Risk factors of non-sentinel lymph node metastasis in breast cancer with 1-2 sentinel lymph node macrometastases underwent total mastectomy: a case-control study.

BACKGROUND: The randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1-2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1-2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1-2 SLN macrometastases undergoing TM. METHODS: The clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis. RESULTS: A total of 273 patients with 1-2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019-1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302-36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1-2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%. CONCLUSIONS: The breast cancer patients with cT1/2N0 stage, undergoing TM and 1-2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration.

Improving the Identification of Lysine-Acetylated Peptides Using a Molecularly Imprinted Monolith Prepared by a Deep Eutectic Solvent Monomer.

To overcome the identification challenge of low-abundance lysine acetylation (Kac), a novel approach based on a molecularly imprinted polymer (MIP) was developed to improve the extraction capacity of Kac peptides in real samples. Green deep eutectic solvents (DESs) were introduced and used as one of the synergistic functional monomers with zinc acrylate (ZnA). Glycine-glycine-alanine-lysine(ac)-arginine (GGAKacR) was chosen as a template and N,N'-methylenbisacrylamide (MBAA) was used as a cross-linker. The obtained GGAKacR-MIP had excellent selectivity for the template with an imprinting factor (IF) of up to 21.4. The histone digest addition experiment demonstrated that GGAKacR-MIP could successfully extract GGAKacR from a complex sample. Finally, the application to the extraction of Kac peptides from mouse liver protein digestion was studied in detail. The number of Kac peptides and Kac proteins identified was 130 and 110, which were 3.71-fold and 3.93-fold higher than those of the untreated sample. In addition, the number of peptides and proteins identified after treatment increased from 5535 and 1092 to 17 149 and 4037 (3.10-fold and 3.70-fold, respectively). The results showed that the obtained MIP may provide an effective technical tool for the identification of Kac-modification and peptide fractionation, as well as a potential approach for simultaneously identifying post-translational-modified proteomic and proteomic information.

Improving sorption performance of a molecularly imprinted monolithic column by doping mesoporous molecular sieve SBA-15.

For the first time a hybrid molecularly imprinted polymer (MIP) doped with 3-(trimethoxysilyl) propyl methacrylate (γ-MPS)-modified mesoporous molecular sieve SBA-15 for target peptide recognition has been developed. Zinc acrylate and methacrylic acid were used as binary functional monomers, and ethylene dimethacrylate was used as cross-linking agent to prepare an imprinted monolith against Val-Tyr-Ala-Leu-Lys(glutarylation) (VYALKglu). The morphology of the polymers was characterized by scanning electron microscopy, FT-IR spectroscopy, energy dispersive spectroscopy, and 1H NMR. The SBA-15-MPS MIP showed high recovery of 87.1% and the IF of 12.9 for the enrichment of the template peptide. When the template peptide concentration ranged from 5 to 90 µg mL-1, the correlation coefficients (R2) for the calibration function obtained was better 0.999. The limit of detection (LOD, 0.30 µg mL-1) and limit of quantification (LOQ, 1.0 µg mL-1) were achieved for signal-to-noise ratios of 3:1 and 10:1, respectively. When other kinds of synthetic peptides were used as analogs, the selectivity of the SBA-15-MPS MIP was much better than the SBA-15-MPS NIP (without template peptides) with relative selectivity coefficients of 52.8-265. In contrast, little quinolones and biogenic amines are adsorbed with the SBA-15-MPS MIP. The SBA-15-MPS MIP could enrich VYALKglu from spiked histone digestion with the average recovery of 87.8% and the relative standard deviation (RSD) of 0.99%. As a conclusion, doping of SBA-15 is an effective approach to the improvement of performance of molecularly imprinted monolith.

[Effect of Shanhaidan Granules combined with tadalafil on erectile dysfunction: A multi-center clinical trial].

OBJECTIVE: To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED. METHODS: In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients. RESULTS: After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators. CONCLUSIONS: Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.

