Incidence of Childhood Type 1 Diabetes in Beijing During 2011-2020 and Predicted Incidence for 2025-2035: A Multicenter, Hospitalization-Based Study.

INTRODUCTION: China has a low incidence of type 1 diabetes mellitus (T1DM); however, based on the large population, the absolute numbers are high. Our aim was to assess the incidence of childhood T1DM in Beijing during 2011-2020, predicted incidence for 2025-2035, and to determine the incidence of diabetic ketosis or diabetic ketoacidosis (DK/DKA) in this population. METHODS: Data on patients aged less than 15 years of age with newly diagnosed T1DM between January 1, 2011 and December 31, 2020 was obtained from five tertiary hospitals in Beijing and retrospectively analyzed. RESULTS: In all, 636 children aged less than 15 years were diagnosed with T1DM during 2011-2020. The incidence of T1DM was 3.11-5.46 per 100,000 per year, with an average increase of 5.10% per year. The age-specific incidence for ages 0-4 years, 5-9 years, and 10-14 years was 2.97, 4.69, and 4.68 per 100,000 per year, respectively. The highest average annual increase (7.07%) in incidence was for the youngest age group. DK or DKA was present at the time of diagnosis of T1DM in 84.6% of patients. The age-specific incidence of T1DM among children aged less than 15 years was predicted to be 7.32, 11.4, and 11.52 per 100,000 in 2035 for ages 0-4 years, 5-9 years, and 10-14 years, respectively. CONCLUSIONS: The was a gentle increase in the incidence of childhood T1DM during 2011-2020 in Beijing. This increase is expected to continue for the next 15 years.

Effect of surgical treatment on prognosis in preterm infants with obstructive hydrocephalus. / æ—©äº§å„¿æ¢—é˜»æ€§è„‘ç§¯æ°´å¤–ç§‘æ²»ç–—ä¸Žé¢„åŽçš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the effect of surgical treatment on prognosis in preterm infants with obstructive hydrocephalus. METHODS: A retrospective analysis was performed on the medical data of 49 preterm infants with obstructive hydrocephalus. According to the treatment regimen, they were divided into two groups: surgical treatment (n=12) and conservative treatment (n=37). The drainage methods, drainage complications, and eventual shunt outcome were analyzed in the surgical treatment group. The two groups were compared in terms of the etiology of hydrocephalus and prognosis. RESULTS: Among the 49 preterm infants with obstructive hydrocephalus, severe intracranial hemorrhage (37 cases; 76%) and central nervous system infection (10 cases, 20%) were the main causes of hydrocephalus. There was no significant difference in the composition of etiology between the two groups (P>0.05). In the surgical treatment group, 4 infants were treated with ventriculosubgaleal shunt and 8 were treated with Ommaya reservoir. One infant had secondary infection and 8 infants eventually underwent ventriculoperitoneal shunt. The surgical treatment group had a significantly higher survival rate than the conservative treatment group (P<0.05). As for the 37 preterm infants with severe intracranial hemorrhage, the surgical treatment group had a significantly higher proportion of infants with normal neurodevelopment than the conservative treatment group (P<0.05). As for the 10 preterm infants with central nervous system infection, neurodevelopmental abnormalities were observed in each of the two groups. CONCLUSIONS: Surgical treatment can improve the survival rate of preterm infants with obstructive hydrocephalus and the prognosis of preterm infants with severe intracranial hemorrhage.

Hollow mesoporous polydopamine nanospheres: synthesis, biocompatibility and drug delivery.

Various polydopamine (PDA) nanospheres were synthesized by utilizing triblock copolymer Pluronic F127 and 1,3,5-trimethylbenzene (TMB) as soft templates. Precise morphology control of polydopamine nanospheres was realized from solid polydopamine nanospheres to hollow polydopamine nanospheres, mesoporous polydopamine nanospheres and hollow mesoporous polydopamine nanospheres (H-MPDANSs) by adjusting the weight ratio of TMB to F127. The inner diameter of the prepared H-MPDANSs can be controlled in the range of 50-100 nm, and the outer diameter is about 180 nm. Furthermore, the thickness of hollow mesoporous spherical shell can be adjusted by changing the amount of dopamine (DA). The H-MPDANSs have good biocompatibility, excellent photothermal properties, high drug loading capacity, and outstanding sustainable drug release properties. In addition, both NIR laser irradiation and acid pH can facilitate the controlled release of doxorubicin (DOX) from H-MPDANSs@DOX.

