SOX4 as a potential therapeutic target for pathological cardiac hypertrophy.

Pathological cardiac hypertrophy can lead to heart failure, making its prevention crucial. SOX4, a SOX transcription factor, regulates tissue growth and development, although its role in pathological cardiac hypertrophy is unclear. We found that the SOX4 expression was elevated in hypertrophic hearts and angiotensin II (Ang II)-treated neonatal rat cardiomyocytes (NRCMs), and knocking down the SOX4 expression in NRCMs and mouse hearts significantly reduced the hypertrophic response. Mechanistically, SOX4 can bind to the SIRT3 promoter, inhibit SIRT3 transcription and expression, and thus affect downstream MnSOD acetylation levels, leading to abnormal increases in ROS and oxidative stress levels and promoting the occurrence of cardiac hypertrophy. In conclusion, this study identified a new role for SOX4 in regulating cardiac hypertrophy, and decreasing SOX4 expression may be a potential treatment for pathological cardiac hypertrophy.

Posaconazole preventive therapy of invasive pulmonary aspergillosis in patients with liver failure / 中华传染病杂志

Objective:To investigate the efficacy and safety of posaconazole in the prevention of invasive pulmonary aspergillosis (IPA) in patients with liver failure treated with glucocorticoids (GC).Methods:The study was an observational study. Patients with early and middle stages of liver failure hospitalized in the Department of Infectious Diseases of Hebei Medical University Third Hospital, who received GC treatment between February 2016 and February 2022 were included. The patients were divided into trial group (with posaconazole suspension (200 mg each time, three times daily)) and control group (without posaconazole) according to whether posaconazole was used during treatment. Two groups of patients were matched of 1∶2 ratio according to age, gender and baseline model for end-stage liver disease (MELD) score. The basic information, laboratory examination results, adverse reactions of posaconazole, incidence of invasive Aspergillus infection and therapeutic effect of patients were collected. Statistical analysis was performed using the chi-square test, logistic regression analysis was used to screen risk factors for IPA, the receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the risk factors, Kaplan-Meier survival curves was used to analyze patient′s survival, and Log-rank test was used to compare the survival rates between the trial group and control group. Results:A total of 108 patients (36 in trial group and 72 in control group) were enrolled. There were no statistical differences between the two groups in terms of the etiology of liver diseases, baseline laboratory findings and risk factors for invasive Aspergillus infection (all P>0.05). There were 21 cases of IPA during hospitalization, with a total infection rate of 19.4%(21/108), including 5.6%(2/36) in the trial group and 26.4%(19/72) in the control group. The difference of IPA incidences between the two groups was statistically significant ( χ2=6.65, P=0.010). Logistic regression analysis suggested that elevated C-reactive protein, GC application more than seven days and cumulative dose of GC were independent risk factors for IPA in patients with liver failure treated with GC (odds ratio ( OR)=1.080, 15.266, 1.004, respectively, all P<0.05). The ROC curve showed that the cut-off value of C-reactive protein was 6.00 mg/L, and cumulative dose of GC was 490 mg. There were no statistical differences between the two groups in terms of adverse effects such as neutropenia, thrombocytopenia, gastrointestinal bleeding, nausea and vomiting rates (all P>0.05), and there were no patients with visual disturbances or discontinuation of medication. Cumulative deaths were 20(18.5%), and 88(81.5%) patients survived in this study. There were 11(52.4%) deaths among 21 patients with IPA and nine (10.3%) deaths among 87 patients without IPA. The difference of survival rates between patients who developed and did not develop IPA was statistically significant ( χ2=21.31, P<0.001). Conclusions:Posaconazole may be helpful in reducing the incidence of concurrent IPA morbidity in patients with liver failure treated with GC, thereby improving survival rates with few adverse effects.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Research on the synchronous detection of neuronal signals under a nerve stimulation system control.

Deep brain stimulation (DBS) provides a recognized research intervention for neurological disease currently. However, there is a lack of traditional electrical stimulator to observe neuronal firing activity synchronously. The aim of the present study was to realize concurrent detection of neuronal signals better under a nerve stimulation system control. Herein, we designed an integrated software, which could control not only neuro-stimulator but also detection instrument at the same time. Moreover, the actual stimulation signals applied to the experiment object could be collected back to data acquisition card and in consistent with the electrophysiological signals. As to basic performance of self-building stimulator, the accuracy of output square signal was verified to be greater than 99.05 % with the change of voltage amplitude. Practicably, combined with homemade microelectrode array (MEA) detecting device, medial forebrain bundle (MFB) DBS effects were observed significantly through the changes of electrophysiological signals in caudate putamen (CPu) of Sprague-Dawley (SD) rat, and the signal-to-noise ratio (SNR) was 5:1 after stimulation. Therefore, the comprehensive nerve stimulation system, which consists of neuro-stimulator and integrated software, could be widely used in the field of neuroscience research with high precision and synchronization.

