mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice.

The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane. However, the molecular mechanism by which sevoflurane activates the NLRP3 inflammasome in microglia remains unclear. The cGAS-STING pathway is an evolutionarily conserved inflammatory defense mechanism. The role of the cGAS-STING pathway in sevoflurane-induced NLRP3 inflammasome-dependent neuroinflammation and the underlying mechanisms require further investigation. We found that prolonged anesthesia with sevoflurane induced cognitive dysfunction and triggered the neuroinflammation characterized by the activation of NLRP3 inflammasome in vivo. Interestingly, the cGAS-STING pathway was activated in the hippocampus of mice receiving sevoflurane. While the blockade of cGAS with RU.521 attenuated cognitive dysfunction and NLRP3 inflammasome activation in mice. In vitro, we found that sevoflurane treatment significantly activated the cGAS-STING pathway in microglia, while RU.521 pre-treatment robustly inhibited sevoflurane-induced NLRP3 inflammasome activation. Mechanistically, sevoflurane-induced mitochondrial fission in microglia and released mitochondrial DNA (mtDNA) into the cytoplasm, which could be abolished with Mdivi-1. Blocking the mtDNA release via the mPTP-VDAC channel inhibitor attenuated sevoflurane-induced mtDNA cytosolic escape and reduced cGAS-STING pathway activation in microglia, finally inhibiting the NLRP3 inflammasome activation. Therefore, regulating neuroinflammation by targeting the cGAS-STING pathway may provide a novel therapeutic target for POCD.

Droplet freeze-thawing system based on solid surface vitrification and laser rewarming / 生物医学工程学杂志

Ultra-rapid cooling and rewarming rate is a critical technical approach to achieve ice-free cells during the freezing and melting process. A set of ultra-rapid solid surface freeze-thaw visualization system was developed based on a sapphire flim, and experiments on droplet freeze-thaw were carried out under different cryoprotectant components, volumes and laser energies. The results showed that the cooling rate of 1 μL mixed cryoprotectant [1.5 mol/L propylene glycol (PG) + 1.5 mol/L ethylene glycol (EG) + 0.5 mol/L trehalose (TRE)] could be 9.2×10 3 °C/min. The volume range of 1-8 μL droplets could be vitrified. After comparing the proportions of multiple cryoprotectants, the combination of equal proportion mixed permeability protectant and trehalose had the best vitrification freezing effect and more uniform crystallization characteristics. During the rewarming operation, the heating curve of glassy droplets containing gold nanoparticles was measured for the first time under the action of 400-1 200 W laser power, and the rewarming rate was up to the order of 10 6 °C/min. According to the droplet images of different power rewarming processes, the laser power range for ice-free rewarming with micron-level resolution was clarified to be 1 400-1 600 W. The work of this paper simultaneously realizes the ultra-high-speed temperature ramp-up, transient visual observation and temperature measurement of droplets, providing technical means for judging the ice free droplets during the freeze-thaw process. It is conducive to promoting the development of ultra-rapid freeze-thaw technology for biological cells and tissues.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.@*METHODS@#A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.@*RESULTS@#Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).@*CONCLUSIONS@#There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Progress in research and development of Xanthoceras sorbifolia / 中国中药杂志

Xanthoceras sorbifolia, an excellent oil-rich woody species, has high comprehensive economic value in edible, medicinal, and ornamental fields. The chemical composition, pharmacological effect, and quality control of X. sorbifolia were introduced, and its development and application were reviewed in this study. As revealed by the previous research, the main chemical constituents of X. sorbifolia were triterpenoids, flavonoids, fatty acids, phenylpropanoids, steroids, phenolic acids, organic acids, etc. It possesses pharmacological effects, such as neuroprotection, bacteriostasis, anti-oxidation, anti-tumor, anti-inflammation, analgesia, anti-HIV, and anti-coagulation. X. sorbifolia is widely applied in medical, food, chemical industry, and other fields, and deserves in-depth research and development.

Apocynin inhibits placental TLR4/NF-κB signaling pathway and ameliorates preeclampsia-like symptoms in rats.

