ObjectiveTo construct a nomogram prediction model for non-valvular persistent atrial fibrillation （PeAF） patients with left ventricular hypertrophy （LVH） ， followed by prognostic analysis through follow-up. MethodsThis study retrospectively enrolled 949 patients with newly diagnosed and hospitalized non-valvular PeAF. Among them， 403 patients presented with LVH. The cohort was randomly stratified into a training set （n=665） and a validation set （n=284）. Univariate and multivariate Logistic regression analyses were employed to identify independent risk factors for PeAF complicated by LVH. A nomogram prediction model was subsequently constructed and evaluated for discriminative ability， calibration， and clinical utility using receiver operating characteristic （ROC） curve analysis， calibration plots， and decision curve analysis （DCA）. ResultsSeven independent risk factors were ultimately identified and included in the prediction model： female sex， hypertension， diabetes， red blood cell distribution width-SD （RDW-SD）， body mass index （BMI）， left atrial diameter （LAD）， and left ventricular ejection fraction （LVEF）. The area under the ROC curve （AUC） in the training set was 0.862 （95% CI： 0.834-0.890）， and in the validation set， it was 0.870 （95% CI： 0.829-0.911）， demonstrating excellent predictive performance. ConclusionIndependent risk factors for LVH in PeAF patients include female， hypertension， diabetes， RDW-SD， BMI， LAD， and LVEF. The prediction model built based on this can help early identification of PeAF patients with high risk of LVH. At the same time， the incidence of major adverse cardiovascular events （MACE） is higher in PeAF patients with LVH. Patients with atrial fibrillation combined with LVH may benefit from catheter ablation.

Houpo Sanwutang， included in the Catalogue of Ancient Classical Prescriptions （Second Batch）， was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining， statistical analysis， and data processing， combined with modern articles， this study employed bibliometrics to investigate the historical origin， composition， decoction methods， clinical application， and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty， it is recommended that 110.4 g Magnolia Officinalis Cortex， 55.2 g Rhei Radix et Rhizoma， and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first， and 1 000 mL should be taken from the decocted liquid. Following this， Rhei Radix et Rhizoma should be added for further decoction， and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL， and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi， relieving stuffiness and fullness， removing food stagnation， and regulating bowels. It can be used in treating abdominal distending pain， guarding， constipation， and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

Ochratoxin A (OTA) is ubiquitous in the food and feed fields. It has strong hepatotoxicity and nephrotoxicity, seriously threatening the health of humans and animals. Enzymatic degradation of mycotoxins is considered to be a promising method to control mycotoxin contaminations. In this study, a new ochratoxin A amidohydrolase from Microbulbifer thermotolerans (MiADH) was obtained. After heterologous expression in Escherichia coli and purification, the recombinant protein was studied regarding the hydrolysis activity, hydrolysis products, enzymatic properties, and substrate binding mode. MiADH can degrade OTA into ochratoxin α (OTα) and phenylalanine, demonstrating a detoxifying ability. It demonstrated the best performance at 70 ℃ and pH 8.0, and Cu²⁺ had the strongest inhibitory effect on the activity of MiADH. MiADH with good thermal stability exhibited huge potential for industrial application. Rational design guided by three-dimensional structural models and substrate docking analysis revealed the important amino acids affecting substrate binding and obtained multiple mutants with improved activity. Among these mutants, V324A had the highest activity, which was 4.2-fold that of the wild type. The identification of MiADH enriches the ochratoxin A degradation enzyme library and provides a new candidate enzyme for the biological detoxification of ochratoxin A in the food and feed industry.
Amidohydrolases/chemistry* ; Ochratoxins/metabolism* ; Substrate Specificity ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Actinomycetales/genetics*

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

OBJECTIVE To establish a method for determining the content of multiple components in Astragalus membranaceus,compare the content differences of Astragalus membranaceus in different regions and with different extraction methods in Gansu,and e-valuate the quality of Astragalus membranaceus from different origins of Gansu.METHODS Astragalus membranaceus samples from 40 origins in Gansu were collected on site.The content of Astragaloside Ⅳ,Calycosin-7-O-β-D-glucopyranoside,Ononin,Form-ononetin and Calycosin was determined by HPLC external standard method,and the quality differences of Astragalus membranaceus from 40 origins of Gansu were analyzed by combining bar graphs and line graphs.RESULTS Weiyuan County and Min County of Dingxi City showed high Astragaloside Ⅳ content in both extraction methods,indicating that the Astragalus membranaceus in these two regions has advantages in Astragaloside Ⅳ as an active component;for Calycosin-7-O-β-D-glucopyranoside and Ononin,although the performance of different regions in different extraction methods was different,in general,Weiyuan County and Min County of Dingxi City and Longnan City showed high content in both extraction methods.Water extraction method was more conducive to the extraction of Calycosin-7-O-β-D-glucopyranoside and Ononin,while alcohol extraction method was more conducive to the extraction of Astragalo-side Ⅳ,Calycosin and Ononin.CONCLUSION The content of chemical components of Astragalus membranaceus from different ori-gins is quite different,and the choice of extraction method has a significant effect on the content of active components,while the change trend of different compounds in the two extraction methods is basically the same.The established HPLC multi-component content de-termination method of Astragalus membranaceus is stable and reliable,which can provide a scientific basis for the quality control and comprehensive evaluation of Astragalus membranaceus medicinal materials.

