[Correlation between bioelectrical impedance and nutritional status in neurocritical care patients].

Objective: To explore the correlation between electrical impedance indicators and commonly used nutritional indicators in neurocritical care patients. Methods: A cross-sectional study was conducted to collect 58 neurocritical care patients in neurosurgery Department of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from June to September 2022. Bioelectrical impedance tests were performed after surgery or one week after injury, and nutrition-related biochemical indicators of the patients were collected on the same day, including nutritional status related indicators, inflammation related indicators, anemia related indicators and blood lipid related indicators. The patients were assessed with acute physiology and chronic health evaluation (APACHE) Ⅱ score and sequential organ failure assessment (SOFA) score. Based on the results obtained, the patients were assessed with nutritional score and spearman correlation analysis. The correlations of electrical impedance with nutrition related indicators and nutrition risk related indicators were analyzed. The prediction model of nutritional status was constructed by multi-factor binary logistic regression. Stepwise regression was used to screen electrical impedance indicators related to nutritional status. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the predictive ability of the nutritional status prediction model. Results: A total of 58 patients were collected, including 33 males and 25 females, and aged 72.0 (59.0, 81.8) years. Extracellular water (ECW) was positively correlated with interleukin 6 (r=0.529, P<0.001). The edema index [ECW/total body water (TBW)] was negatively correlated with albumin (r=-0.700, P<0.001), hematocrit (r=-0.641, P<0.001) and hemoglobin (r=-0.667, P<0.001). The phase angle was positively correlated with albumin (rRA=0.667, rLA=0.649, rRL=0.669, rLL=0.685, all P<0.001), hematocrit (rRA=0.600, rLA=0.604, rTR=0.565, rRL=0.529, rLL=0.602, all P<0.001) and hemoglobin (rRA=0.626, rLA=0.635, rTR=0.594, rRL=0.624, rLL=0.631, all P<0.001). By stepwise regression screening of predictive factors for nutritional status and incorporating age, gender and white blood cells as confounding factors into the model, the final model was obtained as follows: nutritional status=-0.01×age+1.22×gender-0.12×white blood cells+202.20×ECW/TBW+0.5 torso phase angle -82.16 [The OR value of ECW/TBW: 20.8 (95%CI: 3.7-117.1), P<0.001], with the AUC of 0.921. Conclusion: Bioelectrical impedance indicators have good correlations with commonly used clinical nutritional indicators, and can provide a new method for nutritional evaluation of neurocritical care patients.

Expression of miR-182 in patients with fracture of tibial plateau and its regulative effects on the fracture healing.

OBJECTIVE: To investigate the expression of miR-182 in patients with fracture of tibial plateau (FTP) and its effects on osteoblasts and fracture healing. PATIENTS AND METHODS: The patients with fracture of tibial plateau treated in our hospital and healthy subjects who received physical examination from January 2017 to January 2018 were collected. The expression of miR-182 in the serum was detected. The osteoblasts from SD rats were cultured and transfected with miR-182, anti-miR-182, miR-NC or anti-miR-NC using transfection reagent LipofectamineTM 2000. The proliferation, alkaline phosphatase (ALP) activity, calcification and osteogenic gene expression of osteoblasts were detected. The rat models with fracture of tibial plateau were divided into control group, fracture group, fracture+miR-182 group, and fracture+anti-miR-182 group. The levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and transforming growth factor ß (TGFß) in serum were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the controls, the expression of miR-182 in serum was significantly elevated in patients with fracture of tibial plateau. Overexpression of miR-182 inhibited the proliferation of osteoblasts, while the knockdown of miR-182 increased the proliferation. MiR-182 could decrease the ALP activity of osteoblasts, while anti-miR-182 increased the ALP activity. Osteoblast calcification ability was significantly decreased by overexpression of miR-182. Knockdown of miR-182 increased the calcification ability of osteoblasts and the expression of osteogenic genes. MiR-182 could inhibit the expression of osteogenic genes. The levels of VEGF, EGF and TGFß in the fracture group were higher than those in the control group, while the levels in the fracture+miR-182 group were higher than those in the fracture group. The levels of VEGF, EGF and TGFß in the anti-miR-182 group were lower than those in the fracture group. CONCLUSIONS: MiR-182 is elevated in patients with fracture of tibial plateau, which can inhibit the proliferation and differentiation of osteoblasts and affect the fracture healing. The knockdown of miR-182 might be a new method for treating fracture healing.

[Clinical and laboratory characteristics in patients with myeloid neoplasms complicated with clonal T large granular lymphocyte proliferation].

