Association of cerebrospinal fluid advanced oxidation protein products levels with early brain injury and prognosis of aneurysmal subarachnoid hemorrhage: A preliminary prospective study.

OBJECTIVES: In this study, we investigated the time course in the cerebrospinal fluid (CSF) advanced oxidation protein products (AOPPs) levels in patients with aneurysmal subarachnoid hemorrhage (aSAH), and ascertained the relationship between the levels of AOPPs and early brain injury (EBI), hydrocephalus and prognosis of patients with aSAH. METHODS: We measured the CSF AOPPs levels in 50 patients with aSAH at 1-3 d, 4-6 d, 7-9 d, and 10-12 d after hemorrhage. The modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, cerebral edema scores and hydrocephalus were used to assess the severity of brain injury. Modified Rankin Scale (mRS) scores were used to assess the prognosis. Patients with mRS scores greater than 2 were considered to have a poor outcome. RESULTS: CSF AOPPs levels were significantly higher in patients with aSAH with poor prognosis, compared to patients with good prognosis and peaked in the early stage. Among patients with aSAH, the levels of CSF AOPPs on days 1-3 were significantly correlated with modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, and cerebral edema scores. Also, in patients with hydrocephalus, early CSF AOPPs levels were significantly elevated. Levels of CSF AOPPs in aSAH patients on days 1-3, 4-6, and 7-9 were independently associated with poor prognosis at the 90-day follow-up, and the optimal area under the curve (AUC) values for CSF AOPPs levels were found on days 1-3. CONCLUSIONS: AOPPs may serve as the potential biomarker to assess the severity of EBI and prognosis in patients with aSAH.

Oxidative C(sp3)-H functionalization of methyl-azaheteroarenes: a facile route to 1,2,4-triazolo[4,3-a]pyridines.

We herein describe an oxidative [4 + 1] annulation used to prepare 1,2,4-triazolo[4,3-a]pyridines in the presence of I2-DMSO. This protocol enables synthesis of triazolo[4,3-a]pyridine-quinoline linked diheterocycles via a direct oxidative functionalization of sp3 C-H bonds of 2-methyl-azaheteroarenes. The reaction shows a wide substrate scope and good functional group tolerance.

High power, tunable mid-infrared BaGa4Se7 optical parametric oscillator pumped by a 2.1 µm Ho:YAG laser.

We, for the first time, demonstrate a tunable mid-infrared BaGa4Se7-based optical parametric oscillator pumped by a acousto-optical Q-switched Ho:YAG laser at 2090.6 nm. Up to 1.55 W of average power was generated in the 3-5 µm range, corresponding to an optical-to-optical conversion efficiency of 14.4% and a slope efficiency of 19.9%. The mid-IR radiation spectra were also seriously researched at different phase-matched angles. The tunable range was 3.49-4.13 µm for the signal, and 5.19-4.34 µm for the idler.

A 41-W ZnGeP2 optical parametric oscillator pumped by a Q-switched Ho:YAG laser.

We reported a high-power ZnGeP2 (ZGP) optical parametric oscillator (OPO) pumped by a Q-switched Ho:YAG laser. The maximum output power of the ZGP OPO was 41.2 W at 107.0 W incident Ho pump power, corresponding to a slope efficiency of 44.6%. The ZGP OPO produced 16-ns mid-IR pulse laser in the 3.74-3.98 µm and 4.38-4.76 µm spectral regions simultaneously. The beam quality was measured to be M²<4.37. The continuous wave maximum average output power of the Ho:YAG laser was 128 W, corresponding to a slope efficiency of 65.8%.

103 W in-band dual-end-pumped Ho:YAG laser.

An efficient 2 µm in-band pumped Ho:YAG laser was demonstrated. The resonator involves two Ho:YAG crystals, each of which was dual-end-pumped by two orthogonally polarized diode-pumped Tm:YLF lasers. The maximum continuous wave output power of 103 W was achieved, corresponding to a slope efficiency of 67.8% with respect to the incident pump power and an optical-to-optical conversion efficiency of 63.5%. Under Q-switched mode, we obtained 101 W laser output at 30 kHz, corresponding to a slope efficiency of 66.2%. The beam quality or M2 factor was found to be less than 2.

