Brain ; pathology ; Humans ; Infant, Newborn ; Lung ; pathology ; Male ; Seizures ; etiology ; pathology ; Tomography, X-Ray Computed ; Tuberous Sclerosis ; complications ; pathology

As one of the serious complications of diabetes, diabetic retinopathy( DR) has become a main eye disease which causes blindness. The occurrence and development of DR is related to many factors. The pathogenesis is complicated, and the mechanism has not been clear. Early data suggest that the occurrence and development of DR has relations with many factors such as blood sugar level, diabetes duration and the environment. Among the factors, mitochondrial dysfunction and oxidative stress is the important mechanisms of DR and has become research focus in recent years. Consequences of mitochondrial dysfunction within cells include elevation of the rate of reactive oxygen species( ROS) production due to damage of electron transport chain proteins, mitochondrial DNA ( mtDNA ) damage, and loss of metabolic capacity. Clear understanding on the mechanism of mitochondrial functional change under high sugar level and oxidative stress response in the occurrence and development of DR is of great significance on prevention and cure of DR. ln this article, the development of mitochondrial metabolism and oxidative stress of DR is reviewed.

To study the effect of wearing overnight orthokeratology ( OK) contact lens on corneal topography and tears in adolescents.METHODS: The diopter, corneal curvature, corneal surface regularity index ( SRl ) , tear break - up time ( BUT ) , Schirmer l test, and corneal fluorescent ( FL ) were recordedon 40 (80 eyes) adolescent myopia patients (mean age 13. 68±2. 32 years), who had worn OK contact lensfor more than 1 year, with mean spherical equivalent refraction -3. 61 ± 1. 48D before wearing OK contact lens. These indexes were tested and recorded before the patients' wearing OK contact lens and 5 times (1wk and 1, 3, 6, 12mo after the first wearing) during the patients' overnight wearing OK contact lens for 8~10 hours per day.RESULTS: Compared with pre - wearing, at post -wearing OK contact lens 12mo, the mean spherical equivalent refraction was apparently decreased from -3.61±1. 48D to -1. 39±1. 31D(P<0. 01). The corneal curvature was significantly flattened from 42. 29 ± 1. 55D to 40.13±1. 41D (P<0. 01). Mean SRl was increased from 0. 34± 0. 01 to 0. 37 ± 0. 01 ( P<0. 01 ). Mean BUT was decreased from 10. 39±2. 25s to 7. 26±1. 77s (P<0. 01). These indexes were stable at 1wk after wearing OK contact lens overnight and had no significant differences during the following (1, 3, 6, 12mo after wearing) tests (P > 0. 05 ). There were no significant differences on Schirmer▏test during the 12mo of OK wearing(P>0. 05). The cases of corneal fluorescent staining increased were mainly grade l, and the number of corneal staining grade l at 1 wk and 1, 3, 6, 12 mo after wearing were 15 eyes (18. 8%), 9 eyes (11. 3%),13 eyes (16. 3%), 9 eyes (11. 3%), and 12 eyes (15. 0%). BUT of corneal staining grade l wasdecreased significantly, compared with the BUT of corneal staining grade 0 during the 12mo of OK wearing (P<0. 05). CONCLUSlON: OK contact lens can significantly decrease the degree of myopia and K value of corneal curvature without changing tear volume. However, tear film stability weakens, which needs regular follow-up.

Adolescent ; Adult ; Carbon Monoxide Poisoning ; epidemiology ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Young Adult

italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC₅₀ values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

Objective To preliminarily observe the clinical efficacy of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) using helical tomotherapy (HT) in patients with limited-stage small-cell lung cancer (LS-SCLC) after chemoradiotherapy,and compare HT with intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in dose distribution.Methods From April to June,2014,six patients with LS-SCLC who had achieved a complete remission after chemoradiotherapy were assigned to HS-PCI using HT within a month after brain metastasis was ruled out using brain magnetic resonance imaging (MRI).After fusing CT images and MRI images,the hippocampus was contoured in the fusion images and hippocampal avoidance regions were created using a volumetric expansion of 3 mm around the hippocampus.A dose of 25 Gy in 10 fractions to 95％ of planning target volume (PTV) was prescribed in HT,IMRT,and VMAT.The clinical efficacy,adverse reactions,neurocognitive function,and brain metastasis were evaluated for HT.The dose distribution in PTV and hippocampus were compared between HT,IMRT,and VMAT.Results There were one patient with abdominal wall and abdominal lymph node metastases,one patient with local recurrence,and no patient with brain metastasis during the observation period.The numbers of patients with grade 1 and grade 2 headache,dizziness,and hair loss reactions were 3 and 1,3 and 1,and 4 and 2,respectively.There were no significant differences in the average score of the Mini-Mental State Examination before treatment and at 3 and 6 months after treatment (29.7,29.2,and 29.3 ; P =0.083,0.317,and 0.157).The mean dose to the hippocampus was 16.85 Gy for IMRT and 17.59 Gy for VMAT.For HT,the mean doses to the hippocampus and avoidance regions were reduced to 5.26 Gy and 6.21 Gy,respectively.The prescribed dose for HT was reduced by 79％ and 71％ compared with IMRT and VMAT,respectively.The average coverage rate of the prescribed dose was 94.48％ for HT.Conclusions HT achieves promising dose distribution and target coverage in sparing of the hippocampus.Moreover,HT dose not increase the incidence of adverse reactions.The change in neurocognitive function needs to be further studied with longterm observation and large-scale sampling.

