Objective To establish a brucellosis monitoring and testing technique applicable for the rapid field screening of natural epidemic diseases.Methods A rapid testing technique for Brucella was developed based on a double-antibody sandwich testing model using gradient-variant quantum dots as fluorescent tracers.The sensitivity,linearity,precision,and specificity of the technique were evaluated using suspensions of standard Brucella strains.Methodological comparisons across different sample types were conducted to assess the consistency of the test results.Results The gradient-variant quantum dots detection method was evaluated with standard Brucella strains,exhibiting a sensitivity of 1×103 CFU/mL and a linear correlation coefficient(r)of 0.994(95%CI,0.933-1.055).The maximum coefficient of variation was 12.94%in repeated tests,showing good specificity.A comparative assessment of 305 clinical samples was conducted using the Brucella gradient-variant quantum dots detection method,the Rose Bengal plate agglutination test(RBT),and the serum agglutination test(SAT),yielding a Kappa value of 0.95,indicating almost perfect agreement.Additionally,a comparative assessment of 110 environmental samples collected on-site was conducted using the Brucella gradient-variant quantum dots detection method and quantitative real-time PCR(qPCR).The Kappa values for aerosol collection fluid,surface wipes,and wool samples were all above 0.83,demonstrating near-perfect agreement.For fecal and soil samples,the Kappa values were above 0.62,indicating substantial agreement.Conclusion The Brucella detection method based on gradient-variant quantum dots technology is simple and can be conducted rapidly.The detection method demonstrates high sensitivity,linearity,precision,and specificity.It shows consistent performance in clinical sample testing.It is well-suited for field rapid screening of natural epidemic diseases in field settings and shows good application prospects in the monitoring,prevention,and rapid detection of zoonotic diseases.

Objective To develop a new model for predicting compound toxicity and exploring related toxicity mechanisms using transcriptomic data and gene ontology knowledge.Methods Using the TOXRIC database,two toxicity-related datasets were constructed and a Tox VNN model was established that incorporated gene ontology knowledge to evaluate compound toxicity and identify key biological processes.Results Tox VNN demonstrated good predictability.The identification of important biological processes related to CYP enzyme activity and p53 pathway stress response provided insights into the toxicity mechanisms.Conclusion The Tox VNN,which integrates data and knowledge,can not only ensure high predictability,but also effectively identify important biological processes related to toxicity.This model offers a new approach to predicting and understanding compound toxicity in drug safety evaluation.

As a common ophthalmic disease, pterygium exhibits a considerably high incidence in global area, particularly in regions with harsh natural environment. While it is unlikely to cause blindness, pterygium frequently disrupts the normal homeostasis of the tear film, leading to discomfort such as dry eyes and foreign body sensation, thereby significantly impairing patients' quality of life. Furthermore, the high surgical intervention rate for pterygium consumes substantial medical resources. Therefore, investigating the underlying mechanisms of pterygium development is essential for its prevention and control. Extensive research has demonstrated the correlation between solar radiation and pterygium occurrence, confirming that ultraviolet rays within solar radiation contribute to the onset and progression of pterygium through multiple pathways, including direct DNA damage to ocular surface cells, oxidative stress-induced injury, involvement in inflammatory regulation, and extracellular matrix remodeling. This paper reviews both domestic and international epidemiological trends of pterygium, as well as the multifaceted mechanisms by which solar radiation influences pterygium development. The aim is to enhance understanding of the relationship between solar exposure and pterygium occurrence, while emphasizing and guiding public awareness of solar radiation protection in clinical practice.

Identifying drug-drug interactions (DDIs) is essential to prevent adverse effects from polypharmacy. Although deep learning has advanced DDI identification, the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits. Here, we developed a Multi-Dimensional Feature Fusion model named MDFF, which integrates one-dimensional simplified molecular input line entry system sequence features, two-dimensional molecular graph features, and three-dimensional geometric features to enhance drug representations for predicting DDIs. MDFF was trained and validated on two DDI datasets, evaluated across three distinct scenarios, and compared with advanced DDI prediction models using accuracy, precision, recall, area under the curve, and F1 score metrics. MDFF achieved state-of-the-art performance across all metrics. Ablation experiments showed that integrating multi-dimensional drug features yielded the best results. More importantly, we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs. Among 12 real-world adverse drug reaction reports, the predictions of 9 reports were supported by relevant evidence. Additionally, MDFF demonstrated the ability to explain adverse DDI mechanisms, providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Objective:To investigate the essential determinants that are critical to initiating the assembly of outer membrane proteins by replacing the POTRA domains of the translocator protein FhaC and the insertase protein TtOmp85 of the Omp85 family. Methods:FhaC, TtOmp85 proteins and their recombinant chimeric proteins after replacing the POTRA domain were obtained by overexpression and purification in vitro. An in vitro reconstitution system was used to investigate the effects of the different domains on the transport efficiency of the substrate outer membrane protein FhaB and the membrane insertion efficiency of OmpA. Results:Replacing the POTRA domain of FhaC with that of TtOmp85 led to the loss of the transport function of FhaB. During the membrane insertion process of OmpA, the FhaC mutant containing the POTRA of TtOmp85 protein acquired the ability to assemble OmpA. Conclusion:The compositional differences in the POTRA domain of Omp85 family proteins determine their abilities to recognize their substrate proteins.