Resonantly pumped high efficiency Ho:YAG laser.

High-efficient CW and Q-switched Ho:YAG lasers resonantly dual-end-pumped by two diode-pumped Tm:YLF lasers at 1908 nm were investigated. A maximum slope efficiency of 74.8% in CW operation as well as a maximum output power of 58.7 W at 83.2 W incident pump power was achieved, which corresponded to an optical-to-optical conversion efficiency of 70.6%. The maximum pulse energy of 2.94 mJ was achieved, with a 31 ns FWHM pulse width and a peak power of approximately 94.7 kW.

Aerobic Glycolysis Induced by mTOR/HIF-1α Promotes Early Brain Injury After Subarachnoid Hemorrhage via Activating M1 Microglia.

M1 microglial activation is crucial for the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and there is growing evidence that glucose metabolism is frequently involved in microglial activation. However, the molecular mechanism of glycolysis and its role in M1 microglial activation in the context of EBI are not yet fully understood. In this study, firstly, the relationship between aerobic glycolysis and M1 microglial activation as well as SAH-induced EBI was researched in vivo. Then, intervention on mammalian target of rapamycin (mTOR) was performed to investigate the effects on glycolysis-dependent M1 microglial activation and EBI and its relationship with hypoxia-inducible factor-1α (HIF-1α) in vivo. Next, Hif-1α was inhibited to analyze its role in aerobic glycolysis, M1 microglial activation, and EBI in vivo. Lastly, both in vivo and in vitro, mTOR inhibition and Hif-1α enhancement were administered simultaneously, and the combined effects were further confirmed again. The results showed that aerobic glycolysis and M1 microglial polarization were increased after SAH, and glycolytic inhibition could attenuate M1 microglial activation and EBI. Inhibition of mTOR reduced glycolysis-dependent M1 microglial polarization and EBI severity by down-regulating HIF-1α expression, while enhancement had the opposite effects. Blockading HIF-1α had the similar effects as suppressing mTOR, while HIF-1α agonist worked against mTOR antagonist when administered simultaneously. In conclusion, the present study showed new evidence that aerobic glycolysis induced by mTOR/HIF-1α might promote EBI after SAH by activating M1 microglia. This finding provided new insights for the treatment of EBI.

Role of TREM-1 in the development of early brain injury after subarachnoid hemorrhage.

Triggering receptor expressed on myeloid cells-1 (TREM-1) was found to be induced in the context of subarachnoid hemorrhage (SAH) before. This study further investigates its role in the development of SAH-induced early brain injury (EBI). Firstly, rats were randomly divided into Sham and SAH groups for analysis of temporal patterns and cellular localization of TREM-1. Secondly, TREM-1 intervention was administrated to produce Sham, vehicle, antagonist and agonist groups, for analyzing TREM-1, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and NF-κB expressions at 24 h post-modeling, and EBI assessment at 24 h and 72 h. Thirdly, TLR4 inhibitor (TAK-242) was exploited to produce Sham, Sham+TAK-242, SAH, and SAH + TAK-242 groups to analyze the effects of TLR4 inhibition on TREM-1 induction and EBI evaluation at 72 h. Fourthly, the relationship of soluble TREM-1 (sTREM-1) levels in cerebrospinal fluid of SAH patients with Hunt-Hess grades were explored. The results showed that TREM-1 increased in the brain after experimental SAH (eSAH) early at 6 h and peaked at 48 h, which was found to be located in microglia and endothelial cells. TREM-1 inhibition attenuated EBI associated with TLR4/MyD88/NF-κB suppression, while enhancement had the opposite effects. Contrarily, TLR4 inhibition prevented TREM-1 induction and ameliorated EBI. In addition, sTREM-1 levels in SAH patients positively correlated with Hunt-Hess grades. Overall, the present study provides new evidence that TREM-1 increases dynamically in the brain after eSAH and it is located in microglia and endothelial cells, which may aggravate EBI by interacting with TLR4 pathway. And sTREM-1 in patients might act as a monitoring biomarker of EBI, providing new insights for future studies.

Seroprevalence of Maternal and Cord Antibodies Specific for Diphtheria, Tetanus, Pertussis, Measles, Mumps and Rubella in Shunyi, Beijing.

