Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease, characterized by eosinophilic transparent inclusions in the central and peripheral nervous systems, and internal organs. NIID clinical characteristics are varied, including cognitive impairment, muscle weakness, episodic symptoms, movement disorders and autonomic dysfunction. This article reports a patient with NIID who manifested with episodes of aphasia, dysgraphia and dyslexia without fever, headache, nausea and vomiting confirmed by genetic testing. The patient was a 62-year-old female with acute onset who was diagnosed with transient ischemic attack. This article aims to improve the knowledge of NIID with stroke-like onset by this case presentation and avoid misdiagnosis.

Objective    To evaluate the association of intraoperative ventilation modes with postoperative pulmonary complications (PPCs) in adult patients undergoing selective cardiac surgery under cardiopulmonary bypass (CPB). Methods    The clinical data of 604 patients who underwent selective cardiac surgical procedures under CPB in the West China Hospital, Sichuan University from June to December 2020 were retrospectively analyzed. There were 293 males and 311 females with an average age of 52.0±13.0 years. The patients were divided into 3 groups according to the ventilation modes, including a pressure-controlled ventilation-volume guarantee (PCV-VG) group (n=201), a pressure-controlled ventilation (PCV) group (n=200) and a volume-controlled ventilation (VCV) group (n=203). The association between intraoperative ventilation modes and PPCs (defined as composite of pneumonia, respiratory failure, atelectasis, pleural effusion and pneumothorax within 7 days after surgery) was analyzed using modified poisson regression. Results    The PPCs were found in a total of 246 (40.7%) patients, including 86 (42.8%) in the PCV-VG group, 75 (37.5%) in the PCV group and 85 (41.9%) in the VCV group. In the multivariable analysis, there was no statistical difference in PPCs risk associated with the use of either PCV-VG mode (aRR=0.951, 95%CI 0.749-1.209, P=0.683) or PCV mode (aRR= 0.827, 95%CI 0.645-1.060, P=0.133) compared with VCV mode. Conclusion    Among adults receiving selective cardiac surgery, PPCs risk does not differ significantly by using different intraoperative ventilation modes.

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
Adenosine Monophosphate/therapeutic use* ; Alanine/therapeutic use* ; Alveolar Epithelial Cells/virology* ; Antibodies, Neutralizing/therapeutic use* ; COVID-19/virology* ; Down-Regulation ; Drug Discovery ; Human Embryonic Stem Cells/metabolism* ; Humans ; Immunity ; Lipid Metabolism ; Lung/virology* ; RNA, Viral/metabolism* ; SARS-CoV-2/physiology* ; Virus Replication/drug effects*

Objective    To evaluate the effect of driving pressure-guided lung protective ventilation strategy on lung function in adult patients under elective cardiac surgery with cardiopulmonary bypass. Methods    In this randomized controlled trial, 106 patients scheduled for elective valve surgery via median sternal incision under cardiopulmonary bypass from July to October 2020 at West China Hospital of Sichuan University were included in final analysis. Patients were divided into two groups randomly. Both groups received volume-controlled ventilation. A protective ventilation group (a control group, n=53) underwent traditional lung protective ventilation strategy with positive end-expiratory pressure (PEEP) of 5 cm H2O and received conventional protective ventilation with tidal volume of 7 mL/kg of predicted body weight and PEEP of 5 cm H2O, and recruitment maneuver. An individualized PEEP group (a driving pressure group, n=53) received the same tidal volume and recruitment, but with individualized PEEP which produced the lowest driving pressure. The primary outcome was oxygen index (OI) after ICU admission in 30 minutes, and the secondary outcomes were the incidence of OI below 300 mm Hg, the severity of OI descending scale (the Berlin definition), the incidence of pulmonary complications at 7 days after surgery and surgeons’ satisfaction on ventilation. Results    There was a statistical difference in OI after ICU admission in 30 minutes between the two groups (273.5±75.5 mm Hg vs. 358.0±65.3 mm Hg, P=0.00). The driving pressure group had lower incidence of postoperative OI<300 mm Hg (16.9% vs. 49.0%, OR=0.21, 95%CI 0.08-0.52, P=0.00) and less severity of OI classification than the control group (P=0.00). The incidence of pulmonary complications at 7 days after surgery was comparable between the driving pressure group and the control group (28.3% vs. 33.9%, OR=0.76, 95%CI 0.33-1.75, P=0.48). The atelectasis rate was lower in the driving pressure group (1.0% vs. 15.0%, OR=0.10, 95%CI 0.01-0.89, P=0.01). Conclusion    Application of driving pressure-guided ventilation is associated with a higher OI and less lung injury after ICU admission compared with the conventional protective ventilation in patients having valve surgery.

