Zhongda Hospital Southeast University

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

BACKGROUND: Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. METHODS: We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses. RESULTS: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died. CONCLUSIONS: Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; Since the publication of &lt;i&gt;Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition)&lt;/i&gt; in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition &lt;i&gt;(2019 Edition)&lt;/i&gt; was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

Circular RNAs (circRNAs) are a class of long, non-coding RNAs molecules that shape a covalently closed continuous loop which have no 5'-3' polarity and contain no polyA tail. CircRNAs also possess relatively jarless framework and are highly tissue-specific expressed in the eukaryotic transcriptome. Emerging evidences have discovered that thousands of endogenous circRNAs are present in mammalian cells and they mediate gene expression at the transcriptional or post-transcriptional level by binding to microRNAs or other molecules and then inhibit their function. Similarly, increasing evidence indicates that circRNAs may play a role in the development of several types of diseases, including atherosclerotic vascular disease risk, neurological disorders, prion diseases, osteoarthritis and diabetes. Furthermore, circRNAs exhibit aberrant expression in multiform types of cancer, including colorectal cancer, hepatocellular carcinoma and pancreatic ductal adenocarcinoma. And based on the function of circRNAs in cancer, we believe that circRNAs may serve as diagnostic or tumor promising biomarkers. Moreover, it will provide a new therapeutic target for the treatment of cancer.

Abstract Background Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ≥30 L/min; 2) use PaO2:Fi O2 ≤ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:Fi O2 ≤ 315 (if oxygen saturation as measured by pulse oximetry is ≤97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Abstract Background 5-Fluorouracil (5-FU) has been commonly prescribed for patients with colorectal cancer (CRC), but resistance to 5-FU is one of the main reasons for failure in CRC. Recently, microRNAs (miRNAs) have been established as a means of reversing the dilemma by regulating signaling pathways involved in initiation and progression of CRC. However, how to safely and effectively deliver miRNA to target cells becomes a main challenge. Results In this study, Engineered exosomes were exploited to simultaneously deliver an anticancer drug 5-FU and miR-21 inhibitor oligonucleotide (miR-21i) to Her2 expressing cancer cells. Purified engineered exosomes from the donor cells loaded with 5-FU and miR-21i via electroporation to introduce into 5-FU-resistant colorectal cancer cell line HCT-116 5FR . Furthermore, systematic administration of 5-FU and miR-21i loaded exosomes in tumor bearing mice indicated a significantly anti-tumor effect. The results showed that the engineered exosome-based 5-FU and miR-21i co-delivery system could efficiently facilitate cellular uptake and significantly down-regulate miR-21 expression in 5-FU resistant HCT-116 5FR cell lines. Consequently, the down-regulation of miR-21 induced cell cycle arrest, reduced tumor proliferation, increased apoptosis and rescued PTEN and hMSH2 expressions, regulatory targets of miR-21. Of particular importance was the significant reduction in tumor growth in a mouse model of colon cancer with systematic administration of the targeting miR-21i. More excitedly, the combinational delivery of miR-21i and 5-FU with the engineered exosomes effectively reverse drug resistance and significantly enhanced the cytotoxicity in 5-FU-resistant colon cancer cells, compared with the single treatment with either miR-21i or 5-FU. Conclusion The strategy for co-delivering the functional small RNA and anticancer drug by exosomes foreshadows a potential approach to reverse the drug resistance in CRC and thus to enhance the efficacy of the cancer treatment.

Ti3C2 MXene is a new two-dimensional material exhibiting a variety of novel properties including good photothermal effect, and the capability of Ti3C2 for multimodal tumor therapy is in urgent need of development. Herein, ultrathin Ti3C2 MXene nanosheets (∼100 nm) have been synthesized by supplying additive Al3+ to avoid Al loss and employed as a photothermal/photodynamic agent for cancer therapy. The as-obtained nanosheets exhibit outstanding mass extinction coefficient (28.6 Lg–1 cm–1 at 808 nm), superior photothermal conversion efficiency (∼58.3%), and effective singlet oxygen generation (1O2) upon 808 nm laser irradiation. Based on these Ti3C2 nanosheets, a multifunctional nanoplatform (Ti3C2-DOX) is established via layer-by-layer surface modification with doxorubicin (DOX) and hyaluronic acid (HA). In vitro and in vivo experiments disclose that Ti3C2-DOX shows enhanced biocompatibility, tumor specific accumulation, and stimuli-responsive drug release behavior and achieve effective cancer cell killing and tumor tissue destruction through photothermal/photodynamic/chemo synergistic therapy.

