Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

OBJECTIVE To investigate the ameliorative effects of Coptidis Rhizoma-Ophiopogonis Radix herb pair （HLMD） in rats with type 2 diabetes mellitus （T2DM） and its potential mechanisms.METHODS Male Wistar rats were randomly divided into a control group （6 rats） and a model induction group （30 rats）. The T2DM rat model was established by feeding a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The successfully modeled rats were subsequently divided into the model group， the metformin group （200 mg/kg）， and the low-， medium-， and high-dose HLMD groups （100， 200 and 400 mg/kg， respectively）， with six rats in each group. Rats in each group were administered the corresponding drug solution or normal saline by oral gavage once daily for six consecutive weeks. Body weight， fasting blood glucose （FBG）， the area under the curve （AUC） of the oral glucose tolerance test， serum lipid profiles [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， and inflammatory cytokine [interleukin-6 （IL-6）， IL-1β， tumor necrosis factor-α （TNF-α）， and IL-10] levels were measured. Histopathological changes in liver and pancreatic tissues， as well as hepatic lipid accumulation， were evaluated. Changes in gut microbiota composition were analyzed in the control， model， and high-dose HLMD groups. Network pharmacology and molecular docking analyses were performed to identify potential therapeutic targets of HLMD against T2DM， followed by experimental validation.RESULTS Compared with the model group， the body weight generally recovered in rats in all HLMD dose groups， while FBG levels consistently decreased. Histopathological abnormalities， including disrupted pancreatic islet architecture， disorganized hepatocyte arrangement， hepatic cord necrosis， and lipid accumulation， were alleviated to varying degrees. AUC （except for the low-dose group）， levels of TC， TG， LDL-C， IL-6（except for the low-dose group）， IL-1β and TNF-α， Simpson and Shannon indices， as well as the relative abundances of Firmicutes， Proteobacteria， and Clostridium were significantly reduced； meanwhile， the levels of HDL-C（except for the low-dose group） and IL-10 （except for the low-dose group）， as well as the relative abundances of Bacteroidota and Ligilactobacillus were significantly increased （ P ＜0.05）. Network pharmacology and molecular docking analyses suggested that the active constituents of HLMD， including quercetin， adenosine， oleanolic acid， stigmasterol， and ophiopogonin D′， may exert antidiabetic effects by targeting key proteins such as protein kinase B1（Akt1）， TNF， IL-6， P53 and IL-1β. Experimental validation further demonstrated that HLMD significantly downregulated the protein expressions of P53 （except for the low-dose group）， IL-6 （except for the low-dose group）， IL-1β and TNF-α in the liver tissues of T2DM rats （ P ＜0.05）.CONCLUSIONS HLMD alleviates glucose and lipid metabolism disorders， attenuates inflammatory responses， and ameliorates hepatic and pancreatic tissue damage in T2DM rats. These beneficial effects may be associated with the modulation of gut microbiota composition and the downregulation of inflammation-related targets， including P53， IL-6， IL-1β and TNF-α.

Objective To analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the Integrative Epidemiology Unit (IEU) database in August 2023, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratio (OR), and sensitivity analyses were performed to ensure the accuracy of the results. Results Neuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.

OBJECTIVE: To characterize a glycosyltransferase (RpUGT1) from Rheum palmatum and investigate its specificity toward flavonoid compounds. METHODS: The RpUGT1 was expressed in Escherichia coli and screened for catalytic activity against a range of flavonoid substrates using a high-throughput HPLC assay method. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to determine the structure of the product. Homology modeling, molecular docking analyses and site-directed mutagenesis studies were conducted to identify key residues responsible for its function. RESULTS: The recombinant RpUGT1 protein exhibited catalytic activity towards various flavonoids. Notably, RpUGT1 catalyzed the glycosylation of isorhamnetin to form 3-O-glucoside and kaempferol to form 7-O-glucoside, utilizing uridine diphosphate (UDP) glucose as the sugar donor. The homology modeling and molecular docking analyses identified key residues responsible for its activity. Subsequent site-directed mutagenesis studies highlighted the crucial role of K307 in catalysis. CONCLUSION These discoveries offer valuable perspectives on the role of the UGT family and establish a groundwork for forthcoming research on the synthesis of flavonoids in plants.

