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 establish a rapid on-site detection method for methamphetamine(MA)based on surface-enhanced Raman spectroscopy(SERS).Methods Laboratory-synthesized colloidal silver nanoparticles(AgNPs)were employed as SERS substrates to rapidly detect methamphetamine in typical crime scene matrices,including beer,cigarette ash,and plastic containers.Results The method requires no sample pretreatment,is simple to operate,and offers high sensitivity with fast detection speed.The limit of detection(LOD)reached 10 ppb(signal-to-noise ratio,S/N＞3).The qualitative results of methamphetamine analysis from forensic case samples were highly consistent with gas chromatography-mass spectrometry(GC-MS)findings.Conclusion Methamphetamine is frequently encountered in illicit settings and criminal activities.This study achieved rapid detection of methamphetamine in complex matrices(beer,cigarette ash,and plastic containers),demonstrating good application prospects in practice and providing important value for law enforcement,public safety,and criminal investigation.

Objective:To analyze the characteristics of adverse reactions of sodium-glucose cotransporter 2 inhibitors (SGLT2i), and provide a basis for the rational clinical application.Methods:The adverse drug reaction (ADR) cases of SGLT2i reported by Beijing from January 1, 2019 to June 30, 2024 were collected through searching the National Adverse Drug Reaction Monitoring System of China. The Medical Dictionary for Regulatory Activities (MedDRA) terminology set was used to standardize the description of ADR, and the involving system organ class (SOC) and preferred term (PT) was extracted. Data of ADR were analyzed descriptively and statistically. Results:A total of 409 SGLT2i-related adverse reaction reports involving 409 patients were included. Among these patients, there were 232 females and 177 males; the median age was 62(52, 70) years, and 231 cases (56.48%) were under the age of 65 years; 5 types of SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, and henagliflozin proline) were involved, and reports of dapagliflozin was the most (279 cases, 68.22%). The primary indication for medication was diabetes (404 cases, 98.78%). The majority of ADRs did not reach the severe level (395 cases, 96.58%). The 14 cases (3.42%) of severe ADR were primarily about diabetic ketoacidosis (11 cases, 11/14), of which 7 cases presented with normal blood glucose levels and 5 cases occurred after medical stress events. The outcomes of patients were improvement in 241 cases (58.92%) and recovery in 127 cases (31.05%). In total, 476 ADR occurrences were recorded among the 409 patients, involving 82 PTs, 24 of which were not listed in the drug labels. The top 2 SOCs were the infections and infestations [26.26% (125/476)] and renal and urinary disorders [13.87% (66/476)]; the top 3 PTs were urinary tract infection [23.32% (111/476)], urinary ketone detection [6.51% (31/476)], and vulvovaginal pruritus [5.88% (28/476)]; the top 3 newly identified possible ADRs (PTs) were dizziness [2.31% (11/476)], palpitations [1.89% (9/476)], and decreased appetite [1.05% (5/476)].Conclusions:Based on the ADR monitoring data in Beijing in the past 5 and a half years, SGLT2i-associated adverse reactions primarily involved the infections and infestations, and renal and urinary disorders. ADRs identified in the study such as dizziness and palpitations are not documented in the drug labels, euglycaemic ketoacidosis accounts for a high proportion of severe reactions, and most of them occur after acute stress events.

Objective To establish a rapid on-site detection method for methamphetamine(MA)based on surface-enhanced Raman spectroscopy(SERS).Methods Laboratory-synthesized colloidal silver nanoparticles(AgNPs)were employed as SERS substrates to rapidly detect methamphetamine in typical crime scene matrices,including beer,cigarette ash,and plastic containers.Results The method requires no sample pretreatment,is simple to operate,and offers high sensitivity with fast detection speed.The limit of detection(LOD)reached 10 ppb(signal-to-noise ratio,S/N＞3).The qualitative results of methamphetamine analysis from forensic case samples were highly consistent with gas chromatography-mass spectrometry(GC-MS)findings.Conclusion Methamphetamine is frequently encountered in illicit settings and criminal activities.This study achieved rapid detection of methamphetamine in complex matrices(beer,cigarette ash,and plastic containers),demonstrating good application prospects in practice and providing important value for law enforcement,public safety,and criminal investigation.

Objective:To analyze the characteristics of adverse reactions of sodium-glucose cotransporter 2 inhibitors (SGLT2i), and provide a basis for the rational clinical application.Methods:The adverse drug reaction (ADR) cases of SGLT2i reported by Beijing from January 1, 2019 to June 30, 2024 were collected through searching the National Adverse Drug Reaction Monitoring System of China. The Medical Dictionary for Regulatory Activities (MedDRA) terminology set was used to standardize the description of ADR, and the involving system organ class (SOC) and preferred term (PT) was extracted. Data of ADR were analyzed descriptively and statistically. Results:A total of 409 SGLT2i-related adverse reaction reports involving 409 patients were included. Among these patients, there were 232 females and 177 males; the median age was 62(52, 70) years, and 231 cases (56.48%) were under the age of 65 years; 5 types of SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, and henagliflozin proline) were involved, and reports of dapagliflozin was the most (279 cases, 68.22%). The primary indication for medication was diabetes (404 cases, 98.78%). The majority of ADRs did not reach the severe level (395 cases, 96.58%). The 14 cases (3.42%) of severe ADR were primarily about diabetic ketoacidosis (11 cases, 11/14), of which 7 cases presented with normal blood glucose levels and 5 cases occurred after medical stress events. The outcomes of patients were improvement in 241 cases (58.92%) and recovery in 127 cases (31.05%). In total, 476 ADR occurrences were recorded among the 409 patients, involving 82 PTs, 24 of which were not listed in the drug labels. The top 2 SOCs were the infections and infestations [26.26% (125/476)] and renal and urinary disorders [13.87% (66/476)]; the top 3 PTs were urinary tract infection [23.32% (111/476)], urinary ketone detection [6.51% (31/476)], and vulvovaginal pruritus [5.88% (28/476)]; the top 3 newly identified possible ADRs (PTs) were dizziness [2.31% (11/476)], palpitations [1.89% (9/476)], and decreased appetite [1.05% (5/476)].Conclusions:Based on the ADR monitoring data in Beijing in the past 5 and a half years, SGLT2i-associated adverse reactions primarily involved the infections and infestations, and renal and urinary disorders. ADRs identified in the study such as dizziness and palpitations are not documented in the drug labels, euglycaemic ketoacidosis accounts for a high proportion of severe reactions, and most of them occur after acute stress events.

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.

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.

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.

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.