Novel Coronavirus disease (COVID-19) is a newly discovered contagious disease caused by severe acute respiratory syndrome (SARS)–coronavirus (CoV)-2 virus, primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, but it can affect multiple organs such as the kidney, heart, digestive tract, blood, and nervous system.1Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. https://doi.org/10.1001/jama.2020.1585. Accessed March 2, 2020.Google Scholar The rapidly spreading outbreak, which first emerged in Wuhan, Hubei Province, China, in December 2019, has since been declared a global pandemic. As of March 16, 2020, 167,511 cases of COVID-19 have been reported worldwide in 151 countries (and a cruise ship), with 6606 deaths.2World Health OrganizationCoronavirus disease (COVID-2019) situation reports.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reportsDate accessed: March 16, 2020Google Scholar In recent days, the number of cases has risen rapidly in South Korea, Japan, Europe, and the United States. SARS-CoV-2 has been identified as a bat-origin CoV. The full-length genome sequence of the COVID-19 virus shows a close relationship with the bat SARS-like coronavirus strain BatCov RaTG13 belonging to the Betacoronavirus genus.3World Health OrganizationReport of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19).https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdfDate accessed: March 2, 2020Google Scholar Previous coronavirus infections, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-Co-V), have infected more than 10,000 people in the past 2 decades, with mortality rates of 10% and 37%, respectively.4World Health OrganizationSummary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003.https://www.who.int/csr/sars/country/table2004_04_21/en/Date accessed: January 27, 2020Google Scholar,5World Health OrganizationMiddle East respiratory syndrome coronavirus (MERS-CoV). November 2019.http://www.who.int/emergencies/mers-cov/en/Date accessed: February 27, 2020Google Scholar COVID-19 is more contagious than these illnesses, spreads by human-to-human transmission via droplets, fecal, or direct contact, and has an incubation period estimated at 1 to 14 days (usually 3 to 7 days). Infection has been reported in all ages, including children. The majority of infections are mild, presenting with a flu-like illness. The common clinical presentations of COVID-19 are fever (98%), cough (76%), and myalgia and fatigue (18% each),6Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar with accompanying leucopenia (25%) and lymphopenia (63%). Symptoms of upper respiratory infection with rhinorrhea and productive cough are uncommon, except in children. About 16% to 20% cases have been classified as severe or critical. Of the 41 patients described by Huang et al.,6Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar all had pneumonia with abnormalities on computerized tomographic examination of the chest (bilateral lobular and subsegmental areas of consolidation), and 32% required care from the intensive care unit. Higher plasma cytokine levels (interleukin [IL]-2, IL-7, IL-10, granulocyte-colony stimulating factor, interferon-inducing protein-10, monocyte chemoattractant protein 1, macrophage inflammatory protein-1a, tumor necrosis factor α) were present in patients requiring intensive care unit admission. Limited reports suggest that severe complications are uncommon in children.7Center for Disease Control and PreventionFrequently asked questions and answers: Coronavirus Disease-2019 (COVID-19) and children.https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/children-faq.htmlDate accessed: March 2, 2020Google Scholar The diagnosis is mainly based on epidemiological factors (history of contact), clinical manifestations, and laboratory examination (hemogram, chest computed tomography, and virological examination).8Ling L. Taisheng L. The National Health Commission of PRC Guideline for diagnosis and treatment of novel coronavirus disease (version 6).Natl Med J China. 2020; 100: E001Google Scholar Of note, there are recent cases without any travel history or apparent contact with infected individuals. Several COVID-19 nucleic acid detection assays have been developed, both in-house and commercial. They use fluorescence polymerase chain reaction and probe anchoring polymerization techniques. Gene sequencing has also been used. The World Health Organization has appointed referral laboratories in different countries.9World Health OrganizationSpecimen referral for 2019nCoV - operational details of referral laboratories.https://www.who.int/docs/default-source/coronaviruse/who-appointed-2019-ncov-referral-laboratories-7-february-2020.pdf?sfvrsn&equals;c3fa3ec3_4Date accessed: March 2, 2020Google Scholar A serological test has been developed and allowed detection of a cluster of cases in Singapore.10Normile D. Singapore claims first use of antibody test to track coronavirus infections.https://www.sciencemag.org/news/2020/02/singapore-claims-first-use-antibody-test-track-coronavirus-infectionsDate accessed: March 2, 2020Google Scholar More sensitive and convenient detection methods continue to be developed. In previous reports of SARS and MERS-CoV infections, acute kidney injury (AKI) developed in 5% to 15% cases and carried a high (60%–90%) mortality rate. Early reports suggested a lower incidence (3%–9%) of AKI in those with COVID-19 infection.1Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. https://doi.org/10.1001/jama.2020.1585. Accessed March 2, 2020.Google Scholar,11Chen N. Zhou M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 12Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China [e-pub ahead of print]. N Engl J Med. https://doi.org/10.1056/NEJMoa2002032. Accessed March 2, 2020.Google Scholar, 13Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in-hospital death of COVID-19 patients [e-pub ahead of print]. medRxiv 2020.02.18.20023242. https://doi.org/10.1101/2020.02.18.20023242. Accessed