BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.

Objective:To investigate the predictive value of a radiomics model based on biparametric magnetic resonance imaging(bpMRI)for biochemical recurrence(BCR)after radical prostatectomy(RP)in elderly prostate cancer patients(≥60 years old).Methods:A retrospective analysis was conducted on data from 175 patients treated at Beijing Hospital from August 2017 to December 2021.Based on pathological results, image segmentation was performed on preoperative bpMRI T2, diffusion weighted imaging(DWI), and apparent diffusion coefficient(ADC)sequences.Pyradiomics was utilized to extract radiomic features, and Cox regression, Spearman correlation coefficient, and LASSO regression were employed for feature dimensionality reduction, leading to the construction of radiomic labels.Clinical models and image-clinical combined models were developed using multifactorial Cox regression analysis, and the performance of these models in predicting BCR was evaluated using the concordance index(C-index).Results:The 175 patients were randomly divided into a training set(122 cases)and a test set(53 cases)at a ratio of 7∶3, with 24 cases(19.7%, 24/122)and 11 cases(20.8%, 11/53)experiencing BCR, respectively.A total of 5 775 radiomic features were extracted from the three sequences, and after dimensionality reduction, 5 features were selected to construct the radiomic labels.The radiomics model exhibited C-index values of 0.764(95% CI: 0.655-0.872)and 0.769(95% CI: 0.632-0.906)in the training and test sets, respectively.Multifactorial Cox regression analysis revealed serum prostate-specific antigen(PSA)( HR=1.032, 95% CI: 1.010-1.054), postoperative pathology International Society of Urological Pathology(ISUP)grade grouping( HR=1.682, 95% CI: 1.039-2.722), and positive surgical margins( HR=2.513, 95% CI: 1.094-5.774)as independent predictors of BCR.The clinical model exhibited C-index values of 0.751(95% CI: 0.655-0.846)and 0.753(95% CI: 0.630-0.877)in the training and test sets, respectively.Following combined modeling of clinical factors and radiomic labels, the image-clinical combined model demonstrated the highest C-index values, namely 0.782(95% CI: 0.679-0.874)and 0.801(95% CI: 0.677-0.915)in the training and test sets, respectively. Conclusions:The radiomics model based on bpMRI can predict the occurrence of BCR after RP in elderly prostate cancer patients.Combined modeling of clinical factors and radiomic labels can enhance predictive efficiency.

To summarize the experience of 5 children with relapsed and refractory acute B lymphocyte leukemia treated with Blinatumomab, during the whole nursing processes, careful nursing was carried out before, during and after infusion. The key points of nursing include: reasonable cooperation with nursing staff and specialized training, design a condition observation form, timely grasp changes in the condition, early identify adverse reactions such as cytokine storms, neurotoxicity, and allergies, and ensure the safety of the children. Through personnel, articles and personalized liquid preparation table, ensure accurate dose, smooth infusion and save hospital expenses ￥3, 846~201, 910 for children. Payattention to the psychological burden of children and their families and attach importance to psychological care. Follow the psychological burden of children and caregivers, and pay attention to psychological nursing. As the results, 3 chidlren successfully completed the first cycle of Blinatumomab. But 2 chidlren interrupted due to the tumor burden. Follow up for 5-12 months showed that 2 cases survived, 1 case died of progressive disease after discharge, and 2 cases died of transplant complications.

Objective: To investigate the role of nucleotidebinding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in hyperalgesia induced by temporomandibular joint osteoarthritis (TMJOA) in rats. Methods : Twenty 6-week-old male SD rats were randomly divided into NS group and MIA group．The rat model of TMJOA was established by injection monosodium iodoacetate ( MIA) into the upper cavity of temporomandibular joint (TMJ) ．The changes of pain threshold in the TMJ region of rats after MIA injection were detected by Von Frey．The changes of condyle structure were observed by Hematoxylin-eosin ( HE ) and Safranin O-fast green stains．Histopathological changes of trigeminal ganglion (TG) were observed by HE stains．The expression and distribution of TG NLRP3 protein were detected by immunohistochemistry．Western blot was used to detect the protein levels of NLRP3 and interleukin (IL) -1 β in TG．The mRNA levels of NLRP3，apoptosis-associated speck-like protein (ASC) ，cysteinyl aspartate specific proteinase ( Caspase-1) ，IL-1β and IL-18 in TG were detected by quantitative real-time polymerase chain reaction ( qRT-PCR) . Results : Compared to saline group，the pain threshold of experimental TMJ osteoarthritis rats decreased (P＜0. 05) ．TMJ and TG showed obvious pathological changes．The protein and mRNA levels of NLRP3 expressed in the tissues of rats in the TMJOA group increased (P ＜0. 05 ) . Conclusion NLRP3 inflammasome may be involved in the regulation of hyperalgesia in TMJOA rats.

