Author Correction: A new coronavirus associated with human respiratory disease in China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A new coronavirus associated with human respiratory disease in China.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

ITIH4 reversed the effects of thrombin on VSMCs stiffness via JNK and ERK signaling pathway.

Vascular smooth muscle cell (VSMCs) is one of the important cell types in artery. VSMCs stiffening may regulate vascular stiffness and contribute to the development of vulnerable plaques. Thrombin, an enzyme in coagulation system, is involved in pathological processes of atherosclerosis. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays an important role in regulating inflammation and may have cardiovascular protective effect. Therefore, the elucidation of the mechanisms underlying ITIH4-mediated VSMCs stiffening helps to provide new ideas and potential targets for the diagnosis and treatment of atherosclerosis. In this study, we used specific ITIH4 expression vector and siRNA methods to transfect VSMCs. Our results found that ITIH4 expression increased VSMCs stiffness, meanwhile, ITIH4 siRNA decreased VSMCs stiffness. ITIH4 increased acetylated α-tubulin and inhibited ERK1/2 and JNK, but not P38 MAPK. ERK inhibitor (PD98059) or JNK inhibitor (SP600125) treatment increased acetylated α-tubulin expression and cell stiffness in VSMCs. ITIH4 was downregulated by thrombin treatment, ITIH4 partly reversed the effect of thrombin on acetylated α-tubulin and VSMCs stiffness. These results indicated that ITIH4 regulated acetylated α-tubulin expression in VSMCs and was against the effects of thrombin on VSMCs stiffness. JNK and ERK signaling pathways were proved to participate in this process.

Total infectome characterization of respiratory infections in pre-COVID-19 Wuhan, China.

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.

Targeted chemical profiling for p-HAP glycosides by using molecular networking and comparative analysis of their contents between Artemisia japonica and Artemisia capillaris.

A total of 65 phenolic acid compounds were annotated or identified by UHPLC-MS/MS method, among them, 17 p-HAP (p-hydroxyacetophenone) glycosides were firstly targeted profiled based on molecular networking. Their characteristic product ions of MS/MS spectra were found and examined on the guideline of targeted isolation. As a result, a new p-HAP glycoside was thus obtained and determined as 2'-O-caffeoyl-p-HAP-4-O-ß-D-glucopyranoside (33) based on 1D and 2D NMR data. Besides, multicomponents quantitative analysis indicated the distinct regional variability in chemicals distribution of A. japonica, and meanwhile, the contents of p-HAP glycosides from A. japonica were higher than those in A. capillaris as a whole, which further suggested the potential medicinal value of A. japonica.

Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs.

BACKGROUND: As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs. RESULTS: The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways. CONCLUSIONS: In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds.

In Situ Transformable Pro-nanotheranostic Platform for Activable Photoacoustic Imaging and Synergistic Photothermal/Chemodynamic Cancer Therapy.

Nanotheranostic platforms integrated with diagnostic and therapeutic functions have been widely developed for tumor medicine. However, the "always-on" nanotheranostic platforms suffer from poor tumor specificity, which may largely restrict therapeutic efficacy and prevent precise theranostics. Here, we develop an in situ transformable pro-nanotheranostic platform (ZnS/Cu2O@ZIF-8@PVP) by encapsulating ZnS and Cu2O nanoparticles in a metal-organic framework (MOF) nanomaterial of ZIF-8 that allows activable photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT) of tumors in vivo. It is shown that the pro-nanotheranostic platform gradually decomposes and releases ZnS nanoparticles and Cu+ ions in acidic conditions, which spontaneously trigger a cation exchange reaction and synthesize Cu2S nanodots in situ with activated PA signals and PTT effects. Moreover, the excessive Cu+ ions function as Fenton-like catalysts and catalyze the production of highly reactive hydroxyl radicals (•OH) for CDT using elevated levels of H2O2 in tumor microenvironments (TMEs). In vivo studies demonstrate that the in situ transformable pro-nanotheranostic platform can specifically image tumors via PA and photothermal imaging and efficiently ablate tumors through synergistic CDT/PTT. Our in situ transformable pro-nanotheranostic platform could provide a new arsenal for precise theranostics in cancer therapy.

