ObjectiveTo construct and validate a clinical prediction model for inflammatory remission outcomes in rheumatoid arthritis （RA） patients with liver and kidney deficiency syndrome treated with Bushen Zhiwang Decoction （补肾治尪汤， BZD） based on metabolomics. MethodsA prospective cohort study was conducted， enrol-ling 60 RA patients with liver and kidney deficiency syndrome. All patients were treated with BZD and conventional-dose oral conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） for 12 months. Clinical data were collected， and the change in disease activity score in 28 joints （DAS28） after treatment compared with baseline （△DAS28） was used as the primary outcome and grouping criterion. Peripheral blood samples were collected before treatment to analyze plasma metabolites. Differential analysis and least absolute shrinkage and selection operator （LASSO） regression were used to preliminarily screen differential metabolites， followed by machine learning algorithms to further identify a core metabolite combination. Based on the expression levels of the core metabolite combination， a novel metabolite index， namely the metabolomics-based inflammatory remission score （Met-IRS）， was calculated using standar-dized metabolite values， and its clinical applicability was evaluated. A clinical prediction model was constructed by integrating clinical characteristics and Met-IRS， and the model performance was assessed. ResultsAmong the 60 patients， those with △DAS28 ≥ 0.27 were assigned to the high inflammatory remission group， while those with △DAS28 ＜ 0.27 were assigned to the low inflammatory remission group， with 30 cases in each group. Compared to the low inflammatory remission group， the high inflammatory remission group showed a higher frequency of methotrexate use and a lower positive rate of rheumatoid factor （RF） （P＜0.05）. Seven core metabolites were identified as the optimal combination， including mangiferic acid， fatty acid-hydroxy fatty acid ester 40∶6， fatty acid-hydroxy fatty acid ester 18∶0， fatty acid-hydroxy fatty acid ester 36∶1， glucosylceramide， lysophosphatidylcholine 22∶5， and pregnanetriol ketone. The calculated Met-IRS comprehensively reflected the characteristics of differential metabolites and demonstrated clinical applicability. Met-IRS was significantly higher in the high inflammatory remission group than in the low inflammatory remission group， and was positively correlated with high inflammatory remission outcomes （P＜0.05）. Based on the variables Met-IRS， methotrexate use， leflunomide use， and RF positivity， a clinical prediction model for inflammatory remission in RA treatment （Cj-RTRM） was constructed. Model performance evaluation demonstrated that the model had good clinical predictive ability， with an area under the receiver operating characteristic curve （AUC） of 0.880， sensitivity 0.967， specificity 0.700 and Youden's index 0.667. ConclusionThe clinical prediction model Cj-RTRM constructed based on the metabolomics-based inflammatory remission score Met-IRS can effectively predict clinical inflammatory remission outcomes in RA patients treated with BZD and accurately identify the advantageous population for this treatment. This model provides guiding evidence for dynamic inflammation monitoring， targeted management， and identification of populations with advantages in traditional Chinese medicine.

