To the present study aimed to investigate the protective effects of Erlong Zuoci Pills on oxidative stress induced by hydrogen peroxide (H2O2) in House Ear Institute-Organ of Corti 1 (HEI-OC1) and to explore the mechanism by cellular metabolomics. There were 6 groups in the experiment: the control group, model group, three dose groups of ELZC (low, medium, and high), and positive control ascorbic acid group. The oxidative stress injury model was established in the HEI-OC1 by inducing 0.9 mmol/L H2O2 for 12 h. The proliferation of HEI-OC1 cells was observed by CCK-8 assay; the contents and activity of lactate hydrogenase (LDH), reactive oxygen species (ROS), and superoxide dismutase (SOD) in HEI-OC1 cells were detected by corresponding kits. Finally, the endogenous substances of cells were analyzed from the perspective of metabolomics. Compared with the model group, ELZC groups could significantly increase the cell proliferation rate after administration. Moreover, they could also ameliorate the increase of ROS and LDH content and the decrease of antioxidant enzyme SOD caused by H2O2. Metabolomic results revealed significant differences among multiple groups in the scores of partial least squares discriminant analysis. The ELZC group could relocate the model group back to the control group. The metabolic regulation of ELZC on oxidative stress in HEI-OC1 cells mainly affects nucleotide metabolism and amino acid metabolism. In summary, the results indicate that ELZC exhibits protective effects on H2O2-induced oxidative stress in HEI-OC1 cells. Additionally, this protective effect may be produced by increasing the content of amino acids such as uridine and phenylalanine, thereby regulating pathways such as pyrimidine metabolism, phenylalanine metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, and histidine metabolism.

ObjectiveTo investigate the correlation between iron metabolism parameters and various syndrome types of unstable angina pectoris （UAP）. MethodsA cross-sectional study was conducted from October 2021 to October 2023， encompassing 213 patients diagnosed with UAP at Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences. Additionally， 30 healthy individuals were selected as control cases. Single-factor analysis was used to investigate the differences in clinical data among different Traditional Chinese Medicine （TCM） syndrome types of UAP and their correlation with iron metabolism indices. The study conducted a comparative analysis of the aforementioned clinical data among patients with and without heat-toxic and blood-stasis syndrome. Logistic regression was used to analyze the correlation between TCM syndrome types and related factors. The receiver operator characteristic （ROC） curve was employed to assess the predictive value of iron metabolism indices， along with their sensitivity and specificity. ResultsCompared to those in the control group， serum iron （SI） and serum ferritin （SF） levels were significantly increased in the UAP group （P<0.01）， while transferrin （TRF） and total iron binding capacity （TIBC） levels were decreased （P<0.01）. However， there was no significant difference in unsaturated iron binding capacity （UIBC）. Multivariate binary Logistic regression analysis identified apolipoprotein A1 （ApoA1）， homocysteine （HCY）， high-sensitivity C-reactive protein （hs-CRP）， and SF as independent influencing factors for the UAP patients （P<0.05， P<0.01）. Additionally， statistically significant differences were observed in SI， SF， TRF， and TIBC among 213 patients with different TCM types （P<0.01）. Patients with heat-toxic and blood-stasis syndrome had higher SI and SF values than those without the syndrome （P<0.01）， while their TIBC and TRF values were lower （P<0.01）. Multivariate binary logistic regression analysis showed that SI and LDL-C levels were closely associated with the differentiation of heat-toxic and blood-stasis syndrome. ConclusionUAP patients often experience iron metabolism disorders， and the heat-toxic and blood-stasis syndrome are significantly correlated with iron metabolism parameters. The SI and LDL-C levels have high specificity and sensitivity in diagnosing heat-toxic and blood-stasis syndrome.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