OBJECTIVE: We aimed to investigate the potency of apocynin in ameliorating preeclampsia and explore the underlying mechanisms. METHODS: Preeclampsia model was constructed in rats by administering 200 mg/kg/day L-NAME. Apocynin was given orally in drinking water. Systolic blood pressure and proteinuria were monitored during treatment. Survival rate rate of the pups and placental weight were assessed. Serum sFlt-1, PIGF, IL-6 and placental TLR4 levels were measured using ELISA or qRT-PCR. RESULTS: Apocynin dose-dependently decreased systolic blood pressure and proteinuria during gestation. Survival rate of the pups and placental weight were improved by apocynin treatment. Apocynin ameliorated the imbalance of sFlt-1 and PIGF in serum and placenta of rats with preeclampsia. Apocynin attenuated serum inflammatory cytokine expression and placental inflammation most likely due to downregulation of the placental TLR4/NF-kB pathway in L-NAME treated rats. CONCLUSIONS: Apocynin potently ameliorates the L-NAME-induced preeclampsia, which is achieved by re-balancing the sFlt-1 and PIGF levels, attenuating inflammation, and inhibiting TLR4/NF-κB p65 signaling.

Effects of intravitreal injection of triamcinolone acetonide on angiogenesis and Notch pathway in photochemistry-induced retinal branch vein occlusion model in rats / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the effects of intravitreal injection of triamcinolone acetonide(TA)on angiogenesis and Notch pathway in photochemistry induced branch retinal vein occlusion(BRVO)model in rats. <p>METHODS: BRVO model rats were induced by photochemistry induction and randomly divided into BRVO model group and TA(1, 7, 21)d groups; at the same time, blank control group was set for comparison. The intraocular pressure of rats was measured by ophthalmotonometer; the condition of rat fundus was observed fluorescein fundus color photography(FFA)and optical coherence tomography(OCT); retinal angiogenesis related factors vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor 2(VEGFR2), the protein expressions of Notch pathway important factors Notch 1, Jagged 1 and DLL4 were detected in rat retina by Western blotting(WB). <p>RESULTS: In the normal control group, the fundus vessels were arranged neatly and in a clear state. In the BRVO model group, edema appeared in the fundus, the retina turned white, the arrangement of blood vessels was disordered, the optic disc pit was disappeared, retinal vessels were in the state of vasoconstriction. In TA 1, 7 and 21d groups, edema gradually decreased, blood vessels expansion and bending gradually slowed down, and the optic disc pit was restored. Compared with the blank control group, the intraocular pressure of BRVO model group increased, the thickness of the retina increased at the injured site and 250μm far from injured site, the protein expressions of VEGF, VEGFR2, Notch1 and Jagged1 increased, the protein expression of DLL4 protein was decreased(<i>P</i><0.05). Compared with the BRVO model group, in TA 1d group, the retinal thickness decreased at 250μm far from injured site, the protein expressions of VEGFR2, Notch1 and Jagged1 decreased, the protein expression of DLL4 protein increased; in TA 7d group, the retinal thickness was decreased at the injured site and 250μm far from injured site, the protein expressions of VEGFR2, Notch1 and Jagged1 decreased, the protein expression of DLL4 protein increased; the intraocular pressure of TA 21d group decreased, the thickness of the retina decreased at the injured site and 250μm far from injured site, the protein expressions of VEGF, VEGF R2, Notch1 and Jagged1 decreased, the protein expression of DLL4 protein increased(<i>P</i><0.05). <p>CONCLUSION: Vitreous injection of TA may inhibit angiogenesis by regulating Notch pathway to inhibit the activation of VEGF, thus achieving the retinal protection in BRVO rats.