Analysis of prognostic risk factors and establishment of prognosis model in patients with hepatitis B virus-related acute-on-chronic liver failure / 中华传染病杂志

Objective@#To explore the risk factors for prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and to establish a prognostic model.@*Methods@#A total of 193 patients diagnosed with HBV-ACLF who were admitted to the Department of Infectious Diseases of the Third Hospital of Hebei Medical University were collected from 1st January 2013 to 1st November 2018 as a derivation cohort. Thirty-five patients diagnosed with HBV-ACLF who were admitted to the Fifth Hospital of Shijiazhuang during the period from 1st July 2017 to 1st November 2018 were collected as a validation cohort. The survival condition of all patients at week 12 of admission was observed. The risk factors associated with short-term prognosis were analyzed by using multivariate logistic regression analysis, and a logistic regression equation prediction model was established and verified. The diagnostic performance of the prognostic model was evaluated using the receiver operating characteristic (ROC) curve, and was compared with model for end-stage liver disease (MELD) scoring system, Child-Turcotte-Pugh (CTP) scoring system, sequential organ failure assessment (SOFA) scoring system and chronic liver failure (CLIF)-SOFA scoring system.@*Results@#Multivariate logistic regression analysis showed that age (odds ratio(OR)=2.133, 95% confidence interval(CI)1.033-4.405), total bilirubin (OR=3.371, 95%CI 1.610-7.060), serum creatinine (OR=4.448, 95%CI 1.697-11.661), hepatic encephalopathy (OR=5.313, 95%CI 2.463-11.461), and ascites (OR=2.959, 95%CI 1.410-6.210) were independent risk factors for predicting the short-term prognosis of patients with HBV-ACLF. The newly established logistic regression model (LRM)=-1.726+ 0.757×age+ 1.215×total bilirubin+ 1.049 2×serum creatinine+ 1.670×hepatic encephalopathy (with=1, without=0) + 1.085×ascites (with=1, without=0). The area under the ROC curve of the LRM for predicting the short-term prognosis of patients with HBV-ACLF was 0.82 (95%CI 0.76-0.88). Furthermore, the areas under the ROC curve of the models of MELD, CTP, SOFA, CLIF-SOFA were 0.67 (95%CI 0.60-0.75), 0.73 (95%CI 0.66-0.80), 0.77 (95%CI 0.70-0.83) and 0.72 (95%CI 0.65-0.80), respectively. The ROC-area under curve of the validation cohort was 0.81 (95%CI 0.65-0.97).@*Conclusions@#Age, total bilirubin, serum creatinine, hepatic encephalopathy, and ascites are independent risk factors for the prognosis of HBV-ACLF. The prognostic model established based on these factors can accurately predict the patients′ short-term prognosis, which is superior to MELD, CTP, SOFA and CLIF-SOFA.

Analysis of prognostic risk factors and establishment of prognosis model in patients with hepatitis B virus-related acute-on-chronic liver failure / 中华传染病杂志

Objective To explore the risk factors for prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF),and to establish a prognostic model.Methods A total of 193 patients diagnosed with HBV-ACLF who were admitted to the Department of Infectious Diseases of the Third Hospital of Hebei Medical University were collected from 1st January 2013 to 1st November 2018 as a derivation cohort.Thirty-five patients diagnosed with HBV-ACLF who were admitted to the Fifth Hospital of Shijiazhuang during the period from 1st July 2017 to 1st November 2018 were collected as a validation cohort.The survival condition of all patients at week 12 of admission was observed.The risk factors associated with short-term prognosis were analyzed by using multivariate logistic regression analysis,and a logistic regression equation prediction model was established and verified.The diagnostic performance of the prognostic model was evaluated using the receiver operating characteristic (ROC) curve,and was compared with model for end-stage liver disease (MELD) scoring system,Child-Turcotte-Pugh (CTP) scoring system,sequential organ failure assessment (SOFA) scoring system and chronic liver failure (CLIF)-SOFA scoring system.Results Multivariate logistic regression analysis showed that age (odds ratio (OR) =2.133,95％ confidence interval (CI) 1.033-4.405),total bilirubin (OR =3.37 1,95％CI 1.610-7.060),serum creatinine (OR =4.448,95％C1 1.697-11.661),hepatic encephalopathy (OR =5.313,95％CI2.463-11.461),and ascites (OR =2.959,95％CI 1.410-6.210) were independent risk factors for predicting the short-term prognosis of patients with HBV-ACLF.The newly established logistic regression model (LRM) =-1.726 + 0.757 × age + 1.215 × total bilirubin + 1.049 2 × serum creatinine + 1.670 × hepatic encephalopathy (with =1,without =0) + 1.085 × ascites (with =1,without =0).The area under the ROC curve of the LRM for predicting the short-term prognosis of patients with HBV-ACLF was 0.82 (95％CI0.76-0.88).Furthermore,the areas under the ROC curve of the models of MELD,CTP,SOFA,CLIF-SOFA were 0.67 (95％CI 0.60-0.75),0.73 (95％CI 0.66-0.80),0.77 (95％CI 0.70-0.83) and 0.72 (95％CI 0.65-0.80),respectively.The ROC-area under curve of the validation cohort was 0.81 (95％CI0.65-0.97).Conclusions Age,total bilirubin,serum creatinine,hepatic encephalopathy,and ascites are independent risk factors for the prognosis of HBV-ACLF.The prognostic model established based on these factors can accurately predict the patients' short-term prognosis,which is superior to M ELD,CTP,SOFA and C LIF-SOFA.