Correction: Metal-free [3+3] benzannulation of 1-indanylidene-malononitrile with Morita-Baylis-Hillman carbonates: direct access to functionalized fluorene and fluorenone derivatives.

Correction for 'Metal-free [3+3] benzannulation of 1-indanylidene-malononitrile with Morita-Baylis-Hillman carbonates: direct access to functionalized fluorene and fluorenone derivatives' by Ya-Sa Xie et al., Chem. Commun., 2020, 56, 1948-1951, DOI: 10.1039/D0CC00143K.

Metal-free [3+3] benzannulation of 1-indanylidene-malononitrile with Morita-Baylis-Hillman carbonates: direct access to functionalized fluorene and fluorenone derivatives.

An efficient [3+3] benzannulation of Morita-Baylis-Hillman carbonates with 1-indanylidenemalononitrile was achieved under metal-free reaction conditions selectively delivering a wide range of functional multi-substituted fluorene or fluorenone compounds in high yields, respectively (up to 86% yield). Moreover, experiments and quantum chemical calculations were also performed to study the mechanism of the transformation.

Self-assembled polyion complex micelles for sustained release of hydrophilic drug.

Graft copolymer polyethylenimine-graft-poly(N-vinylpyrrolidone) (PEI-g-PVP) was prepared by coupling mono carboxyl-terminated PVP (PVP-COOH) with PEI using N,N'-dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (NHS) as coupling agents. In aqueous medium, PVP-g-PEI can self-assemble into stable polyion complex micelles with an oppositely charged block copolymer, poly(N-vinylpyrrolidone)-block-poly(2-acrylamido-2-methyl-1-propanesulphonic acid) (PVP-b-PAMPS). Transmission electron microscopy images showed that these micelles were regularly spherical in shape. The micelle size determined by size analysis was around 142 nm. To estimate their feasibility as vehicles for drugs, the model drug folic acid (FA) was incorporated into the cores of the micelles via electrostatic interactions. In vitro release test of FA showed that the drug-release rates are dependent on the pH value of the release media. Based on these results, we can conclude that the polyion complex micelles prepared from the PEI-g-PVP/PVP-b-PAMPS copolymers have great potential as drug delivery nanocarriers.

Synthesis and characterization of polyion complex micelles and their controlled release of folic acid.

Stable and narrow distribution polyion complex micelles (PICMs) were prepared in an aqueous milieu through electrostatic interaction between a pair of oppositely charged block copolymers poly(N-vinylpyrrolidone)-block-poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PVP-b-PAMPS) and monomethoxy poly(ethylene glycol)-block-poly(4-vinyl pyridine) (PEG-b-P4VP). The critical aggregate concentration (CAC), hydrodynamic size, and surface morphology of the prepared PICMs were characterized by fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM), respectively. The resulting CAC and the average diameter of the PICMs were about 43 mg/L and 121 nm, indicating high structural stability of micelles and a size favorable for delivery of drug. In addition, the PICMs exhibited good biocompatibility using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293) cells. All of these features are quite feasible for utilizing the PICMs as a novel intelligent drug delivery system. In order to assess its application in the biomedical area, the model drug folic acid (FA) was loaded into the micelles and the in vitro drug release behavior was investigated. We found that by manipulating the pH value and salt concentration of the release solution, it was possible to control the release rate of FA.

Shell-cross-linked amino acid-modified APLA-b-PEG-Cys copolymer micelle as a drug delivery carrier.

