Objective To investigate the association of urinary phthalate metabolites with 4 high-density lipoprotein-cholesterol(HDL-C)-related inflammatory indicators[lymphocyte/HDL-C ratio(LHR),monocyte/HDL-C ratio(MHR),neutrophil/HDL-C ratio(NHR),and platelet/HDL-C ratio(PHR)],and to explain their possible biological mechanisms.Methods The 4 573 adult participants from the National Health and Nutrition Examination Survey(NHANES)were subjected,and then generalized linear regression(GLM),restricted cubic spline(RCS),and weighted quantile sum(WQS)regressions were performed to explore the potential associations of phthalates mono-exposures and mixed exposures,respectively,with the HDL-C-related inflammation metrics.Results Nine urinary phthalate metabolites were significantly positively associated with at least 1 inflammatory marker,while 1 metabolite(MEP)showed a negative association with an inflammatory indicator(LHR).Some exposure metabolites showed a nonlinear association with outcome inflammatory indicators.WQS regression revealed varying weight contributions of individual metabolite to each inflammatory outcome.Subgroup analyses indicated differential association effects of phthalates with HDL-C-related inflammatory metrics across gender,age,and BMI populations.Conclusion There are associations between phthalate exposure and HDL-C-related inflammation indicators,but further studies are needed to reveal the underlying mechanisms.

Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.

Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.

Objective To analyze the risk factors for lung injury and pulmonary arterial hypertension in patients with chronic obstructive pulmonary disease(COPD),and the predictive value of serum SDF-1 and sRAGE for lung injury and pulmonary arterial hypertension.Methods A total of 200 patients with COPD admitted to our hospital from January 2021 to January 2023 were selected as research objects,23 of whom occurred lung injury and the rest 177 had no lung injury,and 31 developed pulmonary hypertension and the remaining 169 had no pulmonary hypertension.The predictive value of serum SDF-1 and sRAGE for pulmonary injury and pulmonary hypertension was analyzed.Results Multi-factor logistic regression analysis showed that D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,pulmonary hypertension,arterial blood oxygen partial pressure,FVC and FEV1 were the main factors affecting lung injury in patients with COPD.D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,arterial partial oxygen pressure,FVC,FEV1 and CT angiographic pulmonary artery volume were the main factors affecting the occurrence of pulmonary hypertension in those patients(P<0.05).Serum SDF-1 and sRAGE were positively correlated with lung injury and pulmonary hypertension in patients with COPD(P<0.05).The sensitivity and accuracy of SDF-1 and sRAGE for predicting lung injury and pulmonary hyperten-sion in patients with COPD were higher than those of SDF-1 and SRage alone(P<0.05).Conclusions Pulmonary injury in patients with COPD is associated with D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,pulmonary hypertension,arterial blood oxygen partial pressure,FVC,FEV1.The occurrence of pulmonary hyper-tension is related to D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,arterial partial pressure of oxy-gen,FVC,FEV1 and CT angiography of pulmonary artery volume.Combined detection of SDF-1 and sRAGE has a higher predictive value for lung injury and pulmonary hypertension.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Objective:To investigate the effects and its mechanism of chronic unpredictable stress on intestine and liver injuries in rats, and explore the possibility of the existence of brain-gut-liver axis.Methods:Twenty male SD rats were randomly divided into control group and stress group (with 10 in each group). The rats in the stress group were stimulated by chronic unpredictable stress for 4 weeks to prepare the chronic stress model. The rats in the control group were fed normally without stress stimulation. After modeling, ten rats in the control group and seven rats in the stress group were included. The depressive behavior of the two groups was evaluated by sugar water preference experiment. Then the rats were sacrificed. The diversity of gut flora in intestinal feces was analyzed by 16S rRNA sequencing analysis. The pathological injuries of ileum and liver were detected by HE staining. The expressions of occludin in ileum and Toll-like receptor 4 (TLR4) in liver were detected by immunohistochemistry. The expression of TLR4 protein in liver tissue was detected by Western blot. The level of lipopolysaccharide (LPS) in rat portal vein serum was detected by AZO chromogenic limulus test and blood biochemical method was used to detect liver function.Statistical analysis was performed using SPSS 25.0 software, and t-test or Mann-Whitney U test was used for comparison between the two groups. Using STAMP software, Wilcoxon rank sum test was used to analyze the difference in bacterial abundance between the two groups. Results:The consumption of sugar water ((7.86±0.90)ml) and the preference rate of sugar water ((43.06±5.65)%) in the stress group were lower than those in the control group ((15.10±1.51)ml, (76.81±6.44)%), and the difference were statistically significant ( t=11.33, 11.16, both P<0.01). Chronic stress caused pathological damage to rat ileum tissue. Compared with the control group, the ileum villi of rats in the chronic stress group were longer ((448.93±12.71)μm, (497.12±16.72)μm, t=-5.88, P<0.01) and thicker ((81.99±16.54)μm, (133.93±6.78)μm, t=-7.12, P<0.01), and the expression of occludin was significantly down-regulated ((0.236±0.011), (0.130±0.026), t=9.12 , P<0.01), the LPS level increased significantly ((18.83±2.62)EU/L, (38.64±2.51)EU/L, t=-5.79, P<0.01). The Beta diversity of rat intestinal flora changed under chronic stress, and the abundance of WPS-2 phylum in intestinal tract of rats in stress group was higher than that in control group ( t=2.76, P<0.05). Chronic stress caused pathological damage to the liver tissue of rats. Compared with the control group, the expression of TLR4 protein in the liver tissue of the chronic stress group increased ((0.169±0.014), (0.475±0.034), Z=-2.37, P<0.05). Compared with the control group, the ALT ((39.7±6.2)U/L, (82.9±43.1)U/L, Z=-2.35, P<0.05) and AST((130.9±28.9)U/L, (472.7±263.3)U/L, Z=-2.64, P<0.05) levels of the chronic stress group increased, especially in AST. Conclusion:Chronic stress cause synchronous damage to the intestine and liver in rats. The mechanism may be related to the results caused by chronic stress such as the changes of the diversity of intestinal flora, the increasing of intestinal permeability, the action of LPS translocated through portal vein blood on TLR4 in liver.

