Aim To investigate the effect of discoidin domain receptor 1(DDR1)on high glucose induced endothelial cell dysfunction and the underlying mecha-nism.Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and divided in-to the control group and high glucose induction group(HG).HUVECs were treated with 33 mmol·L-1 D-glucose for 48 hours to construct endothelial dysfunc-tion.Pyroptosis was detected using propidium iodide staining(PI);lactate dehydrogenase(LDH)and IL-1β,IL-18 levels were determined using enzyme linked immunosorbent assay(ELISA);the expression of DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related proteinses were detected using Western blot.Subsequently,the experiment was divid-ed into the control group,HG group,HG+DDR1 NC group,and HG+DDR1 siRNA group.The effect of high glucose on the proliferation and migration of HU-VECs was observed after transfection with DDR1 siR-NA for 24 hours;ELISA was used to detect the endo-thelial nitric oxide synthase(eNOS),vascular cell ad-hesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),as well as LDH,IL-1β,IL-18 levels;PI was employed to detect pyroptosis;Western blot was applied to detect DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related pro-teins.Results Compared with the control group,HG group decreased eNOS content,increased VCAM-1 and ICAM-1 contents,decreased cell viability and migration ability,and significantly increased the expressions of DDR1,p-NF-κB,NLRP3 and pyroptosis related pro-teins.The levels of LDH,IL-1β,IL-18 and the rate of pyroptosis significantly increased(P＜0.05).Com-pared with HG group,DDR1 siRNA could promote the secretion of eNOS,decrease the levels of VCAM-1,ICAM-1,LDH,IL-1β and IL-1 8,increase cell viability and migration ability,reduce the expression of p-NF-κB,NLRP3 and pyroptosis related proteins,and inhibit high glucose-induced pyroptosis of HUVECs(P＜0.05).Conclusions Gene silencing DDR1 can im-prove vascular endothelial cell dysfunction induced by high glucose,and the mechanism is related to the inhi-bition of NF-κB/NLRP3 signaling pathway mediated pyroptosis.

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.
Animals ; Humans ; Medicine, Chinese Traditional/adverse effects* ; Cardiotoxicity ; Induced Pluripotent Stem Cells ; Arrhythmias, Cardiac/chemically induced* ; Myocytes, Cardiac ; Organoids ; Drugs, Chinese Herbal/adverse effects*

OBJECTIVE: To explore the rules of acupoint selection for aphasia treated with acupuncture and moxibustion using data mining technology. METHODS: From January 1, 2000 to April 1, 2022, the articles for clinical researches of acupuncture and moxibustion for aphasia published in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase were searched. Using Microsoft Excel 2021, the database was set up to analyze the use frequency of acupoint, meridian tropism, acupoint distribution and the use of specific points. SPSS26.0 was adopted for factor analysis, SPSS Modeler 18.0 was for association rule analysis of prescriptions, and Gephi 0.9.5 was to plot the co-occurrence network diagrams of acupoints and meridians. RESULTS: A total of 140 articles were collated, including 146 acupuncture and moxibustion prescriptions and 189 acupoints. The total use frequency of these acupoints was 1 211. Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Baihui (GV 20) and Yamen (GV 15) were the top 5 acupoints of the high use frequency for aphasia treated with acupuncture and moxibustion. Among 189 acupoints collected, the extra points and empirical points were mostly selected. The top 3 involved meridians were the governor vessel, the gallbladder meridian of foot-shaoyang and the conception vessel. These acupoints were mostly distributed on the head, face and neck region. The use frequency of five-shu points was the highest among the specific points. The acupoint combinations of high frequency referred to Yuye (EX-HN 13)-Jinjin (EX-HN 12), Yuye (EX-HN 13)-Lianquan (CV 23)-Jinjin (EX-HN 12), and Fengchi (GB 20)-Yuye (EX-HN 13)-Jinjin (EX-HN 12). Factor analysis extracted 10 common factors for acupoint compatibility in treatment of aphasia with acupuncture and moxibustion. CONCLUSION In clinical treatment of aphasia with acupuncture and moxibustion, the local acupoints are preferred. The core acupoints include Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Baihui (GV 20) and Yamen (GV 15). The acupoint prescription is modified flexibly according to syndrome differentiation to enhance the therapeutic effect.
Humans ; Moxibustion ; Acupuncture Points ; Acupuncture Therapy ; Meridians ; Data Mining ; Aphasia/therapy*

