OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） combined with neoadjuvant chemotherapy in the treatment of early triple-negative breast cancer （TNBC）. METHODS Randomized controlled trials （RCTs） comparing ICIs combined with neoadjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy alone （control group） were retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， Wanfang Data， and VIP databases， as well as relevant studies published at oncology academic conferences. The search period was from database inception to June 30， 2025. After literature screening， data extraction， and quality assessment， a meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 6 RCTs involving 3 786 patients were finally included. The meta-analysis results showed that the experimental group had superior event-free survival [HR＝0.73， 95%CI （0.62， 0.85）， P＜0.000 1]， overall survival [HR＝0.69， 95%CI （0.57， 0.84）， P＝0.000 3]， and pathological complete response （pCR） [OR＝1.57， 95%CI （1.37， 1.80）， P＜0.000 01] compared to the control group. The incidence of ≥grade 3 adverse event （AE）， severe AE （SAE）， and ≥ grade 3 immune-related adverse event （irAE） in the experimental group was significantly higher than that in the control group. There was no statistically significant difference between the two groups in the incidence of any AE or any irAE （P＞0.05）. Subgroup analysis revealed that， regardless of programmed cell death ligand 1 expression status （negative or positive），the pCR in the experimental group was significantly higher than that in the control group （P＜0.05）. Additionally， the pCR of the patients with positive lymph nodes in the experimental group was significantly higher to that in the ontrol group （P＜0.05）. There was no statistically significant difference in pCR between the two groups with negative lymph nodes （P＝0.09）. CONCLUSIONS ICIs combined with neoadjuvant chemotherapy can significantly improve event-free survival and overall survival in patients with TNBC， providing patients with long-term survival benefits. However， the risk of ≥ grade 3 AE， SAE and ≥ grade 3 irAE has increased.

ObjectiveTo explore the application of virtual reality biofeedback training combined with oral localization therapy in dysphagia after oral cancer surgery. MethodsFrom May, 2023 to July, 2024, 86 patients with dysphagia after oral cancer surgery in Zhejiang Provincial People's Hospital were randomly divided into control group (n = 43) and experimental group (n = 43). The control group received conventional swallowing function training, while the experimental group added virtual reality biofeedback training combined with oral positioning therapy, for four weeks. The Standardized Swallowing Function Assessment Scale (SSA), Functional Oral Intake Scale (FOIS) and M.D.Anderson Dysphagia Inventory (MDADI) were used for evaluation before intervention, and two weeks, four weeks and eight weeks after intervention. ResultsFor scores of SSA , the main effects of group (F = 150.190, P < 0.001, η²_p = 0.641) and time (F = 230.870, P < 0.001, η²_p = 0.733), as well as the interaction effect (F = 16.910, P < 0.001, η²_p = 0.168) were all significant. For scores of FOIS, the main effects of group (F = 59.601, P < 0.001, η²_p = 0.415) and time (F = 89.464, P < 0.001, η²_p = 0.516), as well as the interaction effect (F = 7.990, P < 0.001, η²_p = 0.087) were all significant. For scores of MDADI, the main effects of group (F = 33.133, P < 0.001, η²_p = 0.283) and time (F = 49.650, P < 0.001, η²_p = 0.371), as well as the interaction effect (F = 3.224, P = 0.023, η²_p = 0.037) were all significant. ConclusionVirtual reality biofeedback training combined with oral localization therapy could improve the swallowing function, oral feeding ability and overall quality of life of patients with dysphagia after oral cancer surgery.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

