Research indicates that microbe activity within the human body significantly influences health by being closely linked to various diseases.Accurately predicting microbe-disease interactions(MDIs)offers critical insights for disease intervention and pharmaceutical research.Current advanced AI-based technologies automatically generate robust representations of microbes and diseases,enabling effec-tive MDI predictions.However,these models continue to face significant challenges.A major issue is their reliance on complex feature extractors and classifiers,which substantially diminishes the models' generalizability.To address this,we introduce a novel graph autoencoder framework that utilizes decoupled representation learning and multi-scale information fusion strategies to efficiently infer po-tential MDIs.Initially,we randomly mask portions of the input microbe-disease graph based on Bernoulli distribution to boost self-supervised training and minimize noise-related performance degradation.Secondly,we employ decoupled representation learning technology,compelling the graph neural network(GNN)to independently learn the weights for each feature subspace,thus enhancing its expressive power.Finally,we implement multi-scale information fusion technology to amalgamate the multi-layer outputs of GNN,reducing information loss due to occlusion.Extensive experiments on public datasets demonstrate that our model significantly surpasses existing top MDI prediction models.This indicates that our model can accurately predict unknown MDIs and is likely to aid in disease discovery and precision pharmaceutical research.Code and data are accessible at:https://github.com/shmildsj/MDI-IFDRL.

UNLABELLED: OBJECTIVE：To explore the clinical characteristics and genetic etiology of a child with CAKUTHED syndrome. METHODS: A child who was admitted to the neonatal department of Gansu Provincial Maternal and Child Health Care Hospital due to "neonatal asphyxia" in May 2021 was selected as the study subject. Genomic DNA was extracted from peripheral venous blood samples from the child and his parents, and whole exome sequencing (WES) was carried out. Sanger sequencing was used to verify the candidate variant of the PBX1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: 2021GSFY (65)]. RESULTS: The proband, a male neonate, manifested renal dysplasia, congenital heart disease, pulmonary dysplasia, mediastinal hernia, cryptorchidism, and clavicle dysplasia. WES revealed that he had harbored a heterozygous c.863G>A (p.Arg288Gln) missense variant in exon 6 of PBX1 gene, which resulted substitution of Arginine at position 288 by Glutamine, for which both parents were of the wild type. The variant was unreported previously and rated as pathogenic (PS2+PM1+PM2_Supporting+PP2+PP3) based on the ACMG guidelines. CONCLUSION The c.863G>A variant of the PBX1 gene probably underlay the pathogenesis in the proband. Above finding has enriched the mutational spectrum of the PBX1 gene.
Humans ; Male ; Pre-B-Cell Leukemia Transcription Factor 1/genetics* ; Phenotype ; Infant, Newborn ; Exome Sequencing ; Mutation, Missense ; Heart Defects, Congenital/genetics* ; Abnormalities, Multiple/genetics*

The traditional Chinese medicine （TCM） myocardial infarction （MI） unit is a standardized， regulated， and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings， offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused， providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI， delivering prevention， treatment， and rehabilitation during the acute， stable， and recovery phases. Additionally， the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management， reduce the incidence of myocardial infarction， and improve quality of life.

OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

Objective To determine the body weights and blood physiological and biochemical indicators in the Macaca mulatta brevicaudus(M.m.brevicaudus),to provide a reference for the breeding of experimental animals.Methods A total of 180 wild M.m.brevicaudus(female and male)from the South Bay Macaque Reserve in Lingshui were selected as the research subjects.Body weights were measured using electronic scales and blood samples were collected.Routine blood indicators(red blood cell count,hemoglobin,white blood cell count,and platelet count)were detected using an automated blood cell analyzer,and biochemical indicators(alanine aminotransferase,aspartate aminotransferase,glucose,blood urea nitrogen)were measured using an automated biochemical analyzer.Data were analyzed using SPSS 18.0 software for descriptive statistics,and differences in body weights and blood indicators between sexes and age groups were compared using t-tests.Results Adult male wild M.m.brevicaudus were significantly heavier than females(P＜0.05);however,there were no significant differences in complete blood cell counts between female and male macaques(P＞0.05).In terms of blood biochemical indicators,lactate dehydrogenase and total bilirubin levels differed significantly between female and male M.m.brevicaudus(P＜0.05),but there were no significant differences in any other biochemical indicators.Conclusions This study established baseline data on the body weights and blood physiological and biochemical indicators of wild M.m.brevicaudus,providing a reference for their future breeding as experimental animals.

