Liver failure （LF） is a severe clinical syndrome characterized by severe impairment or decompensation of liver function. At present， the key role of immune molecules in the pathogenesis of LF has been well established. These molecules not only directly participate in the pathological process of LF， but also influence the course of LF by modulating the behavior of immune cells. In addition， immune molecules can be used as potential biomarkers for evaluating the prognosis of LF. This article summarizes the role of immune molecules in LF and explores the therapeutic strategies based on these immune molecules， in order to provide new directions for the diagnosis and treatment of LF.

Objective To explore the cost-benefit of computerized tomography perfusion imaging(CTP)in guiding endovascular treatment of patients with large vessel occlusion associated with delayed time window.Methods A total of 365 patients with great vascular occlusive stroke associated with delayed time window(6-24 h),who were admitted to the Tangshan Municipal Workers' Hospital of China to receive endovascular treatment from January 2016 to February 2022,were enrolled in this study.Based on whether the patient received CTP imaging guidance or not,the treatment cost and benefit of different treatment strategies were analyzed.Modified Rankin scale(mRS)was used to evaluate the patient's postoperative 3-month and 12-month neurological functions.The decision tree-Markov model was used to make cost-benefit analysis.Probability sensitivity analysis(PSA)was used to assess the influence of parameter uncertainty.Results The operation cost of CTP-guided endovascular treatment of large vessel occlusion was 1 526.87 Chinese yuan.According to the calculation method of disease and sequelae burden,it could bring direct burden of 1 089.23 Chinese yuan,direct+indirect burden of 3 204.85 Chinese yuan and direct+indirect+intangible burden of 5 083.07 Chinese yuan.Each Chinese yuan could get 0.178 8,0.231 8 and 0.263 4 earnings,respectively.The therapeutic cost of CTP-guided endovascular treatment of great vascular occlusive stroke was 26 689.13 Chinese yuan,producing 2.065 quality-adjusted life-year(QALY)for each patient,while the therapeutic cost and QALY of non-CTP-guided endovascular treatment were 33 299.07 Chinese yuan and 1.776 QALY respectively.PAS-analyzed incremental cost-benefit ratio(ICER)and incremental net monetary benefit(iNMB)were 22 592.82 and 7 846.43 respectively.At the cost-benefit threshold of ￥50 000/QALY,the probability that CTP guidance could get cost-benefit was up to 90.0％.The tornado chart analysis of one-way sensitivity analysis revealed that the initial mRS distribution guided by CTP had the greatest influence on iNMB,followed by the cost input in the first three months after operation.Conclusion For patients with great vascular occlusive stroke associated with delayed time window,CTP-guided endovascular treatment has high cost-benefit and effect value.

Objective:To investigate the effect of high glucose on intracellular cholesterol content in rat glomerular mesangial cells and the underlying mechanism.Methods:Rat glomerular mesangial cells were cultured in vitro and divided into high glucose culture group (high glucose group, medium glucose concentration of 30 mmol/L) and normal glucose culture group (normal group, medium glucose concentration of 5.5 mmol/L). Lipid content was determined by oil red O staining and spectrophotometer colorimetry at 24, 36 and 48 h of culture. Intracellular protein imprinting was used to detect the expression of low density lipoprotein cholesterol receptor (LDLR) and adenosine triphosphate binding cassette A1 (ABCA1). Results:Oil red O staining showed that the intracellular lipid drops in the high glucose group were less than those in the normal group at 36 h, and there was no significant difference between the two groups at 24 h and 48 h of culture. The total cholesterol (TC) and cholesterol ester (CE) in glomerular mesangial cells of rats in the high glucose group were significantly lower than those in the normal group ( P=0.028, 0.029), while there was no significant difference in the free cholesterol (FC) between the two groups ( P=0.306). There was no significant difference in TC, CE and FC between the two groups at 24 and 48 h of culture (all P>0.05). The expression of LDLR in mesangial cells of rats in high glucose group was significantly lower than that in normal group at 24, 36 and 48 h of culture ( P=0.043, 0.004, 0.028), and the expression of ABCA1 was significantly higher than that in normal group at 24, 36 and 48 h of culture, ( P=0.050, 0.009, 0.006). Conclusions:High glucose may reduce intracellular cholesterol content in rat glomerular mesangial cells by reducing LDLR protein expression and increasing ABCA1 protein expression.

Primary hypomagnesemia with secondary hypocalcemia(HSH) is a rare cause of hypoparathyroidism. This article presents a case of a 26-year-old male with recurrent generalized weakness and tetany, and a literature review of diagnosis and treatment of primary HSH. The biochemical tests revealed the patient had severe hypomagnesemia, mild hypocalcemia, hypokalemia, and hypoparathyroidism. Transient receptor potential melastatin-6(TRPM6) gene mutation were detected by gene test, which confirmed the diagnosis of primary HSH. The patient had been treated with long term oral magnesium supplementation, who remained asymptomatic during the follow-up. Primary HSH is a rare autosomal-recessive disorder caused by mutations in the TRPM6 gene which encoding a magnesium permeable channel expressed in the intestine and the kidney. The primary defect is impaired intestinal absorption of magnesium with secondary renal excretion, leading to a series of clinical symptoms. The treatment is mainly through lifelong magnesium supplementation.