Background The contamination of public baths with Legionella pneumophila contamination has become a growing public health concern in recent years. However, research on its association with bacterial community characteristics in water samples remains limited. The integration of 16S rRNA sequencing and random forest modeling provides a new approach to elucidate the bacterial community characteristics of public bath water and their association with Legionella pneumophila contamination. Objective To investigate the bacterial community structure and diversity of public bath water in Shanghai, explore the association between Legionella pneumophila contamination and bacterial community characteristics, and identify key bacterial genera associated with contamination, thereby providing a scientific basis for formulating hygiene management regulations for public bath water. Methods From February to March 2023, water samples were collected from ten public baths in Shanghai which were selected based on business scale, regional distribution, and functional differences. Water quality parameters were evaluated, and the samples were categorized into Legionella-positive and Legionella-negative groups based on the detection results of Legionella pneumophila. The bacterial community structure, α-diversity, and β-diversity were analyzed using 16S rRNA sequencing. Redundancy analysis (RDA) was employed to examine the relationship between physicochemical factors and bacterial community diversity. A random forest model was employed to identify key bacterial genera distinguishing the two groups, with the importance of genera being evaluated based on the mean decrease accuracy (MDA). Results The oxygen consumption in the Legionella-positive group was significantly lower than that in the Legionella-negative group (mean values: 1.85 mg·L⁻¹ vs. 6.81 mg·L⁻¹, P< 0.05), while no significant differences were observed in other physicochemical indicators. The sequencing results revealed a total of 27 bacterial phyla and 454 bacterial genera, with Proteobacteria (63.00%) being the dominant phylum. The dominant genera included Pelomonas (8.50%), Acidovorax (8.13%), Mycobacterium (7.93%), and Acinetobacter (6.59%). The α-diversity analysis indicated that bacterial community richness (Chao1 and ACE indices) was significantly higher in the Legionella-positive group than in the Legionella-negative group (P<0.01). The β-diversity analysis showed no significant difference in the bacterial community structure between the two groups (P>0.05). The RDA analysis demonstrated that the bacterial community diversity was positively correlated with pH and negatively correlated with oxygen consumption and free residual chlorine. The RDA1 and RDA2 explained 23.92% and 21.30% of the bacterial community diversity, respectively. The random forest model identified 20 key genera significantly influencing the microbial community distribution between the two groups, including unclassified_Bradyrhizobiaceae (MDA=2.42), Meiothermus (MDA=2.37), and Flavihumibacter (MDA=2.26). Conclusion The diversity of bacterial communities in public bath water is influenced by pH, oxygen consumption, and free residual chlorine. Samples contaminated with Legionella pneumophila exhibit greater microbial richness and contain characteristic key bacterial genera that contribute to community differences. Machine learning random forest technology helps identify these distinctive key bacterial genera. The findings provide a basis for carrying out risk early warning strategies in such settings.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Purpose To evaluate the static structural changes of mitral annulus and leaflets in mitral valve prolapse via three-dimensional transesophageal echocardiography(3D-TEE),and their continuous dynamic changes during the cardiac cycle.Materials and Methods Twenty-six patients with mitral valve prolapse diagnosed by transesophageal echocardiography in Wuhan Asia Heart Hospital from June 2022 to June 2023 were retrospectively included,and 30 patients who were examined by transesophageal echocardiography in our hospital during the same period due to monitoring of patent foramen ovale or non-cardiac surgery were selected as the control group.The related parameters of the valve annulus were measured.In addition,the meaningful parameters were measured at late diastole(LD),early systole(ES),middle systole(MS)and late systole(LS),and the change rate was calculated.The static structure of mitral valve device was compared between the two groups,and the differences of various parameters at different times were analyzed.Results Compared with the control group,the annulus height(AH)and the ratio of annulus height and combined width(AHCWR)in the case group decreased,and the other parameters increased(t=-7.447-12.472,all P<0.05),but there was no statistical difference in the maximum displacement distance of the annulus between the two groups(P>0.05).Comparing the related parameters of LD,ES,MS and LS at four different time points,compared with the control group,all the parameters in the case group increased except AH and AHCWR(t=-16.224-15.683,all P<0.05).Comparing the continuous changes at four different times,the continuous changes of all parameters in the control group were statistically significant(F=7.632-323.837,all P<0.05),and there were significant differences in the parameters of the control group from LD to ES(all P<0.05).Except anterolateral to posteromedial diameter,intertrigonal diameter and annulus area,the continuous changes of other parameters in the case group were statistically significant(F=3.041-71.082,all P<0.05),and only non-planar angle,AH and AHCWR in the case group had statistical differences in LD to ES(all P<0.05).Compared with the control group,the change rate of parameters in the case group decreased,and the difference was statistically significant(t/U=-7.069-780.000,all P<0.05),and the change rate of C-ring was greater than that of intertrigonal diameter.Conclusion 3D-TEE can quantitatively analyze the dynamic changes of mitral annulus and leaflets,and analyze the continuous changes of mitral valve in cardiac cycle in detail,which can provide more accurate preoperative evaluation for patients and guide treatment.

