Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

The coronavirus disease 2019(COVID-19)pandemic has been a serious threat to global health for nearly 3 years.In addition to pulmonary complications,liver injury is not uncommon in patients with novel COVID-19.Although the prevalence of liver injury varies widely among COVID-19 patients,its incidence is significantly increased in severe cases.Hence,there is an urgent need to understand liver injury caused by COVID-19.Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes.Liver function tests,computed tomography scans,and ultrasound can help evaluate liver injury.Risk factors for liver injury in patients with COVID-19 include male sex,preexisting liver disease including liver transplantation and chronic liver disease,diabetes,obesity,and hypertension.To date,the mechanism of COVID-19-related liver injury is not fully understood.Its pathophysiological basis can generally be explained by systemic inflammatory response,hypoxic damage,ischemia-reperfusion injury,and drug side effects.In this review,we systematically summarize the existing literature on liver injury caused by COVID-19,including clinical features,underlying mechanisms,and potential risk factors.Finally,we discuss clinical management and provide recommendations for the care of patients with liver injury.

Treating traumatic brain injury at sea:how to improve the skills and capabilities of the naval medical personnel

Dear Editor,Recent advances in military technology have led to the development of sophisticated and intelligent weapons, which increase mortality and morbidity. Since the advent of highexplosion weapons, "shock wave" has surpassed "shrapnel" and become the most important injurious component in conventional combat. Traumatic brain injury(TBI) is a leading cause of disability and death among military personnel and civilians during wartime[1]. Clinically, its symptoms and indications vary depending on the location and severity of the injury. The most frequently observed symptoms included altered consciousness and local dysfunction.

DNA hypermethylation of COL4A1 in ultraviolet-Binduced age-related cataract models in vitro and in vivo

AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in vivo.METHODS:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB respectively.The MTT assay was utilized to evaluate cell proliferation.Flow cytometry was employed for analysis of cell apoptosis and cell cycle.COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction(RTPCR).The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence.The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR(BSP).DNMTs and TETs mRNA levels was examined by RT-PCR.RESULTS:UVB exposure decreased HLEB3 cells proliferation,while increased the apoptosis rate and cells were arrested in G0/G1 phase.COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls.Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure.Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls,while expressions of TETs including TET1/2/3 showed the opposite trend.Results from the UVB treated rat model further confirmed the decreased expression of COL4A1,hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure group.CONCLUSION:DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.

Home range variation of two different-sized groups of golden snub-nosed monkeys(Rhinopithecus roxellana) in Shennongjia, China: implications for feeding competition

Knowledge on the home range size of a species or population is important for understanding its behavioral and social ecology and improving the effectiveness of conservation strategies. We studied the home range size of two different-sized groups of golden snub-nosed monkeys(Rhinopithecus roxellana) in Shennongjia, China. The larger group(236 individuals)had a home range of 22.5 km2 from September2007 to July 2008, whereas the smaller group(62 individuals) occupied a home range of 12.4 km2 from November 2008 to July 2009. Both groups exhibited considerable seasonal variation in their home range size, which was likely due to seasonal changes in food availability and distribution. The home range in any given season(winter, spring, summer, or winter+spring+summer) of the larger group was larger than that of the smaller group. As the two groups were studied in the same area, with the confounding effects of food availability thus minimized, the positive relationship between home range size and group size suggested that scramble feeding competition increased within the larger group.

Manufacture and Cytotoxicity of a Lead-free Piezoelectric Ceramic as a Bone Substitute—Consolidation of Porous Lithium Sodium Potassium Niobate by Cold Isostatic Pressing

Aim The piezoelectric properties and cytotoxicity of a porous lead-free piezoelectric ceramic for use as a direct bone substitute were investigated. Methodology Cold isostatic pressing （CIP） was applied to fabricate porous lithium sodium potassium niobate （Li0.06Na0.5K0.44） NbO3 specimens using a pore-forming method. The morphologies of the CIP-processed specimens were characterized and compared to those of specimens made by from conventional pressing procedures. The effects of the ceramic on the attachment and proliferation of osteoblasts isolated from the cranium of 1-day-old Sprague- Dawley rats were examined by a scanning electron microscopy （SEM） and metbylthiazol tetrazolium （MTT） assay. Results The results showed that CIP enhanced piezoelectricity and biological performance of the niobate specimen, and also promoted an extracellular matrix-like topography of it. In vitro studies showed that the CIP-enhanced material had positive effects on the attachment and proliferation of osteoblasts. Conclusion Niobate ceramic generated by CIP shows a promise for being a piezoelectric composite bone substitute.