March 2, 2020.Google Scholar Recent reports, however, have shown higher frequency of renal abnormalities. A study of 59 patients with COVID-19 found that 34% of patients developed massive albuminuria on the first day of admission, and 63% developed proteinuria during their stay in hospital.14Li Z. Wu M. Guo J. et al.Caution on kidney dysfunctions of 2019-nCoV patients. medRxiv 2020.02.08.20021212.Date accessed: March 2, 2020Google Scholar Blood urea nitrogen was elevated in 27% overall and in two-thirds of patients who died. Computed tomography scan of the kidneys showed reduced density, suggestive of inflammation and edema. Cheng et al.13Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in-hospital death of COVID-19 patients [e-pub ahead of print]. medRxiv 2020.02.18.20023242. https://doi.org/10.1101/2020.02.18.20023242. Accessed March 2, 2020.Google Scholar recently reported that amongst 710 consecutive hospitalized patients with COVID-19, 44% had proteinuria and hematuria and 26.7% had hematuria on admission. The prevalence of elevated serum creatinine and blood urea nitrogen was 15.5% and 14.1%, respectively. AKI was an independent risk factor for patients’ in-hospital mortality.13Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in-hospital death of COVID-19 patients [e-pub ahead of print]. medRxiv 2020.02.18.20023242. https://doi.org/10.1101/2020.02.18.20023242. Accessed March 2, 2020.Google Scholar,14Li Z. Wu M. Guo J. et al.Caution on kidney dysfunctions of 2019-nCoV patients. medRxiv 2020.02.08.20021212.Date accessed: March 2, 2020Google Scholar The exact mechanism of kidney involvement is unclear: postulated mechanisms include sepsis leading to cytokine storm syndrome or direct cellular injury due to the virus. Angiotensin-converting enzyme and dipeptidyl peptidase-4, both expressed on renal tubular cells, were identified as binding partners for SARS-CoV and MERS-CoV, respectively.15Li W. Moore M.J. Vasilieva N. et al.Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.Nature. 2003; 426: 450-454Crossref PubMed Scopus (4580) Google Scholar,16Raj V.S. Mou H. Smits S.L. et al.Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC.Nature. 2013; 495: 251-254Crossref PubMed Scopus (1588) Google Scholar Viral RNA has been identified in kidney tissue and urine in both infections.17Peiri J.S.M. Chu C.M. Cheng V.C.C. et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study.Lancet. 2003; 361: 1767-1772Abstract Full Text Full Text PDF PubMed Scopus (1998) Google Scholar,18Ding Y. He L. Zhang Q. et al.Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways.J Pathol. 2004; 203: 622-630Crossref PubMed Scopus (841) Google Scholar Recently, Zhong’s lab in Guangzhou successfully isolated SARS-CoV-2 from the urine sample of an infected patient, suggesting the kidney as the target of this novel coronavirus.19The team of Zhong Nanshan responded that the isolation of SARS-CoV-2 from urine remind us to pay more attention to the cleaning of individuals and families.Guangzhou Daily. Published February 22, 2020; Google Scholar The current treatment of COVID-19 with AKI includes general and supportive management and kidney replacement therapy. There is no effective antiviral therapy available at present. All patients with confirmed COVID-19 need to be quarantined. An N95 fit-tested respirator and protective clothes and equipment are essential. Early admission to intensive care units in designated hospitals is recommended for severely ill patients. Supportive care, namely bed rest, nutritional and fluid support, and maintenance of blood pressure and oxygenation are important measures, as for all critically ill patients. Other measures include prevention and treatment of complications by providing organ support, maintaining hemodynamic stability, and preventing secondary infection. There is no specific effective antiviral drug for COVID-19 at present. The guidelines of the Chinese National Health Commission recommend aerosolized inhalation of interferon α and lopinavir/ritonavir. The specific therapeutic value and safety of lopinavir/ritonavir in patients with COVID-19 are under investigation (ChiCTR2000029308).20Expert Team of Chinese Society of NephrologyExpert consensus on diagnosis and treatment of 2019 novel coronavirus (2019 - nCoV) infection with acute kidney injury.Chin J Nephrol. 2020; 3https://doi.org/10.3760/cma.j.cn441217-20200222-00035Google Scholar Successful treatment with remdesivir has been reported in a patient with COVID-19; a clinical trial on the efficacy of remdesivir in patients with COVID-19 is currently underway in China (NCT0425266; NCT04257656) and is expected to be completed in April 2020. Chloroquine phosphate has been shown to have some efficacy against COVID-19–associated pneumonia in multicenter clinical trials conducted in China.21Gao J. Tian Z. Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.Biosci Trends. 2020; 14: 72-73Crossref PubMed Google Scholar Continuous renal replacement therapy (CRRT) has been successfully applied in the treatment of SARS, MERS, and sepsis.22Chu K.H. Tsang W.K. Tang C.S. et al.Acute renal impairment in coronavirus-associated severe acute respiratory syndrome.Kidney Int. 2005; 67: 698-705Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar,23Arabi Y.M. Arifi A.A. Balkhy H.H. et al.Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection.Ann Intern Med. 2014; 160: 389-397Crossref PubMed Google Scholar High-volume hemofiltration in a dose of 6 l/h removed inflammatory cytokines (IL-6) and improved the Sequential Organ Failure Assessment scores at day 7 in patients with sepsis.24Ghani R.A. Zainudin S. Ctkong N. et al.Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic patients receiving high-volume haemofiltration and continuous venovenous haemofiltration.Nephrology (Carlton). 