AIM:To analyze the influencing factors of visual outcome after vitrectomy for polypoidal choroidal vasculopathy(PCV)combined with vitreous hemorrhage and establish a predictive model.METHODS: A retrospective analysis was conducted on the clinical data of 129 cases(129 eyes)of patients who underwent vitrectomy for PCV combined with vitreous hemorrhage from June 2021 to January 2024 in our hospital. They were divided into elevated group(71 eyes)and non-elevated group(58 eyes)according to visual outcome at early posoperative stage(within 24 mo). Another 30 cases(30 eyes)of PCV with vitreous hemorrhage undergoing vitrectomy were selected as external validation data. The predictive value of the model for the postoperative visual outcomes of both internal and external populations was evaluated.RESULTS: The non-elevated group had a higher proportion of patients aged ≥60 years, diabetes, continuous abnormalities of the ellipsoid zone(EZ)during surgery, bleeding involving the macular fovea, and postoperative retinal scar formation than the elevated group were independent factors affecting postoperative visual acuity(all P<0.05). The AUC of the predictive model for predicting the postoperative visual outcomes of internal and external populations was 0.824(95%CI: 0.750-0.898)and 0.809(95%CI: 0.723-0.865), respectively.CONCLUSION:Patients aged ≥60 years, diabetes, intraoperative continuous abnormalities of EZ, bleeding involving the macular fovea, and postoperative retinal scar formation are influencing factors for visual outcome after vitrectomy in patients with PCV combined with vitreous hemorrhage. A predictive model based on those factors has been established, which has a certain predictive value for postoperative visual outcome.

Biosensors have become powerful tools for real-time monitoring of specific small molecules and precise control of gene expression in biological systems. High-throughput sensors for 1, 4-butanediamine biosynthesis can greatly improve the screening efficiency of high-yielding 1, 4-butanediamine strains. However, the strategies for adapting the characteristics of biosensors are still rarely studied, which limits the applicability of 1, 4-butanediamine biosensors. In this paper, we propose the development of a 1, 4-butanediamine biosensor based on the transcriptional regulator PuuR, whose homologous operator puuO is installed in the constitutive promoter P_gapA of Escherichia coli to control the expression of the downstream superfolder green fluorescent protein (sfGFP) as the reporter protein. Finally, the biosensor showed a stable linear relationship between the GFP/OD₆₀₀ value and the concentration of 1, 4-butanediamine when the concentration of 1, 4-butanediamine was 0-50 mmol/L. The promoters with different strengths in the E. coli genome were used to modify the 1, 4-butanediamine biosensor, and the functional properties of the PuuR-based 1, 4-butanediamine biosensor were explored and improved, which laid the groundwork for high-throughput screening of engineered strains highly producing 1, 4-butanediamine.
Biosensing Techniques/methods* ; Escherichia coli/metabolism* ; Promoter Regions, Genetic/genetics* ; Green Fluorescent Proteins/metabolism* ; Transcription Factors/genetics* ; Escherichia coli Proteins/genetics* ; Diamines/metabolism* ; Gene Expression Regulation, Bacterial