Progress on Z genome biosynthetic pathway of bacteriophage.

There are abundant base modifications in bacteriophages' genomes, mainly for avoiding the digestion of host endonucleases. More than 40 years ago, researchers discovered that 2-amino-adenine (Z) completely replaced adenine (A) and forms a complementary pairing with three hydrogen bonds with thymine (T) in the DNA of cyanophage S-2L, forming a distinct "Z-genome". In recent years, researchers have discovered and validated the biosynthetic pathway of Z-genome in various bacteriophages, constituting a multi-enzyme system. This system includes the phage-encoded enzymes deoxy-2'-aminoadenylosuccinate synthetase (PurZ), deoxyadenosine triphosphate hydrolase (dATPase/DatZ), deoxyadenosine/deoxyguanosine triphosphate pyrophosphatase (DUF550/MazZ) and DNA polymerase (DpoZ). In this review, we provide a concise overview of the historical discovery on diversely modified nucleosides in bacteriophages, then we comprehensively summarize the research progress on multiple enzymes involved in the Z-genome biosynthetic pathway. Finally, the potential applications of the Z-genome and the enzymes in its biosynthetic pathway are discussed in order to provide reference for research in this field.

[Advantage analysis of modified day surgery procedure for concealed penis].

OBJECTIVE: The modified day surgery procedure was compared with traditional inpatient procedure and standard day surgery procedure of concealed penile surgery to investigate its advantages, as well as the feasibility of promoting it in our country. METHODS: Retrospective analyzing the clinical data between 135 cases of the concealed penis in children who underwent modified day surgery (day group) and 101 cases who underwent hospitalization surgery (hospitalization group) at the Second Hospital of Hebei Medical University and the results of follow-up.The modified day surgery procedure involves the establishment of dedicated day wards in each surgical department, where the patient's condition is monitored until 8 o'clock the following morning to assess their discharge eligibility.The children's clinical data was divided into two groups to compare clinical parameters, including age at surgery, bleeding volume, operation time, hospitalization expenses, day of hospitalization, and the occurrence of short-term complications before the initial dressing change after surgery.The satisfaction survey of the children was conducted among three distinct groups: the modified day group, the standard day group, and the hospitalization group enabling a comparison of satisfaction levels among these groups. RESULTS: The mean ages of the inpatient and day surgery groups were 8.92±4.42 years old and 11.85±4.43 years old, respectively. No significant differences were observed between these two groups regarding operation time, bleeding volume, and postoperative complications (P>0.05). Compared to the inpatient group, the mean inpatient time and the hospitalization cost of the day group decreased by 69% and 27%, respectively (P<0.05). The patients in the modified procedure group reported the highest satisfaction among the three groups. CONCLUSION: Modified day surgery procedure offers advantages over the standard day surgery procedure and traditional inpatient surgical procedures for the operative treatment of the concealed penis, which makes it suitable for large-scale popularization in China.

[A new cinnamic acid ester derivative from Liquidambaris Resina].

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17ß-hydroperoxide(4), erythrodiol(5), 13ß,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3ß)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) µmol·L~(-1), respectively.

DNA-Templated Bioorthogonal Reactions via Catalytic Hairpin Assembly for Precise RNA Imaging in Live Cells.

There has been a significant interest in developing proximity-induced bioorthogonal reactions for nucleic acid detection and imaging, owing to their high specificity and tunable reaction kinetics. Herein, we reported the first design of a fluorogenic sensor by coupling a bioorthogonal reaction with a DNA cascade circuit for precise RNA imaging in live cells. Two DNA hairpin probes bearing tetrazines or vinyl ether caged fluorophores were designed and synthesized. Upon target mRNA triggering catalytic hairpin assembly, the chemical reaction partners were brought in a spatial proximity to yield high effective concentrations, which dramatically facilitated the bioorthogonal reaction efficiency to unmask the vinyl ether group to activate fluorescence. The proposed fluorogenic sensor was demonstrated to have a high signal-to-noise ratio up to ∼30 fold and enabled the sensitive detection of target mRNA with a detection limit of 4.6 pM. Importantly, the fluorogenic sensor presented low background signals in biological environments due to the unique "click to release" feature, avoiding false positive results caused by unspecific degradation. We also showed that the fluorogenic sensor could accurately image mRNA in live cells and distinguish the relative mRNA expression levels in both tumor and normal cells. Benefiting from these significant advantages, our method provides a useful tool for basic studies of bioorthogonal chemistry and early clinical diagnosis.