Fatty liver is common disease of nutritional metabolism in the perinatal period,character-ized by elevated levels of NEFA in the blood and disorders of lipid metabolism.High concentra-tions of NEFA damage mitochondria and promote the release of reactive oxygen species(ROS).At the same time,lipid peroxidation occurs in lipid accumulation in hepatocytes,producing free radi-cals such as ROS,which leads to oxidative stress in the liver.When the level of intracellular ROS increases,thioredoxin-interacting protein(TXNIP)activates nucleotide-binding oligomerization structure-like protein 3(NLRP3)inflammasomes,and oxidative stress can regulate pyroptosis,but it is unclear whether reactive oxygen species(ROS)produced by oxidative stress in hepatocytes can mediate pyroptosis and induce liver injury in dairy cows through the TXNIP/NLRP3 pathway.In this study,liver tissue samples from healthy dairy cows and fatty liver cows were collected,and NEFA was used to construct a fatty liver cell model,and triglyceride(TG)content and oxidative stress related indicators were detected by kit.Western blot was used to detect the activation of NL-RP3 inflammasomes,the inflammatory pathway of NF-κB and the expression levels of pyroptosis-related proteins.Fluorescence quantitative PCR was used to detect the relative expression level of inflammatory factor mRNA.The results showed that compared with the healthy(control)group,the TG content of fatty liver tissue and fatty liver cells was significantly increased(P＜0.05),the activities of SOD and GSH-Px were significantly decreased(P＜0.05),and the protein expression levels of TXNIP,NLRP3,GSDMD-N and Caspase-1 were significantly up-regulated(P＜0.05).The results of the antioxidant model of fatty hepatocytes using NEFA and antioxidants(NAC)showed that compared with the fatty hepatocyte model,the content of ROS in hepatocytes was sig-nificantly reduced,and oxidative stress,NLRP3 inflammasome activation and pyroptosis were alle-viated.In summary,this study found that when fatty liver disease occurs in dairy cows,ROS pro-duced by oxidative stress in the liver can mediate pyroptosis through the TXNIP/NLRP3 path-way,which can lead to liver injury in fatty liver cows.

Objective:To identify the risk factors for postpartum hemorrhage(PPH)in patients with gestational diabetes mellitus(GDM)and to develop and validate a predictive model.Methods:A retrospective study was conducted on GDM patients who delivered at The Third Affiliated Hospital of Zhengzhou University between Janu-ary 2021 and December 2023.A total of 137 GDM patients with PPH were included in the case group,and 190 GDM patients without PPH were included in the control group.Univariate analysis and multivariate Logistic regres-sion analysis were used to identify independent risk factors for PPH in GDM patients.Anomogram prediction mod-el was subsequently constructed.The predictive performance of the model was evaluated by the Hosmer-Leme-show goodness-of-fit test,receiver operating characteristic(ROC)curve,Bootstrap resampling method,and deci-sion curve analysis(DCA).Results:Univariate analysis revealed statistically significant differences between the two groups in multiple factors(P<0.05),including age≥35 years,pre-pregnancy body mass index(BMI)≥24 kg/m2,suboptimal glycemic control,assisted reproduction,gestational anemia,polyhydramnios,macrosomia,acute chorioamnionitis,gestational hypertension,prenatal fasting blood glucose(FBG),prenatal glycosylated he-moglobin(HbA1c),fibrinogen(FIB),postpartum blood loss,dystocia,neonatal admission to ICU,neonatal Apgar score at 1 minute,and Apgar score at 5 minutes.Multivariate Logistic regression analysis indicated that age≥35 years,pre-pregnancy BMI≥24 kg/m2,suboptimal glycemic control,gestational anemia,macrosomia,polyhydram-nios,and elevated prenatal HbA1c levels were independent risk factors for PPH(OR>1,P<0.05),while elevat-ed FIB levels were identified as a protective factor for PPH(OR<1,P<0.05).The nomogram demonstrated good calibration(Hosmer-Lemeshow test:χ2=6.367,DF=8,P=0.606).The area under the ROC curve(AUC)was 0.821(95%CI 0.774-0.868),with a sensitivity of 71.5%and a specificity of 83.7%,indicating good discrimi-native ability of the model.Internal validation using the Bootstrap resampling method showed a C-index of 0.821,suggesting good consistency and predictive accuracy.DCA curve further confirmed that the model had favorable clinical application value.Conclusions:age≥35 years,pre-pregnancy BMI≥24 kg/m2,suboptimal glycemic con-trol,gestational anemia,macrosomia,polyhydramnios,and elevated prenatal HbA1c levels are independent risk factors for PPH in GDM patients,while elevated FIB levels are identified as an independent protective factor.The constructed prediction model for PPH in GDM patients exhibits good discriminative ability,calibration,and predic-tive performance,demonstrating high clinical application value.

