OBJECTIVE: To construct a predictive model for the reduction in methadone maintenance treatment (MMT) and evaluate the effects of different interventions and other clinical factors on methadone reduction using Shapley additive explanations (SHAP). METHODS: Two clinical trials of acupuncture for methadone reduction in MMT patients were analyzed, and the baseline data, MMT related information, intervention measures, the data related to dose-reduction outcomes were collected. The predictive model was constructed by means of 6 machine learning algorithms including support vector machine (SVM), K-nearest neighbors (KNN), logistic regression (LR), Naive Bayes (NB), random forest (RF) and categorical-boosting (CatBoost), and 2 integration methods, blending-ensemble method (Blending) and Stacking-ensemble method (Stacking). SHAP was employed for the interpretability analysis of the optimal model. RESULTS: A total of 251 MMT patients were included, 128 cases in the acupuncture group and 123 cases in the non-acupuncture group. CatBoost and Stacking performed optimally in the test set. CatBoost obtained an accuracy of 0.780 0±0.060 8, a precision of 0.500 0±0.120 0, a recall of 0.818 2±0.140 2, F1 score of 0.620 7±0.114 0, and receiver operating characteristic-area under curve (ROC-AUC) of 0.857 8±0.140 2 for the subjects. In MMT patients with acupuncture as an adjunctive therapy, the top 5 important features for methadone reduction, included intervention measures, body mass index (BMI), the duration of MMT, the history of opioid use and occupation; and SHAP values were 1.25, 0.36, 0.21, 0.19 and 0.12, respectively. The SHAP feature dependence plot showed that BMI, MMT duration and the history of opioid use presented a nonlinear negative correlation with the reduction effect. CONCLUSION In acupuncture as adjunctive therapy for methadone reduction, the clinical factors should be considered comprehensively; and the interpretable predictive model provides a scientific basis for it, which is conducive to the improvement of clinical strategy of acupuncture for methadone reduction and the development of personalized reduction scheme.
Humans ; Methadone/therapeutic use* ; Acupuncture Therapy ; Adult ; Female ; Male ; Machine Learning ; Middle Aged ; Opiate Substitution Treatment ; Young Adult

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

[This corrects the article DOI: 10.1016/j.apsb.2021.07.024.].

Nutritional support therapy is one of the extremely important treatment methods for patients in the intensive care unit. Timely and effective nutritional support regimens can improve patients' immune function, reduce complications, and optimize clinical outcomes. Energy expenditure is influenced by multiple factors, including patients' baseline characteristics (such as physical condition, gender, age) and dynamic changes in indicators (such as body temperature, nutritional support regimens, and therapeutic interventions). The currently recognized "gold standard" for accurately assessing energy metabolism in clinical practice is the indirect calorimetry system, also known as the metabolic cart. This device monitors carbon dioxide production and oxygen consumption in real time and uses specific algorithms to estimate the metabolic proportions of the three major nutrients (carbohydrates, fats, and proteins) in energy expenditure. An appropriate nutrient ratio helps maintain the balance between supply and demand in the body's nutritional metabolism. In the management of critically ill patients, the application of the metabolic cart enables personalized nutritional therapy, avoiding over- or under-supply of energy and optimizing the use of medical resources. Furthermore, with real-time, quantitative data support from the energy metabolism monitoring system, clinicians can develop more precise nutritional intervention strategies, thereby improving patient prognosis. This article provides a systematic review of the technical features of the metabolic cart and its application value in various critical care scenarios, aiming to offer a reference for indirect calorimetry in clinical practice.
Humans ; Critical Illness/therapy* ; Nutritional Support ; Energy Metabolism ; Calorimetry, Indirect