Objective: To analyze the clinical manifestations and laboratory features in patients with myeloid neoplasms complicated with clonal T large granular lymphocyte (T-LGL) proliferation. Methods: The clinical data of 5 patients with myeloid neoplasms complicated with clonal T-LGL proliferation from November 2017 to November 2018 in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were analyzed retrospectively. Results: The median age was 60 years old. All patients had a history of abnormal peripheral blood cell counts for over 6 months. The absolute lymphocyte count in peripheral blood was less than 1.0×10(9)/L. In addition to the typical T-LGL phenotype, the immunophenotype was heterogenous including CD4(+)CD8(-) in 2 patients, the other 3 CD4(-)CD8(+). Four patients were αß type T cells, the other one was γδ type. STAT3 mutation was detected in 1 patient by next-generation sequencing, the other 4 cases were negative. Conclusions: Clonal T-LGL proliferation with myeloid neoplasm develops in an indolent manner, mainly in elderly patients. Hemocytopenia is the most common manifestation. The diagnosis of T-LGL proliferation does not have specific criteria, that it should be differentiated from other T cell proliferative disorders, such as T-cell clones of undetermined significance. STAT3 or STAT5b mutation may help distinguish.

The risk of lower gastrointestinal bleeding in low-dose aspirin users.

BACKGROUND: Aspirin increases the risk of gastrointestinal bleeding. AIM: To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users. METHODS: Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers. RESULTS: A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR: 10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR: 8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were significantly associated with LGIB. CONCLUSIONS: The risk of LGIB was higher in low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low-dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.

Dysregulation of the type I interferon system in adult-onset clinically amyopathic dermatomyositis has a potential contribution to the development of interstitial lung disease.

BACKGROUND: It has been speculated that viral infection might be one of the potential aetiologies for adult-onset clinically amyopathic dermatomyositis (CADM). The molecular pathogenesis remains largely unknown. OBJECTIVES: To explore whether dysregulation of the type I interferon (IFN) system is involved in the pathogenesis of CADM. METHODS: We studied 16 patients with CADM and compared them with healthy control subjects (n = 20) and patients with classic dermatomyositis (DM, n = 16) and polymyositis (PM, n = 16). Expressions of mRNA for serial toll-like receptor genes (TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9) and type I IFN-regulated genes (IRF7, ISG15 and MxA) in peripheral blood leucocytes (PBL) were detected by real-time polymerase chain reaction analysis. The level of IFN-α in blood was tested by enzyme-linked immunosorbent assay. RESULTS: The mRNA expressions of TLR7, TLR9 and IRF7 were greatly elevated in the PBL from patients with CADM compared with controls. Upregulation of the ISG15 and MxA genes was detected in the PBL from patients with CADM, as well as from patients with classic DM. Among the four study groups, the overproduction of IFN-α in blood was most significant in the CADM group. Especially, IFN-α level was obviously high in the clinical interstitial lung disease (ILD) subgroup of patients with CADM. Positive correlations were found between IFN-α concentration and other unfavourable prognostic factors of CADM-associated ILD. CONCLUSIONS: Our data suggest that the dysregulation of the type I IFN system may be implicated in CADM pathogenesis. IFN-α may be a useful biomarker for assessing the disease severity of CADM-associated ILD.

Fluorogenic substrates based on fluorinated umbelliferones for continuous assays of phosphatases and beta-galactosidases.

Fluorogenic substrates based on 4-methylumbelliferone (4-MU) have been widely used for the detection of phosphatase and glycosidase activities. One disadvantage of these substrates, however, is that maximum fluorescence of the reaction product requires an alkaline pH, since 4-MU has a pK(a) approximately 8. In an initial screening of five phosphatase substrates based on fluorinated derivatives of 4-MU, all with pK(a) values lower than that of 4-MU, we found that one substrate, 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP), was much improved for the detection of acid phosphatase activity. When measured at the preferred acid phosphatase reaction pH (5.0), DiFMUP yielded fluorescence signals that were more than 10-fold higher than those of 4-methylumbelliferyl phosphate (MUP). DiFMUP was also superior to MUP for the detection of protein phosphatase 1 activity at pH 7 and was just as sensitive as MUP for the detection of alkaline phosphatase activity at pH 10. A beta-galactosidase substrate was also prepared based on 6, 8-difluoro-4-methylumbelliferone. This substrate, 6, 8-difluoro-4-methylumbelliferyl beta-d-galactopyranoside (DiFMUG), was found to be considerably more sensitive than the commonly used substrate 4-methylumbelliferyl beta-d-galactopyranoside (MUG), for the detection of beta-galactosidase activity at pH 7. DiFMUP and DiFMUG should have great utility for the continuous assay of phosphatase and beta-galactosidase activity, respectively, at neutral and acid pH.

