The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Abstract Airborne microorganisms, especially pathogenic microorganisms, are easily transmitted through dust and droplets, leading to various infectious diseases. The study summarizes the status of airborne microbial pollution, potential exposure levels, particle size, and species distribution of microorganisms, discusses the impact of airborne microorganisms on human health, and analyzes specific factors affecting campus air microorganisms from four aspects:climate, anthropogenic factors, time, and space, to provide a scientific basis for formulating effective improvement measures, improving air quality and safeguarding the health of teachers and students.

Objective To investigate the serological changes of blood type and whether hemolytic reactions occurred in a patient with ABw subtype after type A therapeutic plasma exchange(TPE)retrospectively.Methods The ABO blood group identification and genotyping was carried out by microcolumn gel method,microcolumn glass bead method,saline tube method and absorption-elution test,and the laboratory results before and after TPE were analyzed.Results The patient un-derwent 2 000 mL type A TPE in other hospitals and was transferred to our hospital.On the second day of hospitalization,the test showed consistency between forward and reverse blood typing.On the third day,the detection showed that Bc was±～1+,and discrepancy was found between forward and reverse typing.The presence of B antigen was confirmed through tube method and human anti-B absorption-elution test,and was identified as ABw03 by molecular biological method.After type A TPE,Hb and Plt both temporarily decreased,creatinine slightly increased,ALT and AST continued to decrease,while TBIL,DBIL and IBIL showed a temporary decrease followed by an increase,indicating a slight hemolytic reaction.Conclu-sion Infusion of large volume of plasma may cause hemolytic reactions when ABO subtype patients contain weak A or B an-tigens.The blood type should be strictly identified according to the ABO blood type forward and reverse typing standards.Ad-ditional laboratory tests combined with molecular biology techniques are required for weak agglutination,which can reduce the missed detection of ABO subtypes and reduce the occurrence of transfusion reactions.

Objective To investigate the value of dual-energy CT in differentiating intracranial hemorrhage (ICH)from extravasation of contrast medium in patients with acute ischemic stroke (AIS)after mechanical thrombectomy.Methods AIS patients who underwent mechanical thrombectomy from January 2018 to July 2018 were prospectively included.They all underwent dual-energy CT immediately within 1 h after surgery.Virtual non-contrast (VNC),iodine overlay maps (IOM)and mixed energy images (MIX)were obtained and evaluated respectively. Follow-up was performed 48 hours after surgery with dual-energy CT,which was used as a reference standard and compared with the previous evaluation results.Results Among the 34 patients with complete data,6 cases had no obvious high-density shadow on the MIX image.Among the remaining 28 patients with high-density shadow,14 cases had immediate dual-energy CT diagnosis of bleeding,all of which were confirmed as bleeding during follow-up.Twelve cases were diagnosed as extravasation of contrast medium,of which 1 case had secondary hemorrhage transformation during follow-up,and the rest were all extravasation of contrast medium.Two cases were diagnosed as bleeding with extravasation,and both were confirmed during follow-up.The sensitivity was 93%.The specificity was 1 00%.The positive predictive value was 1 00%.The negative predictive value was 9 2% (P＜ 0.05).Conclusion Dual-energy CT can accurately differentiate ICH from extravasation of contrast agent in AIS patients after mechanical thrombectomy,which is of great value in ICH evaluation after surgery.

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.
Animals ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms, Experimental ; immunology ; pathology ; therapy ; Receptor, ErbB-2 ; immunology ; Receptors, Antigen, T-Cell ; immunology ; Stomach Neoplasms ; immunology ; pathology ; therapy ; Tumor Cells, Cultured