2006; 11: 386-393Crossref PubMed Scopus (83) Google Scholar Therefore, CRRT may play a role in patients with COVID-19 and sepsis syndrome. The potential role of extracorporeal therapy techniques needs to be evaluated, however. In a retrospective study of patients with SARS-CoV and sepsis, steroids, at a mean daily dose of 105.3 ± 86.1 mg in 147 of 249 noncritical patients (59.0%), reduced mortality rate and shortened duration of hospitalization, whereas 121 of 152 critical patients (79.6%) received corticosteroids at a mean daily dose of 133.5 ± 102.3 mg, and 25 died.25Chen R.C. Tang X.P. Tan S.Y. et al.Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience.Chest. 2006; 129: 1441-1452Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar A subsequent retrospective, observational study of 309 patients with MERS showed that those who received high-dose steroids were more likely to require mechanical ventilation, vasopressors, and renal replacement therapy (RRT).26Arabi Y.M. Mandourah Y. Al-Hameed F. et al.Corticosteroid therapy for critically ill patients with middle east respiratory syndrome.Am J Respir Crit Care Med. 2018; 197: 757-767Crossref PubMed Scopus (838) Google Scholar In a meta-analysis of corticosteroid use in patients with SARS, 4 studies provided conclusive evidence of harm (psychosis, diabetes, avascular necrosis, and delayed viral clearance).27Stockman L.J. Bellamy R. Garner P. SARS: systematic review of treatment effects.PLoS Med. 2006; 3: e343Crossref PubMed Scopus (986) Google Scholar Therefore, the use of steroids is controversial and not recommended by the World Health Organization because of potential inhibition of viral clearance and prolongation of the duration of viremia.28Russell C.D. Millar J.E. Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury.Lancet. 2020; 395: 473-475Abstract Full Text Full Text PDF PubMed Scopus (1542) Google Scholar Preliminary clinical studies in China have shown that early application of convalescent plasma in patients with COVID-19 could accelerate clinical recovery.6Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar Currently 2 trials, an open-label, nonrandomized clinical trial (NCT04264858) and a multicenter, randomized, and parallel-controlled trial (ChiCTR2000029757) on the efficacy of convalescent plasma in patients with COVID-19, are underway in China. Monoclonal antibody directed against the Ras-binding domain of the S protein of MERS-CoV has been found to have neutralizing activities in plaque assays in vitro.29Park B.K. Maharjan S. Lee S.I. et al.Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex.BMB Rep. 2019; 52: 397-402Crossref PubMed Scopus (20) Google Scholar A monoclonal antibody against COVID-19 has not yet been developed. Tocilizumab, a monoclonal antibody against the IL-6 receptor, has achieved encouraging preliminary clinical results. The safety and efficacy of tocilizumab in COVID-19 infection are undergoing evaluation by a multicenter randomized controlled trial (ChiCTR2000029765). Pregnant women, newborns, the elderly, and patients with comorbidities like diabetes mellitus, hypertension, and cardiovascular disease are susceptible to COVID-19 infection and are likely to have more severe illness often requiring care from an intensive care unit. The impact of COVID-19 on chronic kidney disease has not been reported.30Ma Y. Diao B. Lv X. et al.2019 novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China.https://www.medrxiv.org/content/10.1101/2020.02.24.20027201v2Date accessed: March 2, 2020Google Scholar COVID-19 infection presents a special threat to patients on dialysis. There are 7184 patients on hemodialysis (HD) in 61 treatment centers in Wuhan City. At a single HD center in Renmin Hospital, Wuhan University, 37 out of 230 patients on HD and 4 of 33 staff members developed COVID-19 infection between January 14 and February 17, 2020.30Ma Y. Diao B. Lv X. et al.2019 novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China.https://www.medrxiv.org/content/10.1101/2020.02.24.20027201v2Date accessed: March 2, 2020Google Scholar A total of 7 patients on HD died, of whom 6 had COVID-19 infection. However, the deaths were deemed to be due to cardiovascular causes and not directly to the COVID-19 infection. Patients on HD with COVID-19 had less lymphopenia, lower serum levels of inflammatory cytokines, and milder clinical disease than other patients with COVID-19 infection. COVID-19 infection presents particular challenges for patients on dialysis, in particular, those in in-center HD. Patients with uremia are particularly to infection and may in clinical and HD the risk of transmission of including to staff and patients and all The Chinese Society of Team of Chinese for prevention and of novel coronavirus infection in blood center from Chinese J Nephrol. 2020; Scholar and the Society of Guideline for during COVID-19 Society of accessed: March 16, 2020Google Scholar have recently developed guidelines for units during the COVID-19 A of these guidelines is provided team of and in clinical of COVID-19, of infection at prevention and guidelines from the and The of staff be and by on and cluster history of patient, their of the and at be and care and be and to all care as can be or including and be is recommended that staff members have at different to and be removed and with during be to the of their and the team in or their members suggestive of COVID-19 and of people at risk of of or the and be and accompanying be the Patients and during dialysis. They can such as to with or confirmed COVID-19 infection be to a isolation of the of the isolation is the Care is recommended for patients under the period of for contact with of patients continue HD at the HD center and not to and not and staff to and infection. the who need be for novel coronavirus the on patients with confirmed or novel coronavirus infection be carried out in a designated with for not be used. 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BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 μg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).

