The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international ...borders.
We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China.
Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significantly elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%).
Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection.
Lung transplantation (LT) has been demonstrated as the only effective therapy for patients with end-stage lung diseases. Increasing listed lung transplant candidates and expanding volumes of lung ...transplant centers across China require well-organized programs and registry data collection based on the large population. This study aimed to summarize and analyze the data of LT development in China.
We retrospectively collected and analyzed data from the China Lung Transplantation Registry (CLuTR). Key data were reported from the registry with transplant types, indications, donor and recipient characteristics, outcomes and survival. The survival <30 days, 1-year and 3-year survival rates were estimated with risk factors identified.
CLuTR contained data from 1053 lung transplants performed through January 1st, 2015 to December 31st, 2018 reported by 18 registered transplant centers. The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis. The total <30 days, 1-year and 3-year survival rates in CLuTR were 81.45%, 70.11%, and 61.16% with discrepancy by indications. Large proportion of recipients who were more than 60 years old required higher standard of care. Infection-related complications resulted in more death events in the early post-surgery periods. New York Heart Association grading at listing, extra-corporeal membrane oxygenation usage peri-transplantation, allograft dysfunction (primary graft dysfunction >Grade 0), renal insufficiency (estimated glomerular filtration rate <60 mL·min·1.73 m), were independently associated with a higher risk for 3-year mortality in the entire cohort.
Facing more end-stage of lung diseases and comorbidities, this study analyzed the outcomes and survival of LT recipients in China. Further prospectively stratified analyses with longer follow-up will be needed.
We calculated the crustal stress field using the composite focal mechanism method based on the P-wave initial motion polarity data of the Tengchong volcanic area from January 2011 to April 2019 ...obtained from the Bulletin of Seismological Observations of Chinese stations. The magnitude range of earthquakes used in this study is 0–4, and their magnitudes are mainly approximately 1.0. To investigate the influence of the source location on the stress field and obtain reliable stress fields of the study area, we applied the double-difference algorithm to relocate the seismic events, obtaining more accurate and reliable relative positions of seismic events with a clearer seismic belt. On the basis of relocation results, the study on the stress field along the fault zone was conducted, and the influence of seismic event position on the stress field was analyzed. Results show that, first, the current stress regime in the shallow crust of the Tengchong volcanic area is strike-slip faulting, the orientation of the principal compressive stress axis is NE-SW, the orientation of the principal extension stress axis is SE-NW, the principal compressive and extension stress axes are nearly horizontal, and the dip angle of intermediate principal stress axis is relatively large. This reflects that the volcanic and seismic activities in the Tengchong volcanic area are mainly controlled by the collision and squeezing effect of the Indian-Eurasian plate. It also reflects that the current tensile action caused by deep magma activity has little influence on the shallow crustal stress field. Second, the stress field along fault zones reveals that there exist local stress fields, such as the thrust stress regime at the strike-slip fault terminal area, which is consistent with the compressional area at the intersection of conjugate strike-slip faults indicated by previous study. Third, the stress field results are consistent, regardless of using the original location in the bulletin or the relocated location, indicating that the influence of the event location error can be neglected when there are sufficient data and reflecting the stability of the composite focal mechanism method. The findings can serve as a reference for investigating geological structure movement, seismic activities, and volcanic activities in the Tengchong volcanic area.
Recent studies have found that known functions of circular RNAs (circRNAs) include sequestration of microRNAs (miRNAs) or proteins, modulation of transcription and interference with splicing, and ...even translation to produce polypeptides. The zebrafish model is also demonstrably similar to humans in many studies. To explore the changes in circRNAs during embryonic development and to further research the mechanism of action of circRNAs in development‐related diseases, Zebrafish embryos at the blastula period, gastrula period, segmentation period, throat stage, and incubation period were collected. Illumina deep‐sequencing technology and CircRNA Identifier (CIRI) algorithm were used to detect circRNAs. In total, we identified 1,028 circRNAs (junction reads ≥5 and p < 0.05). Considering that the function of circRNAs is related to host genes, a bioinformatics analysis revealed these differentially expressed host genes are involved in NOTCH signaling pathways, cardiovascular system development, retinal ganglion cell axon guidance, and so on. Moreover, circRNAs can participate in biological regulation through the function of miRNA sponges. TargetScan and miRanda were used to predict 73 miRNAs binding to circRNAs such as miR‐19b, miR‐124, and so on. Some miRNAs play important roles in embryogenesis. The peak expression of circRNAs is distributed at different time points, suggesting that it may be involved in embryogenesis at different stages. Our study provides a foundation for understanding the dynamic regulation of circRNA transcriptomes during embryogenesis and identifies novel key circRNAs that might control embryonic development in a zebrafish model.