Objective:To establish an LC-MS/MS method for the simultaneous determination of acetaminophen and its five metabolites in mice plasma,and investigate the metabolism of acetaminophen by using the method.Methods:Para aminobenzoic acid was used as the internal standard.The plasma samples were precipitated by methanol,and then separated on a C18 column with the mobile phase of methanol and 5 mmol·L-1 ammonium acetate buffer solution containing 0.1% formic acid (55∶45).The flow rate was 0.5 ml·min-1,and the column temperature was 25℃.An electrospray ionization source was applied and operated in a positive ion mode using MRM:APAP,-,m/z 152.0→110.0;APAP-cys,-,m/z 271.2→140.1;APAP-glut,-,m/z 457.0→328.0;APAP-NAC,-,m/z 313.4 →208.0;APAP-sulf,-,m/z 232.4→152.1;APAP-gluc,-,m/z 328.2→152.1;IS,-,m/z 138.2→120.0.Results:The method exhibited good linearity over the concentration range of 0.2-10 μg·ml-1for APAP,1.0-20 μg·ml-1 for APAP-gluc,1.0-20 μg·ml-1 for APAP-sulf,1.0-20 μg·ml-1 for APAP-glut,0.4-15 μg·ml-1 for APAP-NAC and 0.2-10 μg·ml-1 for APAP-cys (r≥0.990 0).The inter-day accuracy and precision of acetaminophen and its five metabolites were all below 15%.The average recovery was between 85% and 115%,and RSDs were all below 15%.Conclusion:The LC-MS/MS method is proved to be quick,sensitive and accurate,and suitable for the determination of acetaminophen and its five metabolites in mice plasma.

Objective To investigate the mortality risk factors of nosocomial infection patients in intensive care unit (ICU), and to guide clinicians to take effective control measures. Methods A retrospectively cohort study was conducted. The relevant information of patients with nosocomial infection treated in ICU of Hengshui Harrison International Peace Hospital Affiliated to Hebei Medical University from June 2009 to December 2015 was analyzed. The patients who admitted to ICU again, with length of ICU stay less than 48 hours, without first etiology of screening within 48 hours of ICU admission, or without complete pathogenic information were excluded. The gender, age, diagnosis, length of ICU stay, invasive operation, nutritional status, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, distribution and drug resistance of the pathogens, and procalcitonin (PCT) levels at 7 days after nosocomial infection were recorded. The risk factors leading to death in patients with nosocomial infection were analyzed by logistic regression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of all risk factors on the outcome of patients with nosocomial infection. Results In 864 enrolled patients with male of 54.75% and mean age of (63.50±15.80) years, 732 (84.72%) patients survived and 132 (15.28%) died. Compared with survivors, the non-survivors had higher age (years: 65.47±15.32 vs. 58.15±13.27), incidence of urgent trachea intubation (32.58% vs. 22.81%), deep venous catheterization (83.33% vs. 63.25%), and multiple drug-resistant infection (65.91% vs. 33.20%), longer length of ICU stay (days: 13.56±4.29 vs. 10.29±4.32) and duration of coma (days: 7.36±2.46 vs. 5.48±2.14), lower albumin (g/L: 23.64±8.47 vs. 26.36±12.84), higher APACHEⅡ score (19.28±5.16 vs. 17.56±5.62), SOFA score (8.55±1.34 vs. 6.43±2.65), and PCT (μg/L: 3.06±1.36 vs. 2.53±0.87, all P < 0.05). There was no significant difference in gender and urinary tract catheterization between survivors and non-survivors (both P > 0.05). The low respiratory tract was the most common site of infection followed by urinary tract and bloodstream in both groups. It was shown by logistic regression analysis that prolonged ICU stay [odds ratio (OR) = 2.039, 95% confidence interval (95%CI) = 1.231-3.473, P = 0.002], APACHEⅡ score (OR = 1.683, 95%CI= 1.002-9.376, P = 0.000), SOFA score (OR = 2.060, 95%CI = 1.208 -14.309, P = 0.041), PCT (OR = 2.090, 95%CI = 1.706-13.098, P = 0.004), and multi-drug resistant pathogens infection (OR = 5.245, 95%CI = 2.213-35.098, P = 0.027) were independent risk factors for ICU mortality in patients with nosocomial infection. The area under ROC curve (AUC) of length of ICU stay, APACHEⅡ score, SOFA score, and PCT level for predicting death of nosocomial infection patients was 0.854, 0.738, 0.786, and 0.849, respectively, the best cut-off value was 16.50 days, 22.45, 6.37 and 3.38 μg/L, respectively, the sensitivity was 83.6%, 90.0%, 81.1%, and 89.6%, and the specificity was 70.3%, 75.6%, 71.3%, and 85.4%, respectively. Conclusions Prol onged ICU stay, nosocomial infection with secondary sepsis and multiple organ dysfunction syndrome were the leading causes of death for nosocomial infection patients in ICU. Prolonged ICU stay, APACHE Ⅱ score, SOFA score, and PCT level could effectively predict death risks for nosocomial infection patients.