Objective To explore the value of the ratio of soluble FmS-like tyrosine kinase-1(sFlt-1)to placental growth factor(PlGF)in predicting vitamin D deficiency in pregnant women with preeclampsia.Methods A total of 740 singleton pregnant women who underwent prenatal examination in Qijiang Health Center for Maternal and Child Care from January to November 2023 and were able to complete follow-up were selected as the research subjects.They were divided into the normal group(n=44)and the deficiency group(n=696)according to the vitamin D[1,25-(OH)2D3]level.Information such as age,BMI,pregnancy histo-ry,family history and medical history of each group was collected.5 mL of peripheral venous blood was drawn after fasting for 6-8 hours at 12-14 weeks of pregnancy to detect the levels of sFlt-1,PlGF and vitamin D in peripheral blood,and evaluated the predictive value of sFlt-1/PlGF for vitamin D deficiency in preeclampsia.Results There were no statistically significant differences in general conditions such as height,age,BMI,edu-cational level and occupation between the two groups(P>0.05).There were statistically significant differ-ences in the prenatal weight,vitamin D level,sFlt-1/PlGF and neonatal birth weight between the two groups(P<0.05).The results of univariate analysis showed that the prenatal weight,sFlt-1/PlGF,and neonatal birth weight were risk factors for vitamin D deficiency in patients with PE.The results of multivariate analysis showed that sFlt-1/PlGF and neonatal birth weight were factors for predicting vitamin D deficiency in patients with PE(P<0.05).All these variables are used to establish the nomogram prediction model.The receiver op-erating characteristic(ROC)curve showed that area under the curve(AUC)of the training group and the val-idation group was 0.66(95%CI:0.56-0.77)and 0.63(95%CI:0.49-0.76),respectively.Conclusion In pregnant women with preeclampsia,elevated sFlt-1/PlGF may be an early warning indicator for predicting vi-tamin D deficiency.

Objective To evaluate the impact of lens capsule diameter and capsular tension ring(CTR)fit on the ro-tational stability and visual function of Toric intraocular lenses(IOLs)in patients with high myopia cataract after surgery,and to explore the main influencing factors.Methods A prospective study included 100 eyes of patients with high myopia(axial length≥26 mm)who underwent phacoemulsification cataract extraction combined with Toric IOL implantation at the Cataract Department of Hebei Eye Hospital from September 2023 to March 2024.Based on the ratio of the capsule equivalent diameter measured by anterior segment OCT(CASIA2)to the standard diameter of CTR,the eyes were divided into the matched group(ratio of 0.8-1.2)and the unmatched group.Follow-up was conducted at 1 week,1 month,3 months,6 months,and 12 months postoperatively to observe the rotation angle of Toric IOL,residual astigmatism,uncor-rected visual acuity,and other indicators.Safety was assessed based on intraoperative and postoperative complications.Correlation analysis and multiple linear regression were used to explore the impact of capsule-CTR fit,corneal astigmatism,axial length,and other factors on Toric IOL rotation and postoperative refractive status.Results The mean IOL rotation angle at each postoperative time point in the matched group was significantly smaller than that in the unmatched group,with statistically significant differences between groups at different time points(all P＜0.05).The matched group showed better stability in IOL decentration distance and tilt angle.At 12 months postoperatively,the residual astigmatism in the matched group was(0.53±0.29)D,which was better than that in the unmatched group(0.71±0.34)D(P=0.08).The matched group also had more significant improvement in uncorrected visual acuity and higher subjective visual quality scores.Multiple linear regression analysis showed that capsule-CTR fit and preoperative corneal astigmatism were the main independent factors affecting the rotation angle of Toric IOL(R2=0.52)and residual astigmatism(R2=0.46).Conclu-sion For patients with high myopia cataract,precise capsule-CTR matching based on CASIA2 measurement helps improve the rotational stability of Toric IOLs,reduce residual astigmatism,and enhance postoperative visual quality.Personalized CTR model selection is worth promoting and applying.

OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress

Objective:To explore the differences of metabolomic profiles in day 3 (D3) culture medium of embryos with varying developmental potentials, in order to provide a theoretical foundation for the establishment of embryo selection technology platform using metabolomics.Methods:Eight patients who received in vitro fertilization and embryo transfer (IVF-ET) treatment at Reproductive Medicine Center of Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital between November 13 and December 5, 2023 were selected as the study subjects. The D3 culture medium from patient embryos was collected and divided into high-quality blastocysts ( n=42), non-high-quality blastocysts ( n=33), and embryos that failed to form blastocysts (non-formation group, n=43) according to the formation of day 5 blastocysts. High-performance liquid chromatography-mass spectrometry was employed to perform non-targeted metabolomic analysis in the D3 culture medium from three distinct groups. Results:1) The metabolites in D3 culture medium of embryos with varying developmental potentials exhibit significant differences. Specifically, 79 differential metabolites were identified between the blastocyst formation group and the non-blastocyst formation group (all P<0.05); additionally, 73 differential metabolites were found between the high-quality blastocyst group and the non-high-quality blastocyst group (all P<0.05). 2) The area under the receiver operating characteristic curve of significantly differential metabolites for predicting potential of D3 embryo blastocyst formation and high-quality blastocyst formation were both greater than 0.9, demonstrating excellent predictive performance. 3) KEGG pathway enrichment analysis revealed that differential metabolites associated with blastocyst formation potential were primarily enriched in pathways including D-amino acid metabolism, glycine-serine-threonine metabolism, arginine biosynthesis, and histidine metabolism ( P<0.05). For high-quality blastocyst formation, the differential metabolites were predominantly enriched in pathways related to tryptophan metabolism, D-amino acid metabolism, serotonergic synapses, and protein digestion and absorption ( P<0.05). Conclusion:Embryos with different developmental potentials have significantly different metabolic profiles, and it is feasible to predict the developmental potential of D3 embryos by metabolomics analysis.

Anaplastic lymphoma kinase (ALK) rearranged renal cell carcinoma (ALK-RCC) is an exceedingly rare malignancy, recently classified as a distinct molecular entity in the 5th edition of the WHO classification for urinary and male genital tumors. Due to its non-specific clinical symptoms and diverse histopathological patterns, accurate diagnosis is difficult. This paper reports a case of ALK-RCC with morphology and immunophenotype resembling papillary renal cell carcinoma. After second-generation sequencing, EML4-ALK gene fusion was found, and positive staining for ALK was confirmed by immunohistochemistry subsequently. Following informed consent from the patient, targeted therapy with crizotinib was initiated. During a 17-month follow-up period, no recurrence or metastasis was observed.

[Objective] To explore the predictive value of HALP score for prognosis in patients with multiple myeloma (MM). [Methods] A retrospective analysis was conducted on laboratory indicators and related clinical data of newly diagnosed multiple myeloma (NDMM) patients, treated at the Affiliated Hospital of North Sichuan Medical College from January 2016 to October 2023, prior to their first treatment. The HALP score was calculated, and the optimal cutoff value for HALP was determined using X-tile software. Survival analysis was performed using Kaplan-Meier curves for high HALP and low HALP groups. Univariate and multivariate analyses were conducted using the Cox regression model, and a forest plot was generated using Graphpad Prism to illustrate factors that may impact patient prognosis. The predictive ability of HALP score combined with β2-microglobulin and ECOG score for prognosis in MM patients was evaluated using receiver operating characteristic curve (ROC) analysis. [Results] A total of 203 MM patients were included, with the optimal cutoff value for HALP score being 29.15 (P<0.05). Among them, 101 patients were in the low HALP score group, and 102 patients were in the high HALP score group. The results of univariate and multivariate analysis using the Cox regression model showed that a HALP score <29.15 was an independent risk factor for progression-free survival (PFS) and overall survival (OS) (P<0.05). ROC curve analysis indicated that the combination of HALP score with β2-microglobulin and ECOG score had a higher predictive value for prognosis in MM patients compared to using HALP score alone. [Conclusion] The HALP score is closely related to the prognosis of patients with NDMM. A low HALP score indicates a poorer prognosis, while the combination of HALP score with β2-microglobulin and ECOG score provides a higher predictive value when assessed together.