Objective To investigate the value of hydrogen proton MR spectroscopy (1H-MRS) and Dixon sequence for the quantitative diagnosis and classification of steatosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods Sixty seven patients with NAFLD confirmed by liver biopsy were prospectively collected from October 2015 to May 2017 in Hangzhou Normal University Hospital. All patients underwent 1H-MRS and Dixon sequence scan within 7 days after liver biopsy, 1H-MRS-based hydrogen proton density fraction (MRS-PDFF) and Dixon-based hydrogen proton density fraction (MRI-PDFF) were obtained. Fat grading based on the fat percentage obtained from liver biopsy. Pearson correlation analysis was performed to analyze the correlation among pathological steatosis and MRS-PDFF, MRI-PDFF. One-way ANOVA analysis was performed to compare the difference of PDFF between patients with different degrees of severity of fatty liver. And the ROC curve analysis was performed to generate the thresholds of MRS-PDFF and MRI-PDFF for determining the presence of fatty liver. Results The steatosis grade of pathological biopsy showed grade S1 in 36 cases, grade S2 in 16 cases, grade S3 in 15 cases, the MRS-PDFF values of S1, S2 and S3 patients were (8.25 ± 4.32)％, (15.67 ± 4.54)％, (23.46 ± 5.82)％and the MRI-PDFF values were (6.31 ± 2.94)％, (15.42 ± 5.07)％, (24.47 ± 6.31)％. Statistically significant differences were observed among them (P<0.01). Both MRS-PDFF and MRI-PDFF were positively correlated with histological fat percentage (r values were 0.840 and 0.892,all P<0.01), there was also a correlation between MRS-PDFF and MRI-PDFF (r=0.930, P<0.01). Area under ROC curve of MRS-PDFF and MRI-PDFF for differential diagnosis of grade S1 steatosis were 0.955 and 0.976, and area under ROC curve for differential diagnosis of grade S3 steatosis were 0.972 and 0.978. Conclusion 1H-MRS and Dixon sequces have high value in liver fat content detection and classification of patients with NAFLD, and both have similar diagnostic efficacy.

Objective To study CT-guided localization of additional pulmonary nodules with microcoils prior to video-assisted thoracoscopic surgery (VATS) resection in patients with suspected lung cancer.Methods Eleven patients suspected lung cancer underwent preoperative microcoils localization towards additional small pulmonary nodules.The head of microcoil was pinpointed adjacent to the target nodule while its end tail remained above the visceral pleura.VATS were performed within 24 hours, and comprehensive assessments were conducted according to surgical and pathological outcomes of primary and additional lesions, and suitable surgical processes were followed.Results All 11 localizing pulmonary nodules (4-15 mm in diameter) were successfully removed after VATS, 9 microcoils'' end tails of which were placed above visceral pleural surface.There were no serious complications related with localizing procedure.Other 16 lesions including 11 primary ones were resected.The surgical and pathological outcomes for lung lesions were utterly assessed.Conclusion Microcoil preoperative localization provides helpful orientation for complete resection and assessment of multiple pulmonary lesions in patients with suspected lung cancer.

This study was aimed to observe the clinical effect of low frequency negative pressure meridian viscera regulating sub-health.According to the diagnostic criteria,34 cases of sub healthy subjects were randomly selected.The low frequency negative pressure meridian viscera regulating method was used.By analyzing the cupping spot color feedback conditioning information of the sub healthy subjects and conditioning before and after the synthesis of the four diagnostic methods of digital and quantitative,its effect was evaluated.After 4 weeks of continuous adjustment,34 cases of sub healthy subjects,compared with preconditioning,cupping spot color of the subjects was shallow or disappeared (P ＜ 0.01);after adjusting,the proportion of light red tongue and thin white tongue coating increased obviously (P ＜ 0.05),the proportion of ecchymosis tongue was decreased compared to precoditioning (P ＜ 0.05);after adjustment,core symptoms such as back pain,neck pain,anxiety and irritability,were alleviated or disappeared;after adjustment,the pulse string tightness decreased significantly (P ＜ 0.01).It was concluded that the low frequency negative pressure meridian viscera regulation can significantly improve discomfort symptoms of sub healthy subjects and promote therecovery of tongue,pulse and cupping spot color in sub healthy subjects.This method is worth popularizing and further exploring.

The single molecule imaging and technologies that developed in 1990 s have successfully probed the dynamics of single molecule enzyme catalysis in real time in vitro. Ever since then, single molecule enzymology has entered the golden age of rapid developing. Individual features of each enzyme hidden in the overall average have been discovered, and many new catalytic mechanisms have been proposed. Single molecule enzymology sheds light on the dynamic interactions between enzymes and substrates or products, deepening the understanding of biochemical reactions. This review described the recent research progresses of single molecule protease and ribozyme.