Isolation, characterization and genomic analysis of a novel phage IME178 with lytic activity against Escherichia coli.

Bacteriophages have been used in phage therapy for the treatment of bacterial infections. They are biological agents that used for management of diseases caused by resistant bacteria. As compared to antibiotics, phages can kill bacteria specifically. It requires more awareness about phage-host interactions by exploring new phages. Escherichia coli (E. coli) is a conditional pathogen and cause infections like pneumonia and diarrhea in hospitalized patients. In the current research work, a virus IME178, a novel strain, was extracted from the sewage of hospital against the clinical E. coli of multidrug resistant nature. Genomic characterization and transmission electron microscopy have exhibited relation of phage to the Tequintavirus genus, Demerecviridae family. The Phage IME178's double-stranded DNA genome was 108588 bp long, with a GC content of 39%. The phage genome transcribes 155 open reading frames, 72 are hypothetical proteins, 81 have putative functions assigned to them, and two are unknown to any database. A total number of 19 tRNA genes were found in the genome of this phage. There were no genes associated with virulence or drug resistance in the phage genome. According to a comparative genomic analysis, the genomic sequence of phage IME178 is 91% identical to E. coli phage phiLLS (NC 047822.1). The phage's host range and one-step growth curve were also estimated. As per genomic and bioinformatics analysis findings, Phage IME178, a propitious biological agent that infects E. coli and have the potential to use in phage therapies.

Circulating monocyte-platelet aggregates with different monocyte subsets and their association with disease severity in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is usually considered an immune inflammatory disease. Interaction between platelets and monocytes is associated with immune inflammation. Cross-talk between platelets and monocytes is reflected by formation monocyte-platelet aggregates (MPAs). This study aims to test MPAs and MPAs with the different monocyte subsets to evaluate their association with disease severity in CKD. METHODS: Forty-four hospitalized patients with CKD and twenty healthy volunteers were enrolled. The proportion of MPAs and MPAs with the different monocyte subsets were tested by flow cytometry. RESULTS: The proportion of circulating MPAs in all patients with CKD were significantly higher than those of healthy controls (p<0.001). A higher proportion of MPAs with classical monocytes (CM) was found in CKD4-5 patients (p=0.007), while another higher proportion of MPAs with non-classical monocytes (NCM) was found CKD2-3 patients (p<0.001). The proportion of MPAs with intermediate monocytes (IM) in CKD 4-5 group was significantly higher in comparison to CKD2-3 group and healthy controls (p<0.001). Circulating MPAs were found to be correlated with serum creatinine (r=0.538, p<0.001) and eGFR (r=-0.864, p<0.001). The AUC for MPAs with IM was 0.942 (95% CI 0.890-0.994, p<0.001). CONCLUSIONS: Study results highlight the interplay between platelets and inflammatory monocytes in CKD. There are alterations in circulating MPAs and MPAs with the different monocyte subsets in CKD patients compared to controls which change with CKD severity. The MPAs may have an important role in the development of CKD or as a predictive marker for monitoring disease severity.

Thyroid Hormone Reference Intervals among Healthy Individuals In Lanzhou, China

Background@#The common reference intervals (RIs) for thyroid hormones currently used in China are provided by equipment manufacturers. This study aimed to establish thyroid hormone RIs in the population of Lanzhou, a city in the subplateau region of northwest China, and compare them with previous reports and manufacturer-provided values. @*Methods@#In total, 3,123 individuals (1,680 men, 1,443 women) from Lanzhou, an iodine-adequate area of China, perceived as healthy were selected. The Abbott Architect analyzer was used to determine the serum concentration of thyroid hormones. The 95% RI was estimated using the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. @*Results@#The serum levels of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), antithyroglobulin (ATG) antibody, and antithyroid peroxidase (ATPO) antibody levels were significantly correlated with sex (P0.05). The established RIs of TSH, ATG, and ATPO in this study differed between sexes (P<0.05). The thyroid hormone RIs established herein were inconsistent with the manufacturer-provided values. @*Conclusion@#The RIs of thyroid hormones in the healthy population of Lanzhou were inconsistent with those in the manufacturer’s manual. Validated sex-specific values are required for diagnosing thyroid diseases.