OBJECTIVE: The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies. METHODS: Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations. RESULTS: HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%-6.93%. Patients who were admitted to the liver disease-related departments (a OR = 10.76; 95% CI, 10.27-11.28), Internal Medicine (a OR = 2.87; 95% CI, 2.75-3.00), and Department of Surgery (a OR = 1.95; 95% CI, 1.87-2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older (a OR = 2.74; 95% CI, 2.69-2.80), testing in infetious disease hospitals (a OR = 2.33; 95% CI, 2.26-2.40) and secondary hospitals (a OR = 1.72; 95% CI, 1.69-1.75). Patients in sentinel hospitals of the Northeast (a OR = 12.75; 95% CI, 12.40-13.11), the Central (a OR = 1.65; 95% CI, 1.61-1.70), and the West (a OR = 1.78; 95% CI, 1.73-1.83) China had higher HCV prevalence than those who were in the Eastern coastal area. CONCLUSION Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.
Humans ; Middle Aged ; Prevalence ; Hepatitis C/complications* ; Hepacivirus ; Hospitals ; Hepatitis C Antibodies ; China/epidemiology* ; Risk Factors

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.
Medicine, Tibetan Traditional ; Reproducibility of Results

OBJECTIVES: To investigate local cerebral blood perfusion in preterm infants with bronchopulmonary dysplasia (BPD) based on cerebral blood flow (CBF) values of arterial spin labeling (ASL). METHODS: A prospective study was conducted on 90 preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g who were born in the Department of Obstetrics and admitted to the Department of Neonatology in the Third Affiliated Hospital of Zhengzhou University from August 2021 to June 2022. All of the infants underwent cranial MRI and ASL at the corrected gestational age of 35-40 weeks. According to the presence or absence of BPD, they were divided into a BPD group with 45 infants and a non-BPD group with 45 infants. The two groups were compared in terms of the CBF values of the same regions of interest (frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, and basal ganglia) on ASL image. RESULTS: Compared with the non-BPD group, the BPD group had a significantly lower 1-minute Apgar score, a significantly longer duration of assisted ventilation, and a significantly higher incidence rate of fetal distress (P<0.05). After control for the confounding factors such as corrected age and age at the time of cranial MRI by multiple linear regression analysis, compared with the non-BPD group, the BPD group still had higher CBF values of the frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, and thalamus at both sides (P<0.05). CONCLUSIONS BPD can increase cerebral blood perfusion in preterm infants, which might be associated with hypoxia and a long duration of assisted ventilation in the early stage.
Infant ; Pregnancy ; Female ; Infant, Newborn ; Humans ; Infant, Premature ; Bronchopulmonary Dysplasia/epidemiology* ; Prospective Studies ; Gestational Age ; Cerebrovascular Circulation

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective To investigate the occurrence and clinical characteristics of the adverse reactions of hyperammonemic encephalopathy caused by sodium valproate and provide reference for the safe clinical use of the drug.Methods CNKI,WanFang Data,VIP,PubMed and Web of Science databases were electronically searched to collect case reports on valproate-induced hyperammonemic encephalopathy from the inception to March 2023.The extracted data was conducted for statistical analysis.Results A total of 37 documents with 41 patients were finally included.Among them,28 patients(68.3%)were males and 13 patients(31.7%)were females,aged 5 to 78 years,the median age was 41 years;most of the patients had no underlying diseases but the blood ammonia concentrations of them were abnormally high in laboratory tests,and the main clinical manifestations were neurological impairment such as cognitive impairment,drowsiness,coma and other disorders of consciousness.After drug discontinuation,drug switch and symptomatic treatment,they gradually recovered consciousness and the blood ammonia concentrations returned to normal.Conclusion It is not easy to recognize and detect the high blood ammonia encephalopathy caused by the application of sodium valproate in clinical practice,so the clinical performance and blood concentration of this drug should be closely monitored,and once the abnormalities are detected,patients should be treated symptomatically in time to ensure the safety of the drug use.

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
Animals ; Anxiety/etiology* ; Chronic Pain/etiology* ; GABAergic Neurons ; Gyrus Cinguli/metabolism* ; Hyperalgesia/metabolism* ; Pancreatitis, Chronic/pathology* ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Trinitrobenzenesulfonic Acid/toxicity*