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.

OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

Blood transfusion is an important life-support measure in modern medicine. As clinical demand for transfusion continues to rise, blood supply remains under persistent strain, making the efficient utilization of this precious medical resource a critical component of blood management. Accurate prediction of transfusion needs is of great significance for optimizing blood resource allocation and conserving blood products. Traditional transfusion decision-making relies on clinical experience and simplified scoring systems, which are insufficient to meet the demands of precision medicine. Machine learning (ML) technology can integrate multidimensional data—including demographic characteristics, laboratory indicators, surgical information, and dynamic physiological waveforms—to construct high-performance predictive models, offering a new approach to transfusion prediction. This article systematically reviews the application progress of ML in transfusion prediction across clinical scenarios such as trauma, the perioperative period, and obstetrics. In trauma, ML has been applied to early massive transfusion prediction, prehospital transfusion decision-making, and precise prediction in pediatric trauma. In the perioperative field, applications span specialties including traumatic brain injury, orthopedic surgery, cardiovascular and major vascular surgery, and hepatic surgery. In obstetrics, models can effectively predict postpartum hemorrhage and transfusion requirements associated with cesarean section. Studies have shown that algorithms such as random forest, gradient boosting machines, and deep neural networks achieve area under the receiver operating characteristic curve (AUC) values of 0.83-0.98 in massive transfusion prediction, 0.75-0.97 in perioperative scenarios, and 0.80-0.89 in obstetric transfusion prediction—significantly outperforming traditional scoring tools. However, current studies are generally limited by single-center retrospective designs, insufficient external validation, and inadequate reporting standards; limited model interpretability and challenges in clinical integration further constrain practical translation. Future research should focus on constructing multicenter data cohorts, integrating multimodal data, conducting prospective implementation studies, and deeply embedding models within electronic health record systems, thereby advancing the application of ML to optimize clinical transfusion decision-making.

OBJECTIVE To explore the therapeutic efficacy and mechanism of oridonin （ORI） against obesity-related glomerulopathy （ORG） based on the liver X receptor α （LXRα） signaling pathway. METHODS Kidney tissues of LXRα wild-type homozygous （LXRα+/+） mice and LXRα homozygous knockout （LXRα－/－） mice were subjected to high-throughput renal transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict key pathways and targets regulated by LXRα， followed by verification via Western blot assay. An ORG mouse model was established by feeding a high-fat diet. The LXRα agonist GW3965 （30 mg/kg） was set as the positive control. After intragastric administration of 50 mg/kg and 100 mg/kg ORI once daily for 4 consecutive weeks， the body weight， renal weight， renal histopathological alterations， serum renal function indicators， blood lipid levels and inflammatory factor levels in renal tissue of mice were detected and observed to evaluate the efficacy of ORI in alleviating ORG. Meanwhile， the mRNA and protein expression levels of LXRα and its downstream targets in mouse renal tissues were detected to validate the mechanism by which ORI relieves ORG. RESULTS Compared with LXRα+/+ mice， the upregulated differentially expressed genes in renal tissues of LXRα－/－ mice were significantly enriched in the arachidonic acid（AA） metabolic pathway， and the expression level of Cyp4a12 was markedly elevated （adjusted P＜0.05）. Western blot results verified that cytochrome P450 family 4 subfamily A member 12（CYP4A12）protein expression was significantly increased in the kidneys of LXRα－/－ mice （P＜0.05）. Pharmacodynamic results showed that both 50 mg/kg and 100 mg/kg ORI notably improved renal pathological lesions in ORG mice； these two doses reduced body weight， renal weight， serum creatinine， blood urea nitrogen， blood lipid levels as well as renal interleukin-6 （IL-6） and IL-1β levels （P＜0.05）. In addition， ORI significantly upregulated the mRNA and protein expression of renal nuclear LXRα and ABCA1， and downregulated the mRNA and protein expression of CYP4A12（P＜0.05）. CONCLUSIONS ORI may exert an ameliorative effect on ORG by activating the LXRα signaling pathway， downregulating CYP4A12 expression， and inhibiting AA-induced inflammatory metabolism.

Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.

Childhood cataract is a disease that affects the development of children's vision. It is divided into infants and adolescents according to the age of onset. Surgery is the main treatment, but the vision after surgery is difficult to reach the level of healthy children. Macular dysplasia is an important factor affecting postoperative visual acuity. In recent years, with the development of optical coherence tomography and optical coherence tomography angiography, more and more research has been done on macular development of children's cataract. The retinal structure in the macular area of children with cataract is abnormal, and the early inflammatory reaction after surgery can also lead to structural changes. In addition, insufficient blood supply to the macular area may affect retinal structure and function. The mechanism by which childhood cataract affects macular structure is still unclear and needs further study. Understanding the relationship between macular structure and vision prognosis is helpful to develop more effective treatment and improve the vision prognosis of children.

Objective To investigate the factors influencing the natural outcome of low-grade squamous intraepithelial lesions(LSIL)of the cervix.Methods A total of 154 patients who underwent colposcopic cervical biopsy in the Third Affiliated Hospital of Zhengzhou University from January 2022 to January 2023 were selected and divided into negative conversion group(55 cases),continuous group(70 cases)and upgraded group(29 cases)according to the follow-up results.Logistic regression was used to analyze the influence of related factors on the outcome of LSIL.Results There were statistically significant differences in the number of vaginal births,the results of thin-prep cytology test,human papilloma virus(HPV)typing,whether vaginal LSIL was combined,whether there were symptoms,and vaginal microecology among three groups(P＜0.05).Multivariate Logistic analysis showed that combined vaginal LSIL,vaginal microecological abnormalities,atypical squamous cell-cannot exclude high-grade squamous intraepithelial lesion(ASC-H)/high-grade squamous intraepithelial lesion(HSIL),HPV 16/18 positive or mixed positive were independent risk factors for persistent infection(P＜0.05),combined vaginal LSIL,symptomatic,vaginal microecological abnormalities,ASC-H/HSIL,HPV 16/18 positive or mixed positive were all independent risk factors for escalation of lesions(P＜0.05).Conclusion Patients with vaginal LSIL,vaginal microecological abnormalities,ASC-H/HSIL,HPV 16/18 positive or mixed positive should be followed up and early intervention to reduce the risk of disease escalation.

Objective To explore the effect of chrysin on intestinal flora in mice with alcoholic liver disease(ALD).Methods Mice were randomly assigned to normal control group,ALD model group,Silymarin group,chrysin low-dose group,chrysin high-dose group(25,50 mg·kg-1).The mice were fed with alcoholic liquid diet and a single dose of alcohol(5 g·kg-1)for eight weeks to establish the ALD model.After eight weeks of oral administration,each group's serum and plasma lipids and liver function indices were collected and detected using kits;then collected the liver and observed the pathological changes of the liver using HE staining;meanwhile,intestinal contents were collected and changes in mouse gut flora were analyzed by 16S rDNA sequencing.Results Compared with the ALD group,the level of aspartate transaminase(AST),alanine transaminase(ALT)and triacylglycerol(TG)of low-dose and high-dose chrysin groups were significantly reduced,and it can alleviate liver cell steatosis and inflammatory reactions caused by alcohol.16S rDNA results showed that the total number and types of intestinal flora in the ethanol group were significantly reduced,as well as a change in the dominant genus to Escherichia-Shigella and Akkermansia.Compared to the ALD model group,the Shannon index of the intestinal microbiota increased significantly in mice treated with low and high doses of chrysin.In addition,at the phylum and genus level,the abundance of the high-dose chrysin group increased significantly,resulting in an overall increase in the total number and amount of microbiota.The abundance of dominant bacterial groups,such as Oscillospirales,irmicutes,andAlloprevotella,was also significantly increased.Conclusion Chrysin may exert therapeutic effects on ALD by improving intestinal flora imbalance in ALD mice.