Objective:To explore the effect of argatroban combined with Kallikrein on progressive cerebral infarction.Methods: One hundred and fifty two progressive cerebral infarction patients were randomized into groups observation (n=76) and control (n=76). Observation group were given treatment ofargatroban and Kallikrein, control only Kallikrein. NIHSS scores, Barthel index, Modified Rankin Scales(MRS) were used to evaluate the efficacy in two groups.Results: The difference of the effect was significant in two groups(x2=11.463,P>0.05).In both of the two groups, NIHSS scores were decreased, there was significant difference between the two groups (t=1.501,t=1.844,t=1.341;P<0.05). The Barthel index in argatroban combined Kallikrein group was higher than Kallikrein group, Modified Rankin Scales was lower than Kallikrein group, and there was significant difference between the two groups (t=2.121,t=2.332,t=2.219;P<0.05). The observation group and the control group patients don''t have bleeding gums,subcutaneous bleeding, gastrointestinal bleeding and other adverse reactions.Conclusion: Argatroban combined with Kallikrein, improve the neurologic impairment symptoms, clinical effect, improve the life quality of the patients, of a relatively good effect in treatment of progressive cerebral infarction, can improve obviously the cognitive ability and neural function and patients, activities of daily living. Moreover, its security and tolerability are good.

OBJECTIVE:To establish a method for determining the plasma concentration of paeoniflorin and phillyrin and phar-macokinetic study before and after intragastric administration of Qianliean granules. METHODS:LC-MS/MS method was adopted. The column was Waters C18 with mobile phase consisted of acetonitrile(A)-2 mmol/L ammonium acetate(containing 0.05% formic acid)(B)(0-9 min:15%A→50%A;9-11 min:50%A→90%A;11-17 min:90%A;17-19 min:90%A→15%A;19-20 min:15%A),at the flow rate of 0.6 ml/min;column temperature was 35 ℃ and the volume was 20 μl;quantitative ions were paeoniflorin m/z 525.2 → m/z 449.0,phillyrin m/z 552.3 → m/z 355.3. 7 SD male rats were docked to collect blood 0.5 ml from angular vein 0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,24 h after administration Qianliean granule solution 1 g(medicinal materials)/kg to determine the blood concentration of drugs. DAS 2.1.1 software was employed to calculate pharmacokinetic parameters. RE-SULTS:The linear range of paeoniflorin and phillyri were 5.0-2500.0 μg/L(r=0.9979)and 2.0-2000.0 μg/L(r=0.9982),re-spectively;RSD of precision test was less than 5.5%(n=5);the method recovery were 96.0%-104.0% and 92.0%-107.0%,the extration recovery were 71.4%-83.5% and 81.5%-92.3% and RSD of stability test was less than 5.0%(n=3). The pharmacokinet-ic parameters of paeoniflorin and phillyrin were as follows as t1/2 of (2.206 ± 0.631) and (1.355 ± 0.317) h;cmax of (1504.069 ± 620.885) and (79.043 ± 15.568)μg/L;tmax of (1.000 ± 0.250) and (1.214 ± 0.267) h;AUC0-24 h of (4897.645 ± 2207.577) and (263.475±54.795)μg·h/L;CL of(5.025±2.773)and(76.253±13.986)L/(h·kg). CONCLUSIONS:The method is highly sensi-tive,exclusive,simple,accurate and reliable,and can be applied to study the pharmacokinetic characteristics of paeoniflorin and phillyrin in rats in vivo.