N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

Objective To describe the outcomes of extracorporeal membrane oxygenation (ECMO) for patients after aortic surgery and to summarize the experience. Methods The clinical data of patients who received ECMO support after aortic surgery in Fuwai Hospital from 2009 to 2020 were retrospectively analyzed. The patients who received an aortic dissection surgery were allocated into a dissection group, and the other patients were allocated into a non-dissection group. The in-hospital and follow-up survival rates were compared between the two groups, and the causes of death were analyzed. Results A total of 22 patients were enrolled, including 17 patients in the dissection group [13 males and 4 females, with a median age of 54 (46, 61) years] and 5 patients in the non-dissection group [3 males and 2 females, with a median age of 51 (41, 65) years]. There was no statistical difference in the age and gender between the two groups (P>0.05). The in-hospital survival rate (11.8% vs. 100.0%, P=0.001) and follow-up survival rate (11.8% vs. 80.0%, P=0.009) of the patients in the dissection group were significantly lower than those in the non-dissection group. The causes of death in the dissection group included massive bleeding and disseminated intravascular coagulation (3 patients), ventricular thrombosis (1 patient), irreversible brain injury (2 patients), visceral malperfusion syndrome (4 patients) and irreversible heart failure (5 patients). Conclusion ECMO after aortic dissection surgery is associated with high mortality, which is related to the pathological features of aortic dissection and severely disrupted coagulation system after the surgery. For these patients, strict indication selection and optimal management strategy are important.

Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.

Objective To explore the independent risk factors that affect the overall survival(OS)of elderly patients with hepatocellular carcinoma(HCC,≥60 years old)and build a nomogram prediction model.Methods Clinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database.In accordance with the inclusion and exclusion criteria,the screened patients were randomly assigned to a training group(70%)and a validation group(30%).The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis.On the basis of the determined variables,nomograms were developed and verified to predict the OS of elderly patients with HCC at 6,12,and 24 months.The consistency index(C index),calibration curve,receiver's operating characteristic(ROC)curve,and area under curve(AUC)were used to evaluate the prediction efficiency and discrimination ability of the prediction model,and decision curve analysis(DCA)was used to evaluate the potential clinical application value of the nomogram.Results A total of 1134 elderly patients with HCC were included,with 793 in the training group and 341 in the validation group.Seven variables,including age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy,were identified as independent prognostic factors of this population.The constructed nomogram shows excellent prediction performance,with C indices of 0.745 in the training group and 0.704 in the validation group.The AUC values of the training group at 6,12,and 24 months were 0.785,0.788,and 0.798,respectively,and those of the validation group were 0.780,0.725,and 0.607,respectively.The calibration curve shows good consistency from the predicted survival probability to the actual probability.The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability.Conclusion Age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy are important influencing factors for the survival of elderly patients with HCC.The prediction model of prognosis nomogram constructed in this study has good predictive value,and it can be used to predict the OS of elderly patients with HCC,which could be helpful for individualized survival assessment and clinical management of these patients.

Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Objective To observe the effect of hyolroxylsafflor(HSYA)on cyclooxygenase-2(COX-2)/prostaglandin E2(PGE2)signaling pathway,and to investigate the protective effect and mechanism of HSYA on cerebral ischemia-reperfusion injury(CIRI).Methods Totally 90 SD male rats were randomly divided into sham-operated group(S group),operation group(CIRI group),HSYA group and celecoxib group(C group),HSYA group subdivided into HSYA low dose group(HSYA-L group),HSYA medium dose group(HSYA-M group)and HSYA high dose group(HSYA-H group),15 rats in each group.CIRI model was prepared by thread embolism method.The rats in each group were given intraperitoneal injection 30 minutes before operation.HSYA groups were given HSYA 10 mg/kg,15 mg/kg,25 mg/kg respectirely;C group was given celecoxib 40 mg/kg;S group and CIRI group were given the same amount of normal saline.Neurofunctional scores of each group of rats were performed immediately after recovery from modeling,cerebral infarction volume was measured 24 hours after reperfusion;At the same time,neuronal injury was observed by Nissl staining,the changes of COX-2 mRNA and protein were detected by Real-time PCR and Western blotting,and the changes of PGE2,tumor necrosis factor α(TNF-α)and interleukin(IL)-1β were detected by ELISA.Results Compared with the S group,in the CIRI group,neurofunctional scores increased dramatically(P＜0.05),the volume of cerebral infarction increased dramatically(P＜0.05),the damage of neurons increased and the number of neurons decreased dramatically(P＜0.05),the expressions of COX-2 mRNA and protein increased dramatically(P＜0.05),meanwhile the expressions of PGE2,TNF-α and IL-1β were also found dramatically increased(P＜0.05);Compared with the CIRI group,in the HSYA group and C group,neurofunctional scores decreased dramatically(P＜0.05),the volume of cerebral infarction was reduced dramatically(P＜0.05),the damage of neurons decreased and the number of neurons increased dramatically(P＜0.05),the expressions of COX-2 mRNA and protein,PGE2,TNF-α and IL-1β decreased dramatically(P＜0.05).The differences between HSYA groups and both HSYA-L group and HSYA-M group compared with the C group were obvious(P＜0.05),while no obvious differences were found in HSYA-H group compared with the C group(P＞0.05).Conclusion HSYA alleviates reperfusion injury in ischemic stroke may be related to the inhibition of COX-2/PGE2 signaling pathway.

Objective To investigate the mechanism of neuronal apoptosis induced by cyclooxygenase-2(COX-2)after cerebral ischemia/reperfusion(CI/R)injury in rats.Methods Totally 45 male SD rats were divided into 3 groups by random number method,sham operation group(sham),model group(CI/R),COX-2 inhibitor group(NS-398).Blocking the middle cerebral artery to create a model,at the beginning of ischemia,NS-398 group was intraperitoneally injected with NS-398(20 mg/kg),while sham group and CI/R group were injected with the same amount of DMSO.Rats were performed for neurofunctional scores after 2 hours ischemia.After 24 hours reperfusion,2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect the infarct volume of rats.Meanwhile,cerebral tissue from penumbra area of frontal parietal cortex on ischemic side was taken,Nissl staining and TUNEL method were used to detect neuronal damage and apoptosis respectively,and finally Western blotting was used to detect the expression levels of COX-2,Bcl-2 and Bax proteins.Results The neurofunctional scores of rats,cerebral infarction volume,apoptosis index,the expressions of COX-2 and Bax in CI/R group were higher than those in the sham group(P＜0.05),the expression level of Bcl-2 and the number of neurons were lower than those in the sham group(P＜0.05);The neurofunctional scores of rats,cerebral infarction volume,apoptosis index,the expression levels of COX-2 and Bax in NS-398 group were lower than those in CI/R group(P＜0.05),the expression level of Bcl-2 and the number of neurons were higher than those in CI/R group(P＜0.05).Conclusion COX-2 may promote neuronal apoptosis after cerebral ischemia/reperfusion injury by regulating the expressions of Bcl-2 and Bax.

Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.