Sequential vs simultaneous revascularization in patients undergoing liver transplantation:A meta-analysis

AIM: We undertook this meta-analysis to investigate the relationship between revascularization and outcomes after liver transplantation.METHODS: A literature search was performed using MeSH and key words. The quality of the included studies was assessed using the Jadad Score and the NewcastleOttawa Scale. Heterogeneity was evaluated by the χ 2and I 2 tests. The risk of publication bias was assessed using a funnel plot and Egger's test, and the risk of bias was assessed using a domain-based assessment tool.A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches.RESULTS: Six studies with a total of 467 patients were included. Ischemic-type biliary lesions were significantly reduced in the simultaneous revascularization group compared with the sequential revascularization group(OR = 4.97, 95%CI: 2.45-10.07; P < 0.00001),and intensive care unit(ICU) days were decreased(MD = 2.00, 95%CI: 0.55-3.45; P = 0.007) in the simultaneous revascularization group. Although warm ischemia time was prolonged in simultaneous revascularization group(MD =-25.84, 95%CI:-29.28-22.40; P < 0.00001), there were no significant differences in other outcomes between sequential and simultaneous revascularization groups. Assessment of the risk of bias showed that the methods of random sequence generation and blinding might have been a source of bias. The sensitivity analysis strengthened the reliability of the results of this meta-analysis.CONCLUSION: The results of this study indicate that simultaneous revascularization in liver transplantation may reduce the incidence of ischemic-type biliary lesions and length of stay of patients in the ICU.

Comparison of simplified and traditional pericardial devascularisation combined with splenectomy for the treatment of portal hypertension

AIM To compare the clinical outcomes of patients with portal hypertension(PH) who underwent treatment with splenectomy plus simplified pericardial devascularisation(SSPD) or splenectomy plus traditional pericardial devascularisation(STPD).METHODS We conducted a single-centre retrospective study of 1045 PH patients treated with either SSPD(S Group, 357 patients) or STPD(T Group, 688 patients) between January 2002 and February 2017. In all, 37 clinical indicators were compared to evaluate the efficacy of SSPD.RESULTS Perioperative indicators in the S Group were significantly better than those in the T Group(P < 0.05). In both groups, the postoperative long-term portal vein diameter and Model for End-Stage Liver Disease score were significantly lower than those in the preoperative and postoperative short-term groups(P< 0.05). The incidence of complications in the S Group was significantly lower than that in the T Group(P < 0.05). Compared to the T Group, postoperative shortterm WBC(white blood cell) and platelet counts were significantly lower and the short-term Hb(haemoglobin) level was significantly higher in the S Group(P < 0.05). In the S Group, postoperative long-term total bilirubin, direct bilirubin, alanine transaminase, and aspartate transaminase and postoperative serum creatinine and cystatin C levels were significantly lower than those in the T Group(P < 0.05), and postoperative albumin was significantly higher than that in the T Group(P < 0.05).CONCLUSION Compared to STPD, SSPD is a simple and easy procedure resulting in less tissue damage. Patients recovered smoothly and steadily with fewer complications. Short-term liver and kidney function damage was less severe, and long-term liver function recovery was better. Therefore, SSPD is worthy of clinical promotion and application for the treatment of PH.

Self-starting all-fiber PM Er:laser mode locked by a biased nonlinear amplifying loop mirror

A compact all-fiber polarization-maintaining Er:laser using a nonlinear amplifying loop mirror is reported. Fundamental single-pulse mode-locking operation can always self start, with a cavity round-trip decreased from ~ 4.7 m to~ 1.7 m. When the pulse repetition rate is 121.0328 MHz, output pulse is measured to have a center wavelength/3-d B spectral bandwidth/radio frequency signal to noise ratio(SNR)/pulse width of 1571.65 nm/18.70 nm/80 d B/477 fs, respectively. Besides, three states including the exponential growth, damping state, and steady state are investigated through the build-up process both experimentally and numerically. Excellent stability of this compact Er:laser is further evaluated,demonstrating that it can be an easy-fabrication maintenance-free ultrafast candidate for the scientific area of this kind.