Application of clustered regularly interspaced short palindromic repeats- associated protein 9 gene editing technology for treatment of HBV infection / 中华肝脏病杂志

A lack of effective drugs and technical means to eradicate hepatitis B virus (HBV) is a bottleneck that limits the ability to fully cure HBV infection. Recently, genome-editing technology based on clustered regularly interspaced short palindromic repeats -associated protein 9 is an emerging technique for editing specific gene loci, which can specifically target HBV covalently closed circular DNA, effectively inhibits HBV DNA replication and regulates HBV functional protein expression, and is expected to become a powerful gene therapy tool for the complete eradication of HBV. Considering this, it has become the focus of attention for scholars at home and abroad that how to use clustered regularly interspaced short palindromic repeats -associated protein 9 to accomplish modification of HBV genomes for complete eradication of HBV. This paper summarizes the latest progress based on the latest research results at home and abroad in the application of clustered regularly interspaced short palindromic repeats -associated protein 9 gene editing technology in anti-HBV infection treatment, and expounds its potential and challenges as a radical cure for HBV infection.

Monitoring of Subthalamic Nucleus Stimulation-induced DopamineFlux and Spike Firing Change of Striatum Neuronswith a Micro-Nano Electrode Array / 分析化学

Subthalamic nucleus (STN) deep brain stimulation (DBS) has become an important surgical treatment of Parkinson disease, but its exact mechanism is still unclear.In this study, a 16-channel implantable microelectrode array (MEA) was prepared by micro-electromechanical system (MEMS) technique and later modified with platinum black/reduced Graphene Oxide/Nafion (Pt/RGO/Nafion) nanocomposites.Extracellular dopamine (DA) content and spike of dorsal striatum neurons were synchronously recorded before and after STN stimulation.The results showed that the dopamine content began to increase within 20 s after electrical stimulation and dropped to normal level after about 50 s, with the highest rising concentration of 1.72 μmol/L.At the same time, there was an increased spike activity of interneurons in the dopamine ascending phase, and the spike firing rate of medium spiny projection neurons (MSNs) was high when the concentration of DA was higher than the normal level.The MEA sensor can simultaneously record dopamine flux and physiological signals in situ, thus providing an ideal tool for neural information detection.

Influence of injection cefotiam on vanadate oxidation method and dry chemical method assay total bilirubin / 国际检验医学杂志

Objective Discuss the interference of injection cefotiam on vanadate oxidation method and dry chemical method assay total bilirubin .Methods Collected 60 examples ,include total bilirubin concentration 20 examples less than 20 μmol/L ,20 examples between 150-220 μmol/L and 20 examples between 350-410 μmol/L ,add an equal volume of various concentrations of cefotiam in each case ,formulated into cefotiam final concentrations of 300 ,150 ,75 mg/L of serum samples as the test group ,add an equal volume of water in each serum samples as the control group ,determine all the samples total bilirubin concentration respectively by vanadate oxidation method and dry chemical method ,compared the interference of cefotiam on determined total bilirubin by two method ,analyze the data by SPSS13 .0 .Results Determined total bilirubin by dry chemical method ,the test group higher than the control group ,the difference was statistically significant(P<0 .05) ,at the same total bilirubin levels ,with cefotiam concentrations decreased ,increased rate of total bilirubin concentration were decreased in the experimental group .Determined total bilirubin by vanadate oxidation method ,when the total bilirubin concentration between 150 -220 μmol/L ,the test group was higher than the control group ,the difference was statistically significant(P<0 .05) .Conclusion Interference of injection cefotiam on determined to‐tal bilirubin by dry chemical method is strong ,and with the drug concentration increased ,effect is more obvious ,but determination of total bilirubin by vanadate oxidation method has almost no effect .