BACKGROUND: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis. METHODS: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9. RESULTS: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period. CONCLUSIONS: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).

BACKGROUND: Inflammatory bowel disease (IBD)-associated dysbiosis is characterized by a loss of Faecalibacterium prausnitzii, whose supernatant exerts an anti-inflammatory effect. However, the anti-inflammatory substances in F. prausnitzii supernatant and the mechanism in ameliorating colitis in IBD have not yet been fully investigated. METHODS: Experimental colitis models were induced and evaluated by clinical examination and histopathology. Levels of cytokines and ratio of T cells were detected by enzyme-linked immunosorbent assay and flow cytometry analysis, respectively. F. prausnitzii supernatant was separated by macroporous resins. After extraction, the substances in supernatant were identified by gas chromatography-mass spectrometer. T-cell differentiation assay was conducted in vitro. Changes in signaling pathways were examined by immunoblot, immunohistochemistry, and immunofluorescent staining. RESULTS: We found that the supernatant of F. prausnitzii could regulate T helper 17 cell (Th17)/regulatory T cell (Treg) differentiation. Then, we identified butyrate produced by F. prausnitzii that played the anti-inflammatory effects by inhibiting interleukin (IL)-6/signal transducer and the activator of transcription 3 (STAT3)/IL-17 pathway and promoting forkhead box protein P3 (Foxp3). Finally, we demonstrated that the target of butyrate was histone deacetylase 1 (HDAC1). CONCLUSIONS: It is butyrate, instead of other substances produced by F. prausnitzii, that maintains Th17/Treg balance and exerts significant anti-inflammatory effects in colorectal colitis rodents, by inhibiting HDAC1 to promote Foxp3 and block the IL-6/STAT3/IL-17 downstream pathway. F. prausnitzii could be an option for further investigation for IBD treatment. Targeting the butyrate-HDAC1-T-cell axis offers an effective novel approach in the treatment of inflammatory disease.

