Research progress on the manifestations and prognosis of neonatal lupus erythematosus in various systems / 中国当代儿科杂志

Neonatal lupus erythematosus (NLE) is caused by the transmission of maternal anti-Ro/SSA antibodies, anti-La/SSB antibodies, and other autoantibodies to the fetus through the placenta. Usually, with the disappearance of autoantibodies in the children's body, abnormal changes in the mucocutaneous, blood system, and digestive system can spontaneously subside, but the damage to various systems caused by autoantibodies may persist for a long time. This article provides a comprehensive review of the manifestations and prognosis of NLE in various systems, including mucocutaneous, blood system, circulatory system, nervous system, digestive system, respiratory system, aiming to provide reference for clinical work.

Research progress on neurodevelopmental outcomes of small for gestational age infants / 中华预防医学杂志

The incidence of perinatal disease and perinatal mortality in small for gestational age infants increased significantly. This group of people is prone to a variety of long-term metabolic diseases and cardiovascular diseases, and is also prone to growth retardation and neurodevelopmental delay, which will seriously affect the long-term quality of life of children. The article studies the neurodevelopmental outcomes of small-for-gestational-age infants. By reviewing and sorting out previous literature, the neurodevelopmental disorders of small-for-gestational-age infants are analyzed according to five aspects: intellectual development, motor development, language development, sensory development, and mental illness. The classification and summary were carried out, and the influencing factors of neurodevelopmental disorders of SGA were also evaluated, so as to provide reference for promoting the improvement of neurodevelopmental outcomes of small-for-gestational-age infants.

The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0<LGE%<5%, 5%≤LGE%<15% and LGE%≥15% groups. There were significant survival differences between these 4 groups whether for primary endpoint or secondary endpoint (all P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.

Age-related changes for the predictors of benign prostatic hyperplasia in Chinese men aged 40 years or older / 亚洲男科学杂志(英文版)

A cross-sectional study was conducted to estimate the age-stratified normal levels and age-related changes in the risk predictors of benign prostatic hyperplasia (BPH) progression. A total of 4706 male participants aged 40 years or older in Zhengzhou (China) were enrolled. The values of the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), prostate volume (PV), and postvoid residual urine volume (PVR) significantly increased with age. Nonlinear relationships between age and IPSS scores ≥8 (P for nonlinearity = 0.046), PSA level ≥1.6 ng ml-1, PV ≥31 ml, or PVR ≥39 ml (all P for nonlinearity <0.001) were observed. After the age of 61 years, the risk indicators related to BPH progression were positively correlated with age (odds ratio [OR] >1), regardless of the predictors of the IPSS score, PSA level, PV, or PVR; and the OR values increased gradually. Therefore, after the age of 61 years, the risk predictors related to BPH progression were positively correlated with age.

Research progress on long-term developmental outcomes of offspring of pregnant women with systemic lupus erythematosus / 中国当代儿科杂志

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that affects multiple organs and systems. It is more common in women of childbearing age. Compared with the general population, pregnant women with SLE are at a significantly increased risk of adverse perinatal outcomes such as preterm birth and intrauterine growth restriction. In addition, the offspring of SLE patients may also be adversely affected by in utero exposure to maternal autoantibodies, cytokines, and drugs. This article summarizes the long-term developmental outcomes of offspring of pregnant women with SLE in terms of the blood system, circulatory system, nervous system, and immune system.

IL-27: a novel cytokine mediating immune related diseases / 生理学报

Interleukin 27 (IL-27) is a pleiotropic cytokine that is involved in the regulation of the body's innate and adaptive immunity. Previous studies have shown that IL-27 mediates a variety of inflammatory responses in vivo. With the development of animal models and technical tools, several studies have shown that it is also closely associated with autoimmune diseases and other immune related diseases, and is considered as an important candidate for the treatment of viral disease, autoimmune diseases, tumors and obesity. Therefore, this paper reviews recent progress on the role of IL-27 in acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis, tumors and obesity, with the aim of providing new ideas for the treatment of immune related diseases.

