Objective To assess the effect of early nutritional intervention on the patients with respiratory diseases at nutritional risk. Methods A total of 130 patients with respiratory disease who were hospitalized in Shanghai Fifth People’s Hospital, Fudan University between May 2023 and December 2024 and had a nutritional risk screening 2002 score ≥3 points. Based on the initiation time of nutritional intervention, patients were divided into an early group (≤5 days, n＝65) and a late group (＞5 days, n＝65). Results In the early group, prealbumin (P-ALB) and retinol-binding protein (RBP) levels were significantly higher (P＜0.01), C-reactive protein (CRP), procalcitonin (PCT) levels were significantly lower after intervention (P＜0.05). Compared with the late group, the hospital costs were lower and hospital stays were shorter in the early group (P＜0.001). Spearman analysis showed ALB, P-ALB, and total protein (TP) were negatively correlated with hospital costs (r＝－0.37, －0.20, and－0.22, P＜0.05). RBP, ALB, P-ALB, and lymphocyte count (LYM) were negatively correlated with CRP (r＝－0.30, －0.26, －0.37, －0.18, P＜0.01), RBP, ALB, P-ALB, hemoglobin (HB), and TP were negatively correlated with PCT (r＝－0.23,－0.36, －0.40, －0.30, －0.19, P＜0.05). Conclusions For patients with respiratory diseases, early nutritional assessment should be underwent, and for patients with nutritional risk screening 2002 score ≥3 points, early nutritional intervention could improve the nutritional status and alleviate inflammatory response, promote recovery, shorten the hospital stays.

For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; ErbB Receptors/metabolism* ; Protein Kinase Inhibitors/adverse effects* ; Aged ; Antineoplastic Agents/adverse effects*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Humans ; Acupuncture Points ; Deglutition Disorders ; Electroacupuncture

Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral microbiome.Herein,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu2+))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)scaffolds.The morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in vitro.The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance.During the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release.The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects.Finally,the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model.Overall,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+)modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

ObjectiveTo investigate the mechanism of modified Shenhong Tongluo prescription on cell apoptosis in rats with myocardial ischemia-reperfusion injury （MIRI）. MethodSixty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， low-， medium-， and high-dose groups of modified Shenhong Tongluo prescription， and a simvastatin group. Except for the blank group， a rat model of MIRI was prepared by ligating the left anterior descending coronary artery. Starting from the first day after successful modeling， the blank group （1.0 mL·kg^-1 physiological saline）， model group （1.0 mL·kg^-1 physiological saline）， low-， medium-， and high-dose groups of modified Shenhong Tongluo prescription （1.031， 2.063， and 4.126 g·kg^-1 Shenhong Tongluo prescriptiona standard concentrate）， and simvastatin group （0.71 mg·kg^-1 simvastatin） were orally administered once daily for 2 weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of cardiomyocytes. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of serum creatine kinase isoenzyme （CK-MB）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）. TdT-mediated dUTP nick-end labeling（TUNEL） staining was used to detect the apoptosis rate of rat cardiomyocytes. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and caspase-3. ResultCompared with the blank group， in the model group， HE staining showed disturbed arrangement of cardiomyocytes， incomplete fibers， focal necrosis of cardiomyocytes， and inflammatory cell infiltration； serum CK-MB， IL-6， and TNF-α levels were significantly increased （P<0.05）； apoptosis rate of cardiomyocytes was significantly increased （P<0.01）， with significantly increased expression levels of Bax and Caspase-3 proteins， and significantly decreased Bcl-2 expression （P<0.05）. Compared with the model group， the low-， medium-， and high-dose groups of modified Shenhong Tongluo prescription significantly reduced CK-MB， IL-6， and TNF-α levels （P<0.05）， significantly downregulated cardiomyocyte apoptosis rate （P<0.05）， significantly decreased Bax and Caspase-3 proteins， and significantly increased Bcl-2 expression levels （P<0.01）. In the modified Shenhong Tongluo prescription groups， the expression levels of Bax and Caspase-3 proteins significantly decreased with increasing dosage， while the expression level of Bcl-2 significantly increased with increasing dosage of modified Shenhong Tongluo prescription （P<0.05）. ConclusionShenhong Tongluo prescription can alleviate myocardial tissue pathological damage and reduce myocardial cell apoptosis， possibly by inhibiting Caspase-3 and Bax expression and promoting Bcl-2 expression.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

The study was aimed to assess the impact of Brucea javanica oil emulsion(BJOE)on the responsiveness of programmed death receptor-1(PD-1)monoclonal antibody to lung adenocarcinoma in mice.The experimental approach involved subcutaneously inoculating Lewis's lung adenocarcinoma(LLC)cells into C57BL/6 mice,which were then divided into four groups:model group,25 ml·kg-1 BJOE group,10 mg·kg-1 PD-1 group,and combination group(25 ml·kg-1 BJOE and 10 mg·kg-1 PD-1).Tumor volume,mass,and inhibition rate were evaluated;the apoptosis within tumor tissue was detected by TUNEL staining;CD4+and CD8+T cell proportions within tumor tissues were analyzed by flow cytometry;the levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and granzyme B in tumor tissue were measured by enzyme-linked immunosorbent assay(ELISA).Additionally,LLC cells were categorized into a control group and three BJOE treatment groups(10,30,50 μl·ml-1),and programmed death ligand 1(PD-L1)expression in tumor tissues and LLC cells were assessed by Western blotting.Data showed that as compared with the model group,PD-1 monoclonal antibody alone did not significantly alter tumor volume,tumor mass,CD4+and CD8+T cell proportions,cytokine levels(IFN-γ,TNF-α,Granzyme B),or apoptosis in lung cancer-bearing mice.However,BJOE treatment reduced tumor volume and mass,enhanced CD4+and CD8+T cell proportions,increased cytokine levels,and augmented apoptosis(all P<0.05).Furthermore,the combination therapy of BJOE and PD-1 monoclonal antibody yielded significantly greater reductions in tumor volume and mass,with heightened CD4+and CD8+T cell proportions,cytokine levels,and apoptosis compared to either treatment alone(all P<0.05).Both BJOE treatment and the combination therapy significantly upregulated PD-L1 protein expression in tumor tissues compared to the model or PD-1 monoclonal antibody groups(P<0.05).Similarly,BJOE treatment at all tested concentrations significantly increased PD-L1 protein expression in LLC cells as compared to the control group(P<0.05).In conclusion,BJOE could upregulate PD-L1 expression in LLC cells and enhance the sensitivity of lung adenocarcinoma-bearing mice to PD-1 monoclonal antibodies.

Objective: To elucidate the biological basis of the heart qi deficiency (HQD) pattern, an in-depth understanding of which is essential for improving clinical herbal therapy. Methods: We predicted and characterized HQD pattern genes using the new strategy, TCM-HIN2Vec, which involves heterogeneous network embedding and transcriptomic experiments. First, a heterogeneous network of traditional Chinese medicine (TCM) patterns was constructed using public databases. Next, we predicted HQD pattern genes using a heterogeneous network-embedding algorithm. We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq. Finally, we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis. Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism, signal transduction pathways, and immune processes. Moreover, we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern. Furthermore, herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD. Conclusion Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes, but also deciphering the basis of HQD pattern. Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns, leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.