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

Objective:To evaluate the effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) on migraine.Methods:Database of PubMed, Embase, Cochrane, CNKI, Wangfang digital journals were searched for randomized controlled trials (RCTs) of CGRP-mAbs in treatment of migraine. Quality of enrolled literature was assessed by the software of Review Manager 5.3 and software of StataMP14 was employed to conduct meta analysis.Results:A total of 13 RCTs were included, including 6 218 adult migraine patients (experimental group: 2 679 patients, placebo group: 3 539 patients). Meta analysis suggested that CGRP-mAbs for preventive treatment of migraine significantly reduced the monthly migraine days from baseline (standardized mean difference (SMD)=-0.35, 95% CI-0.4--0.3) and monthly acute migraine-specific medication consumption from baseline (SMD=-0.38, 95% CI-0.43--0.32), as compared with placebo group. CGRP-mAbs for preventive treatment of migraine significantly increased the ≥50% reduction from baseline in migraine days per month ( RR=1.65, 95% CI 1.54-1.76). The adverse events were similar between the CGRP-mAbs group and placebo group ( RR=1.06, 95% CI 1.01-1.10). Conclusion:CGRP-mAbs are effective and safe for preventive treatment of migraine.

Objective:To investigate the relevant situation of the emergency departments (ED) of general hospitals at all levels in Zhejiang Province participating in the prevention and control of Corona Virus Disease 2019 (COVID-19), and to provide a reference for further improving the capacity of emergency services.Methods:A multi-center cross-sectional investigation study was jointly initiated by the Zhejiang Provincial Emergency Medicine Quality Control Center, the Emergency Medicine Branch of Zhejiang Medical Association, and the Emergency Physicians Branch of Zhejiang Medical Doctors Association. Before investigation, experts were organized to develop a special questionnaire. Then the ED of general people's hospitals or Chinese Medicine hospitals at the county/district-level or above were included and their participations in the prevention and control of COVID-19 epidemic between March 9, 2020 and March 15, 2020 were investigated. The collected information included: basic information of the hospitals; participation of ED in fever clinics; the number of COVID-19 patients admitted to ED; the situation of ED support to the anti-epidemic front-line; and the epidemic prevention facilities of ED, and the early supply of medical protective equipments.Results:A total of 181 hospitals from 11 prefectures and cities across the province were finally included, including 52 (28.7%) Grade-A tertiary hospitals, 45 (24.9%) Grade-B tertiary hospitals, 64(35.4%) Grade-A secondary hospitals, and 20 (11.0%) Grade-B secondary or lower hospitals. Among them, 93 (51.4%) were COVID-19 designated hospitals, and 49 (27.1%) had the ability to detect COVID-19 nucleic acid; 177 (97.8%) set up independent fever clinics and 33 (18.6%) were managed by ED alone or mainly. The medical staffs of 65 (36.7%) fever clinics were all or mainly from ED. A total of 213 cases of COVID-19 were received/treated in 40.3% ED, accounting for 17.3% of the total number of cases in Zhejiang Province. A total of 3 848 doctors and nurses supported the front-line of epidemic prevention, of them, 253 supported Hubei Province (accounting for 12.5% ??of the total number). There were 68.5% and 76.8% ED having spare separate clinic and ordinary rescue single room to deal with the COVID-19. In addition, at the early days of anti-epidemic, more than 50% ED were in short supply or even had no medical protective equipment.Conclusions:The ED of Zhejiang Province plays an important role and has made a great contribution to the prevention and control of the COVID-19 epidemic. It is necessary to improve the conditions of ED to effectively respond to the prevention and control of daily infectious diseases.