Surgical Trauma-induced CCL2 Upregulation Mediates Lung Cancer Progression by Promoting Treg Recruitment in Mice and Patients.

Surgical removal of the tumor is currently the first-line treatment for lung cancer, but the procedure may accelerate cancer progression through immunosuppression. However, whether CCL2 (C-C motif chemokine ligand 2) enhances cancer progression by affecting regulatory T cells (Tregs) remains unknown. We found that the volume and weight of tumors were larger in the surgical trauma group than in the control group. CCL2 expression and Treg abundance were increased in tumor tissues after surgical trauma, and CCL2 expression was positively associated with Treg abundance. These results demonstrated that surgical trauma contributes to lung cancer progression by increasing CCL2 expression, thus promoting Treg recruitment.

LncRNA-599547 contributes the inductive property of dermal papilla cells in cashmere goat through miR-15b-5p/Wnt10b axis.

The lncRNA-599547 (619-nt in length) is identified in secondary hair follicle (SHF) of cashmere goat, but its functional roles in regulating the inductive property of dermal papilla cells (DPCs) remains unknown. We found that lncRNA-599547 had significantly higher expression in dermal papilla of cashmere goat SHF at anagen than its counterpart at telogen. The overexpression of lncRNA-599547 led to a significant increase of ALP and LEF1 expression in DPCs (p < 0.05), whereas, the siLncRNA-1 mediated silencing of lncRNA-599547 significantly down-regulated the expression of ALP and LEF1 in DPCs (p < 0.05). Based on biotin-labeled RNA pull-down assay, we found that lncRNA-599547 directly interacted with chi-miR-15b-5p in DPCs. Based on both overexpression and silencing analysis of lncRNA-599547, our results indicate that lncRNA-599547 promotes the expression of Wnt10b in DPCs but without modulating its promoter methylation level. Using the mRNA-3'UTR fragments of goat Wnt10b containing the predicted binding sites of chi-miR-15b-5p in Dual-luciferase Reporter Assays, we show that lncRNA-599547 modulates the expression of Wnt10b at the chi-miR-15b-5p mediated post-transcriptional level. Taken together, our results indicate that lncRNA-599547 sponges miR-15b-5p to positively regulate the expression of Wnt10 gene, and thereby contributes the inductive property of DPCs in cashmere goat.

Hepatocytes derived increased SAA1 promotes intrahepatic platelet aggregation and aggravates liver inflammation in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the pathological manifestation of metabolic syndrome in liver. Its pathological changes may evolve from the initial simple steatosis to non-alcoholic steatohepatitis, liver fibrosis and even liver cancer. Numerous studies have proved that platelets play a vital role in liver disease and homeostasis. Particularly, anti-platelet therapy can reduce intrahepatic platelet aggregation and improve the inflammation of fatty liver. Previous study has also confirmed that SAA is a gene closely related to high-fat diet (HFD) induced obesity, and SAA1 can promote liver insulin resistance induced by Palmitate or HFD. Here, we found that SAA1 treated platelets presented increased sensitivity of platelet aggregation, enhanced activation and increased adhesion ability, and such function was partly dependent on Toll-Like Receptor (TLR) 2 signaling. In addition, blocking SAA1 expression in vivo not only inhibited platelet aggregation in the liver tissues of NAFLD mice, but also alleviated the inflammation of fatty liver. In conclusion, our findings identify that HFD-induced hepatic overexpressed SAA1 aggravates fatty liver inflammation by promoting intrahepatic platelet aggregation, these results also imply that SAA1 may serve as a potential target for ameliorating NAFLD.

