Objective To investigate the predictive value of the diagnostic model constructed by CT radiomics combined with clin-ical and CT features for the P53 mutation status in lung adenocarcinoma.Methods The data of 177 patients with lung adenocarcinoma were retrospectively collected,including 75 cases of P53 mutant type and 102 cases of wild type.They were randomly divided into training cohort(n=123)and validation cohort(n=54)in a 7∶3 ratio.The region of interest(ROI)was delineated using MaZda software,and the features were screened using the least absolute shrinkage and selection operator(LASSO).The predictive model was devel-oped based on logistic regression analysis,and its diagnostic efficacy was evaluated.Results There were statistically significant differences in lesion diameter,maximum solid component diameter,lobulation sign,and lymph node metastasis between the two groups in the training cohort(P＜0.05).The area under the curve(AUC)in the training cohort of the radiomics score model,clinical imaging feature model,and combined model were 0.778,0.759,and 0.817,and the AUC in the validation cohort were 0.668,0.722,and 0.783,respectively.The clinical decision curve suggested that the combined model demonstrated superior clinical net benefits.Conclusion The combined model constructed by CT radiomics,lesion diameter,and lymph node metastasis has better predictive value for the P53 mutation status in lung adenocarcinoma.

Objective To investigate the predictive value of the diagnostic model constructed by CT radiomics combined with clin-ical and CT features for the P53 mutation status in lung adenocarcinoma.Methods The data of 177 patients with lung adenocarcinoma were retrospectively collected,including 75 cases of P53 mutant type and 102 cases of wild type.They were randomly divided into training cohort(n=123)and validation cohort(n=54)in a 7∶3 ratio.The region of interest(ROI)was delineated using MaZda software,and the features were screened using the least absolute shrinkage and selection operator(LASSO).The predictive model was devel-oped based on logistic regression analysis,and its diagnostic efficacy was evaluated.Results There were statistically significant differences in lesion diameter,maximum solid component diameter,lobulation sign,and lymph node metastasis between the two groups in the training cohort(P＜0.05).The area under the curve(AUC)in the training cohort of the radiomics score model,clinical imaging feature model,and combined model were 0.778,0.759,and 0.817,and the AUC in the validation cohort were 0.668,0.722,and 0.783,respectively.The clinical decision curve suggested that the combined model demonstrated superior clinical net benefits.Conclusion The combined model constructed by CT radiomics,lesion diameter,and lymph node metastasis has better predictive value for the P53 mutation status in lung adenocarcinoma.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human body networks mechanisms and the clinical applications of melatonin were summarized to provide reference for exploring the focus and direction of further clinical application research.

【Objective】 To investigate the distribution characteristics of Rh blood group antigen phenotypes, haplotypes and irregular antibodies between patients in our hospital and local blood donors, so as to ensure safe and effective blood transfusion and improve the rationality and scientificity of clinical blood transfusion. 【Methods】 A total of 113 326 blood samples, from hospitalized patients in our hospital and local blood donors from October 2015 to March 2020, were subjected to Rh antigen typing and irregular antibody detection. The frequency of Rh phenotypes, haplotypes, and irregular antibodies were retrospectively analyzed and calculated. Chi square test was used to compare the data among different population groups. Rh antigen typing and irregular antibody detection were completed using the automatic blood group analyzer. 【Results】 The prevalence of negative RhD was 0.36% (408/113 326). The most prevalent Rh phenotype was DCCee [40.69%(46 112/ 113 326)] followed by DCcEe [36.82%(41 727/ 113 326)]. Anti-E was the most common irregular antibody, accounting for [0.26%(295/ 113 326)], and DCe [62.51%(70 840/ 113 326)] was the most common haplotype. The most common Rh phenotypes and haplotypes in Caucasians in Germany, North Indian and North African were DCcee, DCCee and Dccee, while DCe, DCe and Dce, respectively. 【Conclusion】 The distribution characteristics of Rh phenotypes, haplotypes and irregular antibodies of patients in our hospital and local blood donors were in line with the distribution characteristics of the population in northern China. Corresponding plans concerning blood storage and collection, as well as the establishment of Rh blood type registry should be carried to effectively ensure the safety, rationality and accuracy of clinical blood transfusion.

Acute ischemic stroke (AIS), as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract (GBE) against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell-astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B (GB), against oxygen-glucose deprivation/reoxygenation and glucose (OGD/R) injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein (Na-F), and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.
Animals ; Apoptosis ; drug effects ; Brain Ischemia ; drug therapy ; Cell Survival ; Cells, Cultured ; Disease Models, Animal ; Endothelial Cells ; drug effects ; Ginkgolides ; pharmacology ; Glucose ; Lactones ; pharmacology ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Oxygen ; Plant Extracts ; pharmacology ; Rats ; Stroke ; drug therapy

OBJECTIVETo observe the effect of the extract of Ginkgo biloba (EGb761) and the components isolated from the extract named ginkgolide B (GB) against damage of glutamate in pretreatment modes so that determine their application value and approach.