Maternal antibodies contribute to the protection of young infants from infectious diseases during the early life. However, vaccinations for women of child-bearing age are not routine in China. Therefore, we investigated the level of protective immunity against vaccine preventable diseases in pregnant women and newborns in China. A total of 194 paired maternal and cord blood samples were collected in Beijing from 2016 to 2017. Antibodies specific for the antigens covered by diphtheria-tetanus-pertussis (DTP) and measles-mumps-rubella (MMR) vaccine were determined by ELISA (Euroimmun, Lübeck, Germany). The cut off value of ≥0.1 IU/ml (anti-diphtheria), >0.1 IU/ml (anti-tetanus), >40 IU/ml (anti-pertussis toxin), ≥200 IU/l (anti-measles), ≥45 RU/ml (anti-mumps) and ≥10 IU/ml (anti-rubella) were used to assess the percentage of newborns with protective IgG concentrations, respectively. The results revealed that 61.3%, 73.2%, 97.4%, 30.4%, 65.5% and 17.0% of newborns had no protection against diphtheria, tetanus, pertussis, measles, mumps and rubella. Only 1.0% and 23.7% of newborns had protection against all three components of DTP or MMR, respectively. The finding suggested that most of newborns were susceptible to diphtheria, tetanus, pertussis and mumps, almost one-third of this population had no immune protection against measles, and about one-sixth of them were under threat of rubella infection. These data supported the immunization program for DTP and MMR vaccine in women at child-bearing age.

A General Lack of IgG Against Pertussis Toxin in Chinese Pregnant Women and Newborns.

BACKGROUND: To investigate the level of pertussis-related antibodies in pregnant women and newborns. METHODS: A total of 286 serum samples from healthy pregnant women and 221 cord samples from newborns were collected in 2016 in Beijing. A routine blood sample from pregnant women was obtained at 35 weeks of gestational age, and cord samples were collected in 20 minutes after delivery. The values from cord samples were used as the infant values. Anti-pertussis toxin (PT) IgG concentration was measured by ELISA (Euroimmun, Lübeck, Germany) using purified PT as a coating antigen. Newborns with anti-PT IgG ≤40 IU/mL in cord samples were considered to be unprotected against pertussis. Anti-PT IgG ≥100 IU/mL was considered to be indicative of a recent pertussis infection in pregnant women. RESULTS: The anti-PT IgG concentration below the lower limit of detection (<5 IU/mL) occurred in 74.1% (212/286) of pregnant women and 66.5% (147/221) of newborns. Even with detectable anti-PT antibodies, the majority of pregnant women (79.7%, 59/74) and newborns (73.0%, 54/74) had antibody level of 5 to <20 IU/mL, and 13.5% (10/74) of pregnant and 14.9% (11/74) of newborns had antibody level of 20 to <40 IU/mL. The 75% percentiles for anti-PT IgG of pregnant women and newborns were 5.08 and 6.98 IU/mL, respectively. The prevalence of unprotected newborns as defined by anti-PT IgG ≤40 IU/mL was 95.9% (202/211). The prevalence of recent pertussis infection in pregnant women as defined by anti-PT IgG ≥100 was 0.7% (2/286). CONCLUSIONS: The pregnant women and newborns were generally lack of protective antibody and are vulnerable to pertussis in Beijing, China. Although acellular pertussis vaccine is administrated in infancy in China, a booster vaccination to pregnant women should be considered for protecting young infants who are too young to start pertussis vaccination.

Performances of biological aerated filter employing hollow fiber membrane segments of surface-improved poly (sulfone) as biofilm carriers.