Recent studies have found that known functions of circRNAs include sequestration of miRNAs or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. The zebrafish model is also demonstrably similar to humans in many studies. To explore the changes in circRNAs during embryonic development, further to research the mechanism of action of circRNAs in development‐related diseases, Zebrafish embryos at the blastula period, gastrula period, segmentation period, throat stage, and incubation period were collected. Illumina deep‐sequencing technology and CIRI algorithm were used to detect circRNAs. In total, we identified 1,028 RNAs (junction reads ≥ 5 and p < 0.05). Considering that the function of circRNA is related to host genes, bioinformatics analysis revealed thaht these differentially expressed host genes are involved in NOTCH signaling pathways, cardiovascular system development, retinal ganglion cell axon guidance, and so on. Moreover, circRNAs can participate in biological regulation through miRNA sponge function. TargetScan and miRanda were used to predict 73 miRNAs binding to circRNAs such as miR‐19b, miR‐124, and so on. Some miRNAs play important roles in embryogenesis. The peak expression of circRNAs is distributed at different time points, suggesting that it may be involved in embryogenesis at different stages. Our study provides a foundation for understanding the dynamic regulation of circRNA transcriptomes during embryogenesis and identifies novel key circRNAs that might control embryonic development in a zebrafish model.
To explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their ...translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver. We also demonstrate the dependence receptor (DR) characteristics of ROBO1 in a follow-up mechanistic study. A neutralizing antibody targeting ROBO1 significantly attenuate liver metastasis of PDAC by preventing the coadaptation effect. Thus, we demonstrate that coadaptation is supported by the DR characteristics in the PMN and MMN.
RNA N
-methyladenosine (m
A), the most abundant internal modification of mRNAs, plays key roles in human development and health. Post-translational methylation of proteins is often critical for the ...dynamic regulation of enzymatic activity. However, the role of methylation of the core methyltransferase METTL3/METTL14 in m
A regulation remains elusive. We find by mass spectrometry that METTL14 arginine 255 (R255) is methylated (R255me). Global mRNA m
A levels are greatly decreased in METTL14 R255K mutant mouse embryonic stem cells (mESCs). We further find that R255me greatly enhances the interaction of METTL3/METTL14 with WTAP and promotes the binding of the complex to substrate RNA. We show that protein arginine N-methyltransferases 1 (PRMT1) interacts with and methylates METTL14 at R255, and consistent with this, loss of PRMT1 reduces mRNA m
A modification globally. Lastly, we find that loss of R255me preferentially affects endoderm differentiation in mESCs. Collectively, our findings show that arginine methylation of METTL14 stabilizes the binding of the m
A methyltransferase complex to its substrate RNA, thereby promoting global m
A modification and mESC endoderm differentiation. This work highlights the crosstalk between protein methylation and RNA methylation in gene expression.
Purpose
This is a meta-analysis to compare the results between anterior cervical discectomy fusion (ACDF) and anterior cervical corpectomy fusion (ACCF) for the patients with multilevel cervical ...spondylotic myelopathy (MCSM).
Methods
Systematic review and meta-analysis of cohort studies between ACDF with plate fixation and ACCF with plate fixation for the treatment of MCSM. An extensive search of literature was performed in PubMed, Mediline, Embase and the Cochrane library. The following outcome measures were extracted: JOA scores, fusion rate, cervical lordosis (C2–7), complications, blood loss and operation time. Data analysis was conducted with RevMan 5.0.