METHODBased on glutamate-induced excitotoxicity to primary cultures from neonatal Sprague-Dawley (SD) rat hippocampal neuron, our experiment utilized trypan blue, TUNEL and LDH to study the effect of EGb761 and GB on neuron in different doses pretreatment modes, as well as to compare with the NMDA receptor uncompetitive antagonist-MK-801.

RESULTEGb761 and GB can recrease cell viability, reduce apoptosis rate and decrease LDH leakage in different degree and depended on dose in certain range. The maximal protection was achieved at a concentration of 100 mg x L(-1), 100 micromol x L(-1), but inferior to MK-801 (10 micromol x L(-1)). The protective effect of GB is superior to EGb761.

CONCLUSIONTreatment with EGb761 and GB could protect the neurons against glutamate-induced injury. The maximal protection of GB was achieved by pretreatment is superior to EGb761, so its precautionanary intervention to high-risk population could have more value.

Animals ; Animals, Newborn ; Cells, Cultured ; Dizocilpine Maleate ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Ginkgo biloba ; chemistry ; Ginkgolides ; chemistry ; pharmacology ; In Situ Nick-End Labeling ; L-Lactate Dehydrogenase ; metabolism ; Lactones ; chemistry ; pharmacology ; Neurons ; drug effects ; Neuroprotective Agents ; chemistry ; pharmacology ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley

Objective To investigate the regional cerebral stimulation after central analgesics nasal spray and its mechanism with pharmacological functional magnetic resonance imaging (phfMRI). Methods Eighteen healthy right-handed volunteers participated. Butorphanol tartrate nasal spray was used as the experiment agent. Ethological experiment was carried out to record the participants' subjective feeling and the onset time of the analgesics, followed by the functional MRI (fMRI) scan two weeks later. Block design was adopted. Two phases of fMRI scan were performed at 7 min and 25 min after the nasal spray, respectively. Participants were also given pain stimulation in the dorsum of hand during the fMRI scanning. The data were post-processed with Matlab 6.5 and SPM 2. Results ①Onset time of butorphanol tartrate was 15-35 min after nasal spray administration, which was consistent with its concentration-time curve. ②After nasal spray, activations were observed in the cerebral cortex, including frontal lobe (orbitofrontal gyrus, medial frontal gyrus, superior frontal gyrus), temporal lobe (insula, middle temporal gyrus, inferior temporal gyrus), parietal lobe (precuneal gyrus), limbic system (anterior cingulate gyrus, middle cingulate gyrus, hippocampus, parahippocampal gyrus);subcortical region (globus pallidus) and cerebellum (6-9 of cerebellar cortex, cerebellar peduncle, vermis). ③The number and activation intensity of the second phase were more obvious than those of the first phase (P<0.01). Conclusion The feasibility of phfMRI study on cerebral stimulation and the mechanism of nasal spray is demonstrated. The study of butorphanol tartrate further validates the main distribution of opioid receptors in the central nervous system and the possible mechanism of central analgesia.

Objective To investigate the assistant method for improving and promoting nervous movement functional recovery on neonate hypoxie ischemic encephalopathy. Methods Eighty-five patients with neonate hypoxic ischemic encephalopathy were divided into two groups: observed group (45 cases) and control group(40 cases). Observed group added early exercises intervention on basis of routine synthetic drug treatment, compared to control group which just purely synthetic drug treatment with neonatal behavior neurological assessment (NBNA), mental development index (MDI) and psychomotor development index (PDI). Results NBNA at 14 days [(38.84±1.56)scores] in observed group was significantly higher than that in control group [(36.12±2.23)scores]. PDI at 6, 12 months and MDI at 12 months in observed group were significantly higher than those in control group. Conclusion Early exercises intervention can promote nervous movement functional recovery on neonate hypoxic ischemic encephalopathy, prevent or lessen brain injury sequels, elevate life quality for patients with neonate hypoxic ischemic encephalopathy.

Objective To establish a rat model of middle cerebral artery occlusion (MCAO)by blockage or obstruction of middle cerebral artery. NO precursor L-Arginine (L-ARG) and NO donator Nitroglycerine (NG)are administrated from intraearotid arteries. DWI and PWI are applied to evaluate blood circulation and brain damage of the effected region to elucidate the piotective function of L-ARG and NG in the early stage of brain ischemia. Methods The middle cerebral artery was occluded by insertion of a suture through the internal carotid artery of SD male rats to duplicate ischemia-reperfusion model. Reperfusion was established by suture withdrawal. After 2 hours of blockage, reperfusion and administrate L-ARG,NG by interventional therapy through the internal carotid artery simultaneously. Image indexes such as T1WI, T2WI, DWI and PWI are utilized to assess the changes in different time points. These indexes, Longa score and TTC stain were compared. Results There were obvious decrease in DWI high signal region and Trc pale region in drugs groups, compared with MCAO group(P＜0.01).ADC and rADC values in DWI high signal region increased gradually from 2 hours after ischemia to 24 hours after reperfusion in each group. ADC and rADC values in DWI high signal region of the drugs groups increased obviously(P＜0.01).Conclusion Interventional therapy with NO precursor/donator showed significant protective function in the early stage of brain ischemia.