Molecularly Imprinted Polymers Doped with Carbon Nanotube with Aid of Metal-Organic Gel for Drug Delivery Systems.

PURPOSE: The incidence of breast cancer worldwide has been on the rise since the late 1970s, and it has become a common tumor that threatens women's health. Aminoglutethimide (AG) is a common treatment of breast cancer. However, current treatments require frequent dosing that results in unstable plasma concentration and low bioavailability, risking serious adverse reactions. Our goal was to develop a molecularly imprinted polymer (MIP) based delivery system to control the release of AG and demonstrate the availability of this drug delivery system (DDS), which was doped with carbon nanotube with aid of metal-organic gel. METHODS: Preparation of MIP was optimized by key factors including composition of formula, ratio of monomers and drug loading concentration. RESULTS: By using multi-walled carbon nanotubes (MWCNT) and metal-organic gels (MOGs), MIP doubled the specific surface area, pore volume tripled and the IF was 1.6 times than the reference. Compared with commercial tablets, the relative bioavailability was 143.3% and a more stable release appeared. CONCLUSIONS: The results highlight the influence of MWCNT and MOGs on MIP, which has great potential as a DDS.

Preparation, characterization, and application of soluble liquid crystalline molecularly imprinted polymer in electrochemical sensor.

A novel soluble molecularly imprinted polymer (SMIP) without chemical cross-linker was successfully synthesized. The quinine (QN), which the structure was similar to the template, was chosen as the immobile template to improve the affinity of MIP. 4-Methyl phenyl dicyclohexyl ethylene (MPDE) was used as the liquid crystal (LC) monomer to increase the rigid of the composite. The cooperative effect of QN and MPDE was demonstrated by comparing with the conventional MIP, which synthesized without QN and MPDE. The polymerization conditions of SMIP including the ratio of MAA to MPDE, template to functional monomer, and HQN to QN were also optimized. Moreover, the characterizations of the SMIP were investigated by the transmission electron microscopy (TEM), field emission scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and nitrogen adsorption. In binding behavior, the SMIP presented the maximum adsorption capacity (0.37 ± 0.06 mmol/g) and imprinting factor (3.44 ± 0.25). And above all, the obtained polymer exhibited the solubility in the organic solution. In addition, the proposed SMIP as the electrochemical sensor exhibited a significant conductivity and sensitivity with the detection limit of 0.33 µM for HQN, the recoveries for the sample analysis varied from 97.4 to 100.8%, and the intra-day precision and inter-day precision were within 5.5% and 12.5%, respectively. It turned out that the SMIP had demonstrated more excellent potential than the traditional insoluble MIP in the development of the membrane-based electrochemical sensors.Graphical abstract.

Effect of low-intensity extracorporeal shockwave therapy on nocturnal penile tumescence and rigidity and penile haemodynamics.

The study aims to evaluate the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on nocturnal erection and penile haemodynamics. Patients with erectile dysfunction (ED) were enrolled from January 2018 to March 2019. Self-reported erectile symptoms, the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Scores (EHS), nocturnal penile tumescence and rigidity (NPTR) and cavernous duplex Doppler ultrasound (CDDU) were evaluated. NPTR and CDDU were evaluated by Rigiscan and vascular ultrasound system respectively. Comparisons of NPTR and CDDU parameters were performed before and after Li-ESWT (Renova, once a week, 4 weeks in total). A total of 35 cases (mean age 36.51 ± 11.47 years) were enrolled for analysis. The IIEF-5 (10.60 ± 5.99 vs. 15.13 ± 6.22, p = .003), EHS (p = .016) and self-reported erectile hardness (p = .014) were significantly improved after 1-month treatment. Nocturnal erection frequency (p = .010), duration of total erection (p = .017), duration of erectile rigidity ≥60% at penile tip and base (p = .014 and p = .002) and the best erectile rigidity at penile tip and base (p = .012 and p = .005) improved significantly after treatment. However, no CDDU parameters improved after Li-ESWT (all p > .05). Li-ESWT can effectively improve subjective erectile function and nocturnal erection in ED patients. Large sample and well-designed studies need to be developed for supporting the current findings.