Clinical significance of C reactive protein in haemorrhagic fever with renal syndrome / 国际检验医学杂志

Objective To explore the diagnostic significance of C reactive protein(CRP)in diagnosing haemorrhagic fever with renal syndrome(HFRS).Methods 96 cases of patients with HFRS of different stages were enrolled in this study,and serum speci-men were collected.30 cases of patients with fever of unknown origin(fever of unknown origin group)and and 30 healthy individu-als(healthy control)were selected as control.Serum levels of CRP,alanine aminotransferase(ALT),aspartate amino-transferase (AST),creatine phosphokinase(CK),lactate dehydrogenase(LDH)and creatinine(Cr)were detected.Results Serum levels of CRP in patients with HFRS of different stages were lower than that in the fever of unknown origin group,had statistically significant differences(P <0.05).The variation trend of CRP in each stage of HFRS was consistent with the trend of AST,CK,LDH and Cr. Conclusion CRP has clinical significance in differentiating HFRS from fever of unknown origin.

Clinical significance of serum Cys-C,β2-MG and RBP detection in hemorrhagic fever with renal syndrome / 国际检验医学杂志

Objective To study the changes condition and clinical significance of serum cystatin C(Cys‐C) ,β2 microglobulin(β2‐MG) and retinol binding protein (RBP) detection in different stages of hemorrhagic fever with renal syndrome(HFRS) .Methods The levels of serum Cys‐C ,β2‐MG and RBP were detected in 22 patients with HFRS and 30 cases of healthy physical examination and the detection results were statistically analyzed by the SPSS13 .0 software .Results The serum Cys C and β2‐MG levels in every stage of HFRS were increased compared with the healthy control group(P0 .05) ,while RBP was significantly increased in the oliguria stage ,polyuria stage and convalescence stage(P 0 .05) .Conclusion β2‐MG is more sensitive than Cys‐C in the early stage of HFRS ;RBP has the clinical guidance significance in the progression of HFRS .

All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus

A recent outbreak of novel coronavirus (SARS-CoV-2), the causative agent of COVID-19, has spread rapidly all over the world. Human immunodeficiency virus (HIV) is another deadly virus and causes acquired immunodeficiency syndrome (AIDS). Rapid and early detection of these viruses will facilitate early intervention and reduce disease transmission risk. Here, we present an All-In-One Dual CRISPR-Cas12a (termed "AIOD-CRISPR") assay method for simple, rapid, ultrasensitive, one-pot, and visual detection of coronavirus SARS-CoV-2 and HIV virus. In our AIOD CRISPR assay, a pair of crRNAs was introduced to initiate dual CRISPR-Cas12a detection and improve detection sensitivity. The AIOD-CRISPR assay system was successfully utilized to detect nucleic acids (DNA and RNA) of SARS-CoV-2 and HIV with a sensitivity of few copies. Also, it was evaluated by detecting HIV-1 RNA extracted from human plasma samples, achieving a comparable sensitivity with real-time RT-PCR method. Thus, our method has a great potential for developing next-generation point-of-care molecular diagnostics.

Sensitive quantitative detection of SARS-CoV-2 in clinical samples using digital warm-start CRISPR assay

Quantifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples is crucial for assessing the infectivity of coronavirus disease 2019 and the efficacy of antiviral drugs. Here, we describe a digital warm-start CRISPR (WS-CRISPR) assay for sensitive quantitative detection of SARS-CoV-2 in clinical samples. The WS-CRISPR assay combines low-temperature reverse transcription dual-priming mediated isothermal amplification (RT-DAMP) and CRISPR-Cas12a-based detection in one-pot, attributed to the mediation role by pyrophosphatase and phosphorothioated primers. The WS-CRISPR assay is initiated at above 50 {degrees}C and overcomes undesired premature target amplification at room temperature, enabling accurate digital nucleic acid quantification. By targeting SARS-CoV-2s nucleoprotein gene, digital WS-CRISPR assay is able to detect down to 5 copies/l SARS-CoV-2 RNA in the chip within 90 minutes. It is clinically validated by quantitatively determining 32 clinical swab samples and three clinical saliva samples, showing 100% agreement with RT-PCR results. Moreover, the digital WS-CRISPR assay has been demonstrated to directly detect SARS-CoV-2 in heat-treated saliva samples without RNA extraction, showing high tolerance to inhibitors. Thus, the digital WS-CRISPR method, as a sensitive and reliable CRISPR assay, facilitates accurate SARS-CoV-2 detection toward digitized quantification.