To construct a safe and effective multi-epitope vaccine against the S1 protein of chicken infectious bronchitis virus(IBV).In this study,homologous and non-homologous dominant epitopes of IBV M41,T,QX and H120 virulent strain S1 proteins were screened by various online bioprediction software,respectively,and a new peptide W with high immunogenicity was construc-ted by connecting the screened B-cell and T-cell epitopes with a linker peptide.W was ligated to the truncated sequence of the four viral strains by T2A yietding to the eukaryotic expression vector pEGFP-N1,and it was identified by PCR and double digestion,the obtained recombinant plasmid was transfected into HEK293A cells and target protein expression was measured by Western blot.The constructed plasmid was injected intramuscularly twice to detect the antibody level,cytokine level,and peripheral blood T cell subsets were detected after two immunizations.The epitope pro-tein W was successfully constructed,which was structurally stable,antigenic,and soluble;the re-combinant plasmid pEGFP-WMQtH,pEGFP-W,and pEGFP-MQtH matched the expected size;anti-IBV IgG antibody levels in pEGFP-N1 was increased greatly compared to the PBS group.cyto-kines IL-2,and γ interferon(IFN-γ)were increased greatly(P＜0.05);peripheral blood CD4+/CD8a value(P＜0.05)was increased greatly.The W epitope protein was successfully constructed,which can effectively activate the humoral immunity and cellular immunity against four infectious bronchitis viruses(IBV),laying a foundation for the development of an effective vaccine against IB.

Objective To compare the changes in biological indicators of human corneal epithe-lial(HCET)cells and rabbit corneas after exposure to different doses of ultraviolet B(UVB)radia-tion,so as to evaluate the impact of UVB radiation on corneal injury effects.Methods In cell exper-iment,HCET cells were divided into groups with radiation doses of 0,6,12,18,and 24 mJ/cm2.The effect of UVB radiation on HCET cell viability was detected using the CCK-8 assay,and the level of intracellular DNA damage was assessed by immunofluorescence.In the animal experiment,15 healthy New Zealand white rabbits(30 eyes)were randomly divided into groups with radiation doses of 0,1.35,2.16,4.32,and 6.48 J/cm2.The UVB exposure time for the radiation groups was 30 minutes per day for 3 consecutive days.Corneal injury was evaluated using methods such as slit-lamp microscopy,sodium fluorescein staining,central corneal thickness measurement,optical coherence tomography(OCT)imaging,and hematoxylin and eosin(HE)staining.Results Compared with the control group,cell viability in the radiation groups gradually decreased,and the level of DNA damage gradually increased with increasing radiation dose.As the radiation dose increased in the radiation groups,the degree of corneal opacity in rabbits gradually worsened,the central corneal area gradu-ally thickened,and OCT revealed high-intensity scattered light signals with the formation of shadow areas.Results from HE staining,immunohistochemistry,Western blot(WB),and sodium fluores-cein staining showed that the 1.35 J/cm2 group caused mild corneal injury,with damage reaching the corneal epithelial layer.In the 2.16 J/cm2 group,the corneal injury presented as dense punctate distribution,with damage extending from the epithelial layer to the superficial stroma.The number of ephrin type-A receptor 2(EphA2)protein-stained cells was relatively small,and the staining was light,showing a weak positive result.In the 4.32 J/cm2 and 6.48 J/cm2 groups,the corneal injury was irreversible,with damage gradually progressing from the corneal epithelial layer and superficial stroma to the endothelial layer.The number of EphA2 protein-stained cells was relatively large,and the staining was dark,showing a strong positive result.Conclusion This study comprehensively e-valuates the dose-dependent injury effects of UVB on HCET cells and New Zealand white rabbit cor-neas through cell and animal experiments.It elucidates that UVB radiation could induce corneal cell DNA damage,promote inflammatory responses,and trigger apoptosis by upregulating γ-phosphoryla-ted histone H2AX(γH2AX)and EphA2.The self-repair ability and process of corneal injury are preliminarily explored,providing a basis for further research on mechanisms of corneal injury caused by ultraviolet radiation and the development of protective drugs.

CT-guided thermal ablation is a critical modality for treating lung cancer.Invasive thermometry techniques demonstrated sufficient accuracy for monitoring temperature of the target area during ablation,but their clinical application were limited since procedural invasiveness and relatively high risk of complications.Being non-invasive,safe and capable of global monitoring,non-invasive thermometry techniques have broad application prospects.The status of non-invasive thermometry techniques for CT-guided thermal ablation for lung cancer were reviewed in this article.