Detection of the HBB: c.393T>G Mutation in Two Patients with Hypochromic Microcytic Anemia.

A novel mutation, HBB: c.393T>G on the HBB gene, was detected in two hypochromic microcytic anemia patients from Yulin, in the Guangxi Province of the People's Republic of China (PRC), by next-generation sequencing (NGS). It is a nonsense mutation causing a stop codon at amino acid 131 in exon 3 of the HBB gene. It was found in a heterozygous state in two patients who both presented severe anemia during pregnancy and moderate anemia before pregnancy; Hb A2 levels were slightly increased (more than 4.0%) in both patients. It was also detected in the father of one of the patients. This mutation was pathogenic, and caused the dominant thalassemia-like phenotypes in the two patients.

Emperipolesis mediated by CD8+ T cells correlates with biliary epithelia cell injury in primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty-six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early-stage PBC (stages I and II, n = 39) and late-stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin-eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R2  = 0.318, P < .001; R2  = 0.060, P < .05). The cell numbers of TUNEL-positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R2  = 0.236, P < .001; R2  = 0.267, P < .001). We conclude that emperipolesis mediated by CD8+ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.

Clinical Course and Mortality of Stroke Patients With Coronavirus Disease 2019 in Wuhan, China.

BACKGROUND AND PURPOSE: No studies have reported the effect of the coronavirus disease 2019 (COVID-19) epidemic on patients with preexisting stroke. We aim to study the clinical course of COVID-19 patients with preexisting stroke and to investigate death-related risk factors. METHODS: We consecutively included 651 adult inpatients with COVID-19 from the Central Hospital of Wuhan between January 2 and February 15, 2020. Data on the demography, comorbidities, clinical manifestations, laboratory findings, treatments, complications, and outcomes (ie, discharged or death) of the participants were extracted from electronic medical records and compared between patients with and without preexisting stroke. The association between risk factors and mortality was estimated using a Cox proportional hazards regression model for stroke patients infected with severe acute respiratory syndrome coronavirus 2. RESULTS: Of the 651 patients with COVID-19, 49 with preexisting stroke tended to be elderly, male, had more underlying comorbidities and greater severity of illness, prolonged length of hospital stay, and greater hospitalization expenses than those without preexisting stroke. Cox regression analysis indicated that the patients with stroke had a higher risk of developing critical pneumonia (adjusted hazard ratio, 2.01 [95% CI, 1.27-3.16]) and subsequent mortality (adjusted hazard ratio, 1.73 [95% CI, 1.00-2.98]) than the patients without stroke. Among the 49 stroke patients, older age and higher score of Glasgow Coma Scale or Sequential Organ Failure Assessment were independent risk factors associated with in-hospital mortality. CONCLUSIONS: Preexisting stroke patients infected with severe acute respiratory syndrome coronavirus 2 were readily predisposed to death, providing an important message to individuals and health care workers that preventive measures must be implemented to protect and reduce transmission in stroke patients in this COVID-19 crisis.

Association of tumor necrosis factor-α gene polymorphisms and coronary artery disease susceptibility: a systematic review and meta-analysis.

BACKGROUND: The goal of this study was to review relevant case-control studies to determine the association of tumor necrosis factor-α (TNF-α) gene polymorphisms and coronary artery disease (CAD) susceptibility. METHODS: Using appropriate keywords, we identified relevant studies using PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through April 2019 were considered for inclusion. Based on eligible studies, we performed a meta-analysis of association between 308G/A, 238G/A, 857C/T, 863C/A and 1031 T/C polymorphisms in TNF-α and risk of CAD. RESULTS: We found 25 studies that were consistent with this meta-analysis, including 7697 patients in the CAD group and 9655 control patients. TNF-α 308G/A locus A showed no significant association with CAD susceptibility by the five models in the analysis of the overall population, European, African, South Asian, and North Asian patients. TNF-α 863C/A locus A and 1031 T/C locus C exhibited no significant association with CAD susceptibility. TNF-α 238G/A locus A had no significant association with CAD susceptibility in the overall population. However, TNF-α 238G/A locus A showed significant association with higher CAD susceptibility in the subgroup of Europeans and north Asians. TNF-α 857C/T locus T had no significant association with CAD susceptibility in the analysis of the overall population and Europeans. In the north Asian population, TNF-α 857C/T locus T was associated with lower CAD susceptibility by the heterozygote model. CONCLUSION: TNF-α 308G/A, 857C/T, 863C/A, and 1031 T/C has no significant association with CAD susceptibility. TNF-α 238G/A locus A has significant association with CAD susceptibility in Europeans and north Asians, but has no significant association in the overall population. Studies with a larger sample size are required to confirm the association between TNF-α 238G/A and CAD susceptibility.