Preparation of gold nanorod-incorporated monolith for solid phase extraction of polycyclic aromatic hydrocarbons.

An organic-inorganic hybrid monolithic column doped with gold nanorods (AuNRs) was prepared and evaluated for solid phase extraction (SPE) of polycyclic aromatic hydrocarbons (PAHs). Excellent dispersibility of AuNRs in binary green porogen system consisting of 1-hexyl-3-methylimidazolium tetrafluoroborate and deep eutectic solvents (DESs) was confirmed by energy dispersive spectrometry (EDS). The particle size of the resulting AuNRs (70-90 nm) was thoroughly examined by a transmission electron microscopy (TEM). The redox system including ammonium persulfate (APS) and tetramethylethylenediamine (TEMED) was used to initiate in situ polymerization at 4 °C to prepare the hybrid monolith. The mesoporous structure of the AuNR hybrid monoliths was confirmed by scanning electron microscopy (SEM) and nitrogen adsorption. With enrichment factors (EFs) of 150- to 292-fold, the developed method was successfully applied to the determination of 10 PAHs in wastewater samples. The recoveries at a spiked level were in the range 84.9 to 99.5% with limit of detections (LODs) and relative standard deviations (RSDs) ranging from 0.02 to 0.10 µg L-1 and 1.5 to 4.2%, respectively. The correlation coefficients (R2) for the calibration function obtained were better 0.9991 for the target compounds. Compared to the AuNR-free monolith, the extraction efficiency of the AuNR-incorporated monolith is more than two times higher. The results indicated that the doping of AuNRs is an effective approach to obtain the hybrid monolithic column with good separation ability for PAHs. Graphical abstract.

[Effect of breastfeeding on insulin sensitivity in infants with intrauterine growth retardation: a follow-up study].

OBJECTIVE: To study insulin sensitivity and the serum level of adiponectin in infants with intrauterine growth retardation (IUGR) and the effect of breastfeeding on the insulin sensitivity through a follow-up study. METHODS: A total of 106 full-term IUGR infants who were hospitalized from October 2014 to October 2018 were enrolled as the IUGR group, and 90 full-term appropriate for gestational age (AGA) infants who were born during the same period of time were enrolled as the AGA group. Birth weight and body length were recorded. Serum levels of fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and adiponectin were measured on day 7 after birth. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. According to the feeding pattern, the IUGR group was further divided into a breastfeeding group with 37 infants and a formula feeding group with 42 infants. The above serum indices and growth indices were also measured at the age of 3 and 6 months. RESULTS: Compared with the AGA group, the IUGR group had significantly increased levels in serum insulin and HOMA-IR and a significantly decreased level of adiponectin (P<0.05). There were no significant differences between the breastfeeding and formula feeding groups in growth indices and serum levels of FBG, TG, LDL, and HDL on day 7 after birth and at the ages of 3 and 6 months (P>0.05). In the breastfeeding group, serum insulin and HOMA-IR decreased and adiponectin level increased over the time of breastfeeding (P<0.05). CONCLUSIONS: Insulin sensitivity decreases in the early stage after birth in IUGR infants, and breastfeeding can improve insulin sensitivity.

Investigation of deep eutectic solvents as additives to ß-CD for enantiomeric separations of Zopiclone, Salbutamol, and Amlodipine by CE.

The enantioseparation of chiral drugs via CE was first investigated using ß-CD as chiral additive and deep eutectic solvents (DESs) as auxiliary additive. The results showed that improved separation of tested chiral drugs was obtained in the presence of DESs and ß-CD compared to the single ß-CD separation system. With the optimized condition, resolutions of DESs applied ß-CD separation system for rac-Zopiclone, rac-Salbutamol, and rac-Amlodipine increased 3-4.2 times as single ß-CD separation system. The resolutions reached 4.74, 6.37, and 9.67, respectively. The results demonstrate that DESs are viable additives to CD system in CE for the separation of the chiral drugs.