OBJECTIVES: We performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in ICU in China. DESIGN: A cross-section survey study. SETTING: Forty-four hospitals in mainland China from December 1, 2015, to January 31, 2016. PATIENTS: All septic patients diagnosed according sepsis-1 criteria admitted to participating ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recorded demographic, physiologic, and microbiological data with follow-up for 90 days or death, if sooner. The frequency of sepsis and 90-day mortality rate were computed, and the relationship with gross domestic product determined. Multivariate logistic regression analysis was used to determine risk factors for 90-day mortality in patients with sepsis. Two-thousand three-hundred twenty-two patients with sepsis were included in the analysis, of whom 786 patients (33.9%) had hospital-acquired sepsis. The most common infection site was the lung (68.2%), followed by abdomen (26.6%) and bloodstream (7.8%). The frequency of sepsis in the ICU was 20.6 cases per 100 ICU admissions (95% CI, 15.8-25.4) with a 90-day mortality of 35.5%. The proportion of sepsis, severe sepsis, and septic shock were 3.10%, 43.6%, and 53.3% with a 90-day mortality of 2.78%, 17.69%, and 51.94%, respectively. Older age, low body weight, higher Sequential Organ Failure Assessment score, the number of systemic inflammatory response syndrome criteria, comorbid with heart failure, hematologic cancer, immunosuppression, higher level of lactate, infection site (pneumonia and bloodstream) were associated with 90-day mortality. CONCLUSIONS: Sepsis affects a fifth of patients admitted to ICUs in mainland China with a 90-day mortality rate of 35.5%. Our findings indicate that a large burden of sepsis, and we need to focus on sepsis as a quality improvement target in China given the high mortality. In addition, further studies are needed to delineate the epidemiology of sepsis outside the ICU.