Clinical characteristics and in-hospital outcomes of patients receiving contemporary intensive cardiac care:retrospective study from a large centre in China

BACKGROUND Few studies from developed countries have quantitatively characterized the clinical characteristics and outcomes of patients receiving contemporary intensive cardiac care.We sought to investigate these data in patients admitted to a Chinese intensive cardiac care unit(ICCU).METHODS We conducted a retrospective study using data from 2,337 consecutive admissions to the ICCU at a large centre in China from June 2016 to May 2017.Data were captured after systematic inspection of individual medical records regarding current demographics,primary diagnosis,comorbidities,illnesses severity,and in-hospital outcomes.RESULTS The mean age was 65.6±14.2 years,and females accounted for 32.0%of patients.The Charlson Comorbidity Index and Oxford Acute Severity of Illness Score were 2.4±1.8 and 22.5±10.4,respectively.The top reason for admission was ST-segment elevation myocardial infarction(32.0%),and nonischaemic heart diseases accounted for 31.2%of all primary diagnoses.Noncardiovascular diseases were prevalent in the ICCU population,including chronic illnesses and acute noncardiovascular critical illnesses(ANCIs);in particular,21.7%of patients were marked by acute respiratory failure(14.6%),acute kidney injury(13.7%),sepsis(4.2%),or gastrointestinal bleeding(3.3%).The median length of stay in the ICCU and hospital were 1.1 days[interquartile range(IQR):0.8–2.6 days]and 6.3 days(IQR:3.8−10.9 days),respectively.The overall incidence of in-hospital death or discharge against medical advice under extremely critical conditions was 7.6%(n=177).Multivariate logistic regression analysis showed that the complexity of chronic illnesses and incident ANCIs were strong independent determinants for in-hospital outcomes.CONCLUSIONS Remarkable patient diversity and breadth of critical illnesses were observed in a Chinese ICCU population.Particularly,noncardiovascular diseases were prevalent and associated with adverse outcomes.Reformation of organization and staffing practices may be considered to adapt to the changed landscape.

Hepatic artery bridging lessens temporary ischemic injury to bile canaliculi

AIM: To study whether transfer of blood between the right gastroepiploic artery and gastroduodenal artery could lessens the damage to bile canaliculi.METHODS: Forty male Bama miniature pigs were divided into four groups as follows: a control group, two hepatic artery ischemia groups(1 h and 2 h), and a hepatic artery bridging group. The hemodynamics of the hepatic artery in the hepatic artery bridging group was measured using color Doppler ultrasound. Morphological changes in the bile canaliculus were observed by transmission electron microscopy. Cofilin, heat shock protein 27 and F-actin expression was detected by immunohistochemistry, Western blot, and real-time polymerase chain reaction. Terminal deoxynucleotidyl transferase-mediated nick end-labeling method was used to evaluate liver injury. RESULTS: The hemodynamics was not changed in the hepatic artery bridging group. The microvilli in the bile canaliculus were impaired in the two hepatic artery ischemia groups. The down-regulation of cofilin and F-actin and up-regulation of heat shock protein 27 were observed in the two hepatic artery ischemia groups, while there were no significant differences between thecontrol group and hepatic artery bridging group.CONCLUSION: Hepatic artery ischemia aggravates damage to bile canaliculi, and this damage can be diminished by a hepatic artery bridging duct.

Altered heart rate variability and pulse-wave velocity after spinal cord injury

BACKGROUND Heart rate variability(HRV) and pulse-wave velocity(PWV),indicators of cardiac function,are altered in patients with spinal cord injury(SCI),suggesting that autonomic cardiac function and arterial stiffness may underlie the high risk of cardiovascular complications in these patients.No study has simultaneously investigated HRV and PWV in the same patients.AIM To evaluate cardiovascular complications in SCI patients by comparing HRV and PWV between patients with and without SCI.METHODS In this cross-sectional pilot study,patients with(n = 60) and without SCI(n = 60) were recruited from December 7,2019 to January 21,2020.Each participant received a five-minute assessment of HRV and the cardiovascular system using the Medicore HRV Analyzer SA-3000 P.Differences in HRV and PWV parameters between participants with and without SCI were statistically examined.RESULTS We observed a significant difference between participants with and without SCI with respect to the standard deviation of all normal-to-normal intervals,square root of the mean sum of squared successive risk ratio interval differences,physical stress index,total power,very-low frequency,low frequency,high frequency,and arterial elasticity.CONCLUSION Patients with SCI have weaker sympathetic and parasympathetic activity as well as lower arterial elasticity compared to those without,suggesting that SCI may increase cardiac function loading.

A Ferroelectric Domain-Wall Transistor

On the basis of novel properties of ferroelectric conducting domain walls,the domain wall nanoelectronics emerges and provides a brand-new dimension for the development of high-density,high-speed and energy-efficient nanodevices.For in-memory computing,three-terminal devices with both logic and memory functions such as transistors purely based on ferroelectric domain walls are urgently required.Here,a prototype ferroelectric domain-wall transistor with a well-designed coplanar electrode geometry is demonstrated on epitaxial Bi Fe O_(3)thin films.For the logic function,the current switching between on/off states of the transistor depends on the creation or elimination of conducting domain walls between drain and source electrodes.For the data storage,the transistor can maintain nonvolatile on/off states after the write/erase operations,providing an innovative approach for the development of the domain wall nanoelectronics.

