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.

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

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 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 compare the application effect of remote intelligent rehabilitation system and conventional rehabilitation in rehabilitation of patients with rotator cuff injury following minimally invasive arthroscopic surgery.Methods:A retrospective cohort study was used to analyze the clinical data of 47 patients with rotator cuff injury admitted to Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January to July 2022, including 18 males and 29 females; aged 45-65 years [(56.7±6.3)years]. All patients underwent minimally invasive arthroscopic surgical repair of rotator cuff rupture. After surgery, 25 patients underwent self-rehabilitation with conventional education (conventional rehabilitation group), and 22 patients underwent systematic rehabilitation with remote intelligent rehabilitation system (remote rehabilitation group). Constant shoulder score, University of California at Los Angeles (UCLA) shoulder score, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score and visual analog score (VAS) were compared between the two groups on the day of admission, 4, 8, 12 weeks after surgery and at the last follow-up. Shoulder MRI was applied at 6 weeks after surgery to compare the degree of intra-articular effusion and bone marrow edema between the two groups. The shoulder range of motion of the two groups was compared at 12 weeks after operation. The satisfaction with the rehabilitation of the two groups was compared at the last follow-up.Results:All the patients were followed up for 6-10 months [(8.5±2.2)months]. There was no significant difference in Constant shoulder score, UCLA shoulder score, SAS score, SDS score and VAS between the two groups on the day of admission (all P>0.05). There was no significant difference in Constant score, UCLA score and SAS score between the two groups at 4 weeks after surgery (all P>0.05). The values of SDS score and VAS at 4 weeks after surgery were (31.8±6.6)points and (3.6±1.1)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(40.5±5.6)points and (4.7±1.3)points] (all P<0.05). The values of Constant score, UCLA score, SAS score, SDS score and VAS at 8 weeks after surgery were (62.5±5.5)points, (18.5±3.3)points, (20.5±4.7)points, (22.5±4.6)points and (2.5±0.6)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(41.3±4.7)points, (15.3±3.1)points, (28.5±4.8)points, (38.5±3.7)points and (3.3±1.3)points] ( P<0.05 or 0.01). The values of Constant score, UCLA score, SAS score and SDS score at 12 weeks after surgery were (85.4±6.4)points, (32.2±3.8)points, (13.6±2.8)points and (18.4±3.9)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(60.3±6.7)points, (25.2±4.1)points, (21.5±4.9)points and (26.7±6.6)points] (all P<0.05), while there was no significant difference in VAS between the two groups ( P>0.05). At the last follow-up, there were no significant differences in Constant score, UCLA score, SAS score, SDS score and VAS between the two groups (all P>0.05). MRI of the shoulder joint at 6 weeks after surgery indicated that the degree of intra-articular effusion in the shoulder joint and bone marrow edema of the proximal humerus in the remote rehabilitation group was significantly reduced than that in the conventional rehabilitation group. At 12 weeks after surgery, the remote rehabilitation group had better shoulder range of motion than the conventional rehabilitation group ( P<0.05 or 0.01). At the last follow-up, the satisfaction with the rehabilitation of the remote rehabilitation group was better than that of the conventional rehabilitation group ( P<0.01). Conclusion:For patients with rotator cuff injury who undergo minimally invasive arthroscopic surgery, postoperative application of remote intelligent rehabilitation system, in comparison with the conventional rehabilitation system, can help to facilitate shoulder function recovery, anxiety and depression improvement and pain relief in the early stage, reduce shoulder soft tissue and bone marrow edema of the shoulder, and increase shoulder range of motion and patients′ satisfaction with the rehabilitation.

Objective:To analyze the long-term cumulative survival and tumor-free survival of hepatocellular carcinoma (HCC) patients after liver transplantation, as well as the influencing factors.Methods:We conducted a retrospective study on 228 HCC patients receiving liver transplantation from May 1, 2000 to May 1, 2012 at the Department of Hepatobiliary Surgery, Peking University People's Hospital. A total of 166 patients met the recruit criteria. The patients' perioperative data and follow-up data were collected. We analyzed the cumulative survival and tumor-free survival of the recipients, as well as the influencing factors.Results:The 1-, 5- and 10-year cumulative survival of the 166 HCC patients were 80.7%, 52.4% and 45.8%, respectively, while the 1-, 5- and 10-year tumor-free survival of these patients were 60.2%, 47.6% and 44.0%, respectively. Among these patients,a total of 96 recipients met the University of California, San Francisco (UCSF) criteria, whose 1-, 5- and 10-year cumulative survival were 83.3%, 66.7%, and 59.4%, respectively, and tumor-free survival were 74.0%, 62.5% and 57.3%, respectively. Multivariate analysis showed that beyond the UCSF criteria, alpha fetoprotein (AFP) ≥ 400 ng/ml before transplantation and poorly differentiated carcinoma were independent factors affecting cumulative survival and tumor-free survival ( P < 0.05). Conclusions:Liver transplantation is an effective treatment of HCC. Besides the size and the number of the tumors, AFP ≥ 400 ng/ml before transplantation and poorly differentiated tumors are independent factors affecting the long-term cumulative survival and tumor-free survival of HCC patients.