The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Screening carbonyl reductases with the ability to catalyze the reduction of complex carbonyl compounds is of great significance for the biosynthesis of R-tolvaptan(R-TVP). In this study, the target carbonyl reductase in the crude enzyme extract of rabbit liver was separated, purified, and identified by ammonium sulfate precipitation, gel-filtration chromatography, ion exchange chromatography, affinity chromatography, and protein mass spectrometry. With the rabbit liver genome as the template, the gene encoding the carbonyl reductase rlsr5 was amplified by PCR and the recombinant strain was successfully constructed. After RLSR5 was purified by affinity chromatography, its enzymatic properties were characterized. The results indicated that the gene sequence of rlsr5 was 972 bp, encoding a protein with a molecular weight of 40 kDa. RLSR5 was a dimeric protein, and each monomer was composed of a (α/β)₈-barrel structure. RLSR5 could asymmetrically reduce 7-chloro-1-[2-methyl-4-[(2- methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (prochiral ketone, PK) to synthesize R-TVP. The specific activity of the enzyme was 36.64 U/mg, and the optical purity of the product was 99%. This enzyme showcased the optimal performance at pH 6.0 and 30 °C. It was independent of metal ions, with the activity enhanced by Mn²⁺. This study lays a foundation for the biosynthesis of tolvaptan of optical grade.
Animals ; Rabbits ; Alcohol Oxidoreductases/biosynthesis* ; Recombinant Proteins/metabolism* ; Escherichia coli/metabolism* ; Liver/enzymology*

A qualitative analysis by high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was performed for the identification of main constituents in Gentiana veitchiorum. High-performance liquid chromatography (HPLC) was developed for the quantification of seven major components, including loganic acid (1), swertiamarin (2), gentiopicroside (3), sweroside (4), isoorientin (5), isoscoparin (6), and gentiournoside A (7). A total of 42 compounds, including 31 flavonoids, and 11 Iridoids, were identified based on their retention behaviors, and MS fragment information. Furthermore, regression equations for these seven chemical components were established, with good linear relationships (r2 > 0.9999), and the sample recovery rate was 97.02%-103.08%. This method was successfully applied for simultaneous determination of seven components in 7 batches of G. veitchiorum samples by HPLC-UV method. The method established in this study is simple and reliable, capable of qualitatively and quantitatively analyzing the main chemical components of G. veitchiorum, and is applicable to its quality evaluation.

Objective:To establish and validate a nomogram for predicting the probability of central lymph node metastasis (CLNM) by evaluating risk factors in clinical N 0(cN 0) stage patients with iisolated papillary thyroid carcinoma of isthmus (PTCI). Methods:Retrospectively analyzed the clinicopathological data of 112 PTCI patients who underwent surgical treatment at Lianyungang Municipal Oriental Hospital between January 2019 and December 2024. There were 35 males and 77 females, with an average age of (47.2±12.6) years, ranging from 28 to 71 years. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for CLNM. Nomogram method was used to build the transfer risk prediction model and verify it.Results:The study enrolled 112 patients, with 42 cases (37.5%) exhibiting CLNM. ROC curve analysis demonstrated that tumor diameter predicted CLNM with an AUC of 0.781 (95% CI: 0.694-0.868), identifying an optimal cutoff value of 0.9 cm (sensitivity: 0.762, specificity: 0.700). Multivariate logistic regression revealed that CLNM was independently associated with age, tumor diameter, capsular invasion, and Hashimoto′s thyroiditis (HT), all P<0.05. The logistic regression analysis results were used to construct the nomogram model of CLNM risk prediction. Hosmer lemeshow test resulted χ2=6.876, P=0.442. The calibration curves of the model group and the validation group were basically close, with an average absolute error of 0.065, P=0.099. ROC curve analysis showed that the best cut-off value of nomogram was 160 points, C-index was 0.849 (95% CI: 0.771-0.927), sensitivity was 0.786, specificity was 0.729. Decision curve analysis (DCA) based on net benefit and threshold probability shows that the nomogram can obtain net benefit in a large threshold probability range (0.13-1.00). Temporary recurrent laryngeal nerve injury occurred in 5 patients (4.5%). Temporary parathyroid injury occurred in 4 cases (3.6%), all of which were normal within one month. Conclusions:For patients with cN 0 stage isolated PTCI, CLNM is related to age ≤45 years, tumor diameter>0.9 cm, envelope invasion and HT. HT is a protective factor for CLNM. The ROC curve, calibration curve and DCA curve verified internally showed that the nomogram obtained had good discrimination ability, calibration ability and clinical applicability. When the total score ≥ 160 points indicates that the risk of CLNM is increased.

