ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

A 72-year-old patient with quadricuspid aortic valve underwent transcatheter aortic valve replacement due to severe valve stenosis accompanied by moderate insufficiency. As initially planned, the right coronary artery was protected during the procedure. However, after the artificial valve was released, the left coronary artery was found to be blocked, so a coronary protection stent was implanted in the left coronary artery ostium under the guidance of intravascular ultrasonography. This case indicates that for patients with a quadricuspid aortic valve undergoing transcatheter aortic valve replacement, in addition to preoperative measurement of the aortic root, attention should also be paid to the coronary artery obstruction caused by the displacement of the artificial valve frame during the procedure.
Aged ; Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Coronary Vessels ; Stents ; Transcatheter Aortic Valve Replacement/methods*

BACKGROUND: Lung cancer is one of the most common malignant tumors worldwide and a major cause of cancer-related deaths. Early-stage lung cancer is often manifested as pulmonary nodules, and accurate assessment of the malignancy risk is crucial for prolonging survival and avoiding overtreatment. This study aims to construct a model based on image feature parameters automatically extracted by artificial intelligence (AI) to evaluate its effectiveness in predicting the malignancy of part-solid nodule (PSN). METHODS: This retrospective study analyzed 229 PSN from 222 patients who underwent pulmonary nodule resection at Lanzhou University Second Hospital between October 2020 and February 2025. According to pathological results, 45 cases of benign lesions and precursor glandular lesion were categorized into the non-malignant group, and 184 cases of pulmonary malignancies were categorized into the malignant group. All patients underwent preoperative chest computed tomography (CT), and AI software was used to extract imaging feature parameters. Univariate analysis was used to screen significant variables; variance inflation factor (VIF) was calculated to exclude highly collinear variables, and LASSO regression was further applied to identify key features. Multivariate Logistic regression was used to determine independent risk factors. Based on the selected variables, five models were constructed: Logistic regression, random forest, XGBoost, LightGBM, and support vector machine (SVM). Receiver operating characteristic (ROC) curves were used to assess the performance of the models. RESULTS: The independent risk factors for the malignancy of PSN include roughness (ngtdm), dependence variance (gldm), and short run low gray-level emphasis (glrlm). Logistic regression achieved area under the curves ( AUCs) of 0.86 and 0.89 in the training and testing sets, respectively, showing good performance. XGBoost had AUCs of 0.78 and 0.77, respectively, demonstrating relatively balanced performance, but with lower accuracy. SVM showed an AUC of 0.93 in the training set, which decreased to 0.80 in the testing set, indicating overfitting. LightGBM performed excellently in the training set with an AUC of 0.94, but its performance declined in the testing set, with an AUC of 0.88. In contrast, random forest demonstrated stable performance in both the training and testing sets, with AUCs of 0.89 and 0.91, respectively, exhibiting high stability and excellent generalizability. CONCLUSIONS The random forest model constructed based on independent risk factors demonstrated the best performance in predicting the malignancy of PSN and could provide effective auxiliary predictions for clinicians, supporting individualized treatment decisions.
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Humans ; Male ; Female ; Lung Neoplasms/pathology* ; Middle Aged ; Retrospective Studies ; Artificial Intelligence ; Aged ; Tomography, X-Ray Computed ; Adult ; Solitary Pulmonary Nodule/diagnostic imaging* ; ROC Curve