The protective effects of sinomenine on organotin-injured liver HL02 cells and its mechanism / 中国药理学通报

Aim To investigate the protective effect of sinomenine(SIN)against dibutyltin(DBT)induced injury in HL02 cells and explore the potential mechanism.Methods HL02 cells were cultured and divided into control,model and SIN-treated groups.Cell proliferation was detected by MTT method.Cell morphology was observed.Cell apoptosis was detected by Acridine orange/ethidium bromide(AO/EB)fluorescent staining and Annexin V-FITC/PI double staining.Meanwhile,intracellular reactive oxygen species(ROS)concentration was detected by DCFH-DA staining.Mitochondrial membrane potential(MMP)was tested by JC-1 dye.Moreover,the mRNA expression of apoptosis-related proteins was detected by qRT-PCR,and the protein expression of Bcl-2,Bax,caspase-9,cleaved-caspase-3 were measured via Western blot.Results The pretreatment with SIN increased the cell viability and decreased morphological changes induced by DBT in a dose-dependent manner.Meanwhile,cell apoptotic rates and intracellular ROS decreased,and the loss of MMP was partially restored.Compared to DBT-treated group,SIN treatment could increase the mRNA levels of Bcl-2,Bcl-xL and decrease the mRNA levels of Bax,Bad,cytochrome-c,Apaf-1,caspase-9 and caspase-3.Furthermore,SIN could significantly up-regulated the DBT-induced decrease in Bcl-2/Bax ratio,and down-regulated the DBT-induced over-expressions of caspase-9 and cleaved-caspase-3.Conclusions SIN could protect HL02 cells against DBT-induced cell injury,which is related to the inhibition of ROS-mediated mitochondrial apoptosis.

Suanzaoren Tang and Its Modified Formulas on Prevention and Treatment of Anxiety Disorders： A Review / 中国实验方剂学杂志

Suanzaoren Tang， as documented in the Synopsis of the Golden Chamber （《金匮要略》），consists of Ziziphi Spinosae Semen， Poria， Anemarrhenae Rhizoma， Chuanxiong Rhizoma， and Glycyrrhizae Radix et Rhizoma， and is indicated for dysphoria， consumptive disease， and insomnia. In modern clinical practice，in addition to sleep disorders，Suanzaoren Tang and its modified formulas can also be used to treat anxiety disorders， as well as insomnia，cardiac intervention，myocardial infarction， and other diseases combined with anxiety. It is also used in combination with other Chinese medicinal formulas （such as Zhizichi Tang，Ganmai Dazaotang，Baihe Zhimu Dihuangtang，and Jinlingzi San），western medicines （such as paroxetine，zopiclone，enalapril，amlodipine，metformin，and sertraline hydrochloride）， acupuncture， and acupoint application to treat anxiety， as well as cardiovascular neurosis，cancer，hypertension，type 2 diabetes， and other diseases combined with anxiety. As revealed by clinical treatment results， Suanzaoren Tang and its modified formulas can significantly reduce anxiety scores such as Hamilton Anxiety Rating Scale（HAMA） and Self-rating Anxiety Scale（SAS），and improve anxiety symptoms with significant efficacy and few side effects. As reported by experimental pharmacological studies， Suanzaoren Tang can regulate the content of neurotransmitters such as dopamine（DA），homovanillic acid（HVA），γ-aminobutyric acid（GABA），noradrenaline （NE），5-hydroxyindoleacetic acid （5-HIAA），glutamic acid（Glu），β-endorphin（β-EP），5-hydroxytryptamine（5-HT）， and nitric oxide （NO）in the brain， and mediate immune function by reducing the levels of inflammatory cytokines such as interleukin-1β（IL-1β）and tumor necrosis factor-α（TNF-α），enhancing the proliferation of B lymphocytes，phagocytosis of peritoneal macrophages， and down-regulating the proliferation of T lymphocytes. Besides， it can also regulate the endocrine level to allow the homeostasis of nervous system， endocrine system， and immune system by increasing adrenocorticotropic hormone（ACTH）and corticosterone（CORT）levels and up-regulating glucocorticoid receptor（GR）expression， finally achieving the effect of anxiety prevention and treatment. The present study systematically reviewed the clinical and basic research progress on the prevention and treatment of anxiety with Suanzaoren Tang to provide references for the research on the mechanism and material basis of Suanzaoren Tang and the development of new drugs for anxiety.