Right ventricular-pulmonary artery coupling(RVPAC)refers to the relationship between right ventricular contractility and afterload.Normal RVPAC is maintained only when right ventricular function and pulmonary vascular resistance are appropriately matched.When right ventricular contractility cannot increase to match afterload,thus resulting in right ventricular dysfunction.RVPAC plays an important role in pathophysiology and progression of many cardiovascular diseases,which is crucial for the prognosis of patients.Therefore,early and accurate evaluation of RVPAC has great significance for patient's condition assessment,clinical decision-making,risk stratification and prognosis judgment.There are many evaluation methods currently,which can be divided into invasive and non-invasive methods,among which the non-invasive methods are mainly correlated with ultrasound.This review summarizes pathological mechanism and evaluation methods of RVPAC,advantages and disadvantages of each method and application value of RVPAC in various cardiovascular diseases.

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Janus Kinase 2/genetics* ; Polysaccharides/administration & dosage* ; Colitis, Ulcerative/chemically induced* ; Mice ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Drug Synergism ; Male ; Hesperidin/administration & dosage* ; Platycodon/chemistry* ; Phosphatidylinositol 3-Kinases/genetics* ; Disease Models, Animal ; RAW 264.7 Cells ; Mice, Inbred C57BL

Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

An automatic epileptic seizure detection model based on multi-channel recurrence plots and SE-VGG16 is proposed to enhance the accuracy of automatic detection of epileptic seizures.Firstly,triaxial accelerometer is used to collect patients'motion signals as a substitute of electroencephalogram signals,and these signals are converted into two-dimensional images through recurrence plots and then subjected to multi-channel fusion for generating multi-channel recurrence plots.Subsequently,squeeze-and-excitation module is employed to improve VGG16,which enhances the network's adaptability to different channels and enables precise classification.Experimental results show that the proposed model achieves the best performance across all indicators,attaining an accuracy of 99.3%,precision of 99.2%,recall rate of 98.9%,and F1-score of 99.0%.This model significantly boosts the accuracy and applicability of epileptic seizure detection,expands the potential of wearable devices for epileptic seizure monitoring in non-clinical settings,and provides a new technical pathway for epilepsy management and research.

Objective To investigate the correlation between serum galectin-3(Gal-3),fibroblast growth factor-21(FGF-21)and the lung function and and the Modified British Medical Research Council dyspnea in-dex(mMRC)score in invalids with chronic obstructive pulmonary disease(COPD).Methods A total of 79 patients with COPD who received treatment in the hospital from April 2021 to April 2023 were selected as the observation group,and 60 healthy individuals in the hospital during the same period were selected as control group.The expressions of Gal-3 and FGF-21 in serum were detected and compared.The first second forced ex-piratory volume(FEV1),FEV1/forced vital capacity(FVC)and mMRC score in two groups were compared,and the correlation between the expression levels of Gal-3 and FGF-21 and FEV1,FEV1/FVC and mMRC score in COPD patients was analyzed.Results The expression levels of serum Gal-3 and FGF-21 in the obser-vation group were higher than those in the control group(P＜0.05).The pulmonary function indexes in ser-um of observation group were higher than those in the control group,while the mMRC score was lower than that in the control group(P＜0.05).The expression levels of Gal-3 and FGF-21 were positively correlated with FEV1 and FEV1/FVC(P＜0.05),was negatively correlated with mMRC score(P＜0.05).Conclusion The expression of serum Gal-3 and FGF-21 in COPD invalids is abnormal,and the expression levels of serum Gal-3 and FGF-21 in COPD patients were correlated with FEV1,FEV1/FVC and mMRC score,which could be used as important reference indicators for diagnosis and disease evaluation of COPD.

Objective To identify causal effects and potential mechanisms of oxidative stress (OS)-related genes in lung cancer. Methods OS-related genes were extracted from the GeneCards database. Integration analysis of genome-wide association study (GWAS) data for lung cancer with gene expression and DNA methylation quantitative trait locus (QTL), including eQTL and mQTL in blood was performed using the summary data-based Mendelian randomization (SMR) approach to determine the causal relationship between OS-related genes and lung cancer risk. Colocalization analysis of OS-related gene QTL and lung cancer risk locus was performed to gain insight into the potential regulatory mechanisms of lung cancer risk. Results A total of 1 188 OS-related genes were obtained from the GeneCards database. A potential causal relationship between OS-related genes and lung cancer was identified by SMR analysis. AGER expression level [OR=1.944, 95%CI (1.431, 2.640), P<0.001], and ATF6B expression level [OR=1.508, 95%CI (1.287, 1.767), P<0.001] were associated with lung cancer risk. Meanwhile, ATF6B methylation level was also associated with lung cancer risk. Conclusion OS-related genes are associated with lung cancer, which may be a potential target of anti-cancer drugs.