Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

OBJECTIVES: To evaluate the inhibitory effect of oridonin against proliferation of pancreatic cancer cells and the mechanism underlying the synergistic effect of low-intensity pulsed ultrasound (LIPUS). METHODS: PANC-1 cells treated with different concentrations of oridonin were examined for changes in cell proliferation using CCK-8 assay and in MDA, GSH and ATP levels using flow cytometry. The protein expressions of GPX4, Nrf2 and HO-1 in the treated cells were detected with Western blotting. The effect of Fer-1, a ferroptosis inhibitor, on proliferation of oridonin-treated cells were assessed, and the effects of oridonin combined with LIPUS on PIEZO1 protein expression was evalauted using Western blotting. A C57BL/6J mouse model bearing pancreatic cancer cell xenograft was established and treated with oridonin, LIPUS, or both, and the histological changes in the tumor tissues and tumor cell proliferation were examined with HE staining and immunohistochemistry for Ki67; the changes in GPX4 expression in the tumor tissues were detected using Western blotting and immunofluorescence staining. RESULTS: In PANC-1 cells, oridonin treatment significantly inhibited cell proliferation, increased intracellular Fe²⁺, ROS, and MDA levels, and decreased GSH and ATP levels. Oridonin also resulted in lowered GPX4 and increased HO-1 and Nrf2 protein expression levels in the cells. The combined treatment with LIPUS signficiantly enhanced the inhibitory effect of oridonin on PANC-1 cell viability in vitro and on xenograft growth in the mouse models, resulting also in more obvious reduction of the intensity of Ki67 staining and GPX4 protein expression and more pronounced increase of PIEZO1 protein expression in the tumor tissues in the mouse models. CONCLUSIONS LIPUS enhances the effect of oridonin to promote ferroptosis of pancreatic cancer cells by activating PIEZO1 through the Nrf2/HO-1/GPX4 pathway.
Ferroptosis/drug effects* ; Animals ; Pancreatic Neoplasms/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Cell Line, Tumor ; Mice ; Heme Oxygenase-1/metabolism* ; Diterpenes, Kaurane/pharmacology* ; Cell Proliferation/drug effects* ; Mice, Inbred C57BL ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ion Channels/metabolism* ; Ultrasonic Waves ; Signal Transduction

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Objective To observe the clinical efficacy of therapy focusing on regulating spleen and stomach for the treatment of acoustic hypersensitivity(AH),which also named as auditory hyperaesthesia,and to explore the relevant factors influencing the efficacy.Methods From January 2018 to December 2023,the patients admitted to the outpatient department of otolaryngology-head and neck surgery of the First Affiliated Hospital of Guangzhou University of Chinese Medicine and diagnosed as AH with complete medical data were included as study subjects.Follow-up through telephone or network was carried out for those patients who with uncertain prognosis.The changes in the pre-and post-treatment scores of Indicators of Acoustic Hypersensitivity Severity(IAHS)were used as the reference index for efficacy evaluation,and the cure rate and effective rate were used as the efficacy analysis indexes for statistical analysis.And then the efficacy of traditional Chinese medicine(TCM)medical care combined with health care focusing on regulating spleen and stomach for the treatment of AH was evaluated.Furthermore,multivariate logistic regression was used to explore the relevant factors influencing the efficacy of AH.Results A total of 298 cases of AH patients meeting the inclusion criteria were collected,among which 151 cases(50.67%)were cured,22 cases(7.38%)were markedly effective,75 cases(25.17%)were effective,and 50 cases(16.78%)were ineffective,with a total effective rate of 83.22%(248/298).The univariate analysis results showed that eight factors(including post-treatment lifestyle score,range of lifestyle adjustment,severity of AH,duration of the disease,presence of tinnitus,presence of hearing drop,presence of vertigo,and age)had an influence on the efficacy,and the differences were statistically significant(P<0.05 or P<0.01).However,the factors of gender,occupation,education level,and history of noise exposure had no influence on the efficacy(P>0.05).The multivariate binary logistic regression analysis showed that five factors,namely post-treatment lifestyle score,range of lifestyle adjustment,severity of AH,presence of vertigo and duration of the disease,had a significant correlation with the cure rate of AH(P<0.05 or P<0.01),and four factors,namely post-treatment lifestyle score,severity of AH,range of lifestyle adjustment and age,had a significant correlation with the effective rate of AH(P<0.05 or P<0.01).Conclusion The method of TCM medical care and health care focusing on regulating spleen and stomach exerts a better efficacy for AH patients.And the lifestyle,severity of AH,duration of the disease,age,and presence of vertigo are the relevant factors affecting the outcomes,which is worthy of further in-depth study.