Tenuifolin in Treatment of Dementia： A Review / 中国实验方剂学杂志

Tenuifolin， a main component in Polygalae Radix， is frequently used as an important indicator for quality control of Polygalae Radix and its processed products. Dementia is a serious and persistent cognitive disorder， and the number of dementia patients is increasing worldwide， which brings great economic burden and mental pressure to families and society. At present， cholinesterase inhibitor and other drugs can only alleviate the symptoms of dementia， and there are some toxic and side effects. It has been found that tenuifolin can significantly improve cognitive disorder， learning and memory and is expected to be a potential drug for treating dementia. Tenuifolin exerts protective effects on amyloid-β （Aβ） deposition， acetylcholine reduction， neuroinflammation， cellular oxidative damage and nerve cell apoptosis caused by neurodegenerative diseases via multiple mechanisms， and can be applied to various types of dementia. In addition， it can be quickly absorbed into the blood， mainly distributed in liver and kidney， and can enter into the brain through the blood-brain barrier. However， because of its large molecular mass and poor fat solubility， tenuifolin can be rapidly eliminated， generating some problems such as low oral absoBrbability and permeability of blood-brain barrier. Therefore， the information of chemistry， pharmacology， pharmacokinetics and toxicology of tenuifolin was summarized in this paper to provide reference and ideas for further research and application.

Modern Clinical Applications and Type of Disease Prevention and Treatment of Guipitang： A Review / 中国实验方剂学杂志

The Chinese herbal medicines contained in Guipitang （GPT） were retrieved in the databases， including traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP）， encyclopedia of traditional Chinese medicine （ETCM）， bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine （BATMAN-TCM）， and database for associated traditional Chinese medicine， gene， and disease information using text mining （TCMGeneDIT）， and the compounds and their potential targets were obtained. Disease enrichment analysis on the potential targets of GPT was carried out to obtain the diseases potentially treated by GPT using MetaCore. Disease enrichment results showed that the potential diseases treated by GPT included encephalopathy， gastrointestinal diseases， nutritional/metabolic diseases， tumors/cancers， cardiovascular system diseases， endocrine system diseases， immune system diseases， drug-related side effects/adverse reactions， and congenital/hereditary diseases. On these grounds， the diseases treated by GPT were reviewed. The results of the previous research on diseases treated by GPT were consistent with analysis results of network pharmacology. The modern applications of GPT clinically went beyond its original indications， but its applications were based on the clinical manifestation of qi and blood deficiency in the heart and spleen， presenting the characteristic of "same treatment for different diseases". This study is expected to provide a reference for the further research and development of GPT.