Objective:A two-sample bidirectional Mendelian randomization (MR) analysis was used to analyze the risk factors related to sunburn.Methods:Data were downloaded from the Gene-Wide Association Studies (GWAS) of the IEU Open GWAS project, and a two-sample bidirectional MR was conducted. In the forward MR analysis, the exposure factors were skin color, ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, urticaria, and education attainment, while the outcome factor was sunburn. In the reverse MR analysis, the exposure factor was sunburn, while the outcome factors were skin color, ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, urticaria, and education attainment. The data were analyzed using the "TwoSampleMR" package in R version 4.2.3. The result of the MR analysis were interpreted using the odds ratio ( OR) and the corresponding 95% confidence interval (95% CI), and a P-value <0.05 was considered statistically significant. In the analysis, we set a significance threshold of P-value<5×10 -8 (if sufficient instrumental variables cannot be obtained, the threshold will be adjusted to P-value<5×10 -6), eliminated linkage disequilibrium (with R2<0.001 and within a regional range of 10 000 kb), and screened single nucleotide polymorphisms (SNPs) that were significantly related to the research content, which would be set in the analysis as instrumental variables (IVs). For eligible IVs, a MR was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode method to explore the causal relationships between sunburn and various factors. The result obtained by the IVW method were taken as the main outcome indicator and summarized into a forest plot, while other method were used to supplement the IVW result. The heterogeneity of the IVs was evaluated by the Cochran Q-test. The direction of the causal effect and heterogeneity were evaluated through the scatter plot. The sensitivity of the result was analyzed by the leave-one-out test. The funnel plot was used to assess the potential bias. Results:9 851 867 SNPs related to skin color, 9 851 867 SNPs related to ease of skin tanning, 11 972 414 SNPs related to skin pigmentation, 9 851 867 SNPs related to facial aging, 16 121 213 SNPs related to atopic dermatitis, 24 191 078 SNPs related to contact dermatitis, 24 187 496 SNPs related to urticaria, 11 972 619 SNPs related to education attainment were obtained from the GWAS database. A total of 11 976 212 SNPs were obtained from the sunburn dataset. In the forward MR analysis, the IVW result showed a significant negative correlation between skin color and sunburn ( OR=0.68, 95% CI: 0.66-0.70, P<0.001); and a significant positive correlation between the ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, education attainment, and sunburn (ease of skin tanning: OR=1.30, 95% CI: 1.29-1.32, P<0.001; skin pigmentation: OR=1.76, 95% CI: 1.66-1.87, P<0.001; facial aging: OR=2.25, 95% CI: 1.67-3.04, P<0.001; atopic dermatitis: OR=1.02, 95% CI: 1.00-1.03, P=0.010; contact dermatitis: OR=1.01, 95% CI: 1.00-1.01, P=0.031; education attainment: OR=1.29, 95% CI: 1.22-1.36, P<0.001); while urticaria was not statistically significant ( P=0.056). The Cochran Q-test and scatter plot showed that there was a significant negative correlation between skin color and sunburn and a positive correlations between the ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, education attainment and sunburn. There was some heterogeneity among the IVs in research. The result of the leave-one-out test showed that no SNPs had a distinct impact on the causal effect, and the result of the forward MR analysis were relatively stable. The result of the funnel plot showed that the included SNPs were symmetrically distributed, and there was no potential bias in the result. In the reverse MR analysis, the IVW result showed a significant negative correlation between sunburn and skin color ( OR=0.16, 95% CI: 0.12-0.21, P<0.001); and a significant positive correlation between sunburn and ease of skin tanning, skin pigmentation, facial aging (ease of skin tanning: OR=26.78, 95% CI: 20.52-34.93, P<0.001; skin pigmentation: OR=3.12, 95% CI: 2.57-3.78, P<0.001; facial aging: OR=1.30, 95% CI: 1.24-1.37, P<0.001); while atopic dermatitis ( P=0.477), contact dermatitis ( P=0.318), urticaria ( P=0.328) and education attainment ( P=0.627) as outcome factors were not statistically significant. The Cochran Q-test and scatter plot showed that there was a significant negative correlation between sunburn and skin color and a positive correlations between sunburn and ease of skin tanning, skin pigmentation, facial aging. There was some heterogeneity among the IVs in research. The result of the leave-one-out test showed that no SNPs had a distinct impact on the causal effect, and the result of the reverse MR analysis were relatively stable. The result of the funnel plot showed that the included SNPs were symmetrically distributed, and there was no potential bias in the result . Conclusions:Skin color and sunburn are protective factors against each other; ease of skin tanning, skin pigmentation, and facial aging are bidirectional risk factors of sunburn; atopic dermatitis, contact dermatitis, and education attainment are risk factors of sunburn.