Objective To summarize the whole process comprehensive management experience in transfemoral aortic valve replacement(TF-TAVR)using self-expanding valve in 79 patients with pure native aortic valve regurgitation(PNAR).Methods The nursing team adopted a multi-team collaboration approach.Preoperative nursing assessment and full preparation,enhanced psychological support,and sleep management were carefully carried out;during the operation,nurses well cooperated with doctor,implemented predictive care and intervention for possible complications;and after surgery the hemodynamics and respiratory functions were closely monitored to promptly detect and manage the complications,and to implement the infection prevention cluster management process and discharge preparation services.Besides,the comprehensive management measures throughout the entire process,the occurrence of complications and corresponding nursing responses,as well as the six-minute walk test before and after the operation were recorded.The Discharge Readiness Scale was used to evaluate the implementation of patient discharge readiness services so as to check the implementation effect of the comprehensive whole process management measures.Results Through the implementation of comprehensive whole process management measures,the surgery-related ventricular fibrillation and cardiac arrest obtained accurate and timely treatment,no newly-developed complications such as deep vein thrombosis of lower limbs occurred.Through the implementation of infection cluster nursing measures,the incidence of pulmonary infection in patients decreased from 52.00％in the early stage of carrying out the management measures to 9.26％.Through the implementation of discharge preparation services and continuous quality improvement,the left ventricular ejection fraction(LVEF)value in 64 patients receiving successful TAVR increased from(44.06±5.51)％to(54.67±5.20)％,and the difference was statistically significant(t=19.634,P＜0.001).On the day of discharge,the six-minute walk test distance increased from preoperative(131.39±39.36)meters to postoperative(180.77±29.72)meters,and the difference was statistically significant(t=10.898,P＜0.001).The average self-assessment score of discharge readiness of patients was(7.33±1.41)points.All patients were well recovered when discharged from hospital.Conclusion According to the different surgical key points and the difficult problems,full and effective implementation of comprehensive whole process management measures can ensure that the PNAR patients are able to smoothly pass through the perioperative period and obtain a satisfactory recovery after receiving TF-TAVR.

Objective To investigate the plasma level of interleukin-31(IL-31)in patients with pulmonary arterial hypertension(PAH)and its clinical relevance.Methods The patients who were diagnosed as PAH in Zhongshan Hospital,Fudan University from January 1,2021 to December 30,2023(PAH group)and the healthy people in the same period(control group)were selected.The clinical data and follow-up records were collected.Plasma levels of IL-31,IL-1β,IL-6,IL-10,IL-12p70,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation test was used to evaluate the correlations between IL-31 and right cardiac catheterization parameters,echocardiography parameters and blood indices in patients with PAH.Cox proportional hazard model was used to analyze the prognostic factors of patients in PAH group.Results A total of 50 patients with PAH and 22 healthy controls were included.There was no significant difference in age,gender,body mass index and left ventricular ejection fraction between the two groups.Compared with the control group,the plasma level of IL-31 in the PAH group was significantly higher(168.82[149.14,177.26]pg/mL vs 152.76[145.58,159.41]pg/mL,P=0.001).Pearson correlation test showed that the plasma level of IL-31 in PAH patient was positively correlated with mean pulmonary artery pressure(r=0.652,P＜0.001)and pulmonary vascular resistance(r=0.651,P＜0.001),but was negatively correlated with tricuspid annular plane systolic excursion(r=-0.496,P＜0.001).Cox proportional hazard model showed that higher plasma level of IL-31 was an independent predictor of readmission for heart failure/all-cause mortality in patients with PAH(HR=1.130,95％CI 1.052-1.214,P=0.001).Conclusions Plasma level of IL-31 may be significantly increased in patients with PAH and be positively correlated with the severity of PAH,and elevated level of IL-31 is predictive of poor prognosis in PAH patients.

Objective Polymorphic microsatellite markers developed for Apodemus peninsulae can enrich its genetic data and lay a foundation for genetic quality control and gene mapping.Methods Microsatellite loci were screened based on the genome sequence of Apodemus peninsulae,and microsatellite primers were identified.The genetic diversity of the population was analyzed by multiplex PCR.Results Thirty microsatellite markers were successfully developed and evaluated using 60 samples of Apodemus peninsulae.A total of 152 alleles were detected,with an average of 5.067 alleles per locus.The average observed heterozygosity was 0.592.The average Shannon index was 1.265.The average polymorphism information content was 0.598.Conclusions Based on the microsatellite loci developed in this study,the genetic diversity of Apodemus peninsulae can be effectively analyzed,laying a foundation for establishing genetic quality standards and detection method.