Protective Effect of Modified Danshenyin and Erchentang on Intimal Injury Caused by Carotid Atherosclerosis / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of modified Danshenyin and Erchentang in treating carotid atherosclerosis （CAS）， and the effect on intimal injury. Method:Patients （151 cases） were divided into control group （75 cases） and observation group （76 cases）. Specifically， 69 cases in control finished the treatment （4 cases fell off in follow-up， and 2 cases were eliminated）， and 69 cases in observation group finished the treatment （3 cases fell off in follow-up， and 4 cases were eliminated）. Patients in both group got atorvastatin calcium tablets， 10 mg/time， 1 time/day， and aspirin enteric-coated tablets， 100 mg/time， 1 time/day. Patients in control group got Hedan tablets， 2 tablets/time， 3 times/day. Patients in observation group got modified Danshenyin and Erchentang， 1 dose/day. The treatment lasted for 4 months. Before and after treatment， color Doppler ultrasound of carotid artery was detected， and carotid intima-media thickness （IMT）， plaque number， plaque area， plaque thickness and hemodynamics were recorded. Levels of nitric oxide （NO）， endothelin-1 （ET-1）， von Willebrand factor （vWF）， soluble intercellular adhesion molecule-1 （sICAM-1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， whole-blood low-shear viscosity （LBV）， whole-blood high-shear viscosity （HBV）， plasma viscosity （PV）， platelet aggregation rate （PAR）， fibrinogen （FIB）， homocysteine （Hcy）， interleukin-6 （IL-6）， IL-10， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， oxidized low density lipoprotein （ox LDL） and circulating glutathione peroxidase （GSH-Px） were detected before and after treatment. And the safety was evaluated. Result:After treatment， IMT， number， area and thickness of plaque in observation group were less than those in control group （<italic>P</italic><0.01）. Peak systolic velocity and end diastolic velocity in observation group were higher than those in control group （<italic>P</italic><0.01）， while pulsatility index and resistance index were lower than those in control group （<italic>P</italic><0.01）. And levels of ET-1， vWF， sICAM-1， VEGF， MMP-9， TG， TC， LDL-C， LBV， HBV， PV， PAR， FIB， Hcy， IL-6， TNF-<italic>α</italic>， MDA and ox-LDL were lower than those in control group （<italic>P</italic><0.01）， whereas levels of NO， HDL-C， IL-10， SOD and GSH-Px were higher than those in control group （<italic>P</italic><0.01）. And there was no adverse reaction caused by traditional Chinese medicine. Conclusion:Modified Danshenyin and Erchentang can reduce plaque， improve hemodynamics and hemorheology， and regulate blood lipid metabolism and vascular endothelial factor， with anti-inflammatory and anti-oxidation damages. It can protect vascular intima， and inhibit the occurrence and development of CAS， with a safety in clinical use.

Expression and Significance of Leucine-rich Repeat-containing G-protein Coupled Receptor 5/6 in Wnt Pathway in Children with Acute Lymphoblastic Leukemia / 中国医学科学院学报

Objective To study the expression and significance of leucine-rich repeat-containing G-protein coupled receptor(LGR)5/6 in childhood acute lymphoblastic leukemia(ALL). Methods A total of 39 children who had ALL and achieved complete remission on day 33 after induction therapy were enrolled.The children before induction therapy were considered as the incipient group,and those who achieved complete remission on day 33 by induction therapy were considered as the remission group.According to the degree of risk,they were assigned into 3 groups:low-risk(

Perinatal conditions of late preterm twins versus early term twins / 中国当代儿科杂志

OBJECTIVE@#To study the perinatal complications of late preterm twins (LPTs) versus early term twins (ETTs).@*METHODS@#A retrospective analysis was performed for the complications of 246 LPTs, 496 ETTs, and their mothers. The risk factors for late preterm birth were analyzed. According to gestational age, the twins were divided into five groups: 34-34@*RESULTS@#Maternal hypertension, maternal thrombocytopenia, placenta previa, and premature rupture of membranes were independent risk factors for late preterm birth in twins (@*CONCLUSIONS@#Compared with ETTs, LPTs have an increased incidence of perinatal complications. The incidence of perinatal complications is associated with gestational ages in the LPTs and ETTs.

Altered dopamine metabolism and its role in pathogenesis of Parkinson's disease / 生理学报

Parkinson's disease (PD), one of the most frequent neurodegenerative disorders, is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). Genetic vulnerability, aging, environmental insults are believed to contribute to the pathogenesis of PD. However, the cellular and molecular mechanism of dopaminergic neurons degeneration remains incompletely understood. Dopamine (DA) metabolism is a cardinal physiological process in dopaminergic neurons, which is closely related to the loss of dopaminergic neurons in the SN. DA metabolism takes part in several pathological processes of PD neurodegeneration, such as iron metabolism disturbance, α-synuclein mis-folding, endoplasmic reticulum stress, protein degradation dysfunction, neuroinflammatory response, etc. In this review, we will describe altered DA metabolism and its contributions to PD pathogenesis.