Cysteine modified amphiphilic block copolymer acetate-polylactide-block-poly(ethylene glycol)-Cysteine (APLA-b-PEG-Cys) was synthesized and characterized. The polymer could self-assemble to form micelles with nano-size and regularly spherical in shape in aqueous solution. Folic acid (FA) was then used as a model drug to incorporate into APLA-b-PEG-Cys micelles. To enhance the stabilization of APLA-b-PEG-Cys micelle and control the drug release, the shell of APLA-b-PEG-Cys micelle was cross-linked by the in situ polycondensation of amino acid moieties on its surface. The effects of shell-cross-linking on the micelle physical chemistry properties were investigated in detail. It was found that, after cross-linking, the CMC of the APLA-b-PEG-Cys micelle was decreased, indicating that the shell-cross-linked micelle is more stable as compared to the uncross-linked one. In addition, the shell-cross-linking also changed the surface potential, micelle size and model drug (FA) release behaviour, but it did not significantly affect the micelle morphology and drug encapsulation efficiency of APLA-b-PEG-Cys micelles.

Preparation of an amphiphilic triblock copolymer with pH- and thermo-responsiveness and self-assembled micelles applied to drug release.

A novel amphiphilic ABC triblock copolymer, poly(N-isopropylacrylamide)-b-poly(styrene-alternate-maleic anhydride)-b-polystyrene (PNIPAAm-b-PSMA-b-PSt), was designed and synthesized by reversible addition fragmentation chain transfer polymerization. The copolymer can disperse in aqueous media at room temperature to self-assemble into pH- and thermo-responsive core-shell-corona micelles, with the hydrophobic PSt block as core, the pH-sensitive PSMA block as shell, and the thermo-sensitive PNIPAAm block as corona. The aqueous copolymer solutions exhibited lower critical solution temperature (LCST) values around 33.5-35 degrees C under pH 2.1-9.2 conditions via optical transmittance measurements. The critical micelle concentration values of the self-assembled micelles were about 18.6 mg/L at pH 2.1 and 21.1 mg/L at pH 6.9, respectively, relying on fluorescent probe techniques. An interesting pH- and thermo-dependent size of the micelles was observed by dynamic light scattering techniques, which showed that the micelle diameters were about 100-120 nm at 40 degrees C and 120-160 nm at 25 degrees C, corresponding to pH 2.1-9.2, respectively. Transmission electron microscopy observations showed that the resulting micelles as uniform nanoparticles existed in regularly spherical shapes. The folic acid-loaded micelles showed a remarkable pH- and thermo-responsive drug release behavior. These results indicate that the copolymer micelles may serve as a promising "intelligent" drug delivery system.

Preparation, characterization and drug release behavior of polyion complex micelles.

Double-hydrophilic block copolymer composed of poly(N-vinylpyrrolidone) (PVP) and poly(styrene-alter-maleic anhydride) (PSMA) has been synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Poly(N-vinylpyrrolidone)-block-poly(styrene-alter-maleic anhydride) (PVP-b-PSMA) thus formed was characterized by gel permeation chromatography (GPC), (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy and FTIR spectroscopy. In acid solution, this block copolymer spontaneously formed polyion complex (PIC) micelles with a cationic polyelectrolyte, chitosan. The PSMA/chitosan polyelectrolyte complex formed an inner core while PVP chains surrounded it as a shell. Transmission electron micrographs (TEMs) and dynamic light scattering (DLS) showed the PIC micelles to be spherically shaped, with mean hydrodynamic diameter around 146 nm. The model drug coenzyme A (CoA) was loaded into the micelles and the in vitro drug release behavior was investigated. We found that by manipulating the pH value and salt concentration of the release solution, it was possible to control the releasing rate of CoA.

Preparation and characterization of thermo-responsive amphiphilic triblock copolymer and its self-assembled micelle for controlled drug release.