Synthesis of novel fluorinated coumarins: excellent UV-light excitable fluorescent dyes.

Two new fluorinated fluorescent dyes, 6,8-difluoro-7-hydroxy-4-methylcoumarin (Marina Blue) and 3-carboxy-6,8-difluoro-7-hydroxycoumarin (Pacific Blue), exhibit excellent photophysical properties among a series of novel fluorinated 7-hydroxycoumarins. Most of these fluorinated coumarins have quantum yields (0.63 to 0.89) equal to or higher than that of the parent compound (0.63), which, in combination with their lower pKaS and higher photostability, make them superior fluorescent dyes for use as reporter molecules in biological systems.

Electrophysiological and behavioral responses of turnip moth males,Agrotis segetum to fluorinated pheromone analogs.

The electrophysiological and behavioral responses of maleAgrotis segetum to fluorinated analogs of (Z)-5-decenyl acetate (Z5-10∶OAc) were investigated. The single sensillum recordings showed that 4,4-difluoro-(Z)-5-decenyl acetate (4,4-F2), 7,7-difluoro-(Z)-5-decenyl acetate (7,7-F2), 10,10,10-trifluoro-(Z)-5-decenyl acetate (10,10,10-F3) and 7,7,8,8-tetrafluoro-(Z)-5-decenyl acetate (7,7,8,8-F4) were each 100-fold less active than the natural Z5-10 ∶ OAc, whereas the 7,7,8,8,9,9,10,10,10-nonafluoro-(Z)-5-decenyl acetate (F9) analog was essentially inactive. A mixture of Z5-10 ∶ OAc, Z7-12 ∶ OAc, and Z9-14 ∶ OAc on a filter paper dispenser was as attractive as female gland extracts when tested in a flight tunnel. With Z5-10∶OAc omitted, the two-component mixture elicited a significantly lower male response. Four analogs, 7,7-F2, 10,10,10-F3, 7,7,8,8-F4, and F9, were added separately to the two-component mixture to replace Z5-10∶OAc. The responses elicited by the mixtures containing the 7,7-F2, 10,10,10-F3, and 7,7,8,8-F4 analogs did not differ significantly from that of the natural three-component mixture and the two-component mixture, whereas the mixture containing F9 elicited a significantly lower male response, as low as the response to the two-component mixture. In a field test the mixtures containing 10,10,10-F3 and 7,7,8,8-F4 were significantly more active than the two-component mixture, but still less active than the natural three-component mixture. It appears that field tests provided greater discrimination among pheromone analogs in assessing their behavioral activity than the flight-tunnel test did. Structure-activity analyses demonstrate the importance of the lipophilic interaction between the terminal alkyl chain and the receptor site for the activity of the stimulus. The lipophobicity of the fluorinated analogs impedes a productive receptor interaction.

[Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro].

The cytotoxicities of 2 derivatives of artemisinin B and 2 derivatives of artemisic acid (designated as Compound A, B, C, and D) were investigated, using trypan blue dye exclusion test and colony-forming units assay. At the concentration of 5 micrograms.ml-1, the inhibition rates of these 4 compounds against murine leukemia cell line P388 were > 85%. When tested against human hepatoma cell line SMMC-7721 at 25 micrograms.ml-1, the inhibition rates of Compound A, B, C, and D were found to be 92.3%, 96.9%, 84%, and 82.1%, respectively, and 27%, 8%, 37.8%, 1.7% against normal human embryonic lung cell line WI-38, respectively. These 4 compounds all showed an inhibition rate of 100% against human gastric cancer cell line SGC-7901 at 50 micrograms.ml-1.

Activity of perfluorobutyl-containing components in pheromone blend of cabbage looper moth,Trichoplusia ni.

Substitution of nine hydrogens by nine fluorines in the butyl terminus of (Z)-7-dodecenyl acetate, the major component of the pheromone blend of the cabbage looper,Trichoplusia ni (Lepidoptera: Noctuidae), produces a highly volatile analog that is significantly less active as a replacement for the natural pheromone component, either alone or substituted in the sixcomponent pheromone blend of this species. When 9,9,10,10,11,11,12,12, 12-nonafluoro-(Z)-7-dodecenyl acetate (nf-Z7-12: OAc) was tested in a wind tunnel as a single component or as part of the six-component blend, males exhibited preflight activation, but they did not orient in the pheromone plume and fly upwind over a five-decade range of doses at levels comparable with those of the natural component and blend. Addition of large amounts of nf-Z7-12:OAc to the optimal dose of the natural blend also did not effect flight arrestment as when increased amounts of Z7-12:OAc were added. The nonafluoro (nf) analog of (Z)-9-tetradecenyl acetate, a minor component in theT. ni blend, did not affect male behavior when substituted in the sixcomponent blend, and substitution of both nf analogs in the natural blend produced the same results as observed for blends containing nf-Z7-12:OAc. The lack of an effect with substitution of nf-Z9-14:OAc is discussed in relation to the reported redundancy in the action of minor components inT. ni.

