Objective: To systematically evaluate the influencing factors for repeated implantation failure (RIF) after in vitro fertilization-embryo transfer (IVF-ET) in China, so as to provide the evidence for prevention of RIF. Methods: Literature on influencing factors for RIF in China were retrieved from CNKI, Wanfang Data, VIP, China Medical Literature Service System, PubMed, Web of Science, Cochrane Library and Embase from inception to September, 2024. A meta-analysis was performed using RevMan 5.3 and Stata 14.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was evaluated using Egger's test. Results: Initially 4 836 relevant articles were retrieved, and 12 of them were finally included, with a total sample size of 11 554 individuals. There were 10 case-control studies, 1 cohort study, and 1 cross-sectional study; and 10 high-quality studies and 2 medium-quality studies. The meta-analysis showed that factors including advanced age (OR=1.121, 95%CI: 1.035-1.215), prolonged infertility duration (OR=1.237, 95%CI: 1.091-1.403), abnormal hysteroscopy findings (OR=2.205, 95%CI: 1.119-4.348), positive anti-nuclear antibody (ANA) (OR=2.393, 95%CI: 1.473-3.886), and positive anti-beta2 glycoprotein Ⅰ antibody (β2-GPⅠ-Ab) (OR=2.824, 95%CI: 1.987-4.013) were associated with an increased risk of RIF; while factors including the large number of embryos transferred (OR=0.309, 95%CI: 0.098-0.973), thicker endometrium (OR=0.601, 95%CI: 0.556-0.650), and higher granulocyte colony-stimulating factor (G-CSF) levels (OR=0.657, 95%CI: 0.511-0.845) were associated with a reduced risk of RIF. Conclusion IVF-ET RIF is associated with age, infertility duration, number of embryos transferred, endometrial thickness, hysteroscopy findings, G-CSF levels, ANA and β2-GPⅠ-Ab.

BACKGROUND: Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP. METHODS: Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo . RESULTS: 4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model. CONCLUSIONS Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism* ; Humans ; Animals ; Succinates/pharmacology* ; Mice ; Male ; Female ; Adult ; Middle Aged ; Flow Cytometry ; Tumor Necrosis Factor-alpha/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Purpura, Thrombocytopenic, Idiopathic/metabolism* ; Glycolysis/drug effects* ; Metabolic Reprogramming

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

Drug-drug interaction (DDI) refers to the interaction between two or more drugs in the body, altering their efficacy or pharmacokinetics. Fully considering and accurately predicting DDI has become an indispensable part of ensuring safe medication for patients. In recent years, many deep learning-based methods have been proposed to predict DDI. However, most existing computational models tend to oversimplify the fusion of drug structural and topological information, often relying on methods such as splicing or weighted summation, which fail to adequately capture the potential complementarity between structural and topological features. This loss of information may lead to models that do not fully leverage these features, thus limiting their performance in DDI prediction. To address these challenges, we propose a relation-aware cross adversarial network for predicting DDI, named RCAN-DDI, which combines a relationship-aware structure feature learning module and a topological feature learning module based on DDI networks to capture multimodal features of drugs. To explore the correlations and complementarities among different information sources, the cross-adversarial network is introduced to fully integrate features from various modalities, enhancing the predictive performance of the model. The experimental results demonstrate that the RCAN-DDI method outperforms other methods. Even in cases of labelled DDI scarcity, the method exhibits good robustness in the DDI prediction task. Furthermore, the effectiveness of the cross-adversarial module is validated through ablation experiments, demonstrating its superiority in learning multimodal complementary information.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Immature permanent teeth refer to those that have erupted but have not yet formed and matured in terms of shape and structure. The characteristics of their disease onset and treatment methods are different from those of ordinary permanent teeth. Children with special healthcare needs often lack the capacity to cooperate during routine dental procedures, making treatment under general anesthesia (GA) the preferred option. With social advancements, the demand for pediatric dental GA has considerably increased. This study discuss the treatment strategies for immature permanent teeth under GA, including diagnosis, therapeutic principles, key considerations, and clinical approaches for dental caries, pulpitis periapical periodontitis, etc.
Child ; Humans ; Anesthesia, General ; Dental Caries/diagnosis* ; Dentition, Permanent ; Periapical Periodontitis/therapy* ; Pulpitis/therapy*

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective To investigate the effect of eosinophil(EOS)/neutrophil(NER)in peripheral blood on asthma recurrence in children with bronchial asthma(BA)after treatment.Methods A prospective cohort study was conducted in the study.BA children admitted to the hospital from February 2020 to February 2022 were selected as the research objects.All children were treated regularly and their condition was under con-trol.After a follow-up of 6 months,the recurrence of the children was recorded.EOS/NER,interleukin(IL)-4 and IL-5 of children with and without relapse before treatment and at 1 week of treatment were compared.Lo-gistic regression analysis model was established to test the effect of EOS/NER on the recurrence of asthma in children with BA after treatment.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of EOS/NER,IL-4 and IL-5 before treatment for the recurrence risk of BA children after treatment.Results A total of 128 children with BA were included.25 cases recurred after 6 months of follow-up,with a recurrence rate of 19.53%.EOS/NER,IL-4 and IL-5 of BA children after 1 week of treatment were lower than those before treatment(P<0.05).EOS/NER,IL-4 and IL-5 of recurrent children before treat-ment and 1 week after treatment were higher than those of non-recurrent children(P<0.05).There were no statistically significant differences in EOS/NER,IL-4,IL-5 levels between children of different genders,age groups,and treatment regimens before and after 1 week of treatment(P>0.05).Increased EOS/NER,in-creased level of IL-4 and increased level of IL-5 had effect on the recurrence of BA children after treatment and may be risk factors for recurrence(OR>1,P<0.05).The ROC curve showed that area under the curve of EOS/NER before treatment for predicting the recurrence was 0.810(95%CI:0.724-0.896,P<0.001)in BA patients after 6 months of treatment,with moderate predictive value.Conclusion EOS/NER before treat-ment in BA children may be an independent risk factor for recurrence after treatment,and has moderate pre-dictive value for recurrence risk.

International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.