A case report of mitochondrial enoyl-CoA hydratase short chain 1 deficiency caused by enoyl-CoA hydratase short chain 1 gene mutation / 中华神经科杂志

Objective:To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency (ECHS1D) caused by enoyl-CoA hydratase short chain 1 ( ECHS1) gene mutation. Methods:The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed, and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results:The child was a 6 months and 4 days old male, with acute onset, the main clinical manifestation being limb movement disorder after admission. The child had slow motor development, his head was still upright and cannot turn over, the child also cannot sit alone, follow up and make a laugh, and the muscle tension of limbs was increased. The child′s blood lactate was increased to 6.2 mmol/L, which suggested metabolic acidosis, and magnetic resonance imaging (MRI) of the head showed abnormal signals in the basal ganglia on both sides, abnormal enhancement of the meninges of the left cerebral hemisphere. Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene, c.563C>T (p.A188V) and c.5C>T (p.A2V), respectively. The child′s father carried c.563C>T mutation, the mother carried c.5C>T mutation, all of which were missense mutations. Conclusions:ECHS1 gene mainly has missense mutations, most of which are compound heterozygous mutations, and a few are homozygous mutations. The ECHS1D caused by ECHS1 gene mutation often affects infants and young children. MRI suggests abnormal signals in the basal ganglia; for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI, genetic testing should be considered to confirm the diagnosis.

Effects of endovascular treatment and prognostic factors for recovery of oculomotor nerve palsy caused by posterior communicating artery aneurysms: a multi-center retrospective analysis.

BACKGROUND: Oculomotor nerve palsy (ONP) may result from posterior communicating artery (PcomA) aneurysms. We aimed to evaluate the resolution of ONP after endovascular treatment with the intention of clarifying predictors of nerve recovery in a relatively large series. METHODS: A total of 211 patients with ONP caused by PcomA aneurysms underwent endovascular coiling between May 2010 and December 2020 in four tertiary hospitals. We evaluated the demographics, clinical characteristics, aneurysm morphology parameters and ONP resolution to analyze the predictors of ONP recovery using univariate and multivariate analyses. RESULTS: At the last available clinical follow-up, ONP resolution was complete in 126 (59.7%) patients, partial in 73 (34.6%) patients, and no recovery in 12 (5.7%) patients. The median resolution time after endovascular treatment was 55 days (interquartile range: 40-90 days). In multivariate analysis, degree of ONP (incomplete palsy) on admission (OR 5.396; 95% CI 2.836-10.266; P < 0.001), duration of ONP (≤ 14 days) before treatment (OR 5.940; 95% CI 2.724-12.954; P < 0.001) were statistically significant predictors of complete recovery of ONP. In the subgroup analysis of patients with unruptured aneurysms, aspirin showed a higher complete recovery rate in univariate analysis (OR 2.652; 95% CI 1.057-6.656; P = 0.038). CONCLUSION: Initial incomplete ONP and early management might predict better recovery of ONP after endovascular treatment.

Efficacy of Liquid Embolic Agent Treatment in Hemorrhagic Peripheral Intracranial Aneurysms: A Single-Center Experience.

Objective: To evaluate the efficacy of liquid embolization agents for treating various hemorrhagic peripheral intracranial aneurysms. Methods: We retrospectively analyzed 38 patients who suffered from hemorrhagic peripheral intracranial aneurysms and were treated with liquid embolization agents. We used the modified Rankin scale for follow-up at 6 months postoperatively, and digital subtraction angiography follow-up was performed 6 months postoperatively. Results: Of the 38 patients (ten of simple peripheral intracranial aneurysms, six of Moyamoya disease (MMD), and 22 of arteriovenous malformation (AVM)), posterior circulation accounted for the most significant proportion (57.9%), followed by anterior circulation (21.1%) and intranidal aneurysms (21.1%). Intraoperative hemorrhage occurred in four cases, postoperative cerebral infarction occurred in four cases, two patients encountered microcatheter retention, and intraoperative thrombosis took place in the basilar artery of a patient with an arteriovenous malformation. A postoperative hemorrhage occurred in only one patient. At 6-month follow-up, 84.2% of patients had good prognosis outcomes, and 13.5% had poor outcomes. Conclusion: Liquid embolization agents are effective for hemorrhagic peripheral intracranial aneurysms; however, safety depends on the subtypes. For peripheral hemorrhagic aneurysms in MMD, the vessel architecture must be carefully evaluated before embolization.