Expression and Significance of Low-Density Lipoprotein-Related Receptors 5 and 6 in the Wnt/β-Catenin Signaling Pathway in Childhood Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the significance of low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) in the Wnt/β-catenin signaling pathway in the pathogenesis and prognosis of childhood acute lymphoblastic leukemia (ALL).@*METHODS@#A total of 43 children who were newly diagnosed and achieved complete remission after remission induction therapy were enrolled. The children before treatment were included in incipient group, and after treatment when achieved complete remission included in remission group. A total of 39 children with immune thrombocytopenia were enrolled in control group. Three milliliter bone marrow samples were collected from above-mentioned each group. QRT-PCR was used to determine the mRNA expression of LRP5 and LRP6 in blood mononuclear cells of bone marrow. Western blot was used to detect the protein expression of LRP5 and LRP6. According to the protein expression levels of LRP5 and LRP6, the children were divided into low-expression group and high-expression group, and the clinical biological characteristics were compared between these two groups. Survival analysis was performed by Kaplan-Meier method.@*RESULTS@#Both mRNA and protein expression levels of LRP5 and 6 were upregulated in the incipient group compared with the control and remission group (P<0.05). The mRNA and protein expressions of LRP5 and LRP6 in the high-risk group were higher than those in the medium-risk group (P<0.05), it is the same as in the medium-risk group than the low-risk group (P<0.05). The mRNA and protein expressions of LRP5 and 6 positively correlated with risk degree in the incipient group (r@*CONCLUSION@#The high expression of LRP5/6 may be one of the pathogenesis of childhood ALL, and the degree of LRP5/6 increase may be related to the risk level.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China / 中华医学杂志(英文版)

BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

Measurement of Scars Using Structured-Light 3D Scanning in Forensic Practice / 法医学杂志

Objective To validate the accuracy and reliability of structured-light three-dimensional （SL-3D） scanning in measuring the length and area of the regular and irregular scars on body surface and discuss its value in forensic practice. Methods The lengths of 30 cases of simulated linear scars and 50 cases of linear scars after injury were measured using soft ruler, vernier caliper + thin line method, and SL-3D scanning. The areas of 35 cases of simulated patchy scars and 15 cases of patchy scars after injury were measured using length × width, film tracing with coordinate paper method, pixel method, and SL-3D scanning, and then statistically analyzed. Results The differences between the length of the simulated linear scars measured by SL-3D scanning and standard length had no statistical significance. When simulated patchy scars and patchy scars after injury were measured with high surface curvature and large irregular areas, the differences between the results of SL-3D scanning measurement and the standard area had no statistical significance. When the length of 50 cases of linear scars after injury were measured using SL-3D scanning, the correlation coefficient between the measurement results of two different investigators was 0.998, and the correlation coefficient between the two measurement results by the same investigator was 1.000. The correlation coefficient between the results of SL-3D scanning and that of vernier caliper + thin line method was 0.996. Conclusion The three-dimensional information of the scars on the body surface can be acquired using SL-3D scanning. The measurement of the length and area of the scars is not influenced by the location of scars, curvature of surface, and human factors. The measurement results are accurate, reliable and has unique advantages.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study / 中华医学杂志(英文版)

BACKGROUND@#Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.@*METHODS@#We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.@*RESULTS@#Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.@*CONCLUSION@#A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Construction of A Microfluidic Intestine-liver-breast Cancer Chip and Analysis of Its Application in PK-PD in Vitro of Drugs / 中国实验方剂学杂志