A review of time-effect research on acupuncture in experimental rats/mice in the recent 10 years / 针灸推拿医学（英文版）

Objective: To summarize the influence patterns of related time factors on acupuncture effectiveness in different disease model rats/mice, and to provide reference for acupuncture clinical practice. Methods: Retrieved the relevant literatures on time-effect experimental studies of acupuncture in rats/mice in the recent 10 years. The correlations between the key time factors (such as different intervention timings of acupuncture, acupuncture moments, operation durations, needle-retaining times, intervals and treatment courses) and the acupuncture effect were analyzed and summarized. Results: From the mainstream perspective of quantification, the earlier the acupuncture intervention, the better. The proper time to implement acupuncture varied depending on disease models and points. The best operation time varied widely between different diseases. The most frequently needle-retaining time was 20-30 min. The frequency of acupuncture was usually 1 time/day; the length of the treatment course was determined according to practitioners' experience. Conclusion: Throughout the time-effect studies of acupuncture intervention in experimental rats/mice, conclusions are inconsistent, especially the lack of quantitative research on acupuncture operation time, acupuncture frequency, acupuncture treatment duration, and optimal stimulation amount. Future research should explore and determine the best time-quantity parameters that affect the effectiveness of acupuncture intervention, which is the key and goal of the acupuncture time-effect research. Independent intervention-time experiments throughout the entire course of a single disease (dominant disease) need to be done to guide clinical and disciplinary development.

Effects of intravitreal injection of triamcinolone acetonide on angiogenesis and Notch pathway in photochemistry-induced retinal branch vein occlusion model in rats / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the effects of intravitreal injection of triamcinolone acetonide(TA)on angiogenesis and Notch pathway in photochemistry induced branch retinal vein occlusion(BRVO)model in rats. <p>METHODS: BRVO model rats were induced by photochemistry induction and randomly divided into BRVO model group and TA(1, 7, 21)d groups; at the same time, blank control group was set for comparison. The intraocular pressure of rats was measured by ophthalmotonometer; the condition of rat fundus was observed fluorescein fundus color photography(FFA)and optical coherence tomography(OCT); retinal angiogenesis related factors vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor 2(VEGFR2), the protein expressions of Notch pathway important factors Notch 1, Jagged 1 and DLL4 were detected in rat retina by Western blotting(WB). <p>RESULTS: In the normal control group, the fundus vessels were arranged neatly and in a clear state. In the BRVO model group, edema appeared in the fundus, the retina turned white, the arrangement of blood vessels was disordered, the optic disc pit was disappeared, retinal vessels were in the state of vasoconstriction. In TA 1, 7 and 21d groups, edema gradually decreased, blood vessels expansion and bending gradually slowed down, and the optic disc pit was restored. Compared with the blank control group, the intraocular pressure of BRVO model group increased, the thickness of the retina increased at the injured site and 250μm far from injured site, the protein expressions of VEGF, VEGFR2, Notch1 and Jagged1 increased, the protein expression of DLL4 protein was decreased(<i>P</i><0.05). Compared with the BRVO model group, in TA 1d group, the retinal thickness decreased at 250μm far from injured site, the protein expressions of VEGFR2, Notch1 and Jagged1 decreased, the protein expression of DLL4 protein increased; in TA 7d group, the retinal thickness was decreased at the injured site and 250μm far from injured site, the protein expressions of VEGFR2, Notch1 and Jagged1 decreased, the protein expression of DLL4 protein increased; the intraocular pressure of TA 21d group decreased, the thickness of the retina decreased at the injured site and 250μm far from injured site, the protein expressions of VEGF, VEGF R2, Notch1 and Jagged1 decreased, the protein expression of DLL4 protein increased(<i>P</i><0.05). <p>CONCLUSION: Vitreous injection of TA may inhibit angiogenesis by regulating Notch pathway to inhibit the activation of VEGF, thus achieving the retinal protection in BRVO rats.

Mangiferin ameliorates gestational diabetes mellitus-induced placental oxidative stress, inflammation and endoplasmic reticulum stress and improves fetal outcomes in mice.

Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which causes maternal diabetic symptoms and abnormal fetal development, and influence the health of maternal-child in clinical practice. Mangiferin is a bioactive ingredient with anti-inflammation, anti-oxidation and anti-endoplasmic reticulum stress activities. In current study, the effects of mangiferin on GDM were evaluated. We reported that mangiferin greatly improved altered glucose and lipid profile, insulin tolerance, and reproductive outcomes of the GDM mice. Mangiferin ameliorated placental oxidative stress, inflammation and ER stress in GDM mice. Therefore, we demonstrated that mangiferin displayed protective effects on gestational diabetes mellitus symptoms by suppressing placental oxidative stress, inflammation and endoplasmic reticulum stress in GDM mice.