Cost-effective imprinting to minimize consumption of template in room-temperature ionic liquid for fast purification of chlorogenic acid from the extract of E. ulmoides leaves.

One of the main challenges in large-scale applications of molecularly imprinted polymers (MIPs) is the significant amount of template needed in polymer preparation. A new strategy based on room-temperature ionic liquids (RTILs) was suggested to solve this problem by reducing the amount of template in the polymerization recipe. The MIP was synthesized with a mixture of dimethyl sulfoxide and RTIL (1-butyl-3-methylimidazolium tetrafluoroborate) as porogen, in which chlorogenic acid (CGA) was used as template, 4-vinylpyridine (4-VP) as functional monomer, and ethylene glycol dimethacrylate (EDMA) as cross-linker. The influence of polymerization variables, including CGA concentrations, and the ratio of 4-VP to EDMA on imprinting effect were investigated comprehensively. Moreover, the properties involving the column permeability, the number of binding sites, and the polymer morphology of the CGA-MIP monoliths were studied thoroughly. The MIP monolith had an excellent column permeability (1.53 × 10-13 m2) and allowed an ultra-fast on-line SPE, which dramatically shortens the separation time (< 10 min) and improves the separation efficiency. At high flow velocity (5.0 mL min-1), 50 µL of the extract from Eucommia ulmoides leaves can be loaded directly on the CGA-MIP monoliths and CGA with high purity can be obtained with a recovery of 89.01 ± 0.05%. As a conclusion, the resulting RTIL-induced approach of preparing MIP may be an effective tool in fabricating MIP in a low-cost way. Graphical abstract ᅟ.

Synergistic effect of organic-inorganic hybrid monomer and polyhedral oligomeric silsesquioxanes in a boronate affinity monolithic capillary/chip for enrichment of glycoproteins.

A boronate affinity monolith with improved affinity and selectivity for glycoproteins was prepared starting from two monomers. The first is 3-aminopropyltriethoxysilane-methacrylic acid (APTES-MAA), and the other is a polyhedral oligomeric silsesquioxane (POSS) monomer. In the next step, 3-(acrylamido)benzeneboronic acid was adopted as boronate affinity ligand, and ethylene glycol dimethacrylate as the crosslinker, and iso-propanol and octanol as binary porogens. The synergistic effect of APTES-MAA and POSS warrants good affinity and selectivity for glycoproteins, which results in a number of attractive features including (a) a wide operation pH range (from 5 to 8); (b) higher enrichment factors ranging from 19.3 to 20.6; (c) greater recoveries of glycoproteins between 95.8 and 107.1%; (d) lower relative standard deviations of ≤4.2%. Compared to the corresponding APTES-MAA/POSS-free monolith, the new boronate material had 1.7-fold increased glycoprotein recovery from complex samples. Glycoproteins in 500-fold diluted serum samples can be enriched by the boronate monolith. Graphical abstractSchematic representation of the preparation of 3-aminopropyltriethoxysilane-methacrylic acid/polyhedral oligomeric silsesquioxanes boronate affinity monolith. This sorbent exhibits high selectivity and wide pH operation range for capturing glycopeptides.

Enhanced molecular recognition for imprinted monolithic column containing polyhedral oligomeric silsesquioxanes by dendritic effect of mesoporous molecular sieve scaffolds.