A case of pituicytoma was observed in a Han-Wistar rat from the control group of a 2-year carcinogenicity study. No obvious abnormality were found in clinical observation and necropsy. Hematoxylin and Eosin (HE) staining results showed that nodular hyperplasia in the pars nervosa of the pituitary, which was well demarcated and compressed the adjacent normal tissue. The tumor cells were similar to the glial cells with round or oval nuclei, cytoplasm rich in eosinophilic or vacuole. The tumor cells differentiated well, with no obvious cell pleomorphism and visible mitotic figures. Some tumor cells were arranged in a pseudorosette formation. Immunohistochemical staining (IHC) analysis confirmed positive expression of Glial fibrillary acidic protein (GFAP) and S-100 protein. The tumor was diagnosed as the spontaneous benign pituicytoma combining the HE and IHC staining results.

OBJECTIVE To study the effects of Jinbei oral liquid against influenza A H 1N1 virus and secondary Streptococcus pneumoniae infection of rats ，and to provide reference for its clinical application . METHODS Oseltamivir phosphate capsule （25.6 mg/kg）was used as a positive control . Influenza A H 1N1 virus infection model of mice was established by nasal drops of H 1N1 virus containing 0.8 median lethal dose （LD50）. The body mass ，lung index ，lung viral load ，pathological changes of lung tissue ， and serum levels of tumor necrosis factor α（TNF-α），interleukin-1β（IL-1β）and IL -6 were used as indexes to investigate the anti - H1N1 virus effect of 15.6，7.8 and 3.9 mL/kg Jinbei oral liquid in vivo . The model of secondary S. pneumoniae infection was established by nasal drops of H 1N1 virus solution containing 0.5 LD50 and S. pneumoniae solution containing 1×109 colony forming units. The death ，lung index ，nasal and lung bacterial load ，serum levels of interferon -β（IFN-β），IL-17 and IL -23 were used as indexes to investigate the effects of 15.6 mL/kg Jinbei oral liquid against secondary S. pneumoniae infection. RESULTS After 6 days of administration ，both 15.6 and 7.8 mL/kg Jinbei oral liquid significantly increased the abnormally reduced body weight of influenza A H 1N1 virus infected mice ，significantly reduced the abnormally increased lung index and serum levels of TNF -α，IL- 1β，IL-6（P＜0.05）；it also significantly reduced the viral load in the lung （P＜0.05）and alleviated the degree of lung tissue lesions. At the same time ，15.6 mL/kg Jinbei oral liquid significantly prolonged the survival time of mice co -infected 2020CXGC010505， with virus and bacteria （P＜0.05）and reduced the mortality rate；it also significantly increased the abnormally reduced body weight and serum levels of IL -17 and IL -23（P＜0.05）， while reduced the nasal and lung bacterial loads and the abnormally increased serum level of IFN -β （P＜0.05）. CONCLUSIONS Jinbei oral liquid has a certain anti -influenza A H 1N1 virus infection effect of rats and can help the body resist secondary S. pneumoniae infection by restoring the type 17 antibacterial immune function .

Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution. Unfortunately, classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification. We developed a single-cell DNA library preparation method without preamplification in nanolitre scale (scDPN) to address these issues. The method achieved a throughput of up to 1800 cells per run for copy number variation (CNV) detection. Also, our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification (MDA) method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation. We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepato-cellular carcinoma (HCC). We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome. Furthermore, we observed that a minor clone of the primary tumor containing additional alterations in chro-mosomes 1q, 10q, and 14q developed into the dominant clone in the recurrent tumor, indicating clonal selection during recurrence in HCC. Overall, this approach provides a comprehensive and scalable solution to understand genome hetero-geneity and evolution.