Objective:To explore the clinical, imaging, and pathological features of glottic squamous cell carcinoma of the larynx and their relationship with prognosis. Methods:A retrospective analysis was conducted on the clinical, imaging, and pathological data of 130 patients with glottic squamous cell carcinoma of the larynx who were treated at the First People's Hospital of Yinchuan and the General Hospital of Ningxia Medical University from January 2018 to March 2023. Imaging examinations （CT and MRI） were used to evaluate the lesion boundary clarity, density, enhancement nature, and enhancement degree. Postoperative pathological examination was used to determine the pathological nature, immunohistochemistry, etc. Statistical methods such as χ² test, Spearman correlation analysis, multivariate logistic regression analysis, and Kaplan-Meier method were used to analyze the data. Results:Among the 130 patients, 127 were male and 3 were female, with an average age of （61.92±9.595） years. There was a correlation between clinical, imaging, and pathological features. Multivariate analysis showed that heterogeneous MRI density （OR=12.414;P=0.019） and squamous cell carcinoma as a subtype were correlated. The initial symptom of non-hoarseness （HR=6.045;P=0.010） and unclear MRI boundary （HR=12.559; P=0.029） were independent risk factors for poor prognosis in patients with glottic squamous cell carcinoma of the larynx. Conclusion:There is a correlation between the clinical, imaging, and pathological features of patients with glottic squamous cell carcinoma of the larynx, and they can affect prognosis. The initial symptom of non-hoarseness and unclear MRI boundary of the tumor are independent risk factors for poor prognosis.
Humans ; Laryngeal Neoplasms/diagnosis* ; Prognosis ; Male ; Female ; Retrospective Studies ; Middle Aged ; Carcinoma, Squamous Cell/diagnosis* ; Magnetic Resonance Imaging ; Glottis/pathology* ; Tomography, X-Ray Computed ; Aged

Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

ObjectiveTo observe the efficacy of Huoxue Jiedu Formulas （活血解毒方药， HJF） as an adjunctive treatement for patients with binding of stasis and toxin syndrome during the vulnerable period after acute myocardial infarction （AMI） percutaneous coronary intervention （PCI） surgery， and to explore its potential mechanism from the perspective of serum neutrophil extracellular traps （NETs）. MethodsA total of 129 patients with binding of stasis and toxin syndrome within 6 months after PCI for AMI were enrolled and divided into a treatment group （65 cases） and a control group （64 cases） based on patients' willingness to take Chinese herbal medicine. The control group received standard western medical therapy alone， while the treatment group additionally received HJF， one dose daily. Both groups were treated for four weeks. Before and after treatment， TCM syndrome scores were assessed. Seattle angina questionnaire （SAQ） was used to record angina stability and frequency scores， while the short form-36 health survey （SF-36） was employed to assess quality of life across eight dimensions， including physical functioning， role-physical， bodily pain， general health， vitality， social functioning， role-emotional， and mental health. The Pittsburgh sleep quality index （PSQI） was used to evaluate sleep quality， and the patient health questionnaire-15 （PHQ-15） was used to assess psychosomatic symptoms； Duke activity status index （DASI） was used to measure daily physical activity. Serum levels of neutrophil extracellular traps （NET） markers including myeloperoxidase-DNA （MPO-DNA）， neutrophil elastase-DNA （NE-DNA）， and citrullinated histone H3 （CitH3） were measured in 20 patients from the treatment group. ResultsAfter treatment， TCM syndrome score， PSQI score and PHQ-15 score in both groups significantly decreased， while DASI score， angina stability and frequency scores， and all eight dimensions of the SF-36 scale significantly increased （P＜0.05）. Compared to the control group， the treatment group had significantly lower TCM syndrome scores and significantly higher DASI， angina stability and frequency scores （P＜0.05）， as well as higher scores in the SF-36 dimensions of physical functioning， role-physical， social functioning， bodily pain， and vitality （P＜0.05）. After treatment， serum levels of MPO-DNA， CitH3， and NE-DNA in the treatment group were significantly reduced （P＜0.05）. ConclusionHJF combined with conventional therapy can significantly improve angina symptoms， TCM syndrome scores， and psychosomatic conditions in patients with binding of stasis and toxin syndrome during the vulnerable period after AMI. It also enhances quality of life， sleep quality， and daily physical activity. The underlying mechanism may be associated with the inhibition of serum NETs level.