The dendritic effect of nano mesoporous molecular sieve was first used to enhance molecular recognition of molecularly imprinted polymers (MIPs)-based polyhedral oligomeric silsesquioxanes (POSS). In this study, the MIPs were made using S-naproxen (S-NAP) as template molecule, 4-vinylpyridine (4-VP) as functional monomer, ethylene glycol dimethacrylate as cross-linker, 1-butyl-3-methylimidazoliumtetrafluoroborate ([BMIM]BF4)/DMSO as binary porogens, 1-propylmethacrylate-heptaisobutyl substituted as POSS monomer, and mesoporous molecular sieve (Mobil composition of matter No. 41, MCM-41) as dendritic scaffold. The influence of synthesis parameters on the imprinting effect, including the content of POSS monomer and derivatized MCM-41-MPS, the ratio of template to monomer, and the ratio of binary porogens were also investigated, respectively. The morphology of the polymers was characterized by scanning electron microscopy, nitrogen adsorption, and X-ray powder diffraction. The results showed that POSS&MCM-41-MPS MIP had a stronger imprinting effect with an imprinting factor 6.86, which is approximately 2.4, 2.3, and 3 times than that of POSS MIP, MCM-41-MPS MIP, and conventional MIP, respectively. The increase of affinity might be attributed to impediment of the chain motion of polymer due to improved POSS aggregation and the dipole interaction between the POSS units by introduce of MCM-41-MPS as scaffolds. The resulting POSS&MCM-41-MPS MIP was used as adsorbent for the enrichment of S-NAP in solid-phase extraction with a high recovery of 97.65% and the value of RSD was 0.94%.

A strategy of utilizing Zn(II) as metallic pivot in room temperature ionic liquid to prepare molecularly imprinted polymers for compound with intramolecular hydrogen bonds.

A method of preparing molecularly imprinted polymers (MIPs) with Zn(II) as a metallic pivot was adopted to solve the problem of imprinting compound with intramolecular hydrogen bonds by forming stronger coordination binding interaction among the template-functional monomer-Zn2+ complex. A ternary porogenic system including dimethyl sulfoxide, dimethylformamide, and room temperature ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate was employed to fabricate imprinted monolith with high porosity and good flow-through properties, in which chicoric acid (CA), zinc acetate, 4-vinylpyridine (4-VP), and ethylene glycol dimethacrylate (EDMA) was the template, metallic ion, functional monomer, as well as crosslinker, respectively. The influence of polymerization factors including the 4-VP-CA ratio, monomer-crosslinker ratio, template-Zn2+ ratio on imprinting factors was systematically investigated. When the ratio of 4-VP to CA was 24:1, the greatest IF value (24.81) was achieved on the CA-MIP prepared with zinc acetate. In addition, off-line SPE with the optimal MIPs monolith led to high purity of CA (98.0% ± 0.5%) from extraction of Cichorium intybus L. roots with the recovery of 77.5% ± 2.5% (n = 6). As a conclusion, the strategy of introducing metal ions as metal pivot to prepare MIPs was a powerful method for the MIPs synthesis to the template molecules with intramolecular hydrogen bonds.

A star-shaped molecularly imprinted polymer derived from polyhedral oligomeric silsesquioxanes with improved site accessibility and capacity for enantiomeric separation via capillary electrochromatography.

A star-shaped molecularly imprinted coating was prepared starting from octavinyl-modified polyhedral oligomeric silsesquioxanes (Ov-POSS). It possesses a relatively open structure and has good site accessibility and a larger capacity even at lower cross-linking. The imprinted coating was prepared from S-amlodipine (S-AML) as the template and analyte, Ov-POSS as the cross-linker, and methacrylic acid as the functional monomer. The preparation and chromatographic parameters were optimized, including ratio of template to functional monomer, apparent cross-linking degree, pH value, ACN content and salt concentration in the mobile phase. The best resolution in enantiomer separation by means of capillary electrochromatography reaches a value of 33. A good recognition ability (α = 2.60) was obtained and the column efficiency for S-AML was 54,000 plates m-1. The use of Ov-POSS as a cross-linker significantly improves the column capacity and thus the detection sensitivity. The results show that Ov-POSS is an effective cross-linker for the preparation of imprinted polymers with good accessibility and large capacity. Graphical abstract Schematic presentation of the preparation of star-shaped imprinted polymer using octavinyl-modified polyhedral oligomeric silsesquioxanes (Ov-POSS) and by using methacrylic acid (MAA) as functional monomer. The best enantiometric resolution (33) for amlodipine (AML) can be achieved in capillary chromatography (CEC).