Objective:To evaluate the clinical efficacy of Sanren Decoction combined with triple therapy in the treatment of Hp-related chronic atrophic gastritis (CAG).Methods:A randomized controlled trial was conducted. A total of 118 patients with Hp-related CAG admitted to Department of Spleen and Stomach Diseases of Xi'an Affiliated Hospital of Shaanxi University of Chinese Medicine from February 2021 to February 2023 were selected as observation subjects, and were divided into two groups according to random number table method, with 59 cases in each group. The control group received triple therapy (amoxicillin+clarithromycin+omeprazole), whereas the observation group was combined with modified Sanren Decoction on the basis of the control group. Both groups were continuously treated for 10 days. TCM symptoms were scored before and after treatment. Updated Sydney System (UAS) was applied to evaluate the gastric mucosal lesions. ELISA was applied to detect serum levels of cluster of differentiation 47 (CD47), VEGF and pepsinogenⅠ/pepsinogen Ⅱ (PGⅠ/PGⅡ). The Hp infection status was evaluated by Urea Breath Test (UBT). In addition, the adverse reactions were observed and recorded during treatment.Results:After treatment, the scores of gastric fullness, stomachache, acid reflux and bitter taste in observation group were lower than those in the control group ( t=4.52, 3.46, 4.34, 4.83, P<0.01), and the scores of gastric mucosal inflammation, atrophy, intestinal metaplasia and dysplasia were also lower compared to control group ( t=3.68, 2.88, 3.73, 4.45, P<0.01 or P<0.05). After treatment, the levels of serum CD47 [(4.46±1.29) μg/L vs. (5.01±1.37) μg/L, t=2.25] and VEGF [(70.53±10.47) ng/L vs. (79.34±10.56) ng/L, t=4.55] in observation group were lower ( P<0.05 or P<0.01), while the level of PGⅠ/PGⅡ [(12.45±1.78) vs. (10.82±1.62), t=5.20] was higher compared with that of the control group ( P<0.01). After treatment, the negative conversion rate of Hp was 96.61% (57/59) in observation group and that in control group was 81.36% (48/59) ( χ2=7.00, P=0.008). During treatment, the incidence of adverse reactions was 23.73% (14/59) in observation group and 15.25% (9/59) in control group, revealing no statistical significance between the two groups ( χ2=1.35, P=0.245). Conclusion:Modified Sanren Decoction combined with triple therapy can improve gastric mucosal lesions, reduce serum CD47 and VEGF levels, and increase PGⅠ/PGⅡ ratio and Hp negative conversion rate in patients with Hp-related CAG, with good safety.

Pancreatic cancer is a common malignant tumor of the digestive system,with a low early diagnosis rate,a high surgical mortality rate,a low cure rate,and a poor overall prognosis.In recent years,with the continuous development of artificial intelligence in the medical field,artificial intelligence techniques,such as machine learning and deep learning,have been widely used in medical research.This article reviews the application of artificial intelligence techniques in the screening,diagnosis,treatment,complications,and prognosis prediction of pancreatic cancer,so as to provide a basis and new ideas for the application of artificial intelligence in the diagnosis and treatment of pancreatic cancer.

In order to understand the current status of the knowledge, attitude and practice (KAP) about prevention and control of COVID -19 in college students, and to provide theoretical basis for prevention and control work in college campus. This study investigated the KAP of COVID -19 of 1 847 college students in Shaanxi province by questionnaire using the convenience sampling method. Chisquare test and multivariate logistic regression analysis were used to analyze the influencing factors for the KAP of COVID -19. The results demonstrated that 48.3% of the students had a higher knowledge level of COVID -19, 11.7% had a fear attitude and 39.6% had good protective practices. Logistic regression results showed that female and urban household college students had higher cognitive level of COVID -19. The college students with anxiety state were more likely to have fear attitude. Students of female, urban household, anxiety, higher cognition and fear attitude showed better protective practices. The above results indicated that the knowledge level of COVID -19 in college students are not enough, and the attitude and protective practices need to be further improved. Therefore, relevant departments should follow the rules of KAP, carry out targeted propaganda and education on COVID -19 for college students, to improve their ability to cope with public health emergencies.

Ischemic stroke （IS） is a serious cerebrovascular disease common in clinical practice. Targeting the pathogenesis of IS， intravenous thrombolysis for restoring blood flow is still the most effective therapy. However， intravenous thrombolysis has shortcomings such as increased bleeding risk， narrow therapeutic window， and contraindications， which limited its clinical application. Protection of the ischemic brain tissue before full recovery of blood flow is associated with the prognosis of IS. Studies have identified multiple pathways in the alleviation of the brain injury caused by IS， such as the mammalian target of rapamycin （mTOR） signaling pathway. Traditional Chinese medicine （TCM） has abundant therapies and unique advantages in the treatment of IS， especially in alleviating symptoms and improving the quality of life of patients. After the onset of IS， TCM can be integrated with Western medicine to play a role in the whole process of treatment， rehabilitation， and recurrence prevention as soon as possible， thus maximizing patient benefits. TCM has clinical significance for the recovery of neurological and motor functions after IS. Studies have shown that TCM can reduce the cerebral injury caused by IS by regulating and activating the mTOR signaling pathway， thereby regulating autophagy， inhibiting apoptosis of nerve cells， and reducing oxidative stress and inflammation. TCM exerts a positive effect for achieving cerebral protection and improving the prognosis of IS and provides new ideas for the prevention and treatment of IS. This article introduces the role of the mTOR signaling pathway in the pathogenesis of IS and reviews the research progress in the TCM regulation of this pathway in the treatment of IS， aiming to provide new therapeutic ideas and systematic scientific reference for the treatment of IS with TCM.