Objective To explore the effect of muscle energy technique(MET)on dynamic posture control and lumbar neuromuscu-lar function in patients with non-specific low back pain. Methods From March to June,2022,30 college students with non-specific low back pain from Shandong Sport Universi-ty were randomly divided into control group(n=15)and intervention group(n=15).The control group received health education,and the intervention group received MET,for four weeks.They were assessed with Visual Ana-logue Scale(VAS)of pain,Oswestry Disability Index(ODI),Y-balance test and trunk flexion-relaxation test be-fore and after intervention. Results VAS scores decreased in both groups after intervention(|t|>2.449,P<0.05),and it was less in the intervention group than in the control group(t=-5.068,P<0.001);while ODI score decreased in the intervention group(t=4.785,P<0.001),and it was less in the intervention group than in the control group(t=-2.895,P=0.007);the performance of Y-balance test increased(t=-3.662,P=0.003)in the intervention group,as well as flexion-re-laxation ratio of multifidus(t=-2.460,P=0.029). Conclusion MET is effective on alleviating pain and lumbar dysfunction,improving dynamic posture control and en-hancing the function of the multifidus during flexion in patients with non-specific low back pain.

Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.

ObjectiveTo observe the clinical efficacy and relative mechanism of the Modified Wenshen Yixin Formula （温肾益心方加减， MWYF） as an auxiliary treatment of coronary heart disease （CHD） complicated with hypothyroidism of spleen-kidney yang deficiency. MethodsA total of 135 CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency were included and divided into control group （67 cases） and experimental group （68 cases） according to the patients' wishes of herbal medicine administration. The control group was given conventional western medicine， while the treatment group was additionally given MWYF， 1 dose per day； both groups were treated for 8 weeks. The traditional Chinese medicine （TCM） syndrome scores， angina scores， SF-36 scores， thyroid function indicators including thyroid stimulating hormone （TSH）， thyroxine （T4） and triiodothyronine （T3）， as well as serum cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， monocyte chemoattractant ligand 2 （CCL2）， and tumor necrosis factor-related activator protein （CD40L） levels before and after treatment were compared between the two groups. The dosage and reduction and discontinuation rate of thyroid hormone preparations after treatment were compared between the two groups. The effectiveness regarding TCM syndrome and angina pectoris was evaluated， and the safety was assessed. ResultsBias was adjusted by matching on propensity score， and 102 cases were finally included in the statistical analysis， with 51 cases in each group. The total effective rate regarding TCM syndrome ［94.12% （48/51） versus 64.71% （33/51）］， the total effective rate regarding angina pectoris ［80.39% （41/51） versus 62.75% （32/51）］， and the reduction and discontinuation rate of thyroid hormone preparation ［39.21% （20/51） versus 5.88% （3/51）］ were significantly higher in the experimental group than those in the control group （P＜0.05 or P＜0.01）. After treatment， the total TCM syndrome score， individual scores of major symptoms ， the major symptoms score， the secondary symptoms score， angina pectoris score， and TSH level were significantly reduced （P＜0.01）， while all dimensions of SF-36 scores， T4， T3， and cAMP levels significantly increased in both groups （P＜0.05 or P＜0.01）. The dosage of thyroid hormone preparations and the levels of cGMP， CCL2， and CD40L in the experimental group significantly decreased after treatment （P＜0.01）. When compared between the two groups after treatment， the total TCM syndrome score， the major symptoms score， the scores of individual major symptom （chest tightness， chest pain， fear of cold， cold limbs， waist and kness soreness and weakness）， the secondary symptoms score， angina pectoris score， TSH， cGMP， CCL2， and CD40L levels of the experimental group were significantly lower than those of the control group （P＜0.05 or P＜0.01）， while all dimension scores of SF-36， T4， T3， and cAMP levels were significantly higher （P＜0.01）. A total of three adverse events occurred during treatment， none of which were judged to be related to the interventions of this study. ConclusionMWYF can significantly ameliorate the TCM syndrome， angina pectoris， quality of life and thyroid function in CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency， and can promote the reduction and disconti-nuation of thyroid hormone preparations. The mechanism may be related to the regulation of cAMP/cGMP balance， the regulation of hypothalamic-pituitary-thyroid metabolic axis and the reduction of immune inflammation.