A polymer monolith incorporating stellate mesoporous silica nanospheres for use in capillary electrochromatography and solid phase microextraction of polycyclic aromatic hydrocarbons and organic small molecules.

An inorganic-organic hybrid monolith incorporated with stellated mesoporous silica nanoparticles (SMSNs) was prepared. Using binary solvents, deep eutectic solvents and room temperature ionic liquids, an SMSN-incorporated poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith demonstrated uniform structure with good column permeability. A systematic investigation of preparation parameter was performed, including SMSN content, crosslinking monomer content, and the component of binary solvent. The optimized monoliths were characterized by field emission scanning electron microscopy, transmission electron microscopy, area scanning energy dispersive spectrometry, and nitrogen adsorption. Column performance was tested by separating four groups of analytes (alkylbenzenes, anilines, naphthalenes and phenols) by capillary electrochromatography (CEC). Baseline separation of all analytes was obtained with column efficiencies of up to 266,000 plates m-1. The performance of the resulting monolith was further investigated in detail by separating mixtures of polycyclic aromatic hydrocarbons (PAHs), nonsteroidal antiinflammatory drugs (NSAIDs), and hydroxybenzoic acid isomers. Compared with the corresponding SMSN-free monolith, the CEC performance was improved by about six times. Successful extraction of PAHs and quinolones (QNs) were also performed using this capillary. Improved extraction efficiency (20.2%) for complex samples, lake water, was also found when the material was applied to solid phase microextraction of fluoranthene. Graphical abstract A poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith incorporated with stellated mesoporous silica nanoparticles was prepared. It demonstrated column efficiency up to 266,000 plates m-1 in capillary electrochromatography and ability as solid phase microextraction for organic small molecules with good column permeability.

1,4-ß-d-Glucomannan from Dendrobium officinale Activates NF-кB via TLR4 to Regulate the Immune Response.

2,3-O-acetylated-1,4-ß-d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale. DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography⁻high-performance liquid chromatography. Then, a detailed study on the effects of DOP-1-1 on a human leukemia monocytic cell line (THP-1) under normal conditions was undertaken. DOP-1-1 promoted the translocation of nuclear factor-kappa B (NF-κB) and degradation of IκB proteins. The expression of genes and proteins closely associated with the immune, survival and apoptotic functions of NF-κB were analyzed by quantitative real-time RT-PCR. Furthermore, CCL4 and IP10 were confirmed to be the novel targets of the immune response stimulated by DOP-1-1. The phosphorylation of NF-кB was inhibited by treatment with a toll-like receptor 4 (TLR4) antagonist (TAK-242) and myeloid differentiation factor 88 (MyD88) inhibitor (ST2825). These data suggested: (i) the O-acetylated glucomannan DOP-1-1 is present in the steady state in low-pH solutions; (ii) DOP-1-1 can induce an immune response through NF-кB mediated by a TLR4 signaling pathway; and (iii) CCL4 and IP10 could be the novel targets of the immune response stimulated by O-acetylated glucomannan.

Green Synthesis of Carbon Nanotubes-Reinforced Molecularly Imprinted Polymer Composites for Drug Delivery of Fenbufen.