Effect of histone deacetylase and its inhibitor on tumor / 国际肿瘤学杂志

The occurrence and progress of tumor is the result of the interaction of heredity and epigenetics. Histone deacetylation modification,as an important epigenetic modification,plays an important role in tumorigenesis and development. The abnormal expression of histone deacetylase in normal tissues and cells promotes the development of tumor and is related to the proliferation and apoptosis,angiogenesis,metastasis and drug resistance of tumor cells,and becomes a new target of tumor therapy. Histone deacetylase inhibitors as anti-tumor drugs have a good prospect of application.

Analysis on the Countermeasures and the Investigation of the Current Situation of Medical Students'Humanistic Quality / 医学信息学杂志

The paper analyzes the current problems of medical students'humanistic quality and the causes,points out the necessity of strengthening the humanistic quality of medical students,and puts forward the countermeasures to be taken by libraries of medical colleges in the humanistic quality education for college students,including strengthening the construction of medical humanistic resources,doing well of medical humanistic reading guide and entrance education for new students,and strengthening reading promotion activities,etc.

Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia.

BACKGROUND/AIMS: Accumulating evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with exaggerated activation of the innate immune system plays a critical role in the development of preeclampsia (PE). In this study, we investigated whether polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with susceptibility to PE in the Chinese Han population. METHODS: We recruited 987 PE patients and 1227 healthy pregnant women. Two polymorphisms (rs3775291 and rs3775296) located in TLR3 were genotyped by TaqMan allelic discrimination real-time PCR. The association between the genotype or allele frequencies and PE was examined using chi-square tests. Clinical data were compared between cases and controls using Student's t test. RESULTS: No significant difference was determined in the genetic distribution of rs3775291 and rs3775296 between cases and controls. There were also no significant differences in the genotype and allele frequencies of either SNP between healthy pregnant women and patients with late or early onset PE, or with mild or severe PE. CONCLUSION: Although this is the first study of the association between TLR3 polymorphisms and preeclampsia, we found that TLR3 polymorphisms are unlikely to play a significant role in the development of preeclampsia in the Chinese Han population.

Study on stability and degradation kinetics of ketoprofen-paeonol conjugate / 中国中药杂志

<p><b>OBJECTIVE</b>To study the stability and degradation kinetics of Ketoprofen-Paeonol conjugate (Ket-Pae).</p><p><b>METHOD</b>RP-HPLC method was used to determine the solubility and partition coefficient of Ket-Pae. Stability test was carried out to investigate the factors affecting Ket-Pae. The kinetic studies of Ket-Pae degradation were conducted in different pH buffer solutions and 80% rat plasma at 37 degrees C.</p><p><b>RESULT</b>Ket-Pae showed significant degradation phenomenon at high temperature. The solubility of Ket-Pae was decreased about 200 to 300 times compared with parent drugs in water while the lnP increased about 4 times. The degradation curve displayed a V-shape, and kept maximum stability at week acidic (pH 5.0, t(1/2) = 11.4 d). Ket-Pae degraded quickly with very short half life of 1.3 min in plasma, therefore easily released ketoprofen and paeonol.</p><p><b>CONCLUSION</b>The lipophilicity of Ket-Pae is increased, its stability is affected by temperature and pH value.</p>

Preparation and in vitro evaluation of dispersible tablet of total notoginseng saponin / 中成药

AIM: To establish the preparative method of dispersible tablet of total notoginseng saponin (DTTNS) by powder direct compression,and to evaluate it pharmaceutical characteristics. METHODS: The effect of factors on the disintegration of DT-TNS was investigated by single factor method,and the formulation was optimized through orthogonal design. RESULTS: The disintegration time of DT-TNS containing 40% total notoginseng saponin was within 1 min while the formulation mainly consisted of 49% MCC as filler,12% of PVPP mixed with 3% L-HPC as disintegrating agent. In addition,the dissolution of DT-TNS was almost finished in 10-15 min. CONCLUSION: The preparative method of DT-TNS by powder direct compression is simple,with short disintegration time and high dissolution rate.