Objective To investigate the clinical value of neutrophil to lymphocyte ratio (NLR) in evaluation of inflammation and prediction of cardiovascular events in maintenance hemodialysis (MHD) patients.Methods One hundred and eight stable MHD patients were recruited from Dialysis Center of Beijing Tongren Hospital from October 2015 to December 2015.The general information,complete blood count,hsCRP,biochemical test,iron metabolic indicators,pre-dialytic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded.MHD patients were divided into the low NLR group and high NLR group according to the median of NLR (2.82).All patients were followed up for 18 months,cardiovascular events (CVE) were recorded during this period.Results In the high NLR group the dialysis vintage,white blood cell count,neutrophil count,NLR and hsCRP were significantly higher than those in the low NLR group [(88.0 ± 50.4) vs.(62.4 ± 40.6) months (t =2.48,P =0.02),(6.96 ± 1.82) × 109/L vs.(5.83 ± 1.33) × 109/L(t =3.14,P=0.00),(4.94 ± 1.38) × 109/L vs.(3.36 ±0.87) × 109/ L(t=6.08,P=0.00),(4.16±1.25) vs.(2.15 ±0.46) points(t=9.48,P=0.00),(7.85±4.92) vs.(3.13 ± 2.23) mg/L (t =4.97,P =0.00)].In the high NLR group lymphocyte count and transferrin saturation were significantly lower than those in the low NLR group[(1.25 ± 0.40) × 109/L vs.(1.58 ± 0.34) ×109/L,t=3.97,P=0.00;(25.7±10.2)％ vs.(32.6±17.2)％,t=2.17,P=0.03].There were no significant differences in age,sex,diabetes proportion,pre-dialytic SBP,pre-dialytic DBP,urea clearence index(Kt/V),hemoglobin,serum ferritin,serum calcium,serum phosphorus,intait parathyroid hormone,albumin,serum creatinine,carbon dioxide binding capacity and blood lipids between the two groups (P ＞ 0.05).Bivariate correlation analysis showed that NLR was positively correlated with dialysis vintage and hsCRP (r =0.311,P =0.01;r =0.574,P =0.00);white blood cell count and neutrophil count were positively correlated with hsCRP (r =0.327,P =0.00;r =0.488,P =0.00).During follow-up period 9 cases of CVE (16.7％) and 20 cases of CVE (37.0％) occurred in the low NLR group and high NLR group,respectively (x2 =5.70,P =0.03).Cox regression analysis showed that age,NLR and serum phosphorus level were risk factors of CVE in MHD patients (HR =1.075,P =0.00,HR =1.646,P =0.00;HR =1.912,P =0.02).Conclusion NLR can predict inflammation and is one of the risk factors for CVE in MHD patients.

[Objective]To explore the relationship between peripheral arterial disease(PAD)and diabetic retinopathy(DR)in type 2 diabetes patients.[Methods]A total of 99 patients diagnosed with PAD were classified into grade 1-3 by their total scores of peripheral arterial stenosis assessed by color doppler ultrasound examinations,where the degree of stenosis 30% ~ 49% scored 0, 50%~99%scored 1,lumen occlusion(i.e. degree of stenosis 100%)scored 2,and therefore the total score 0-2 was categorized into Grade 1 ,3~4 into Grade 2 ,5~12 into Grade 3. The bilateral anterior tibial artery ,posterior tibial artery and dorsalis pedis artery of these patients were analyzed. The presence of diabetic retinopathy(DR)was graded from retinal photographs using a standard protocol.[Results]Among 99 cases of type 2 diabetic patients with peripheral arterial disease ,58.6%of them were male with average age of 67.3 ± 7.9 years old. Patients of Grade 1,Grade2,Grade 3 lesion accounted for 45.4%,30.3%,24.2%,respectively. Age, gender,smoking history,SBP,DBP,BMI,FBG,TC,TG,LDL-C,HDL-C,HbA1C among 3 groups were not statistically signifi-cant. The associations of DM duration and HbA1C value were significantly larger in DR than in PAD. The proportion of DR patients increased with the severity degree of PAD(p for trend=0.004). Degree of stenosis Grade 2 and Grade 3 could be predictive for DR.[Conclusions]DR is associated with the severity degree of PAD in type 2 diabetes patients as evaluated by duplex ultrasonography.Degree of stenosis Grade 2 and 3 could be used for screening or finding DR. Strategies for optimum treatment and early prevention are needed.

Objective To investigate the risk factors of hemorrhagic transformation(HT) in patients with acute cerebral infarction(ACI).Methods A total of 335 patients with ACI from June 2013 to September 2016 was enrolled in this study,including 47 patients in hemorrhagic transform group(HT group) and 288 patients in non-hemorrhagic transformation group(NHT group).The general clinical situation,laboratory indexes,imaging features and treatment measures of the two groups were collected and compared,and then the risk factors of HT in the patients with ACI were analyzed by Logistic regression analysis.Results Univariate analysisshowed that there were significant differences between the two groups in the history of diabetes mellitus,hìstory of atrial fibrillation,NHISS score,systolic blood pressure at admission,fasting blood glucose,glycosylated hemoglobin,low density lipoprotein cholesterol,fibrinogen,infarct location,large area infarction and thrombolytic therapy(P＜0.05).Logistic regression analysis showed that history of atrial fibrillation(OR =2.703,95 ％ CI 1.169-6.250),high fasting blood glucose(OR =2.098,95 ％ CI 1.532-2.875),large area infarction(OR=9.999,95％CI 4.648-21.510) and thrombolytic therapy(OR=6.557,95％CI 1.954-22.003) were independent risk factors for HT.Conclusion The history of atrial fibrillation,high fasting blood glucose,large area infarction and thrombolytic therapy are the risk factors for HT in patients with ACI.Corresponding nursing measures should be arranged to facilitate the disease treatment.