Objective To investigate the role of TNSALP gene detection in prenatal diagnosis of HPP. Method The clinical data and the results of complete exon sequencing of TNSALP gene in one neonate with low alkaline phosphatase (HPP) were analyzed retrospectively. Peripheral bloods from his family members were collected. The amniotic fluid cell in fetuses at 17 weeks was tested for candidate gene mutations by Sanger sequencing. Results Mainly manifestations in 6-day-old baby were multiple fractures, limb shortening and bending and dyspnea. He died of respiratory failure 9 days after birth. The serum alkaline phosphatase was decreased and serum calcium was decreased slightly; serum phosphorus, serum 25 hydroxyvitamin-D and parathyroid hormone were normal. X-ray showed that the whole body bone was very poorly mineralized, and the long diaphysis was enlarged with shape of a cup at the end and multiple fractures existed. Gene sequencing revealed a complex heterozygous missense mutation in the TNSALP gene, including the heterozygous missense mutation c.542C>T in exon sixth causing 181st amino acids changed from serine to leucine (p.S181L), and tenth exon heterozygous missense mutation in c.1016G>A causing 339th amino acid changed from glycine to glutamic acid (p.G339E). The parental phenotypes were normal. The c.542C>T mutation is inherited from his father and the c.1016G>A mutation is inherited from his mother. These two mutations were not detected in the fetus. Conclusion TNSALP gene analysis can be applied to the diagnosis and prenatal diagnosis of HPP.

ObjectiveTo investigate bone marrow mesenchymal stem cells(BMSC) express brain derived neurotrophic factor(BDNF) and nerve growth factor(NGF) and their protective effect for neural stem cells (NSCs).MethodsBMSC were obtained from rat tibiae and femurs and centrifuged with Ficoll. The passage 3 cells were chosen to make immunocytochemical stain for CD44, CD71 and CD45. The expression of BDNF and NGF was detected in BMSC with RT-PCR, as well as in the media with ELISA. The media that cultured BMSC were collected as BMSC condition media. NSCs were obtained from cerebral cortex of new-born rat and cultured in vitro. After different ratio of BMSC condition midia were added, NSCs were induced to apoptosis with heat-shock, then NSCs were dyed with Annexin V-FITC/PI apoptosis kit and apoptosis rates were tested with flow cytometry. ResultsBMSC were CD44(+), CD45(-), CD71(+) and expressed BDNF and NGF mRNA. BDNF and NGF could be tested in the media of cultured BMSC and increase with cultured time. BMSC condition media could reduce the ratio of heat-induced apoptosis of NSCs, and more BMSC condition media showed better effect. ConclusionBMSC can express neurotrophic factores and protect neural stem cells from heat-induced apoptosis.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Cathepsin B from Helicoverpa armigera (HCB) belongs to the group of cysteine proteinases. HCB is proved being involved in the degradation of yolk proteins during embryonic development,which is an acidic preferring enzyme and is resistant to SDS. The expression of the proenzyme may offer a model for investigating the activation of the enzyme. The HCB gene was constructed into pPIC9K and expressed in Pichia pastoris KM71 strain . After induction by methanol, HCB was expressed and secreted into the medium. The molecular weight of the recombinant procathepsin B was determined as about 38 kDa. The expressed product was confirmed to be HCB by immunoblotting assay using specific rabbit anti-HCB polyclonal antibody. The activity of the product was assayed by in situ hydrolysis (gelatin-SDS-PAGE). These results showed that HCB with proteolytic activity was expressed in P. pastoris KM71. This proenzyme can be used for further research on the activation of the proenzyme or industrial production.