Identifying drug-drug interactions(DDIs)is essential to prevent adverse effects from polypharmacy.Although deep learning has advanced DDI identification,the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits.Here,we developed a Multi-Dimensional Feature Fusion model named MDFF,which integrates one-dimensional simplified molec-ular input line entry system sequence features,two-dimensional molecular graph features,and three-dimensional geometric features to enhance drug representations for predicting DDIs.MDFF was trained and validated on two DDI datasets,evaluated across three distinct scenarios,and compared with advanced DDI prediction models using accuracy,precision,recall,area under the curve,and F1 score metrics.MDFF achieved state-of-the-art performance across all metrics.Ablation experiments showed that integrating multi-dimensional drug features yielded the best results.More importantly,we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs.Among 12 real-world adverse drug reaction reports,the predictions of 9 reports were supported by relevant evidence.Additionally,MDFF demon-strated the ability to explain adverse DDI mechanisms,providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Objective To investigate the prevalence of scoliosis and congenital heart disease(CHD)and their correlation among children and adolescents of Drung nationality in Yunnan Province.Methods A cross-sectional survey was conducted in November 2022 among all Drung school-aged children and adolescents aged 5-18 years in Gongshan Drung and Nu Autonomous County,Yunnan Province.Visual inspection,Adams for-ward flexion test,and trunk rotation angle(ATR)measurement were comprehensively used for school prelim-inary screening of scoliosis.Individuals who tested positive in the school preliminary screening underwent fur-ther X-ray examination for auxiliary diagnosis.Cardiac auscultation and echocardiography were used for school preliminary screening of CHD.The personal information of the screening subjects,the screening results,etc.were recorded.The prevalence of scoliosis and CHD among children and adolescents of the Drung nationality and the relationship between the two diseases were statistically analyzed,and the positive predictive value of school-based scoliosis screening and its influencing factors were also analyzed.Results A total of 1 036 chil-dren and adolescents of Drung nationality were enrolled,with a mean age of(10.72±3.75)years,icluding 542 males and 494 females.A total of 45 subjects tested positive for scoliosis in the school preliminary screening,with a preliminary positive rate of 4.34%.A total of 22 cases were finally diagnosed with scoliosis,with a prevalence rate of 2.12%.Among them,21 cases were idiopathic scoliosis(accounting for 95.45%),and 1 case was congenital scoliosis(accounting for 4.55%).The prevalence rate was higher in females(2.83%)than that in males(1.48%),higher in the 10 to 18-year-old group(2.30%)than that in the 5 to<10-year-old group(1.87%),and higher in the secondary school group(2.78%)than that in the primary school group(1.78%),hut there were no statistically significant differences(P>0.05).Most idiopathic scoliosis cases were mild(Cobb angle 10° to<20°,90.48%)and classified as Lenke type Ⅴ(57.14%).Two cases of CHD were confirmed,both of which were atrial septal defects,with a prevalence rate of 0.19%.The co-occurrence rate of idiopathic scoliosis and CHD was 4.76%(1/21).The positive predictive value of school-based scoliosis pre-liminary screening was only 48.89%.When the BMI was<18.5 kg/m2,the positive predictive value was sig-nificantly higher than that for BMI≥18.5 kg/m2(P<0.05).Conclusion The prevalence rate of scoliosis a-mong adolescents of the Drung ethnic group in Yunnan Province is 2.12%,predominantly idiopathic scoliosis,with Lenke type V being the most common classification.The prevalence rate of congenital heart disease is 0.19%.BMI is a significant influencing factor for the positive predictive value of school-based scoliosis prelimi-nary screening.