in unfamiliar environments. In this work, we propose a novel global path planning algorithm, based on the value iteration network (VIN), which is embedded within a differentiable planning module, built on the value iteration (VI) algorithm, and has emerged as an effective method to learn to plan. Despite the capability of learning environment dynamics and performing long-range reasoning, the VIN suffers from several limitations, including sensitivity to initialization and poor performance in large-scale domains. We introduce the double value iteration network (dVIN), which decouples action selection and value estimation in the VI module, using the weighted double estimator method to approximate the maximum expected value, instead of maximizing over the estimated action value. We have devised a simple, yet effective, two-stage training strategy for VI-based models to address the problem of high computational cost and poor performance in large-size domains. We evaluate the dVIN on planning problems in grid-world domains and realistic datasets, generated from terrain images of a moon landscape. We show that our dVIN empirically outperforms the baseline methods and generalize better to large-scale environments.

[Application of three-in-one intelligent screening in outpatient department of children's hospital during COVID-19 epidemic].

OBJECTIVE: To evaluate the application of three-in-one intelligent screening in outpatient pre-inspection in children's hospital. METHODS: We randomly enrolled 100 children pre-screened by traditional method in the outpatient department of Children's Hospital of Zhejiang University from February 6th to 16th, 2020, and another 100 children by the intelligent three-in-one mode from February 17th to 27th, 2020. The traditional triage was conducted by nurses based on face-to-face, one-by-one interview of the epidemiological history and consultation department, and the temperature was measured before manual triage. The intelligent three-in-one model combined online rapid pre-inspection and triage, on-site manual confirmation, as well as synchronized online health education system. For on-line registered patients, the system automatically sent the COVID-19 epidemiological pre-screening triage questionnaire one hour before the appointment, requiring parents to complete and submit online before arriving at the hospital. The on-site registered patients were controlled at 100 m away from the hospital entrance. The nurses guided the parents to scan the QR code and fill in the COVID-19 epidemiological pre-examination triage questionnaire. At the entrance of the hospital, the nurse checked the guidance sheet and took the temperature again. The children with red guidance sheet were checked again and confirmed by pre-examination nurses, and accompanied to the isolation clinic through COVID-19 patients-only entrance. The children with yellow guidance sheet were guided to fever clinic. The children with green guidance sheet could go with their parents to the designated area, and then went to the corresponding consultation area. Health education was carried out throughout the treatment, and the system automatically posted the corresponding outpatient instructions and education courses. Parents would read the courses on their mobile phones and counsel online. The time of pre-examination and the coincidence rate of triage were compared between the two groups. RESULTS: The three-in-one intelligent pre-inspection mode took an average of (25.6±8.0) s for each child, which was significantly shorter than the traditional pre-inspection mode (74.8±36.4) s (t=13.182, P<0.01). The triage coincidence rate of the intelligent pre-inspection model was 98%, which was similar to that of traditional model (97%, χ2=0.251, P>0.05). CONCLUSIONS: The three-in-one intelligent pre-inspection model can effectively shorten the patient pre-check time, with similar triage coincidence rate to traditional model.

[Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)].

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold.

Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven't been reported yet. Herein, we designed a series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and molecular hybridization strategies. Among them, compound 7j showed the most potent inhibitory activity against HDAC6 with IC50 of 34 nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 with IC50 of 9 µM in vitro. Meanwhile, the compound also exhibited moderate FGFR1 inhibitory activities. This study provides new tool compounds for further exploration of dual HDAC/FGFR1 inhibition.