Objective:To evaluate the clinical value of cognitive and motor function in predicting conversion to neurodegenerative disorders in patients with isolated rapid eye movement sleep behavior disorder (iRBD).Methods:Forty-seven patients with iRBD were collected from the Department of Neurology of Tianjin Medical University General Hospital and Tianjin Medical University General Hospital Airport Site during October 2018 and June 2022. All participants received comprehensive evaluations of cognitive and motor function at baseline. The visuospatial function was evaluated by Rey-Osterrieth Complex Figure Test (ROCF)-copy, the memory function was evaluated by Auditory Verbal Learning Test and ROCF-recall, the attention-executive function was evaluated by Trail Making Test (TMT) and Stroop Color-Word Test, and the language function was evaluated by Boston Naming Test. The motor function was evaluated by Unified Parkinson′s Disease Rating Scale-Ⅲ, Alternate-tap Test (ATT), and 3-meter Timed Up and Go Test. The iRBD patients with phenoconversion were identified during follow-up. Receiver operating characteristic curve and generalized linear model Logistic regression were applied to identify the optimal combination of cognitive and motor tests in distinguishing the converters from non-converters in patients with iRBD. Multivariate Cox regression analyses were applied to evaluate the independent risk factors in predicting conversion to neurodegenerative diseases in patients with iRBD.Results:The median follow-up duration was 3 years. Forty-five iRBD patients were included in the analysis eventually, as 2 dropped out at follow-up. Twenty-one iRBD patients developed neurodegenerative disorders, with 14 presenting motor phenotype and 7 cognitive phenotype. Baseline ROCF-copy, TMT-A and ATT were best combination in identifying iRBD patients with phenoconversion [sensitivity: 90.0%, specificity: 87.5%, area under curve (AUC): 0.931, P<0.001]. Baseline TMT-A and ATT were best combination in identifying iRBD patients with motor phenotype conversion (sensitivity: 100.0%, specificity: 66.7%, AUC: 0.872, P<0.001); Baseline TMT-A performed best in identifying iRBD patients with cognitive phenotype conversion (sensitivity: 83.3%, specificity: 91.7%, AUC: 0.917, P<0.001). Multivariate Cox regression analysis showed that individuals with poorer performance of TMT-A (cut-off value: 63.0 s) and ATT (cut-off value: 205.5 taps/min) than the cut-off values at baseline had higher risks for developing to neurodegenerative disorders, with HR values of 5.455 (95% CI 1.243-23.941, P=0.025) and 11.279 (95% CI 1.485-85.646, P=0.019), respectively. Conclusions:In iRBD, ROCF-copy, TMT-A and ATT served as optimum combination in predicting phenoconversion, whereas TMT-A and ATT served as optimum combination in predicting motor phenotype, and TMT-A performed best in predicting cognitive phenotype. The performance in TMT-A and ATT in iRBD could predict the risk of developing to neurodegenerative disorders independently.

Objective To simulate the microflow field environment between the anastomotic nail surface and intestinal wall tissue after implantation and to study the effect of hydrophobic surfaces on the flow rate of extracellular fluid and the fluid shear force on the wall to regulate bacterial adhesion through changes in the flow field.Methods The microstructure of shark skin was observed,and a simplified two-dimensional(2D)movement model of bacteria in a microflow field was established.Using computational fluid dynamics(CFD)numerical simulation,the movement of bacteria on a smooth surface and micro-textured surface in a static and dynamic flow field were simulated.The flow field characteristics around bacteria and the magnitude of fluid shear force under the two surface environments were compared,and the internal mechanism of the fluid shear force affecting bacterial adhesion was analyzed.Results The addition of the biomimetic microtexture enhanced the flow rate of the extracellular fluid in the microflow field,and the fluid had little viscous effect on the bacteria in the static flow field.The fluid in the dynamic flow field had a stronger pushing effect on the bacteria.The fluid shear force on the microtextured wall increased when the pit width was within a specific range.Conclusions The bionic micro-textured surface of the anastomotic nail can accelerate the flow rate of extracellular fluid,increase the fluid shear force of micro-textured walls and bacteria,and influence bacterial adhesion.These result provide a theoretical basis for studying bacteriostatic surfaces of anastomotic nails.