Using the surface of poly (sulfone) hollow fiber membrane segments as grafted layer, the hydrophilic acrylamide chain was grafted on by UV-photoinduced grafting polymerization. The gained improvement of surface wettability for the modified membrane was tested by measuring the contact-angle as well as FTIR spectra. Then correlation between the hydrophilic ability of support material and the biofilm adherence ability was demonstrated by comparing the pollutant removal rates from urban wastewater via two identical lab-scale up-flow biological aerated filters, one employed the surface wettability modified poly (sulfone) hollow fiber membrane segment as biofilm carrier and the other employed unmodified membrane segment as biofilm carrier. The experimental results showed that under the conditions of influent flux 5 L/h, hydraulic retention time 9 h and gas to liquid ratio (G/L) 10:1, the removal rates of chemical oxygen demand (COD) and ammonium nitrogen (NH4(+)-N) for the modified packing filter and the unmodified packing filter was averaged at 83.64% and 96.25%, respectively, with the former filter being 5%-20% more than the latter. The effluent concentration of COD, NH4(+)-N and turbidity for the modified packing filter was 25.25 mg/L, 2 mg/L and 8 NTU, respectively. Moreover, the ammonium nitrogen removal performance of the filter packing the modified PSF was compared with the other bioreactor packing of an efficient floating medium. The biomass test indicated that the modified membrane matrixes provided better specific adhesion (3310-5653 mg TSS/L support), which gave a mean of 1000 mg TSS/L more than the unmodified membrane did. In addition, the phenomenon of simultaneous denitrification on the inner surface of the support and nitrification on the outer surface was found in this work.

Ultravilolet-radiation-induced graft polymerization of acrylamide onto the melt-blown polypropylene filter element by dynamic method.

By dynamic method under UV irradiation, commercial melt-blown polypropylene (PPMB) filter element was modified with acrylamide (AAm) using benzophenone (BP) as initiator. Attenuated total reflection-Fourier transform infrared spectroscopy and scanning electron microscope verified that polyacrylamide chain was grafted on the fiber surface of PPMB filter element. Elemental content analysis with energy dispersive X-ray of fibers revealed that the polymerization content in the inner part of filter element was relatively higher than that in the outer. Degree of grafting changed with initiator concentration, monomer concentration, reaction temperature and reached 2.6% at the reaction condition: CBP=0.06 mol/L, CAAm=2.0 mol/L, irradiation time: 80 min, temperature: 600 degrees C. Relative water flux altered with the hydrophilicity and pore size of filter element. In the antifouling test, the modified filter gave greater flux recovery (approximately 70%) after filtration of the water extract of Liuweidihuang, suggesting that the fouling layer was more easily reversible due to the hydrophilic nature of the modified filter.

Gas-initiation under UV and liquid-grafting polymerization on the surface of polysulfone hollow fiber ultrafiltration membrane by dynamic method.

Using the inner-surface of polysulfone hollow fiber ultrafiltration membranes as grafted layer, the method of gas-initiation and liquid-polymerization has been studied, which aimed to adjust the diameter of the pores in the membranes. The degree of polymerization varied with the changes of the parameters, such as irradiation time, monomer concentration, temperature and time of polymerization and soon. The results indicated that using benzophenone (BP) which is in a gaseous condition as photo-initiator, acrylamide as graft monomer, the polyacrylamide chain was grafted on the surface of membranes. After the surface membrane being modified, the water flux and retention altered, and thus it can be seen that the diameter of the pores in the membrane was altered. These experiments contribute to finding a new way to produce the hollow fiber membrane with the small pore size and are extraordinarily worth developing and studying.

[Experimental study of traditional Chinese medicine in the treatment of vascular dementia].

To explore the new progress of the experimental study of traditional Chinese medicine in the treatment of vascular. Consulted the relevant papers and integrated the elementary theory, we summarized the virtue of Chinese medicine in the treatment of vascular dementia and insufficient and future development of the experimental study of it. It was confirmed that the traditional Chinese medicine has a lot of target spots in the brain and less ill-effect, it could ameliorate several phenotypes of pathophysiology of vascular dementia and improve the ability of learning and memory of animals with vascular dementia.

[Inflammatory-modulating mechanism of transcutaneous electrical acupoint stimulation combined with general anesthesia or controlled hypotension on postoperative hippocampal neuroprotection].