In this paper, we present a semi-supervised deep learning approach to accurately recover high-resolution (HR) CT images from low-resolution (LR) counterparts. Specifically, with the generative adversarial network (GAN) as the building block, we enforce the cycle-consistency in terms of the Wasserstein distance to establish a nonlinear end-to-end mapping from noisy LR input images to denoised and deblurred HR outputs. We also include the joint constraints in the loss function to facilitate structural preservation. In this process, we incorporate deep convolutional neural network (CNN), residual learning, and network in network techniques for feature extraction and restoration. In contrast to the current trend of increasing network depth and complexity to boost the imaging performance, we apply a parallel 1×1 CNN to compress the output of the hidden layer and optimize the number of layers and the number of filters for each convolutional layer. The quantitative and qualitative evaluative results demonstrate that our proposed model is accurate, efficient and robust for super-resolution (SR) image restoration from noisy LR input images. In particular, we validate our composite SR networks on three large-scale CT datasets, and obtain promising results as compared to the other state-of-the-art methods.

A cluster of patients of novel coronavirus pneumonia (NCP) have been identified in Wuhan in December 2019 and soon this virus spread at a tremendous rate which swept through the whole China and more than 93 countries and regions around the world [1, 2]. This emerging, rapidly evolving situation has threatened the health of all mankind and WHO has raised COVID-19 risk to “very high” at global level. Up to now, 80,859 cases were confirmed, among which 10–15% patients were critically ill and 3100 (3.83%) died in China. The large number of transmission population between Jiangsu and Hubei provinces led to the infinite burden in controlling the COVID-19 epidemic in Jiangsu Province [3, 4]. By 24:00 on March 7, a total of 631 confirmed cases of NCP were reported with a portion of critically ill patients whose ages ranged from 9 months to 96 years old. A total of 610 cases have been discharged from hospital, and the cure rate of confirmed cases in our province has reached 96.67%, which is far exceeding that of national data [5,6,7,8]. Since the outcome of NCP patients in Jiangsu was much better than that in Hubei where the mortality of NCP patients was nearly 4.34%, we retrospectively summarized our therapeutic process and figured out that critical care-dominated treatment patterns might be the core in reducing mortality.

Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

Incidence of hepatocellular carcinoma (HCC) is on the rise due to the prevalence of chronic hepatitis and cirrhosis. Although there are surgical and chemotherapy treatment avenues the mortality rate of HCC remains high. Immunotherapy is currently the new frontier of cancer treatment and the immunobiology of HCC is emerging as an area for further exploration. The tumor microenvironment coexists and interacts with various immune cells to sustain the growth of HCC. Thus, immunosuppressive cells play an important role in the anti-tumor immune response. This review will discuss the current concepts of immunosuppressive cells, including tumor-associated macrophages, marrow-derived suppressor cells, tumor-associated neutrophils, cancer-associated fibroblasts, and regulatory T cell interactions to actively promote tumorigenesis. It further elaborates on current treatment modalities and future areas of exploration.

Another interesting finding of this case series is that hypertension was the most common chronic comorbidity among patients who died. A previous 2020 case series 1 also reported a higher rate of hypertension among patients with COVID-19 who were admitted to intensive care units than among patients with COVID-19 who were not admitted to intensive care units. However, hypertension usually is not an independent risk factor associated with mortality in patients with sepsis. According to a study from earlier this year, 6 severe acute respiratory syndrome coronavirus 2 infects the lungs through the angiotensin-converting enzyme II receptor. Further research is needed to find the mechanism of COVID-19. In addition, clinical studies are also needed to confirm whether angiotensin-converting enzyme inhibitors and angiotensin receptor blockers could be beneficial for patients with COVID-19.