AIM: To investigate the pharmacokinetic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS / MS. METHODS: An UPLC-MS / MS method was established to simultaneously detect tetrahydropalmatine, nobiletin and costunolide in the plasma and tissues of SD rats. The method was applied to investigate the pharmacokinetic characteristics and tissue distribution. RESULTS: After a single oral administration, the three active components were rapidly absorbed into the body, with a peak concentration (Cmax) of (13.73 ± 7.50), (27.01 ± 17.69) and (6.73 ± 29.94) ng / mL for tetrahydropalmatine, nobiletin, and costunolide, respectively. The time to reach the peak concentration (Tmax) was (1.40 ± 0.93), (0.63 ± 0.28) and (2.38 ± 8.81) h, respectively. The area under the curve (AUC) was (80.43±40.03), (41.30±28.69) and (303.90 ± 136.69) ng · h · mL

Objective:To investigate the predictive value of procalcitonin to platelet ratio (PPR) and C-reactive protein to albumin ratio (CAR) in severe acute pancreatitis (SAP) and the value of SAP and concomitant acute liver injury (ALI).Methods:Total of 195 patients with AP from June 2021 to December 2022 from 374 patients were screened for inclusion in the study and were divided into non-severe acute pancreatitis (NSAP) and SAP groups. The ALI group was divided into non-acute liver injury (NALI) and ALI groups according to ALI criteria, and then into hepatocellular ALI subgroup, cholangiocellular ALI subgroup and mixed ALI subgroup. Laboratory tests for procalcitonin (PCT), C-reactive protein (CRP), albumin and platelet (PLT) were completed within 48 h. Risk factors for SAP, ALI and each subgroup of ALI were analysed by binary logistic regression. Subject work characteristic (ROC) curves were plotted and the optimal thresholds for PPR and CAR were calculated. The predictive value of PPR, CAR and their combination for SAP, ALI and each type of ALI was determined.Results:The AUCs for predicting SAP by plotting ROC curves and calculating the bedside index score of acute pancreatitis severity (BISAP score), PPR, CAR, PPR combined with CAR, PPR combined with BISAP score, CAR combined with BISAP score and combined PPR, CAR and BISAP score were 0.82, 0.85, 0.79 and 0.86. The areas under the ROC curves for PPR, CAR and combined prediction of ALI were 0.81, 0.85 and 0.88, respectively; the areas under the ROC curves for PPR, CAR and combined prediction of hepatocellular ALI were 0.93, 0.77 and 0.92, respectively; and the areas under the ROC curves for PPR, CAR and combined prediction of cholangiocellular ALI were 0.76, 0.76 and 0.77, respectively. The area under the ROC curves for PPR, CAR and combined prediction of mixed ALI were 0.83, 0.76 and 0.82Conclusions:Elevated PPR and CAR are risk factors for SAP and for the development of ALI in AP. PPR has better predictive value than CAR for hepatocellular and mixed ALI, and CAR has better predictive value than PPR for cholangiocellular ALI.

Objective:To investigate the influence of COX-2 expression in hepatocellular carcinoma (HCC) on the infiltration and immune response of conventional type 1 dendritic cells (cDC1).Methods:Clinicopathological data from 111 HCC patients undergoing radical hepatectomy at Peking University People's Hospital from Jan 2016 to Jun 2017 were retrospectively analyzed. Immunofluorescence staining was employed to evaluate the cDC1 infiltration and COX-2 expression in tumor tissues. Patients were divided into two groups based on cDC1 infiltration: cDC1 enrichment and cDC1 depletion, and the correlation between COX-2 expression and cDC1 infiltration was analyzed. Single-cell sequencing of HCC tumor tissues was used to further investigate the correlation between PTGS2, the encoding gene of COX-2, and cDC1 infiltration. Hematopoietic stem cells (HSC) were utilized for in vitro generation of cDC1. HSC-derived cDC1s were sorted by FACS and cocultured with HCC cell line SNU423. Celecoxib, a selective COX-2 inhibitor, was used to suppress the COX-2 expression in HCC cell line SNU423. The functions of cDC1 were explored by FITC-dextran uptake assay, flow cytometry, and Luminex multiplex cytokine assay. Results:COX-2 expression was significantly higher in the cDC1 depletion group ( n=73) compared to the cDC1 enrichment group ( n=38) ( P=0.004 2). Patients with higher PTGS2 expression had significantly lower proportion of cDC1. Increased cDC1 infiltration in the HCC tumor microenvironment correlated with improved patient overall survival rates ( P=0.037) and disease-free survival rates ( P=0.048). Results from FITC-dextran uptake assay, flow cytometry, and Luminex assay indicated that cDC1 co-cultured with HCC showed significantly reduced antigen uptake function, co-stimulatory molecule expression, and cytokine secretion, but partially abrogated with celecoxib treatment. Conclusions:The intratumoral infiltration of cDC1 is positively correlated with favorable prognosis in HCC patients. Elevated COX-2 expression in HCC impedes the intratumoral accumulation of cDC1 and compromises their immune response capabilities. COX-2 inhibitors hold promise for enhancing cDC1 function in HCC.