The facile fabrication of single-walled carbon nanotubes (SWCNTs)-doping molecularly imprinted polymer (MIP) nanocomposite-based binary green porogen system, room-temperature ionic liquids (RTILs), and deep eutectic solvents (DESs) was developed for drug delivery system. With fenbufen (FB) as template molecule, 4-vinylpyridine (4-VP) was used as functional monomer, ethylene glycol dimethacrylate as cross-linking monomer, and 1-butyl-3-methylimidazoliumtetrafluoroborate and choline chloride/ethylene glycol as binary green solvent, in the presence of SWCNTs. The imprinting effect of the SWCNT-MIP composites was optimized by regulation of the amount of SWCNTs, ratio of RTILs and DES, and the composition of DES. Blue shifts of UV bands strongly suggested that interaction between 4-VP and FB can be enhanced due to SWCNT doping in the process of self-assembly. The reinforced imprinted effect of CNT-doping MIP can provide superior controlled release characteristics. Compared with the control MIP prepared without SWCNTs, the imprinting factor of the SWCNT-MIP composites exhibited a twofold increase. In the analysis for the FB release kinetics from all samples, the SWCNT-reinforced MIP produced the lowest value of drug diffusivity. The relative bioavailability of the SWCNT-MIP composites (F %) displayed the highest value of 143.3% compared with the commercial FB tablet, whereas the control MIP and SWCNT-non-MIP composites was only 48.3% and 44.4%, respectively. The results indicated that the SWCNT-MIP nanocomposites developed here have potentials as the controlled-release device.

[Value of arterial blood lactic acid in the evaluation of disease severity and prognosis in neonatal shock].

OBJECTIVE: To evaluate the value of blood lactic acid (BLA) as a predictor for the severity and prognosis of neonatal shock. METHODS: A total of 326 neonates with shock were enrolled and divided into three groups based on the severity, namely mild group (n=147), moderate group (n=105), and severe group (n=74). BLA level was measured during and early after (about 6 hours later) fluid resuscitation, and lactate clearance rate (LCR) was calculated. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of BLA in neonatal shock. RESULTS: BLA level was high in all subjects prior to treatment, and was highest in the severe group and lowest in the mild group (P<0.01). BLA level was significantly higher among patients with septic shock than among those with hypovolemic, cardiogenic, and asphyxiating shock (P<0.05). BLA level was significantly reduced in patients in recovery after treatment (P<0.05). Mortality was significantly lower in patients with BLA level ≤4 mmol/L or LCR ≥10% than in those with BLA level >4 mmol/L or LCR <10% (P<0.01). BLA at 11.15 mmol/L had 100% sensitivity and 96.8% specificity in predicting severe shock. BLA at 10.65 mmol/L had 88.9% sensitivity and 74.1% specificity in predicting the prognosis (survival or dead) of newborns with shock. CONCLUSIONS: In neonates with shock, arterial BLA level increases as the disease severity increases and is associated with prognosis, so it is a useful predictor of the severity and prognosis of neonatal shock.

Molecularly imprinted polymer prepared with polyhedral oligomeric silsesquioxane through reversible addition-fragmentation chain transfer polymerization.

Polyhedral oligomeric silsesquioxane (POSS) was utilized to prepare imprinted polymer through reversible addition-fragmentation chain transfer polymerization (RAFT) successfully. The imprinted polymer was made with a mixture of RAFT agent, 4-vinylpyridine (4-VP), POSS monomer [PSS-(1-propylmethacrylate)-heptaisobutyl substituted, MA 0702], and ethylene glycol dimethacrylate (EDMA), with ketoprofen (KET) as template. The influence of polymerization variables, the amount of RAFT agent and POSS monomer, the ratio of KET to 4-VP, and the ratio of 4-VP to EDMA, were investigated on the retention factor and imprinting effect. The greatest imprinting factor of the RAFT agent-based POSS MIP was 15.2, about 1.5 times higher than the RAFT agent-free agent POSS MIP. The permeability, surface morphology, as well as pore size distribution of POSS MIP monoliths made with RAFT agent and without RAFT agent were also studied. The optimal MIP was applied to solid phase extraction for KET from commercial tablets. The mean recoveries of KET for RAFT-based POSS MIP was 85.2% with a relative standard deviation of 2.6%.