OBJECTIVES: To analyze the clinical characteristics of 71 patients with coronavirus disease 2019 (COVID-19). METHODS: The general data, epidemiological data, laboratory tests, imaging examinations, and treatment of 71 patients with COVID-19 admitted to the Sixth People's Hospital of Zhengzhou from January 19, 2020 to March 3, 2020 were retrospectively analyzed. RESULTS: Of the 71 COVID-19 patients, the ages were 4-84 (41.29±15.21) years, 38 (53.5%) patients were male, 33 (46.5%) were female, and 52 (73.2%) were in 22 clusters. The main clinical manifestations were fever (78.9%), cough (64.8%), and sputum (38.0%). The fever was mainly low and moderate, with 49 patients (69.0%) at 37.3-39.0 ℃. Most of the leukocytes, neutrophils, and lymphocytes were normal, accounting for 47 (66.2%), 51 (71.8%), and 51 (71.8%) patients, respectively; a few of them were decreased, accounting for 21 (29.6%), 16 (22.5%), and 20 (28.2%) patients, respectively. There were 38 (53.5%) and 31 (43.7%) patients with the decreased CD4 and CD8 T cell counts, respectively. There were 41 (57.7%), 38 (53.5%), 32 (45.1%), 26(36.6%), 22 (31.0%), 20 (28.2%), 14 (19.7%), 14 (19.7%), and 9 (12.7%) patients with the increased levels of C-reactive protein, erythrocyte sedimentation rate, procalcitonin, fibrinogen,interleukin 6, lactate dehydrogenase,-dimer,alanine aminotransferase, and aspartate aminotransferase, respectively. Of the 71 patients, the lung was involved in 60 (84.5%) patients, the double lung was involved in 47 (66.2%) patients, and the single lung was involved in 13 (18.3%) patients. The course of the disease was long, and the time from symptom onset to the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid negative transformation was (17.22±6.34) days.There were no significant differences in the incubation period (=-0.453, >0.05), the complicates (χ=0.042, >0.05), and the time from symptom onset to diagnosis (=-1.330, >0.05) in patients between the non-severe group and the severe group. The onset age, gender, SARS-CoV-2 nucleic acid negative time, lymphocyte count, -dimer, C-reactive protein, total bilirubin, direct bilirubin, lactate dehydrogenase, calcium ion, CD4 T cell count, CD8 T cell count, calcitonin, procalcitonin, and troponin were significantly different between the severe group and the non-severe group (all <0.05). Among the 71 patients, 4 (5.6%) patients were mild, 59 (83.1%) were normal, and 8 (11.3%) were severe or critical. CONCLUSIONS The aggregation phenomenon of COVID-19 is obvious. Fever and cough are the main clinical manifestations. White blood cells, neutrophils, and lymphocytes in the most patients in the early onset are normal. Most COVID-19 patients are light and ordinary type, with good prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Betacoronavirus ; Child ; Child, Preschool ; China ; Coronavirus Infections ; diagnosis ; physiopathology ; Cough ; virology ; Female ; Fever ; virology ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; physiopathology ; Retrospective Studies ; Young Adult

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Objective To observe the effects of dredging collaterals and activating blood worm Chinese materia medica on angiogenesis related factors of lung cancer in hypoxic environment. Methods The lung cancer A549 cells were cultured in vitro to simulate tumor hypoxia microenvironment by the hypoxia workstation, and different concentrations of Scorpio, Scolopendra and Gecko medicated serum were added. MTT method was used to detect cell proliferation and screen the best medicine concentration and duration of action. Lung cancer A549 cells were administrated by the three kinds of medicated serum, and cells were collected and supernatant was cultured. Contents of VEGF, TGF-β1, and bFGF were detected by ELISA. Results Three kinds of medicated serum had the inhibitory effect on both added normoxia and hypoxia in cultured A549 lung cancer cells. 7.5% concentration of medicated serum was selected, and 24 h later were used in later experiments. Scorpio, Scolopendra and Gecko medicated serum can more reduce the contents of VEGF, TGF-β1 and bFGF in the supernatant of A549 cell compared with the control group (P<0.05, P<0.01). Conclusion Dredging collaterals and activating blood worm Chinese materia medica had inhibitory effect on cancer cells and the regulation of angiogenesis related cytokines in the condition of normoxia and hypoxia.