Ferricyanide-Promoted Oxidative Activation and Ligation of Protein Thioacids in Neutral Aqueous Media

Ferricyanide-promoted oxidative activation of Nacylatedα-aminothioacids for amide bond formation withα-aminonitriles was recently shown to be a plausible pathway for prebiotic peptide synthesis.Herein we describe the finding that by adding sodium azide and thiols,ferricyanide oxidation can elicit highly efficient and clean conversion of fully unprotected peptide or protein thioacids in neutral aqueous media to the corresponding thioesters.This transformation enables the development of ferricyanide-promoted thioacid-based native chemical ligation(NCL)as a new redox-based method for chemical protein synthesis,which does not need to change pH and is therefore operationally easy for ligation at small scales.The effectiveness of the ferricyanide-promoted thioacid-based NCL was illustrated by synthesis of an ISG15-modified MDA5 segment under nondenaturing conditions and synthesis of an acetylated ubiquitin(Ub)-modified histone H2A through an N-to-C sequential ligation.This work broadens the concept of on-demand oxidative activation strategy for protein ligation and provides a new useful supplement to the repertoire of methods for chemical protein synthesis,particularly for studies on proteins carrying Ub family modifications.

混流风机整机数值模拟及流固耦合分析（英文）

为了改进叶型设计方法、提升SWF型号风机的通风效率,运用数值模拟的方法,并结合fluent软件分析了该混流式风机整机的内部流场状态,获得了风机内部压力场和速度场等有价值的信息,再运用流固耦合的原理,借助Ansys workbench平台将所得到的风机流场内部的表压添加到风机固体模型上,得出了风机运行时的应力和位移结果。最后通过改变流速,得到了多组不一样的全压和效率值,利用Matlab软件可以拟合出风机的效率曲线。结果表明:应力从叶根位置到叶顶位置逐渐减小,叶根位置的应力值为最大值;位移从叶根位置到叶顶位置逐渐变大,最大的位移值出现在叶顶位置。同时得出了风机的运行工况在流速为6-8时的效率最高。

叶轮与蜗壳的相对位置对离心风机性能的影响

在原风机的基础上调整叶轮在蜗壳内的安放位置,采用正交试验方法,耦合叶轮在X轴,Y轴,Z轴三个方向上移动的距离为x,y,z三个因素,通过正交表确定试验方案。利用Fluent数值模拟软件,对各方案风机内部三维流场进行数值模拟和对比分析。研究结果表明,原风机叶轮安放位置不合适,使得蜗壳与叶轮的适配性较差,蜗壳流道内存在着较大的速度梯度,且二次流旋涡的强度较大。叶轮位置经过调整后可以有效减小蜗壳流道内的速度梯度和二次流旋涡,风机在设计工况下的效率提高了1.26%。

不同后导风锥对斜流风机性能的影响

本文的研究对象为一款工业用后置导叶式斜流风机,基于改善斜流风机尾部流动状况,设计了三种不同结构的导风锥。采用数值模拟方法对原风机和三款加装不同导风锥后的风机的整机模型进行了稳态三维流场计算,对比分析了四种风机模型的气动性能和内流状况,计算证明在设计的三组导风锥中,平顶型导风锥效果最优,并对平顶型导风锥进行了试验验证。模拟和试验的结果表明:合理的导风锥结构能有效地改善斜流风机尾部流场的涡结构,减少尾部回流,降低流动损失,风机的全压和全压效率都有明显提高。

Postoperative survival analysis and prognostic nomogram model for patients with portal hypertension

AIM To analyse the postoperative survival of patients with portal hypertension and determine the factors that influence survival and construct nomograms.METHODS We retrospectively followed 1045 patients who underwent splenectomy plus pericardial devascularisation(SPD) between January 2002 and December 2017. Two SPD types are used in our department: splenectomy plus simplified pericardial devascularisation(SSPD) and splenectomy plus traditional pericardial devascularisation(STPD). The Kaplan-Meier method and Cox regression analysis were used to evaluate the prognostic effects of multiple parameters on overall survival(OS), diseasespecific survival(DSS) and bleeding-free survival(BFS). Significant prognostic factors were combined to build nomograms to predict the survival rate of individual patients.RESULTS Five hundred and fifty-seven(53.30%) patients weresuccessfully followed with 192 in the SSPD group and 365 in the STPD group; 93(16.70%) patients died, of whom 42(7.54%) died due to bleeding. Postoperative bleeding was observed in 84(15.10%) patients. The 5-and 10-year OS, DSS and BFS rates in the group of patients who underwent SSPD were not significantly different from those in patients who underwent STPD. Independent prognostic factors for OS were age, operative time, alanine transaminase level and albumin-bilirubin score. Independent prognostic factors for BFS were male sex, age, intraoperative blood loss and time to first flatus. Independent prognostic factors for DSS were the Comprehensive Complication Index and age. These characteristics were used to establish nomograms, which showed good accuracy in predicting 1-, 3-and 5-year OS and BFS.CONCLUSION SSPD achieves or surpasses the long-term survival effect of traditional pericardial devascularisation and is worthy of clinical promotion and application. Nomograms are effective at predicting prognosis.

