Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "

Objective To explore the mechanism of action of lamotrigine in the treatment of major depressive disorder(MDD).Methods Information on the drug targets of lamotrigine and the therapeutic targets of MDD were collected for intersection target gene analysis and protein-protein interaction screening.Various biological pathways related to lamotrigine in treatment of MDD were determined through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.The screened core targets were preliminarily validated using molecular docking technology.Further validation of Mendelian randomization was conducted using genome-wide association analysis data from gamma-aminobutyric acid recep tor-associated protein-like 1(GABARAPL1)and MDD in the OpenGWAS database.Results The biological pathways related to lamotrigine in treatment of MDD were identified,which included gamma-aminobutyric acid(GABA)ergic synapses,nicotine addiction,glutamatergic synapses,endogenous cannabinoid signaling.Molecular docking showed that the docking energy of lamotrigine with GABRA1,GABRB2,GABRA6,GABRD,GABRG2,GABRG1,GABRA5,GABRA4,GABRB3,and GABRA2 receptors was-5.8 kCal·mol-1.Among them,the GABRB3 receptor showed the strongest docking energy with lamotrigine,which was-9.5 kCal·mol-1.In the genome-wide association analysis data of GABARAPL1,303 single nucleotide polymorphisms were associated with GABARAPL1(P＜5 × 106).15 single nucleotide polymorphisms were screened and retained for Mendelian randomization analysis,and the results showed that GABA receptors may be an important therapeutic target for MDD.Conclusion The treatment of MDD with lamotrigine may be achieved by acting on GABA receptors,which provided a research basis for the clinical application of lamotrigine in treating MDD.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Objective:To provide reference for hospital drug selection and clinical rational drug selection,through evaluating the nutritional value of six commonly used balanced compound amino acid injection (BCAA) in clinical practice,including 18AA (250 mL:12.5 g),18AA-I (250 mL:17.5 g),18AA-Ⅱ(250 mL:21.25 g),18AA-IV (250 mL:8.7 g),18AA-V (250 mL:8.06 g),and 18AA-V-SF (250 mL:8.06 g). Methods:Based on the whole egg protein model,the nutritional value of six varieties of BCAA from two aspects were evaluated,including the first limiting amino acid chemical score (CS),value of essential amino acid (EAA) and the comprehensive quality of total EAA (both essential amino acid index and closeness to standard protein). Results:The first limiting amino acid CS value from high to low was 18AA-Ⅱ>18AA>18AA-V=18AA-V-SF>18AA-I=18AA-Ⅳ. Total EAA comprehensive quality:the essential amino acid index from high to low was 18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. The closeness to whole egg protein from high to low was 18AA-Ⅱ=18AA=18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Ultimately,the nutritional value of the 6 varieties of BCAA decreased from high to low:18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Conclusions:Among the six varieties of BCAA,18AA-Ⅱ has the highest nutritional value and the highest amino acid content in the same liquid volume,making it the preferred drug for patients with normal liver and kidney function.

Objective:To explore the gene mutations of Langerhans cell histiocytosis in children,and to analyze the correlation of BRAF V600E mutation with clinical features and prognosis of LCH,so as to provide reference for clinical diagnosis and treatment. Methods:Fluorescence PCR was used to detect gene mutations in paraffin-embedded tissue samples from 78 children with LCH,and the correlation of BRAF V600E mutation with clinical characteristics and prognosis of LCH in children was analyzed. Results:Among the 78 children,41 cases (52.6％) had BRAF V600E mutation,8 cases (10.3％) had MAP2K1 mutation,1 case (1.3％) had BRAF Exon 12 mutation,1 case (1.3％) had ARAF mutation,and 1 case (1.3％) had PIK3CA mutation. BRAF V600E mutation was not significantly correlated with sex,age,multisystem involvement,risk-organ involvement,CNS-risk lesions,and early treatment response in children with LCH (P>0.05),and it was also not significantly correlated with the recurrence and event-free survival (EFS) of children with LCH (P>0.05). Conclusion:LCH is an inflammatory myeloid tumor. BRAF V600E mutation is not correlated with clinical features,early treatment response,recurrence and prognosis of LCH.