Objective To retrospectively analyze the distribution and differences of oral behavior among patients with acute and chro-nic painassociated with temporomandibular disorders(TMD).Methods A total of 212 patients with pain TMD in West China Hospital of Stomatology completed oral behaviors checklist(OBC).SPSS statistical software was used to analyze all the data.Results The pa-tients with pain-related TMD had specific oral behaviors,such as"pressure on the jaw during sleep"(49.5%),"unilateral chewing"(49.5%),"upper and lower teeth contact when not eating"(37.7%),etc.Scores of"upper and lower teeth contact when not eating"and"muscle tension when teeth are not clenched or teeth are not in contact"in patients with chronic pain TMD were higher than those of acute patients,and the difference was statistically significant(P＜0.05).The total OBC scores and daytime OBC scores of chronic pain TMD patients were higher than those of acute pain patients,and the difference was statistically significant(P＜0.05).There was no significant difference in OBC scores of patients with acute and chronic pain TMD during sleep(P＞0.05).Conclusion Pain-related TMD patients had specific oral behaviors,and patients with chronic pain TMD exhibited higher levels of total OBC,daytime OBC,"upper and lower teeth contact when not eating"and"muscle tension when teeth do not bite or teeth are not in contact"oral behavior than acute pain TMD patients.In the treatment of patients with painful TMD,correcting the patient's bad oral behavior can help the treatment of pain-related TMD.

Objective To explore the relationship between blood pressure at baseline and significant decline in cognitive function after 4 years in middle-aged and elderly people in rural Xi'an,and the potential effect of age on the relationship.Methods Data were collected from a cohort of middle-aged and elderly people with cognitive impairment in rural Xi'an,Shaanxi Province.The cohort consisted of people aged≥40 years from a village in Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.Blood pressure parameters studied included hypertension and high systolic blood pressure(≥140 mmHg vs.＜140 mmHg),and high diastolic blood pressure(≥90 mmHg vs.＜90 mmHg).The Mini-Mental State Examination(MMSE)was used to assess the whole cognitive function,and the decline of MMSE score ≥4 points in 4 years was defined as significant decline of cognitive function.Multivariate Logistic regression was used to analyze the relationship between blood pressure and cognitive function at baseline.Subgroup analysis was used to study the effect of age(＜65 vs.≥65 years)on the relationship.Results We recruited a total of 1 350 subjects in the analysis,including 235 subjects(17.4％)with baseline age ≥65 years and 533 male subjects(39.5％);671 subjects(49.7％)had hypertension,with systolic blood pressure of(131.71±17.79)mmHg;840 subjects(62.2％)had high systolic blood pressure,with diastolic blood pressure of(82.18±10.56)mmHg;395(29.3％)had high diastolic blood pressure.During the 4-year follow-up,56 cases(4.2％)met the criteria for significant decline of cognitive function.We did not find significant association of hypertension and high systolic blood pressure with cognitive decline in the general population,＜65-year-old subgroup,or ≥ 65-year-old subgroup.The incidence of significant cognitive decline was not statistically significant in the total population(3.6％vs.5.6％,P=0.092),the ≥65-year-old subgroup(7.5％vs.8.2％,P=0.855),the normal diastolic blood pressure group,or the high diastolic blood pressure group.However,in the subgroup＜65 years,the incidence of cognitive decline was higher in the high diastolic blood pressure group than in the normal diastolic blood pressure group(2.7％vs.5.1％,P=0.043).Multivariate analysis showed that high diastolic blood pressure was not found to be associated with significant cognitive decline in the total population(OR=1.744,95％CI:0.953-3.192,P=0.071),the subgroup of ≥65 years old(OR=0.858,95％CI:0.221-3.338,P=0.825),or the subgroup of ≥65 years old.In the＜65 age group,high diastolic blood pressure was significantly associated with cognitive decline(OR=2.051,95％CI:1.005-4.186,P=0.048).Conclusion High diastolic blood pressure is associated with 4-year cognitive decline in people aged 40-65 years,but not in those aged ≥65.No association is found between hypertension or high systolic blood pressure and significant cognitive decline.