Objective:To clarify the effects of bortezomib combined with or without siramesine on the proliferation of multiple myeloma cell lines, the expression changes of transcription factor EBC (TFEB) nuclear translocation and the level of autophagy, and to provide basis for further exploring the regulation mechanism of transcription factor TFEB on autophagy.Methods:The multiple myeloma cell lines RPMI8226 and U266 were cultured in vitro, and the multiple myeloma cells were treated with a certain concentration of bortezomib and siramesine. The changes of cell proliferation inhibition were detected by CCK-8 method. Real time PCR and Western blot were used to detect the relative expression of TFEB, autophagy-related factor LC3B, Beclin1, p62, LAMP1 mRNA and protein.Results:As the concentration of bortezomib increased and the duration of action increased, the proliferation inhibition rates of the two cell lines gradually increased ( P<0.05) . The combination of the two drugs has a synergistic inhibitory effect on the proliferation of the above-mentioned multiple myeloma cell lines ( P<0.05) . In the blank control group, single drug group, and combination drug group, the relative expression of TFEB mRNA and protein in the cytoplasm decreased sequentially ( P<0.05) , and the relative expression of TFEB mRNA and protein in the nucleus increased sequentially ( P<0.05) . The relative expression of autophagy-related factors LC3B, Beclin1, LAMP1 mRNA and protein increased sequentially, and the relative expression of p62 mRNA and protein decreased sequentially ( P<0.05) . Conclusion:Bortezomib and siramesine can synergistically inhibit the growth of multiple myeloma cells, which is related to the increased autophagy expression in multiple myeloma cell lines and the expression of TFEB with nuclear translocation is also enhanced.

To evaluate the relationship between atherosclerosis and hemodynamic of coronary artery in mice detecting by ultrasound bio‐microscopy flow imaging . Methods Double 14 20‐week‐old LDL‐R‐/‐and C57BL/6 male mice were selected ,and randomly divided into two groups in each genotype according to weight . Each two groups were fed to 28 weeks or 36 weeks age respectively with west diet . Coronary artery hemodynamics in these mice were assessed in vivo by Vevo ?2100 ultrasound imaging system ,then the intima‐media thickness( IM T ) of aorta in histopathology were analyzed . T he differences of coronary artery hemodynamic parameters such as maximum velocity ( Vmax ) ,mean velocity ( Vmean) and velocity time integral ( V T I) were compared between mice of different genotypes of the same week and mice of different weeks of the same genotype . And the relationship between coronary artery hemodynamic in ultrasound and aortic IM T in histopathology were analyzed . Results ① All coronary hemodynamic parameters in LDL‐R‐/‐ mice were significantly lower than those of wild‐type mice except the Vmax between two 28‐week‐old genotypes group at the same weeks of age of different genotypes ( all P ＜0 .05) . But there was no significant difference in coronary artery hemodynamic parameters between mice of the same genotype at different weeks of age( P ＞0 .05) . ②T he histopathological measurements of aortic IM T in LDL‐R‐/‐mice were significantly higher than those of wild type mice ( all P ＜ 0 .05 ) ,and those of 36‐week‐old mice were significantly higher than those of 28‐week‐old mice ( all P ＜ 0 .05 ) . ③ All coronary hemodynamic parameters such as Vmax ,Vmean and V TI were negatively correlated with pathological measurements of aortic IM T ( r ＝ －0 .532 , －0 .423 , －0 .524 ; all P ＜ 0 .05 ) . Conclusions The parameters of coronary artery hemodynamics obtained by ultrasound bio‐microscopy are well correlated with the pathological results of atherosclerosis . Ultrasound bio‐microscopic flow imaging can be used as a new method to evaluate the degree of atherosclerosis in mice by detecting the hemodynamic parameters of coronary artery .

Objective To observe the prevention effect of Hubai powder applied on navel for nausea and vomiting induced by chemotherapy with cisplatin.Methods 97 patients who received chemotherapy with cisplatin (75mg/m2 )were randomly divided into observation group(n =49)and control group(n =48).In the control group, 30min before chemotherapy,the patients were treated with intravenous granisetron 3mg as antiemetic;Based on the control group,the observation group were treated with Hubai powder 10g applied on Shenque point in the night before the chemotherapy until the end of the next morning after chemotherapy.The curative effect of the two groups were observed.Results The acute vomiting rate of the observation group was 83.7%,which was significantly higher than that of the control group(60.4%)(χ2 =5.423,P =0.019);The delayed vomiting rate of the observation group was 85.7%,which was significantly higher than that of the control group(56.3%)(χ2 =8.867,P =0.003);The patient appetite of the observation group was obviously better than that of the control group,0 -Ⅰ degree occurrence rate of the two groups had statistical significance(χ2 =6.469,4.552,P =0.011,0.033);Ⅱ -Ⅲ degree occurrence rate of the two groups did't have statistical significance.Conclusion Hu Bai powder umbilicus can effectively prevent nausea and vomiting induced by chemotherapy with cisplatin.