Objective:To evaluate the risk of HBV recurrence after liver transplantation in patients with end-stage hepatitis B related liver disease, and to explore the indications for antiviral therapy withdrawal.Methods:The data of HBV DNA, cccDNA in liver puncture tissues and peripheral blood in 31 patients after liver transplantation was retrospectively analyzed.Results:Among the 31 patients, 15 (48%) had detectable and quantified HBV DNA in liver biopsy tissue, while their HBV related serological indicators were negative, suggesting an occult HBV infection in some patients. The study found 15 out of 19 cases who were taking Entecavir were cccDNA negative (78.9%), compared to 5 out of 12 cases (41.6%) in Lamivudine regiment ( P=0.03). Conclusions:Hidden HBV infection can be detected by amplifying cccDNA and HBV DNA in liver puncture tissue by using ddPCR. Entecavir is superior to lamivudine in the clearance of cccDNA.

OBJECTIVE: To investigate the predictive value of pancreatitis activity scoring system (PASS) combined with Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) for infected pancreatic necrosis (IPN) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected, including basic information, vital signs at admission, first laboratory indexes within 48 hours of admission. The PASS scores at admission and 24, 48 and 72 hours after admission were calculated. According to the diagnostic criteria of IPN, the patients were divided into the non-IPN group and the IPN group, and the independent risk factors of SAP complicating IPN were determined by using univariate analysis and multifactorial Logistic regression. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of NLR, CRP, and PASS score, alone and in combination for IPN in patients with SAP. RESULTS: A total of 149 SAP patients were enrolled, including 102 in the non-IPN group and 47 in the IPN group. The differences in PASS score at each time point, NLR, CRP, procalcitonin (PCT), blood urea nitrogen, blood chloride, and days of hospitalization between the two groups were statistically significant. Multifactorial Logistic regression analysis showed that 72 hours admission PASS score [odds ratio (OR) = 1.034, 95% confidence interval (95%CI) was 1.005-1.065, P = 0.022], NLR (OR = 1.284, 95%CI was 1.139-1.447, P = 0.000), and CRP (OR = 1.015, 95%CI was 1.006-1.023, P = 0.001) were independent risk factors for IPN in patients with SAP. ROC curve analysis showed that the area under the ROC curve (AUC) of the PASS score at 72 hours of admission, NLR, and CRP alone in predicting IPN in SAP patients were 0.828, 0.771, and 0.701, respectively. The AUC of NLR combined with CRP, PASS combined with NLR, and PASS combined with CRP were 0.818, 0.895, and 0.874, respectively. The combination of PASS score at 72 hours after admission, NLR, and CRP had a better predictive ability for IPN in patients with SAP (AUC = 0.922, 95%CI was 0.877-0.967), and the sensitivity was 72.3% when the cut-off value was 0.539. CONCLUSIONS The predictive value of the PASS score at 72 hours after admission, NLR and CRP in combination for IPN in SAP patients is better than that of the combination of each two and individual detection and has better test efficacy.
Humans ; Pancreatitis, Acute Necrotizing/diagnosis* ; C-Reactive Protein/metabolism* ; Acute Disease ; Neutrophils/metabolism* ; Retrospective Studies ; ROC Curve ; Lymphocytes ; Prognosis