Numerical investigation of the interaction of the turbulent dual-jet and acoustic propagation

In order to study the interaction between two independent jets, a three-dimensional（3D） transient mathematical model is developed to investigate the flow field and acoustic properties of the two-stream jets. The results are compared with those of the single-stream jet at Mach number 0.9 and Reynolds number 3600. The large eddy simulation（LES） with dynamic Smagorinsky sub-grid scale（SGS） approach is used to simulate the turbulent jet flow structure. The acoustic field is evaluated by the Ffowcs Williams–Hawkings（FW-H） integral equation. Considering the compressibility of high-speed gas jets, the density-based explicit formulation is adopted to solve the governing equations. Meanwhile, the viscosity is approximated by using the Sutherland kinetic theory. The predicted flow characteristics as well as the acoustic properties show that they are in good agreement with the existing experimental and numerical results under the same flow conditions available in the literature. The results indicate that the merging phenomenon of the dual-jet is triggered by the deflection mechanism of the Coanda effect, which sequentially introduces additional complexity and instability of flow structure. One of the main factors affecting the dual-jet merging is the aperture ratio, which has a direct influence on the potential core and surrounding flow fluctuation. The analysis on the noise pollution reveals that the potential core plays a fundamental role in noise emission while the additional mixing noise makes less contribution than the single jet noise. The overall sound pressure level（OASPL） profiles have a directive property, suggesting an approximate 25° deflection from the streamwise direction, however, shifting toward lateral direction of about 10° to 15° in the dual-jet. The conclusion obtained in this study can provide valuable data to guide the development of manufacturing-green technology in the multi-jet applications.

Point source detection performance of Hard X-ray Modulation Telescope imaging observation

The Hard X-ray Modulation Telescope（HXMT） will perform an all-sky survey in the hard X-ray band as well as deep imaging of a series of small sky regions.We expect various compact objects to be detected in these imaging observations. Point source detection performance of HXMT imaging observation depends not only on the instrument but also on the data analysis method that is applied since images are reconstructed from HXMT observed data with numerical methods. The denoising technique used plays an important part in the HXMT imaging data analysis pipeline along with demodulation and source detection. In this paper we have implemented several methods for denoising HXMT data and evaluated the point source detection performances in terms of sensitivities and location accuracies. The results show that direct demodulation with 1-fold cross-correlation should be the default reconstruction and regularization method, although both sensitivity and location accuracy could be further improved by selecting and tuning numerical methods in data analysis used for HXMT imaging observations.

N6-methyladenine-modified DNA was decreased in Alzheimer’s disease patients

BACKGROUND In recent years,the prevalence of Alzheimer’s disease(AD)has increased,which places a great burden on society and families and creates considerable challenges for medical services.N6-methyladenine(m6A)deoxyribonucleic acid(DNA)adenine methylation is a novel biomarker and is abundant in the brain,but less common in AD.We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls(NCs)in China.AIM To analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.METHODS A total of 179 AD patients(mean age 71.60±9.89 years;males:91;females:88)and 147 NCs(mean age 69.59±11.22 years;males:77;females:70)who were age-and sex-matched were included in our study.All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination.Apolipoprotein E(APOE)genotypes were measured through agarose gel electrophoresis.Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit(colorimetric).Global m6A levels in total DNA from ten AD patients with 18F-AV-45(florbetapir)positron emission tomography(PET)positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.RESULTS Our ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs(P=0.002;<0.05).And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting.There were significant differences between the two groups,which indicated that the leukocyte m6A DNA levels were different(P=0.005;<0.05).The m6A level was approximately 8.33%lower in AD patients than in NCs(mean 0.011±0.006 vs 0.012±0.005).A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population(r=0.143,P=0.01;<0.05).However,no relationship was found with APOEε4(P=0.633,>0.05).Further studies should be performed to validate these findings.CONCLUSION Our results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33%in China.