Elevated Soluble Podoplanin Associates with Hypercoagulability in Patients with Nephrotic Syndrome.

Podoplanin (PDPN) promotes platelet aggregation and activation by interacting with C-type lectin-like receptor 2(CLEC-2) on platelets. The interaction between the upregulated PDPN and platelet CLEC-2 stimulates venous thrombosis. PDPN was identified as a risk factor for coagulation and thrombosis in inflammatory processes. Hypercoagulability is defined as the tendency to develop thrombosis according to fibrinogen and/or D dimer levels. Nephrotic syndrome is also considered to be a hypercoagulable state. The aim of this study is to investigate the association of soluble PDPN/CLEC-2 with hypercoagulability in nephrotic syndrome. Thirty-five patients with nephrotic syndrome and twenty-seven healthy volunteers were enrolled. PDPN, CLEC-2 and GPVI concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Patients with nephrotic syndrome showed higher serum levels of PDPN and GPVI in comparison to healthy controls (P < .001, P = .001). PDPN levels in patients with nephrotic syndrome were significantly correlated with GPVI (r = 0.311; P = .025), hypoalbuminemia (r = -0.735; P < .001), hypercholesterolemia (r = 0.665; P < .001), hypertriglyceridemia (r = 0.618; P < .001), fibrinogen (r = 0.606; P < .001) and D-dimer (r = 0.524; P < .001). Area under the curve (AUC) for the prediction of hypercoagulability in nephrotic syndrome using PDPN was 0.886 (95% CI 0.804-0.967, P < .001). Cut-off value for the risk probability was 5.88 ng/ml. The sensitivity of PDPN in predicting hypercoagulability was 0.806, and the specificity was 0.846. When serum PDPN was >5.88 ng/ml, the risk of hypercoagulability was significantly increased in nephrotic syndrome (OR = 22.79, 95% CI 5.92-87.69, P < .001). In conclusion, soluble PDPN levels were correlated with hypercoagulability in nephrotic syndrome. PDPN has the better predictive value of hypercoagulability in nephrotic syndrome as well as was a reliable indicator of hypercoagulable state.

Cerebrospinal fluid metabolic profiling reveals divergent modulation of pentose phosphate pathway by midazolam, propofol and dexmedetomidine in patients with subarachnoid hemorrhage: a cohort study.

BACKGROUND: Agitation is common in subarachnoid hemorrhage (SAH), and sedation with midazolam, propofol and dexmedetomidine is essential in agitation management. Previous research shows the tendency of dexmedetomidine and propofol in improving long-term outcome of SAH patients, whereas midazolam might be detrimental. Brain metabolism derangement after SAH might be interfered by sedatives. However, how sedatives work and whether the drugs interfere with patient outcome by altering cerebral metabolism is unclear, and the comprehensive view of how sedatives regulate brain metabolism remains to be elucidated. METHODS: For cerebrospinal fluid (CSF) and extracellular space of the brain exchange instantly, we performed a cohort study, applying CSF of SAH patients utilizing different sedatives or no sedation to metabolomics. Baseline CSF metabolome was corrected by selecting patients of the same SAH and agitation severity. CSF components were analyzed to identify the most affected metabolic pathways and sensitive biomarkers of each sedative. Markers might represent the outcome of the patients were also investigated. RESULTS: Pentose phosphate pathway was the most significantly interfered (upregulated) pathway in midazolam (p = 0.0000107, impact = 0.35348) and propofol (p = 0.00000000000746, impact = 0.41604) groups. On the contrary, dexmedetomidine decreased levels of sedoheptulose 7-phosphate (p = 0.002) and NADP (p = 0.024), and NADP is the key metabolite and regulator in pentose phosphate pathway. Midazolam additionally augmented purine synthesis (p = 0.00175, impact = 0.13481) and propofol enhanced pyrimidine synthesis (p = 0.000203, impact = 0.20046), whereas dexmedetomidine weakened pyrimidine synthesis (p = 0.000000000594, impact = 0.24922). Reduced guanosine diphosphate (AUC of ROC 0.857, 95%CI 0.617-1, p = 0.00506) was the significant CSF biomarker for midazolam, and uridine diphosphate glucose (AUC of ROC 0.877, 95%CI 0.631-1, p = 0.00980) for propofol, and succinyl-CoA (AUC of ROC 0.923, 95%CI 0.785-1, p = 0.000810) plus adenosine triphosphate (AUC of ROC 0.908, 95%CI 0.6921, p = 0.00315) for dexmedetomidine. Down-regulated CSF succinyl-CoA was also associated with favorable outcome (AUC of ROC 0.708, 95% CI: 0.524-0.865, p = 0.029333). CONCLUSION: Pentose phosphate pathway was a crucial target for sedatives which alter brain metabolism. Midazolam and propofol enhanced the pentose phosphate pathway and nucleotide synthesis in poor-grade SAH patients, as presented in the CSF. The situation of dexmedetomidine was the opposite. The divergent modulation of cerebral metabolism might further explain sedative pharmacology and how sedatives affect the outcome of SAH patients.

Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit / 中华儿科杂志

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

Effect of general anesthesia guided by electroencephalography monitoring on postoperative delirium in elderly patients with non-acute fragile brain function / 中华麻醉学杂志

Objective:To evaluate the effect of general anesthesia guided by electroencephalography (EEG) monitoring on postoperative delirium (POD) in elderly patients with non-acute fragile brain function.Methods:Sixty patients of both sexes with non-acute fragile brain function, aged 65-85 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with body mass index of 18-30 kg/m 2, undergoing hip replacement, were divided into 2 groups ( n=30 each) by a random number table method: conventional general anesthesia group (group C) and general anesthesia guided by EEG monitoring group (group E). Anesthesia was maintained by intravenous infusion of propofol 50-150 μg·kg -1·min -1 and remifentanil 0.05-0.30 μg·kg -1·min -1 and intermittent intravenous boluses of rocuronium.In group E, the dose of anesthetic was reduced when the EEG burst-suppression ratio≥10% for more than 1 min or anesthesia index (AI) <40.If the situation mentioned above still existed after 1 min, the dose of anesthetic was continued to be reduced or norepinephrine was injected intravenously.In group C, the amount of intraoperative anesthesia was adjusted according to the changes in hemodynamics.Norepinephrine 4-10 μg or dopamine 1 mg was given intravenously in the light of the patients′ heart rates when intraoperative hypotension occurred.At 10 min after anesthesia induction, immediately after skin incision, immediately at the end of surgery and at 1 h after surgery, blood samples were obtained from the artery and jugular venous bulb for blood gas analysis and for calculation of jugular bulb blood oxygen content (CjvO 2), artery-jugular bulb blood oxygen content difference (Ca-jvO 2), cerebral oxygen uptake rate (CERO 2) and jugular-arterial blood lactate concentration difference (Djv-aLac). The emergence time, amounts of intraoperative anesthetics, use of noradrenaline, cumulative time of EEG burst inhibition and duration of AI<40 were recorded.The development of POD was assessed within 5 days after surgery by the confusion assessment method for the intensive care unit and the duration was recorded. Results:Compared with group C, recovery time, cumulative time of EEG burst inhibition and duration of AI<40 were significantly shortened, the intraoperative consumption of propofol and remifentanil was decreased, the requirement for intraoperative noradrenaline was increased, CjvO 2 was increased, Ca-jvO 2 and CERO 2 were decreased immediately at the end of surgery and at 1 h after surgery, the incidence of POD within 5 days after surgery was decreased, and POD duration was shortened in group E ( P<0.05). Conclusion:General anesthesia guided by EEG monitoring can reduce the development of POD in elderly patients with non-acute fragile brain function.

Biocompatibility evaluation of collagen suture and collagen biofilm / 国际生物医学工程杂志

Objective:To evaluate the biocompatibility of collagen suture (CS) and collagen biofilm (CB) preliminarily.Methods:The pyrogenic contaminants test was used to analyze the pyrogen in CS and CB. The skin stimulation and intradermal stimulation tests were used to evaluate the stimulation effects of CS and CB to the skin. The hemolytic test was used to evaluate the hemolytic effect of CS and CB. The muscle implantation experiment was used to evaluate the stimulation and toxicity of CS and CB.Results:The results of pyrogenic contaminants test show that the temperature increment of rabbits in each group is lower than 0.6 ℃, and the total temperature increment is lower than 1.4 ℃ indicating that the two materials meet the requirements of pyrogenic examination and the pyrogenic contaminants test is qualified. The results of skin stimulation test and intradermal stimulation test of collagen suture and collagen biofilms were negative indicating that the two materials have no skin irritation. The hemolysis rates of collagen suture and collagen biofilm were 2.943% and 4.127% respectively (all P<0.05) indicating that the two materials will not cause hemolysis. The muscle was tolerated well and the tissue response was not serious after two biomaterials were embedded, which was reduced over time gradually. Conclusions:Both the collagen suture and collagen biofilm have good biocompatibility.