Objective To evaluate the clinical effects of cast post and cores with traction design in coronal extrusion of upper anterior teeth with subgingival fracture.Methods Twenty-five upper anterior teeth with subgingival fracture were treated by root canal therapy,then cast post and cores with traction design and composite resin crown restorations were made for orthodontic extrusion.Position reten-tion and gingival margin modification were performed before crown restoration of these teeth.The correlation between extrusion length and extrusion time was evaluated,as well as the correlation between extrusion length and migration distance in coronal direction about the gingival margin.Crown-root ratio and post-root ratio below the alveolar crest was evaluated after the crown restorations were finished.Evaluation of restoration effects was carried out in 3,6,12 months follow-up period.Results Root resorption began to appear on one tooth at six weeks;the remaining 24 teeth were migrated to target position and prosthesis were finished.There was a positive correlation between the extrusion length(x)and extrusion time(y1),also between the extrusion length(x)and migration distance in coronal di-rection about the gingival margin(y2)by statistical analysis.There was no significant difference(P＞0.05)between the extrusion teeth and compared teeth on crown-root ratio.More than 1/2 of the ratio between the length of post to the length of root below the alveolar crest.The prognostic stability was satisfied in 3,6,12 months follow-up period.Conclusion There are satisfactory clinical application effects of cast post and cores with traction design in coronal extrusion of upper anterior teeth with subgingival fracture.

Objective To explore the expression changes of KIAA1199 and Linc00673 genes in non-small cell lung cancer patients before and after chemotherapy,and to further evaluate the potential value of these two genes as molecular markers in predicting chemotherapy efficacy.Methods A total of 58 patients with stage Ⅲ-ⅣNSCLC admitted to the Third Hospital of Shijiazhuang and Fengfeng General Hospital of North China Medical Health Group from August 2019 to August 2021 were selected.Peripheral blood PBMCs were collected from patients 2 days before treatment and after two cycles of treatment to detect the expression levels of KIAA1199 and Linc00673 genes.The chemotherapy efficacy of patients was statistically analyzed,and the value of KIAA1199 and Linc00673 genes as molecular markers in predicting chemotherapy efficacy was assessed using ROC curve analysis.Results After 2 cycles of chemotherapy,20 out of 58 patients showed disease progression,accounting for 34.48%.qPCR results showed no statistically significant difference in the expression levels of KIAA1199 and Linc00673 genes between progressed and non-progressed patients before treatment(P>0.05).After treatment,the expression levels of KIAA1199 and Linc00673 genes were significantly lower in non-progressed patients compared to progressed patients(P<0.01).ROC curve analysis showed that the AUC of combined detection was significantly higher than that of KIAA1199 gene and Linc00673 gene alone(Z=3.054,5.178,P<0.05).Conclusion In NSCLC patients undergoing chemotherapy,the expression of KIAA1199 and Linc00673 genes shows significant differences based on therapeutic efficacy,with KIAA1199 being more suitable as a biomarker for predicting chemotherapy efficacy.

Objective To investigate the expression and clinical value of long non-coding RNA GAS5(lncRNA GAS5)and matrix metalloproteinase 9(MMP9)in the serum of patients with non-small cell lung cancer(NSCLC).Methods A total of 115 NSCLC patients who were treated in our hospital from December 2018 to December 2019 were collected as the NSCLC group.Based on prognosis,they were grouped into a survival group of 94 cases and a death group of 21 cases;another 115 volunteers who were physically healthy in our hospital during the same period were selected as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)was applied to measure serum lncRNA GAS5 level;Enzyme linked immunosorbent assay(ELISA)was applied to measure serum MMP9 level;Pearson was applied to analyze the correlation between serum lncRNA GAS5 level and MMP9 level in NSCLC patients;receiver operating characteristic curve(ROC)was applied to evaluate the value of serum lncRNA GAS5 and MMP9 levels in the diagnosis of NSCLC;multivariate Cox regression was applied to analyze the influencing factors of prognosis in NSCLC patients.Results Compared with the control group,the serum lncRNA GAS5 level in the NSCLC group obviously decreased,while the MMP9 level obviously increased(P＜0.05);a negative correlation between serum lncRNA GAS5 level and MMP9 level in NSCLC patients(r=-0.523,P＜0.05);the levels of serum lncRNA GAS5 and MMP9 were correlated with tumor diameter,TNM staging,and lymph node metastasis(P＜0.05);the area under the curve(AUC)of serum lncRNA GAS5 and MMP9 levels for diagnosing NSCLC was 0.842 and 0.916,respectively,the AUC of the combined diagnosis of the two was 0.952,which was superior to their individual diagnoses(Z=3.904 and 1.982,P＜0.05);the serum lncRNA GAS5 level in the death group was obviously lower than that in the survival group,while the serum MMP9 level in the death group was obviously higher than that in the survival group(P＜0.05);Multivariate Cox regression analysis showed that high levels of lncRNAGAS5 were independent protective factors for poor prognosis in NSCLC while high levels of MMP9 and lymph node metastasis Migration is an independent risk factor for poor prognosis in NSCLC(P＜0.05).Conclusion The serum lncRNA GAS5 level is significantly reduced and MMP9 level is significantly increased in NSCLC patients,both of which have certain potential value in the clinical diagnosis of NSCLC and are factors affecting the poor prognosis of NSCLC.