Objective: To observe the effect of the combination of acupuncture and medication on orthostatic hypotension after incomplete cervical spinal cord injury. Methods: Ninety-two patients with orthostatic hypotension after incomplete cervical spinal cord injury were divided into two groups according to the random number table method, with 46 cases in each group. The control group was treated with oral midodrine hydrochloride on the basis of conventional treatment, and the observation group was treated with acupuncture in addition to the intervention used in the control group. Both groups were treated for 4 weeks. The changes in supine and orthostatic blood pressures, motor and sensory scores, quadriplegic function index score, clinical efficacy, and safety evaluation were observed. Results: During the treatment, 2 cases dropped out in the observation group, and 3 cases dropped out in the control group. After 4 weeks of treatment, the clinical efficacy of the observation group was better than that of the control group (P<0.05). After treatment, the supine systolic blood pressure and diastolic blood pressure in the two groups had no significant changes (P>0.05), while the orthostatic systolic blood pressure and diastolic blood pressure, the motor and sensory scores, and the quadriplegic function index score were significantly higher than those before treatment (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). Adverse reactions were mild in both groups. Conclusion: The combination of acupuncture and medication can significantly improve the orthostatic blood pressure, motor and sensory function and daily living ability of patients with orthostatic hypotension after incomplete cervical spinal cord injury, and it is safe and reliable.

OBJECTIVE: To develop and validate a mechanical power (MP)-oriented nomogram prediction model of weaning failure in mechanically ventilated patients. METHODS: Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and were weaned using a T-tube ventilation strategy were collected from the Medical Information Mart for Intensive Care-IV v1.0 (MIMIC-IV v1.0) database. Demographic information and comorbidities, respiratory mechanics parameters 4 hours before the first spontaneous breathing trial (SBT), laboratory parameters preceding the SBT, vital signs and blood gas analysis during SBT, length of intensive care unit (ICU) stay and IMV duration were collected and all eligible patients were enrolled into the model group. Lasso method was used to screen the risk factors affecting weaning outcomes, which were included in the multivariate Logistic regression analysis. R software was used to construct the nomogram prediction model and build the dynamic web page nomogram. The discrimination and accuracy of the nomogram were assessed by receiver operator characteristic curve (ROC curve) and calibration curves, and the clinical validity was assessed by decision curve analysis (DCA). The data of patients undergoing mechanical ventilation hospitalized in ICU of the First People's Hospital of Lianyungang City and the Second People's Hospital of Lianyungang City from November 2021 to October 2022 were prospectively collected to externally validate the model. RESULTS: A total of 3 695 mechanically ventilated patients were included in the model group, and the weaning failure rate was 38.5% (1 421/3 695). Lasso regression analysis finally screened out six variables, including positive end-expiratory pressure (PEEP), MP, dynamic lung compliance (Cdyn), inspired oxygen concentration (FiO₂), length of ICU stay and IMV duration, with coefficients of 0.144, 0.047, -0.032, 0.027, 0.090 and 0.098, respectively. Logistic regression analysis showed that the six variables were all independent risk factors for predicting weaning failure risk [odds ratio (OR) and 95% confidence interval (95%CI) were 1.155 (1.111-1.200), 1.048 (1.031-1.066), 0.968 (0.963-0.974), 1.028 (1.017-1.038), 1.095 (1.076-1.113), and 1.103 (1.070-1.137), all P < 0.01]. The MP-oriented nomogram prediction model of weaning failure in mechanically ventilated patients showed accurate discrimination both in the model group and external validation group, with area under the ROC curve (AUC) and 95%CI of 0.832 (0.819-0.845) and 0.879 (0.833-0.925), respectively. Furthermore, its predictive accuracy was significantly higher than that of individual indicators such as MP, Cdyn, and PEEP. Calibration curves showed good correlation between predicted and observed outcomes. DCA indicated that the nomogram model had high net benefits, and was clinically beneficial. CONCLUSIONS The MP-oriented nomogram prediction model of weaning failure accurately predicts the risk of weaning failure in mechanical ventilation patients and provides valuable information for clinicians making decisions on weaning.
Humans ; Respiration, Artificial/methods* ; Ventilator Weaning/methods* ; Nomograms ; Lung ; Risk Factors