ObjectiveTo demonstrate the long-term effect of Yishi Therapy for primary tinnitus and analyze the factors affecting the effectiveness. MethodsWe conducted long-term follow-ups of primary tinnitus cases treated with Yishi Therapy during 1 January 2017 to 30 June 2023 by face-to-face， online and telephone between 1 July 2023 and 31 January 2024， to understand the final regression of primary tinnitus and lifestyle changes. We retrospectively analysed the basic data of patients before treatment， and statistically analysed the recovery rate and overall effective rate of tinnitus treated by the Yishi Therapy， and the factors affecting the effectiveness such as lifestyle， age， duration of disease， gender， tinnitus location， severity of tinnitus， accompanying symptoms and complications on the overall effective rate. ResultsA total of 496 cases of primary tinnitus completed follow-ups successfully， and the total Tinnitus Evaluation Questionnaire （TEQ） at follow-up was significantly lower than that before treatment （P＜0.001）. Among the 496 cases， 101 （20.36%） cases cured， 189 （38.10%） cases showed significant improvement， 116 （23.39%） cases were effective， 90 （18.15%） cases were ineffective， and the overall effect rate was 81.85% （406/496）. At follow-up， the score of lifestyle was higher than that before treatment （P＜0.001）. Grouped by the score of lifestyle at follow-up， the effective rates of better lifestyle group and poor lifestyle group were 97.53% （237/243） and 66.80% （169/253）， respectively， with statistical significance （P＜0.001）. Grouped by the mean value of the difference in lifestyle scores before and after treatment， the effective rates of the group with greater lifestyle adjustment and the group with smaller adjustment were 97.55% （239/245） and 66.53% （167/251）， respectively， and the differences were statistically significant （P＜0.001）. Binary logistic regression showed that the better lifestyle， the greater lifestyle adjustment and the severity of tinnitus were positively correlated with the total effective rate of tinnitus （P＜0.001）， while older and hearing loss were negatively correlated with the total effective rate of tinnitus （P＜0.05）. ConclusionYishi Therapy on primary tinnitus shows good long-term effect， lifestyle， severity of tinnitus， hearing loss or not， age are the relevant factors affecting the efficacy of tinnitus， lifestyle is the main factor affecting clinical efficacy.

[Objective]The clinical characteristics and the possible risk factors were explored for the low triiodothyronine syndrome(LTS)in elderly patients with chronic heart failure(CHF),and the risk prediction model of LTS was established.[Methods]For this research,291 elderly patients with CHF were selected as sample and retrospectively reviewed was used as analytical method.According to the thyroid function of admission patients,two groups including LTS group(n=107)and normal thyroid function group(n=184)were divided.The general information and biochemical indicators of patients were collected and recorded,and the risk factors for LTS were assigned scores,in which numerical variables(except age)were grouped by median.The chi-squared test was used for statistical analysis of each variable,and multivariate regression model was used to analyze the independent risk factors of LTS in elderly patients with CHF,then the nomogram model for LTS was established based on the results from the final regression analysis.Furthermore,the prediction model was evaluated using C-index,calibration curve and receiver operating characteristic(ROC)curve.[Result]Serum creatinine(Scr),C-reactive protein(CRP),interleukin-6(IL-6)and the cardiac functional grading according to the New York Heart Association(NYHA)were positively correlated with LTS(OR values were 1.893,2.356,1.021 and 1.815,respectively,P<0.05),serum Albumin(Alb)was negatively correlated with LTS(OR=0.412,P<0.05).This means that,the LTS was easily occurred as the serum Alb level declined.When introduce the above statistically significant variables into nomogram obtained the C index with 0.807[95%CI=(0.757,0.856)].The calibration curve verified by internal verification showed that the calibration degree of this prediction model was well calibrated.ROC curve analysis showed that the prediction model was well differentiated.[Conclusion]The Scr,CRP,IL-6,Alb and cardiac functional grading in elderly CHF patients may be risk factors for incidence of LTS,while serum Alb may be a protective factor for LTS.Based on the above risk factors,the nomogram model for predicting the occurrence of LTS in elderly CHF patients had good differentiation and accuracy,and can provide guidance for clinical individualized prevention and treatment.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.