OBJECTIVE To evaluate the anticoagulant efficacy and safety of nafamostat mesylate （NM） in the treatment of uremic patients at high risk of bleeding undergoing continuous veno-venous hemofiltration （CVVH） with different methods （pre- dilution and post-dilution）. METHODS A total of 130 uremic patients at high risk of bleeding who underwent CVVH treatment in the nephrology department of Chongqing University Three Gorges Hospital from July 2023 to September 2024 were selected. They were divided into pre-dilution group and post-dilution group according to the random number table method， with 65 cases in each group. Both groups of patients received CVVH treatment under NM anticoagulation. The pre-dilution group adopted the pre-dilution replacement method， while the post-dilution group adopted the post-dilution replacement method. The coagulation， pressure， and usage duration of the filter and dialysis circuit venous reservoirs were compared between the two groups. The changes in prothrombin time （PT）， prothrombin time-international normalized ratio （PT-INR）， activated partial thromboplastin time （APTT）， and fibrinogen （FIB） in the peripheral venous blood before the heparin pump and after the filter at 1， 4 and 7 h of CVVH treatment， as well as 20 min after the end of treatment， were compared between the two groups. The single-compartment urea clearance rate （spKt/V）， β2-microglobulin （β2-MG） clearance rate and the incidence of adverse reactions were duni2007@foxmail.com compared between the two groups. RESULTS Both the pre-dilution and post-dilution groups had 60 patients who completed the study. The incidence of grade Ⅱ-Ⅲ coagulation of the filter and venous reservoirs， as well as the number of patients with transmembrane and venous pressure alarm intervention in the post- dilution group were significantly higher or more than those in the pre-dilution group （P＜0.05）， while usage time of the filter and the pipeline in the post-dilution group was significantly shorter than that in the pre-dilution group （P＜0.05）. The APTT values before the heparin pump as well as PT and APTT values after the filter at 1 h， 4 h， and 7 h of CVVH treatment in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There were no significant differences in PT， PT- INR， APTT and FIB between the two groups of patients 20 min after the end of treatment （P＞0.05）. The spKt/v and β2-MG clearance rates in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS When NM is used as an anticoagulant in the CVVH treatment of uremic patients at high risk of bleeding， compared with the pre-dilution treatment method， the post-dilution treatment method has a higher incidence of filter and dialysis tubing venous reservoir， a shorter usage time of the filter and pipeline， and a greater impact on extracorporeal coagulation， but has a higher solute clearance rate. Clinically， different dilution methods can be selected according to the different treatment needs of patients.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Brain-computer interface (BCI) has high application value in the field of healthcare. However, in practical clinical applications, convenience and system performance should be considered in the use of BCI. Wearable BCIs are generally with high convenience, but their performance in real-life scenario needs to be evaluated. This study proposed a wearable steady-state visual evoked potential (SSVEP)-based BCI system equipped with a small-sized electroencephalogram (EEG) collector and a high-performance training-free decoding algorithm. Ten healthy subjects participated in the test of BCI system under simplified experimental preparation. The results showed that the average classification accuracy of this BCI was 94.10% for 40 targets, and there was no significant difference compared to the dataset collected under the laboratory condition. The system achieved a maximum information transfer rate (ITR) of 115.25 bit/min with 8-channel signal and 98.49 bit/min with 4-channel signal, indicating that the 4-channel solution can be used as an option for the few-channel BCI. Overall, this wearable SSVEP-BCI can achieve good performance in real-life scenario, which helps to promote BCI technology in clinical practice.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual/physiology* ; Electroencephalography ; Wearable Electronic Devices ; Algorithms ; Signal Processing, Computer-Assisted ; Adult ; Male

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To verify the efficacy of a domestic human DNA quantification kit based on real-time fluorescence quantitative PCR in detecting the total human DNA concentration,male DNA concen-tration in mixed male/female DNA samples,the degree of DNA degradation and inhibitor tolerance.Methods Samples with different concentrations,different male/female ratios,different concentrations of inhibitors,and different degradation degrees were tested using the domestic human DNA quantification kit based on real-time fluorescence quantitative PCR.This kit was compared with a similar product on the market and was applied to the detection of DNA from real cases.Results This human DNA quan-tification kit can effectively detect human DNA as low as 0.001 65 ng/μL,and 6.25 pg/μL of male DNA in mixed samples with a male-to-female ratio of 1∶15 000.Even when the sample contains as high as 400 ng/μL of humic acid or 1 000 μmol/L of hemin alone,the DNA concentration can still be accurately detected.The degradation index can effectively characterize the degradation degree of the sample.This kit has been successfully applied in forensic practice.Conclusion This human DNA quan-tification kit is accurate and reliable in detection.It can accurately reflect the degradation of DNA and inhibitor tolerance.It has good performance in quantitative accuracy,determination of the male/female ratio in mixed samples,and inhibitor tolerance.It has application potential in forensic case examination.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the clinical significance of constructing a nomogram based on a combined model of clinical-pathological-imaging data for predicting postoperative recurrence/metastasis of breast cancer.Meth-ods:A retrospective study was conducted on 194 breast cancer patients who were admitted to the department of breast and thyroid surgery from June 2019 to June 2022.unvariate and multivariate Logistic regression analyses were used to screen independent predictors of postoperative recurrence/metastasis of breast cancer,and a model was con-structed based on the independent predictors.Another 83 breast cancer patients from July 2022 to February 2023 were taken as the validation set to verify the model with the ratio of 7∶3(training set∶validation set).Results:The postopera-tive recurrence/metastasis rate of breast cancer was 29.90％.Ki-67 expression level ≥20％,tumor location in the inner upper quadrant and outer upper quadrant,lesion size ≥20 mm,multiple lesions,and BI-RADS grade of 5 were indepen-dent risk factors for postoperative recurrence/metastasis of breast cancer(P＜0.05).PR positive expression was an inde-pendent protective factor for postoperative recurrence/metastasis of breast cancer(P＜0.05).The diagnostic performance of the combined clinical-pathological-imaging model(AUC:0.900)was superior to that of the clinical-pathological pa-rameters(AUC:0.655)and the MRI parameter model(AUC:0.857).In its nomogram model constructed based on a com-bined clinical-pathological-imaging model to predict breast cancer recurrence/metastasis after surgery,the AUC in the training set was 0.900(95％CI:0.859～0.942)with good discrimination,the maximum Yoden value was 0.710,the sensi-tivity was 0.931,and the specificity was 0.779,and the AUC in the validation set was 0.820(95％C/:0.712～0.928),well differentiated,with a maximum Yoden value of 0.554,a sensitivity of 0.630,and a specificity of 0.914.The theoretical and actual values of the calibration curves of the two sets were in good agreement,and the decision curve indicated the net benefit of the breast cancer recurrence-metastasis prediction model after surgery,which showed good predictive ability.Conclusion:The nomogram constructed based on the combined model of clinical-pathological-imaging data has good predictive ability,accuracy,and clinical applicability,which is helpful for clinicians to evaluate the risk of postoperative re-currence/metastasis of breast cancer.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.