Investigation of AIDS cognition and testing willingness among freshmen in Fengtai District, Beijing / 中国学校卫生

Objective@#To examine college students awareness of AIDS (acquired immunodeficiency syndrome) and HIV (human immunodeficiency virus), as well as their willingness to undergo testing, and to provide guidance for further education targeted towards AIDS prevention.@*Methods@#The respondents were selected from two companies of military training camps in 4 universities in Fengtai District of Beijing using cluster sampling, and a questionnaire was used to obtain relevant information among 1 248 college freshmen. The content of the questionnaire included basic information about the students, awareness of AIDS, and willingness to undergo testing.@*Results@#A total of 87.18% students were familiar with AIDS related knowledge, and 62.98% students intended to have HIV tests in the future. Willingness to be tested for HIV was higher among not local students (67.39%) than among local students(55.65%)(χ 2=17.32, P<0.05). The willingness to get HIV testing was higher among students who had an understanding of AIDS (65.26%) than among those who lacked an awareness(47.50%)(χ 2=18.87, P<0.05). In terms of the willingness to be tested for HIV, the main concerns focused on personal privacy (23.24%) and the cost (18.59%). Multivariate regression analysis showed that improving students awareness of five of the items related to a basic knowledge of AIDS may increase their willingness to get HIV testing(P<0.05). Most students indicated a preference to get HIV testing at a hospital (68.51%) or at the Centers for Disease Control and Prevention(42.79%).@*Conclusion@#The willingness to get HIV testing can be increased by launching an AIDS health education program that targets weak knowledge points with respect to AIDS awareness.

[Progress on clinical treatment of Kümmell's disease].

Kümmell's disease is a delayed complication of osteoporotic vertebral compression fracture (OVCF) . The disease can occur months or even years after the initial spinal injury. Unlike the common osteoporotic compression fracture, it develops slowly and causes intractable pain or neurological dysfunction due to intraspinal instability. So far, the pathogenesis of Kümmell's disease has not been completely clear, there is no standard treatment or single effective treatment for Kümmell's disease. The effect of conservative treatment is often not good. Minimally invasive treatment has become the main treatment for patients with Kümmell's disease due to its short operation time, small trauma and exact effect. However, there are complications such as leakage of bone cement and delayed displacement of bone cement. Moreover, minimally invasive treatment is not suitable for all types of Kümmell's disease patients. Patients with posterior cortical fracture and spinal cord compression need to be opened Radiotherapy, whether anterior or posterior, has the disadvantages of long operation time, large trauma and high treatment cost. This article reviews the progress in the treatment of Kümmell's disease to provide guidance for clinical treatment.

Association of non-thyroidal illness syndrome with interleukin-6 and interleukin-10 in critically ill children with sepsis / 中国当代儿科杂志

OBJECTIVE@#To study the incidence rate of non-thyroidal illness syndrome (NTIS) in critically ill children with or without sepsis and the association of NTIS with interleukin-6 (IL-6) and interleukin-10 (IL-10).@*METHODS@#A retrospective analysis was performed on the medical data of 97 children with sepsis (sepsis group) and 80 non-sepsis children with bacterial infection (non-sepsis group). The correlations of IL-6 and IL-10 with the thyroid function parameters triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were analyzed.@*RESULTS@#There were no significant differences in age and sex between the sepsis and non-sepsis groups (P>0.05). Compared with the non-sepsis group, the sepsis group had a significantly higher Sequential Organ Failure Assessment score, a significantly longer length of hospital stay, and a significantly higher rate of use of ventilator (P0.05), but the pooled analysis of the two groups showed that IL-6 level was negatively correlated with T3 and T4 levels (P<0.001).@*CONCLUSIONS@#Children with sepsis have a higher incidence rate of NTIS than those without sepsis. The high level of IL-6 may be associated with the development of NTIS.