Objective::A multi-organ chip of intestine-liver-breast cancer was constructed based on microfluidic technology and used for pharmacokinetics-pharmacodynamics (PK-PD) study of drugs in vitro. Method::A multi-organ chip comprising a 4-layer polydimethylsiloxane (PDMS) substrate and a 2-layer poly(methyl methacrylate) (PMMA) cover was constructed by microfluidic technology. The connection between cells was investigated by staining the 21-day-grown human colon cancer cell line Caco-2 cell layer and the 3-day-grown human umbilical vein endothelial cell line HUVEC cell layer with CellTracker Red/Green and Hoechst, respectively. The transmission rates of 2 g·L-1 fluorescein sodium and 33.28 mg·L-1 propranolol acrossing the cell layer were employed to verify the function of the constructed intestinal module. The metabolic level of the liver module was investigated by comparing the inhibition rate of 125 μmol·L-1 cyclophosphamide against human breast cancer cell line MCF-7 cells treated with human hepatoma cell line HepG2 cells in a conventional well plate and chip liver module for 48 h. The secretion of albumin by HepG2 cells in the chip was detected to verify the synthesis function of hepatic module. Caco-2 cell layer, HUVEC cell layer, HepG2 cell layer, MCF-7 cell layer and dialysis membrane were assembled on the chip, the culture medium containing 55 mg·L-1 propranolol was injected into the upper channel of the chip for 4 h, and then changed into the normal culture solution. The mass concentration of propranolol in the lower circulating culture medium at each time point within 72 h was determined, and the drug-time curve was drawn. The culture medium containing 125 μmol·L-1 cyclophosphamide, 5 μmol·L-1 paclitaxel, 50 μmol·L-1 capecitabine was injected into the circulating fluid in the upper layer of the chip, in order to study the inhibition rates of the three anti-tumor drugs on the MCF-7 cell layer on the chip within 72 h, and the results were compared with those of the 96-well plate. Result::The constructed chip performed well. The Caco-2 and HUVEC cell layers were tightly connected. The transmission of fluorescein sodium and propranolol between the cell layers demonstrated that the constructed intestinal module had good absorption and transport function. The inhibition rate of MCF-7 by 125 μmol·L-1 cyclophosphamide after metabolism of HepG2 cells on the well plate was 22.12%, and the inhibition rate of MCF-7 by the unmetabolized cyclophosphamide was 1.84%. The inhibition rate of MCF-7 increased to 32.13%after injected 125 μmol·L-1 cyclophosphamide from the upper layer of the chip liver module, and the inhibition rate of MCF-7 after injection from the lower layer of the chip liver module was 7.23%. The mass concentration of propranolol on the chip changed with time, which was basically consistent with that in vivo. The inhibition rate of MCF-7 on the plate with 125 μmol·L-1 cyclophosphamide was lower than that on the chip, and the inhibition rates of MCF-7 on the plate with 5 μmol·L-1 paclitaxel and 50 μmol·L-1 capecitabine were higher than those on the chip. Conclusion::The constructed multi-organ chip of intestine-liver-breast cancer has the absorption and transport function of the intestine and the metabolic function of the liver. The chip can reflect the pharmacokinetic properties of propranolol in vivo, and can be used for pharmacodynamic studies of paclitaxel and capecitabine.

Bioprinted HepG2 cells for studying sonodynamic anticancer activity of chlorine e6 / 药学学报

This paper showed bioprinted HepG2 tumor tissues used for studying the sonodynamic anticancer activity of chlorine e6 (Ce6). HepG2 cells were printed by using alginate/gelatin/hydroxyethyl cellulose composite biomaterial as bio ink and cell viability was detected with Live-Dead assay and MTT proliferation. The ultrasonic intensities of self-built micro ultrasonic device under different powers were estimated by using the temperature change caused by the conversion of acoustic energy to heat energy. Ce6 of 14.3 and 28.6 μg·mL-1 were acted on two-dimensional cultured and three-dimensional printed HepG2 cells, and the antitumor activity of Ce6 was detected by MTT method with ultrasound intensity of 0.15 W·cm2 for 60 s. The results showed that the activities of bioprinted HepG2 cells were as high as 95%, and tumor microspheres were formed after 7 days of culture. The ultrasound intensity was lower than 3 W·cm2, which belonged to low ultrasound intensity and had no damage to normal hepatocyte LO2 cells. By comparing the antitumor activity of Ce6 on 2D cultured and printed HepG2 cells, it was found that the anticancer activity of Ce6 on bioprinted HepG2 cells was 63.4% lower than that on 2D culture cells, indicating the acoustic drug resistance of three-dimensional tumor model. Bioprinted tumor tissues show the potential in the application of in vitro activity evaluation models for sonodynamic therapy.