OBJECTIVE: To observe the effects of transcutaneous electrical acupoint stimulation (TEAS) combined with general anesthesia or controlled hypotension on hippocampal neuronal damage and the inflammatory response in peripheral circulation and central nervous system (CNS) after surgery, and to investigate its brain protection mechanism. METHODS: Eighteen healthy male beagles aged 6 - 8 months were randomly divided into a general anesthesia group (group G), a controlled hypotension group (group C) and a compound anesthesia acupuncture group (group A), 6 cases in each group. Dogs in group G was anesthetized by isoflurane inhalation, and group C was combined with intravenous infusion of sodium nitroprusside based on isoflurane inhalation to induce hypotension, and followed surgery after achieving the target blood pressure, and group A was combined with TEAS at "Quchi" (LI 11), "Hegu" (LI 4) "Zu sanli" (ST 36) and "Sanyinjiao" (SP 6) based on controlled hypotension, and then brain tissue was taken out on the 72 h after mean arterial pressure (MAP) was returned to baseline levels. The concentration of IL-1beta,TNF-alpha in serum at different time points were detected by ELISA. The expression of IL-1beta, TNF-alpha, Bcl-2, Bax and cleaved caspase-3 were measured by immunohistochemistry, and the apoptosis of hippocampus were detected by TUNEL. RESULTS: (1) At different time points, the concentration of TNFalpha showed the trend of increase first and then decrease, while IL-1beta concentration represented a trend of decrease first and then increase in both group C and group A, but there were no significant differences in cytokine expression between the two groups (all P > 0.05). (2) The ratio of positive cells of IL-1beta, TNF-alpha and caspase-3 in CA1 and CA3 of hippocampus in both group C and A were higher than those in group G (all P < 0.01), and cytokines expression in group A were lower than those in group C (all P < 0.01), and caspase-3 in CA1 in group A was lower than that in group C (P < 0.01). The ratio of Bcl-2/Bax in both group C and A were lower than that in group G (all P < 0.01), and that in group A was higher than that in group C (P < 0.01 in CA1, P < 0.05 in CA3). (3) The apoptosis index (AI) of hippocampal neurons in both group C and A was significantly higher than that in group G (P < 0.01), while AI in CA1 in group A was lower than that in group C (P < 0.01). CONCLUSION: The TEAS can regulate the expression of inflammatory factor in hippocampus in animals undergoing general anesthesia or con trolled hypotension surgery, further improving Bcl-2/Bax ratio, inhibiting the expression of caspase-3 and reducing neuron apoptosis in hippocampus so as to play a neuroprotection.

Effects of brain histamine on memory deficit induced by nucleus basalis-lesion in rats.

AIM: To investigate whether or not brain histamine was involved in memory deficits induced by lesions of nucleus basalis magnocellularis (NBM) in rats. METHODS: Passive avoidance response was used to measure memory process in rats, and NBM was bilaterally lesioned by injection of ibotenic acid (6 microg/site). RESULTS: Icv injection of histamine (500 ng), and ip injection of histidine (1500 mg/kg), metoprine (10 mg/kg) or tacrine (3, 5 mg/kg) ameliorated memory impairment induced by NBM lesion regarding passive avoidance response. The ameliorating effect of histidine was antagonized by pyrilamine (2-5 mg/kg), a H1-antagonist, but not by zolantidine, a H2-antagonist. CONCLUSION: Histaminergic neurons play an important role in learning and memory via H1-receptor, and its action may be due to cholinergic neurons.

Effects of histidine, a precursor of histamine, on pentylenetetrazole-induced seizures in rats.

AIM: The effect of histidine on pentylenetetrazole-induced seizures was investigated in rats. METHODS: Chemical kindling was elicited by repeated ip injection a subconvulsant dose of pentylenetetrazole (35 mg/kg) once every 48 h until the occurrence of seizure stages 4-5, and seizure activity of kindling was recorded for 30 min. RESULTS: In the kindling development process, ip injection of histidine (200, 500 mg/kg), a precursor of histamine, prolonged latency for the onset of myoclonic jerks and the clonic generalized seizure, and inhibited seizure stage in a dose-dependent manner. In the kindling challenge process, histidine (500, 1000 mg/kg) and H3 antagonist thioperamide (10, 20 microg) al so showed a significant anticonvulsant effect. The inhibitory action of histidine was enhanced significantly by thioperamide (5 microg), however, was antagonized by both alpha fluoromethylhistidine (20 microg), a selective histidine decarboxylase inhibitor and H1 ant agonist pyrilamine (2, 5 mg/kg), dose-dependently and significantly. In addition, H2 antagonist zolantidine appeared no appreciable effect, even at a dose of 10 mg/kg. CONCLUSION: These results indicated that brain endogenous histamine may play certain important role in protect against generalized clonic seizures, its action may via presynaptic H3-receptors and postsynaptic H1-receptors.