Blood biochemical indicators, IgM and IgG antibodies in 56 confirmed and suspected COVID-19 cases / 上海预防医学

Objective To provide reliable indicators for effective prevention and control of COVID-19, we examined the biochemical indicators as well as anti-SARS-CoV-2 IgM and IgG antibodies in confirmed and suspected COVID-19 patients. Methods A total of 56 confirmed and suspected COVID-19 cases quarantined during January-March, 2020 in Gansu Provincial People′s Hospital and People′s Hospital of Xigu District, Gansu Province were included.Based on the results of nucleic acid testing and CT scan finding, they were divided into three groups: positive in both nucleic acid testing and CT scan finding; positive in nucleic acid testing but negative in CT scan finding; negative in both nucleic acid testing and CT scan finding.COVID-19 viral nucleic acid was detected and chest CT scan was performed.The following biochemical indicators were examined: total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, creatine kinase and lactate dehydrogenase.SPSS 22.0 statistical software was used to analyze the differences in the biochemical indicators among these three groups, as well as the temporal trend of IgM and IgG antibodies at different points of time. Results There were significant differences in the mean values of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase between these three groups (P < 0.05), whereas no significant difference in the mean value of total protein and albumin (P>0.05).ROC curve indicated that aspartate aminotransferase had the largest maximum area under the curve (AUC, 0.834), whereas alanine aminotransferase had the highest sensitivity (1.0) and total bilirubin had the highest specificity (0.927).Thus, aspartate transaminase provided the best prediction for the diagnosis of COVID-19, with sensitivity of 0.786, specificity of 0.854, and the maximum AUC of 0.834.In 12 of 16 confirmed COVID-19 patients tested IgG positive after 10 days of diagnosis, and 10 of 10 confirmed COVID-19 patients tested IgG positive after 14 days of diagnosis. Conclusion Aspartate aminotransferase may be the most useful indicator in the diagnosis of COVID-19.

Role of hepatic lymphangiogenesis in the progression of liver fibrosis / 临床肝胆病杂志

Liver fibrosis can progress to liver cirrhosis and end-stage liver disease, which may lead to poor prognosis. In addition to pathological angiogenesis and hepatic sinusoid remodeling, hepatic lymphangiogenesis also plays an important role in the progression of liver fibrosis. This article briefly describes lymphatic vessel markers and their expression in the liver, introduces the role of lymphangiogenesis in liver fibrosis, and reviews the role of liver macrophages (Kupffer cells) and lymphatic endothelial cells in lymphangiogenesis. It is pointed out lymphangiogenesis may become a potential target for the intervention of liver fibrosis, which plays an important role in the early treatment and reversal of liver fibrosis and the prevention of liver cirrhosis and end-stage liver disease.

Aneurysmal Subarachnoid Hemorrhage Onset Alters Pyruvate Metabolism in Poor-Grade Patients and Clinical Outcome Depends on More: A Cerebrospinal Fluid Metabolomic Study.

Cerebral metabolism alterations influence cerebrospinal fluid (CSF) composition and are sensitive to brain injury. In subarachnoid hemorrhage (SAH) patients, Fisher scale, Hunt-Hess scale, and World Federation of Neurological Societies (WFNS) grading scale evaluating SAH severity are inadequate to predict long-term outcome; therefore, in an effort to determine metabolite pattern disparity and discover corresponding biomarkers, we designed an untargeted CSF metabolomic study covering a broad range of metabolites of SAH patients with different severity and outcome. The present study demonstrated the SAH altered the cerebrospinal fluid metabolome involving carbohydrate, lipid, and amino acid metabolism. Pyruvate metabolism was enhanced in SAH patients with Hunt-Hess scale above III, and the CSF pyruvate level was significantly associated with WFNS grading scale above III. There is no significant variation among CSF metabolome in SAH patients with merely different amounts and distribution of bleeding. SAH patients with unfavorable outcome present upregulated CSF amino acids level and enhanced lipid biosynthesis. The present study provides a novel possibility of early identification of patients who might possess unfavorable outcome and further clarification of the underlying pathophysiology.