Aim To explore the antimicrobial activity of a novel R-type phage tail-like bacteriocin(PTLB)secreted by Enterobacter cloacae SHAMU191747 a-gainst methicillin-resistant Staphylococcus aureus(MR-SA).Methods Antagonistic activity of E.cloacae SHAMU191747 against MRS A was detected by LB agar plate antagonistic test and LB broth micro-fermentation test.The crude extract of fermentation supernatant of E.cloacae SHAMU191747 was prepared by ultra-high-speed centrifugation and density gradient centrifuga-tion.The novel R-type PTLB in the crude extract was detected by transmission electron microscopy.The an-timicrobial activity of the crude extract against MRSA was verified by LB agar plate spot-seeding method.The molecular weight of the novel R-type PTLB was detected by SDS-PAGE electrophoresis.Results E.cloacae SHAMU191747 secreted a novel R-type PTLB,and had a strong antagonistic effect on MRSA.The no-vel R-type PTLB had a molecular weight of approxi-mately 35 ku and could efficiently kill MRSA.The physical dimensions of its tail-sheath-uncontracted functional molecules were(142.7±4.3)×(13.8±0.6)nm,and those of the tail-sheath-contracted non-functional molecules were(57.7±1.2)×(20.8±1.5)nm.Conclusions The novel R-type PTLB pro-duced by E.cloacae SHAMU191747 can efficiently kill MRSA,and has the potential to be developed into a novel antimicrobial drug with great prospects for clini-cal application.

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.
Infant, Newborn ; Female ; Pregnancy ; Humans ; Premature Birth ; Diabetes, Gestational ; Obstetric Labor, Premature ; Hospitals ; Iatrogenic Disease

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

AIM: To identify the pathogenic gene in a family with primary open angle glaucoma(POAG)from Nantong, Jiang Province, and to analyze its clinical phenotype and pathogenic mechanism.METHOD: A POAG pedigree was reviewed and recruited from January 2020 to December 2020, which spans 5 generations, with 33 people in total. A total of 13 family members were enrolled in our study, of whom 4 members were diagnosed with POAG, 1 with ocular hypertension(OHT), and the other 8 members were unaffected. Detailed medical history was collected and a comprehensive ophthalmic examination was performed. High throughput sequencing was used to screen for possible pathogenic gene, and Sanger sequencing was used to verify candidate pathogenic gene.RESULT: All patients in this family were found to have elevated intraocular pressure(IOP)and diagnosed with glaucoma at a young age, requiring surgical treatments to control the IOP. The highest IOP of proband was up to 55mmHg. A heterozygous mutation(c.1197C>A, p.Phe399Leu)of LTBP2 gene was found in the proband genome by whole exon sequencing(WES). Sanger sequencing verified that the mutation was not isolated from the family disease.CONCLUSION: LTBP2 (c.1197C>A)mutation was not the pathogenic gene of POAG in this family. However, the pathogenic potential of LTBP2 gene in POAG cases is worth studying.

Aim To apply network pharmacology, molecular docking, and in vitro experimental techniques to predict as well as verify the antidepressant pharmacological mechanisms of Mengyao Anshen Buxin Liuwei pills. Methods TCMSP database and literature mining were used to obtain the active ingredients of Anshen Buxin six flavor pills , Swiss Target Prediction was applied to predict the ingredient related target information, and Cytoscape was employed to construct a medicinal herb ingredient target network. Depression targets were retrieved through GeneCards , Drugbank , OMIM and other databases. STRING database was used to obtain protein interaction relationship network information. DAVID database was used for GO biological process enrichment analysis and KEGG signaling pathway enrichment analysis. Autodock vina software was applied for molecular docking validation. In vitro injury model was established in BV2 microglial cells, cell viability was assessed by CCK-8 assay, and the mRNA expression of relevant core targets was assessed by qPCR. Results A total of 34 active components of Anshen Buxin Liuwei pills were screened, involving 140 potential targets and 59 core targets, involving 99 signaling pathways. Molecular docking results showed that betulinic acid, stigmasterol p-stiosterol 10 active components such as sitosterol and quercetin had good binding ability with AKT1, APP, ALB, MAPK3, VE GFA and MAPK 1 targets. The re suits in vitro showed that the activity of BV2 cells increased significantly compared with the model group. Anshen Buxin Liuwei pills could regulate the mRNA expression of each core target. Conclusion Anshen Buxin Liuwei pills may play an antidepressant role mainly through serotonin synaptic and other signaling pathways and related core targets.