OBJECTIVE To identify and characterize the chemical ingredients of Anchang formulation,further screen the active ingredients of this formulation treating ulcerative colitis by network pharmacology,and explore the potential targets and pathways,provi-ding scientific basis for its mechanism research and clinical application.METHODS Chemical ingredients in Anchang formulation were acquired by Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technology and literature retrieval.The potential active ingredients and key targets for the treatment were obtained from Swiss Target Prediction,GeneCards,STRING,and then Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were analyzed in the DAVID database.The interactions between the active ingredients and the core targets were verified by using the AutoDock software.The RAW 264.7 murine-derived macrophage inflammation model was also established to val-idate the anti-inflammatory activity of the pre-screened chemical ingredients and further explore the related mechanisms.RESULTS In this study,108 chemical ingredients of Anchang formulation were characterized by UPLC-Q-TOF-MS technology,and expanded to 134 through literature search.The component-target network where 39 core active components were screened was further constructed,and 15 key therapeutic targets were screened by the protein-protein interaction network constructed.The enrichment analysis of KEGG pathway indicated that Anchang formulation can regulate TNF,PI3K-Akt,MAPK,cancer and other related signaling pathways and ex-ert a therapeutic effect.The results of cell experiments showed that Anchang formulation and its active ingredients could inhibit the re-lease of NO,TNF-α and IL-6 in the LPS-induced RAW 264.7 cell inflammation model.CONCLUSION Based on the concept of"ingredient-target-pathway",this study evaluates the anti-inflammatory effect of Anchang formulation and its active ingredients,pre-dicts the potential mechanism of treatment for UC,and provides a theoretical basis and research ideas for the quality control of the for-mulation and its treatment for UC.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To evaluate the safety and efficacy of secondary transport on extracorporeal membrane oxygenation (ECMO) for critically ill children.Methods:This was a retrospective cohort study. Data from 222 pediatric patients who underwent ECMO transport from May 2019 to May 2024 at 5 ECMO centers and Chinese Database of Pediatric Extracorporeal Life Support Organization were collected. The cases were divided into primary and secondary transport groups by nature of transport. The clinical data, including demographics, ECMO indications, transport distance, pre-transport lab results, prognosis and complications were analyzed. Two independent samples t-test, Wilcoxon test, and χ2 test or Fisher′s exact probability method were used to compare the differences between 2 groups and evaluate the safety and efficacy of secondary transport. Results:Among the 222 children transported with ECMO, there were 135 males and 87 females, with an age of 3.0 (0.2, 7.0) years. There were 202 cases in the primary transport group and 20 cases in the secondary transport group. All secondary transport patients had failed attempts at weaning ECMO before transfer. The patients in the secondary transport group were older, had higher rates of surgical cannulation, circulatory support, and pre-ECMO lactate levels compared to the primary transport group (7.0 (2.8, 10.0) vs. 3.0 (0.2, 6.0) years old, 55.0% (11/20) vs. 3.6% (7/202), 80.0% (16/20) vs. 41.6% (84/202), (10±4) vs. (7±6) mmol/L, Z=3.41, χ 2=66.31, 10.99, t=2.24, all P<0.05). In the secondary transport group, the vasoactive-inotropic scores of patients on circulatory support and the oxygenation index for patients requiring respiratory support were higher than those in the primary transport group (83±33 vs. 82±68, 51.0±1.8 vs. 37.4±10.2, t=2.36, 2.63, respectively; both P<0.05). There were no statistically significant differences between the 2 groups in sex, transport distance, pre-ECMO creatinine, arterial blood gas BE values, and ECMO duration (all P>0.05). No life-threatening complications occurred during the transport in either group. Two patients in the secondary transport group underwent heart transplantation, and 1 patient underwent radiofrequency ablation. The overall survival rate between the 2 groups showed no statistically significant difference (45.0% (9/20) vs. 55.4% (112/202), χ2=1.15, P>0.05). Conclusions:Secondary ECMO transport for critically ill children don't increase mortality or life-threatening complications during transport. ECMO patients who cannot receive effective treatment locally can benefit from secondary transport to an advanced ECMO center provides further treatment opportunities.

Metanephric adenoma is a rare renal epithelial tumor with a low incidence and lack of specific clinical manifestations，resulting in a lack of uniformity in clinical understanding and treatment. Its etiology and pathogenesis are still unclear，and it may be related to the abnormal number and structure of chromosomes 2，7，and 17，as well as mutations in genes such as BRAF V600E，NF1，and NOTCH1，etc. There may be a transformed relationship between this tumor and Wilms’ tumor and papillary renal cell carcinoma. For diagnosis，it has diverse but non-specific clinical manifestations，and it is difficult to accurately differentiate it from other tumors in the imaging examination，and the confirmation of diagnosis relies on pathological and immunohistochemical staining. Treatment is mainly based on surgery to preserve the renal unit，such as partial nephrectomy，etc.，but the difficulty of preoperative diagnosis often leads to over-treatment，and there is a lack of standardized treatment protocols for metastatic posterior renal adenoma. The aim of this article is to provide a reference for the in-depth understanding of posterior renal adenomas and to optimize the clinical diagnosis and treatment strategies.