Recent advances in microglial activation for treatment of chronic neuropathic pain / 药学学报

As the primary innate immune cells in the central nervous system, microglia can be activated by external noxious stimulus and in turn interact with astroglia and neurons to induce neuroinflammation and facilitate the transmission of pain signals. This response can help the central nervous system adapt to the changes of the internal environment induced by noxious stimulus, leading to the long-term sensitivity of peripheral and central pain nerve conduction pathways and chronic neuropathic pain. Numerous researches found that activation of microglia participated in the occurrence and maintenance of chronic neuropathic pain, and inhibition of microglial activation in the spinal cord or the brain had analgesic effect in animal experiments. Due to the fact that molecular and cellular mechanisms between the activation of microglia and pain remittence are unclear, there are many difficulties in designing of new drugs selectively targeting to the activation of microglia for treatment of chronic neuropathic pain. We review here the research articles on microglia and chronic neuropathic pain, sorting out the relationship between microglia and chronic neuropathic pain, and provide new ideas for the development of new drugs targeting to microglia for the treatment of chronic neuropathic pain.

Advances in JAK2 inhibitors for treatment of myeloproliferative neoplasms / 药学学报

Myeloproliferative neoplasms (MPNs) result from clonal expansion of haematopoietic stem cells and are characterized by abnormal proliferation of myeloid lineage cells in the bone marrow. Sustained activation of JAK-STAT signaling pathway due to JAK2 phosphorylation is an important cause of MPNs, and mutation of JAK2 kinase can keep it in a state of continuous phosphorylation. The most typical mutation in JAK2 is a site mutation of V617F in the pseudokinase domain. The JAK2V617F-activating mutation is highly prevalent in MPNs, with frequencies estimated at approximately 95% in polycythaemia vera (PV) and 50% in primary myelofibrosis (PMF) and essential thrombocytosis (ET) patients. It is now clear that JAK2 is an important target for treatment of MPNs. Inhibiting aberrant activation of the JAK2-STAT signaling pathway has become a popular trend in research for effective treatment of MPNs. This review summarizes the research progress in developing JAK2 inhibitors for treatment of MPNs in recent years, including the new discoveries of the biological functions of JAK2, the relationship between JAK2 and MPN, and the status of development of JAK2 small molecule inhibitors.

Changes in intestinal microbiota and phenotypes of immune cells in mice with atherosclerosis and arthritis / 中华微生物学和免疫学杂志

Objective To investigate the changes in intestinal microbiota and immune cells in mice with atherosclerosis and arthritis. Methods Two groups were set up with 8-week-old ApoE knockout (ApoE-/ -) and C57BL/ 6 mice. All mice were fed with high fat diet. The severity of atherosclerosis was evaluated through analyzing the level of serum lipid by ELISA and arteriosclerotic plaques by oil red O stai-ning. K/ BxN serum was intraperitoneally injected into ApoE-/ - and C57BL/ 6 mice at 17 to 26 weeks of age until 26 weeks to induce arthritis. The development of arthritis in mice was evaluated with vernier caliper-measured ankle width and clinical score. Total DNA was extracted from fecal samples of mice to amplify the 16S V4 region by PCR, and then sequencing analysis was performed on Illumina HiSeq PE250. Splenocytes and bone marrow cells were isolated and stained by antibodies to analyze the changes in immune cell distribu-tion by flow cytometry. Results The levels of low density lipoprotein cholesterol (LDL-C) and total choles-terol (TCHO) in serum and the atherosclerotic plaques in aorta were significantly increased in ApoE-/ - mice than in C57BL/ 6 mice, suggesting that the symptoms of atherosclerosis in ApoE-/ - mice were more severe than those in C57BL/ 6 mice. Ankle width measurements and clinical scores of arthritis showed that the ApoE-/ - mice had less severe ankle swelling than the C57BL/ 6 mice. Moreover, the ApoE-/ - mice had de-creased intestinal microbiota diversity, especially in the number of Verrucomicrobiae. Flow cytometry analy-sis showed that CD3+T and CD19+B cells were down-regulated, while CD11b+ macrophages were up-regula-ted in splenocytes and bone marrow cells of the ApoE-/ - mice. Conclusions Immune cell distribution was changed in the ApoE-/ - mice with atherosclerosis and arthritis. Compared with the C57BL/ 6 mice, the ApoE-/ - mice had decreased intestinal microbiota diversity and altered bacterial composition. Moreover, the abundance of Akkermansia, a potential biomarker of healthy intestinal environment, in the ApoE-/ - mice was also decreased. It was suggested that the changes in intestinal microbiota might be involved in the pathogene-sis of atherosclerosis complicated by arthritis.