Results
Four cohorts (six studies) involving 258 patients were included in this study. The pooled analysis showed that there was no significant difference in the postoperative JOA score WMD = −0.14 (−1.37, 1.10),
P
= 0.83, fusion rate OR = 0.84 (0.15, 4.86),
P
= 0.85 between two group. However, there was significant difference in the cervical lordosis WMD = 3.38 (2.52, 4.23),
P
< 0.00001, surgical complication rate and instrument related complication rate (
P
= 0.01, 0.005 respectively), blood loss WMD = −52.53 (−73.53, −31.52),
P
< 0.00001, and operation time WMD = −14.10 (−20.27, −7.93),
P
< 0.00001.
Conclusions
As compared with ACCF with plate fixation, ACDF with plate fixation showed no significant differences in terms of postoperative JOA score, fusion rate, but better improved cervical lordosis, lower complication and smaller surgical trauma. As the limitations of small sample and short follow-up in this study, it still could not be identified whether ACDF with plate fixation is more effective and safer than ACCF with plate fixation.
In February 2020, the exponential growth of COVID-19 cases in Wuhan city posed a huge economic burden to local medical systems. Consequently, Wuhan established Fangcang Shelter hospitals as a One ...Health approach for responding to and containing the COVID-19 outbreak by isolating and caring for mild-to-moderate cases. However, it is unclear to what degree the hospitals contained COVID-19. This study performed an interrupted time series analysis to compare the number of new confirmed cases of COVID-19 before and after the operation of Fangcang Shelter hospitals. The initial number of confirmed cases in Wuhan increased significantly by 68.54 cases per day prior to February 4, 2020. Compared with the number of cases noted 20 days before the use of Fangcang Shelter hospitals, a sustained reduction in the number of confirmed cases (trend change, −125.57; P < 0.0001) was noted 41 days after the use of the hospitals. Immediate-level changes were observed for confirmed cases (level change, 725.97; P = 0.025). These changes led to an estimated 5148 fewer confirmed cases (P < 0.0001). According to the mean confirmed cases of 395.71 per day before the intervention, we estimated that Wuhan had advanced the terminal phase of COVID-19 by 13 days. Furthermore, immediately after introduction of Fangcang Shelter Hospitals on February 5, the reproduction number dropped rapidly, from a pre-introduction rate of 4.0 to 2.0. The Fangcang Shelter hospitals most likely to reversed the epidemic trend of COVID-19 while a containment strategy was implemented in Wuhan. In a One Health perspective, Fangcang Shelter hospitals, with their functions of isolation and treatment of confirmed COVID-19 patients, engaging professionals from many disciplines, such as medicine, engineering, architecture, psychology, environmental health, and social sciences. The results of this study provide a valuable reference for health policy makers in other countries.
•A sustained reduction and immediate increase in the number of cases were observed in Wuhan city after Fangcang Shelter hospitals were established.•The above changes resulted in an estimated 5148 fewer confirmed cases in Wuhan.•According to the mean confirmed cases of 395.71 per day before the intervention, we estimated that Wuhan had advanced the terminal phase of COVID-19 by 13 days.•Compared to the approximate real-time effective reproduction number R(t) of 4.0 in the pre-operation periods of Fangcang Shelter hospitals, the R(t) was less than 2.0 in the post-operation periods.
Ursolic acid (UA) is a promising natural compound for cancer prevention and therapy. We previously reported that UA induced apoptosis in CML-derived K562 cells. Here we show that the apoptotic ...process is accompanied by down-regulation of Bcl-xL and Mcl-1 expression and dephosphorylation of Bad. These events are associated with Stat5 inhibition, which is partially mediated through elevated expression of transcriptional repressor Gfi-1. Gfi-1 knockdown using siRNA abrogates the ability of UA to decrease Stat5b expression and attenuates apoptosis induction by UA. We also demonstrate that UA suppresses the Akt kinase activity by inhibiting Akt1/2 expression, which correlates with Stat5 inhibition. Stat5 activity inhibited by a chemical inhibitor or siRNA, Akt1/2 mRNA expression is suppressed. Moreover, we show that UA exerts growth-inhibition in Imatinib-resistant K562/G01. UA has synergistic effects when used in combination with Imatinib in both K562 and K562/G01. Altogether, the data provide evidence that UA's pro-apoptotic effect in K562 cells is associated with the Gfi-1/Stat5/Akt pathway. The findings indicate that UA could potentially be a useful agent in the treatment of CML.
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