Behavioral and neurosensory responses of the boll weevil,Anthonomus grandis Boh. (Coleoptera: Curculionidae), to fluorinated analogs of aldehyde components of its pheromone.

Competitive field tests with α-fluorinated analogs of compounds III and IV (III-α-F and IV-α-F, respectively) of the boll weevil,Anthonomus grandis Boh., aggregation pheromone showed these compounds, when combined with the other pheromone components [(±)-I and II], to be as attractive as grandlure [(+)-I, II, and III+IV]. Dose-response curves constructed from electroantennograms of male boll weevils to serial stimulus loads of III, IV, III-α-F, IV-α-F, and the corresponding acyl fluorinated analogs (III-acyl-F and IV-acyl-F) showed the α-fiuorinated analogs to be as active as the pheromone components (threshold=0.1 µg), while the acyl fluorinated analogs had a 10-100 x higher threshold (=1-10 µg). Single-neuron recordings showed that IV neurons and II neurons (Dickens, 1990) responded to IV-α-F and III-α-F, respectively, while IV-acyl-F and III-acyl-F were inactive. Since a previous study showed compounds I, II, and IV to be essential for behavioral responses in the field, it seems likely that the activity of the α-fluorinated analogs observed here is due to the stimulation of IV neurons by IV-α-F as indicated in single neuron recordings.

Perfluorinated moth pheromones : Synthesis and electrophysiological activity.

Perfluoroalkyl analogs of pheromone constituents were synthesized and responses from male antennal olfactory receptor neurons from three moth species were recorded during stimulation by these analogs. In each analog, the hydrophobic terminus, either a butyl or hexyl substituent on the (Z)-alkenyl chain, was replaced with a perfluorobutyl (Pfb, C4F9) or perfluorohexyl (Pfh, C6F13) moiety. Perfluoroalkyl analogs were more volatile than their hydrocarbon analogs, showing a decrease in gas chromatographic retention time by two to four methylene equivalents (Kovàts retention indices). Specialist neurons of maleHeliothis zea responded to a 0.02-µg dose of (Z)-11-hexadecenal (Z11-16∶Al) and a dose of 200 µg of Pfb-Z11-16∶Al with similar spike discharge rates. The HS(a) neurons ofTrichoplusia ni responded to a dose of 0.02 µg ofZ7-14∶OAc and a dose of 10 µg of Pfb-Z7-12∶Ac with similar discharge rates. The same difference in sensitivity to Pfb-Z7-12∶OH andZ7-12∶OH was observed for the responses of the HS(b) neuron and for the responses of theNS(a) neurons to Pfb-Z9-14∶Ac andZ9-14∶Ac. Sensilla ofDiatraea grandiosella similarly showed 100- to 1000-fold greater sensitivity toZ9-16-Al andZ11-16∶Al than to Pfh-Z9-16∶Al and Pfb-Z11-16∶Al. Thus, replacement of terminal alkyl groups with perfluoroalkyl groups in pheromone components produced biologically active compounds with increased volatility and displaced electrophysiological response profiles. Because of the diminished receptor cell sensitivity, we suggest that the binding of the fluorinated analogs to a putative receptor is reduced as a result of less favorable interaction between the hydrophobic protein binding site and the more rigid and more polar perfluoroalkyl moiety.

Fluorinated analogs of aldehyde components of boll weevil pheromone : Synthesis and biological activity.

Analogs of the two geometrical isomers of the dimethylcyclohexylidene acetaldehyde component of the pheromone of the boll weevilAnthonomus grandis were synthesized in which the α-vinylic proton or the aldehydic proton were replaced by fluorine. These isosteric substitutions substantially alter charge distribution and reactivity of the enal system, as documented by spectroscopic changes and changes in reactivity. The electrophysiological activity of the (E)- and (Z)-acyl fluorides is two orders of magnitude lower than that of the natural aldehyde. In contrast, the EAG response of female antennae to the (E)- and (Z)-α-fluoro compounds show that the thresholds are quite similar to (and in one isomer lower than) those of the natural aldehyde isomers.