Objective:To describe the clinical and pathological features of patients with myofasciitis.Methods:The clinical manifestations and auxiliary examination (laboratory, electromyogram, imaging and muscle biopsy) results of 52 patients with myofasciitis diagnosed by pathology at Peking University First Hospital from August 2002 to December 2024 were collected and analyzed.Results:Among the 52 patients (33 males and 19 females), the age of disease onset was (34.4±16.4) years (6.0-73.0 years) and the disease duration was 17.7 (0.3, 120.0) months; the main symptoms included myalgia in the distal limbs (28 cases, 53.8%), diffuse cutaneous or muscle sclerosis (21 cases, 40.4%), muscle weakness (22 cases, 42.3%) and limited joint activity (23 cases, 44.2%); 12 patients (23.1%) were combined with other diseases. All patients had no history of vaccination. Laboratory examinations showed that 80.8% (21/26) of patients had elevated C-reactive protein, 80.0% (20/25) had elevated erythrocyte sedimentation rate, and 26.5% (9/34) had elevated creatine kinase. Among 19 patients undergoing electromyography, 6 cases showed myogenic changes, 4 cases showed neurogenic changes, 1 case showed both myogenic and neurogenic changes, and 8 cases showed no obvious abnormality. Myofascial edema was observed in all 15 patients who underwent muscle magnetic resonance imaging, with partial involvement of adjacent muscles in some cases. According to myopathological changes, the 52 patients were divided into macrophagic myofasciitis in 41 cases (78.8%), lymphocytic myofasciitis in 7 cases (13.5%), and eosinophilic fasciitis in 4 cases (7.7%). Among the 52 patients, fibroblast proliferation in the myofascia was present in 39 cases (75.0%), subfascial muscle fiber atrophy in 28 cases (53.8%), and scattered muscle fiber necrosis and regeneration in 15 cases (28.8%). Major histocompatibility complex class Ⅰexpression on muscle fibers was positive in 89.5% (34/38) of patients, and membrane attack complex deposition on muscle fibers and/or capillary walls was present in 39.5% (15/38) of patients. Among 25 patients with follow-up, all received low-dose oral glucocorticoids, and 7 additionally received methotrexate, intravenous immunoglobulin, or hydroxychloroquine. During follow-up, 22 patients showed clinical improvement, 1 patient remained stable, and 2 patients died.Conclusions:Non-vaccine-associated macrophagic myofasciitis is the most common pathological subtype of myofasciitis. A few patients are concomitant with other diseases. Muscle magnetic resonance imaging is helpful in the diagnosis of the disease. Most patients respond to immunosuppressive treatment.

Objective To develop and validate a prediction model for risk of amputation in patients with diabetic foot ulcers(DFU)based on systematic review and meta-analysis.Methods The studies on the risk factors of amputation in DFU patients was retrieved by using subject words+free words.After screening,37 cohort studies were finally included,and the Newcastle-Ottawa scale(NOS)was used for quality evaluation.Meta-analysis was performed on the risk factors of amputation in DFU.Then a prediction model for DFU amputation risk were constructed based on the statistically significant risk factors in the meta-analysis.The corresponding β value was calculated based on the combined odds ratio(OR)value of each risk factor,and each risk factor was scored to establish a scoring system model.The clinical data of 453 DFU patients hospitalized in our department from 2021 to 2023 were collected as a validation cohort.Receiver operating characteristic(ROC)curve analysis was used to evaluate the model performance.The area under the curve(AUC)was calculated,and the optimal cutoff score was determined by calculation of the maximum Youden index through sensitivity and specificity.Results Our meta-analysis showed a cumulative amputation rate of approximately 34.65%in 11 779 DFU patients.The final risk prediction models include gangrene[OR=11.92(5.86～24.24)],ulcer depth[OR=4.93(2.52～9.64)],osteomyelitis[OR=3.19(2.36～4.29)],previous amputation history[OR=3.19(2.00～5.09)]and lower extremity arterial disease[OR=3.10(2.31～4.17)].According to the weights of each risk factor,the total score of the model is 76,and the optimal cut-off score is 36.5.The prediction model performed well,with an AUC value of 0.864(0.824,0.903),a sensitivity of 0.743,a specificity of 0.859,and an accuracy rate of 83.00%.Conclusion A prediction model for DFU amputation risk is developed based on risk factor scoring,and has good discrimination and calibration,providing effective scientific basis for clinical research and clinical decision-making related to DFU amputation.

ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

Objective To investigate the effects of patient bone mass differences on the stability of unicondylar knee arthroplasty(UKA)prostheses.Methods A UKA finite element model was established to quantify the effects of five different bone quality conditions on the proximal tibial von Mises stress,bone-prosthesis fixation interface contact stress,and bone-prosthesis fixation interface micromotion,using the medial knee force and joint motion predicted by the individualized UKA musculoskeletal multibody dynamics model as boundary conditions.Results The influences of bone strength on the proximal tibia von Mises stress and bone-prosthesis fixation interface contact stress were not obvious,and the difference in peak values of the proximal tibia von Mises stress between two groups of models with the largest difference in bone strength was not more than 5％,and the difference in peak values of the bone-prosthesis fixation interface contact stress was only 2.37 MPa.However,the influence of bone strength on the bone-prosthesis fixation interface micromotion was significant,and the weaker bones were more prone to cause the bone-prosthesis fixation interface micromotion.However,bone strength had a significant effect on the bone-prosthesis fixation interface micromotion,and weak bone was more likely to cause changes in the bone-prosthesis fixation interface micromotion.Compared to patients with the neutral bone quality,the prosthesis fixation interface micromotion increased by 84.67％at 20％gait cycles for patients with the weakest bone quality.Conclusions UKA patients with a weaker bone quality have a higher risk of prosthesis loosening.It is recommended that surgeons should carefully choose their surgical strategy in order to reduce the rate of postoperative revision in UKA.