Propofol Affects Non-Small-Cell Lung Cancer Cell Biology By Regulating the miR-21/PTEN/AKT Pathway In Vitro and In Vivo.

BACKGROUND: Propofol is a common sedative-hypnotic drug traditionally used for inducing and maintaining general anesthesia. Recent studies have drawn attention to the nonanesthetic effects of propofol, but the potential mechanism by which propofol suppresses non-small-cell lung cancer (NSCLC) progression has not been fully elucidated. METHODS: For the in vitro experiments, we used propofol (0, 2, 5, and 10 µg/mL) to treat A549 cells for 1, 4, and 12 hours and Cell Counting Kit-8 (CCK-8) to detect proliferation. Apoptosis was measured with flow cytometry. We also transfected A549 cells with an microribonucleic acid-21 (miR-21) mimic or negative control ribonucleic acid (RNA) duplex and phosphatase and tensin homolog, deleted on chromosome 10 (PTEN) small interfering ribonucleic acid (siRNA) or negative control. PTEN, phosphorylated protein kinase B (pAKT), and protein kinase B (AKT) expression were detected using Western blotting, whereas miR-21 expression was examined by real-time polymerase chain reaction (RT-PCR). In vivo, nude mice were given injections of A549 cells to grow xenograft tumors; 8 days later, the mice were intraperitoneally injected with propofol (35 mg/kg) or soybean oil. Tumors were then collected from mice and analyzed by immunohistochemistry and Western blotting. RESULTS: Propofol inhibited growth (1 hour, P = .001; 4 hours, P ≤ .0001; 12 hours, P = .0004) and miR-21 expression (P ≤ .0001) and induced apoptosis (1 hour, P = .0022; 4 hours, P = .0005; 12 hours, P ≤ .0001) in A549 cells in a time and concentration-dependent manner. MiR-21 mimic and PTEN siRNA transfection antagonized the suppressive effects of propofol on A549 cells by decreasing PTEN protein expression (mean differences [MD] [95% confidence interval {CI}], -0.51 [-0.86 to 0.16], P = .0058; MD [95% CI], 0.81 [0.07-1.55], P = .0349, respectively), resulting in an increase in pAKT levels (MD [95% CI] = -0.82 [-1.46 to -0.18], P = .0133) following propofol exposure. In vivo, propofol treatment reduced NSCLC tumor growth (MD [95% CI] = -109.47 [-167.03 to -51.91], P ≤ .0001) and promoted apoptosis (MD [95% CI] = 38.53 [11.69-65.36], P = .0093). CONCLUSIONS: Our study indicated that propofol inhibited A549 cell growth, accelerated apoptosis via the miR-21/PTEN/AKT pathway in vitro, suppressed NSCLC tumor cell growth, and promoted apoptosis in vivo. Our findings provide new implications for propofol in cancer therapy and indicate that propofol is extremely advantageous in surgical treatment.

Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study.

BACKGROUND: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear. METHODS: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models. RESULTS: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P < 0.05). Cox regression analyses revealed that platelet count was an independent risk factor associated with in-hospital mortality in a dose-dependent manner. An increment of per 50 × 109/L in platelets was associated with a 40% decrease in mortality (hazard ratio: 0.60, 95%CI: 0.43, 0.84). Dynamic changes of platelets were also closely related to death during hospitalization. CONCLUSIONS: Baseline platelet levels and changes were associated with subsequent mortality. Monitoring platelets during hospitalization may be important in the prognosis of patients with coronavirus disease in 2019.