An amphiphilic thermo-responsive ABA triblock copolymer, poly(methyl methacrylate)-b-poly(N-isopropylacrylamide-co-poly(ethylene-glycol) methyl ether methacrlate)-b-poly(methyl methacrylate) (PMMA-b-P(NIPAM-co-PEGMEMA)-b-PMMA), was designed and synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization, and subsequently characterized by FT-IR, (1)H NMR and GPC. The copolymer can disperse in water and self-assemble into nanoscaled micelles in a "flower-like" arrangement at room temperature; the hydrophobic PMMA tucks in the core while the hydrophilic and improved biocompatible P(NIPAM-co-PEGMEMA) forms a thermosensitive outer shell. The resulting micelles were investigated using fluorescence spectroscopy, dynamic light scattering technique (DLS) and transmission electron microscopy (TEM). The copolymer exhibited a lower critical solution temperature (LCST) of around 39 degrees C via optical transmittance measurements. Notably, there was no copolymer precipitation observed at the LCST, which was propitious to in vivo use of the micelle. The micelles loaded with folic acid as a model drug showed a desired thermo-responsive drug release behavior. It was found that the rate and amount (maximum percentage 85%) of the drug release was much higher above the LCST than that (maximum percentage 36%) below the LCST. These results indicate that the thermosensitive triblock copolymer possesses promising potential applications as a "smart" drug carrier in biomedical science.

Preparation and drug controlled-release of polyion complex micelles as drug delivery systems.

Block copolymers, poly(N-vinylprrolidone)-block-poly(styrene-alter-maleic anhydride) (PVP-b-PSMA) and poly(N-vinylprrolidone)-block-poly(N,N-dimethylaminoethyl methacrylate) (PVP-b-PDMAEMA), were synthesized by reversible addition- fragmentation chain transfer (RAFT) polymerization. In aqueous media, this a pair of oppositely-charged diblock copolymers could self-assemble into stable and narrow distribution polyion complex micelles (PICMs). Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that the micelles to be spherically shaped with mean hydrodynamic diameter around 70nm. In addition, the PICMs display ability to response to external stimuli. All of theses features are quite feasible for utilizing it as a novel intelligent drug delivery system. In order to assess its application in biomedical area, release profiles of coenzyme A (Co A) from PICMs were studied under both simulated gastric and intestinal pH conditions. The release was much quicker in pH 7.4 buffer than in pH 2.0 solution. Based on these results, these PICMs could be a potential pH-sensitive carrier for colon-specific drug delivery system.

Preparation and characterization of temperature and pH-sensitive chitosan material and its controlled release on coenzyme A.

A novel copolymer P(CS-Ma-DMAEMA) was synthesized with chitosan (CS), maleic anhydride (Ma) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) by grafting and copolymerization. The copolymer obtained was analyzed by FT-IR, (1)H NMR and UV, and the molecular weight and polydispersity were determined by gel permeation chromatography (GPC). The average size and distribution of copolymer micelles were determined by dynamic light scattering (DLS). Their aqueous solution properties and controlled coenzyme A delivery were also studied. It was found that the copolymer had temperature sensitivity and pH sensitivity. The factors affecting release behavior, such as concentration, pH and temperature were discussed in this paper. The higher concentration of the copolymer aqueous solution absorbed more coenzyme A than the lower one. The increasing temperature accelerated the drug release from the copolymer. The pH of the copolymer solution had significant impact on the release of coenzyme A. The results suggested that the novel copolymer could be used as drug delivery carrier.

Preparation and characterization of pH sensitive comb-shaped chitosan material for the controlled release of coenzyme A.

A novel kind of pH sensitive comb-shaped copolymer P(CS-Ma-PEGMA) was synthesized with chitosan (CS), maleic anhydride (Ma) and Poly (ethylene glycol) methacrylate (PEGMA) by grafting and co-polymerization. The structure of P(CS-Ma-PEGMA) was characterized by FT-IR and (1)H-NMR, and it was found that PEGMA was grafted onto CS and PEGMAylated chitosan was soluble. The copolymer was subjected to coenzyme A adsorption study in order to assess its application in biomedical area. The factors affecting release behavior, such as concentration and pH were discussed in this paper. The higher concentration of the copolymer showed higher absorbance peak than the lower one. The pH of the solution also had significant impact on the release of coenzyme A, and the mechanism of adsorption was suggested. The results suggested that the novel copolymer could be used as drug delivery carrier.