Malignant tumors remain one of the most critical global public threats to human health. The early diagnosis and precise therapeutic interventions are pivotal for improving patient survival rates and prognosis. Gold nanoclusters (Au NCs), distinguished by their ultra-small size (<3 nm), tunable optical properties, and exceptional biocompatibility, have emerged as transformative agents in precision oncology. This comprehensive review systematically summarizes the multifaceted applications of Au NCs in malignant tumor treatment. We discuss their roles as follows. (1) Intelligent delivery vehicles for targeted chemotherapy and controlled release through surface functionalization. (2) Therapeutic agents for chemodynamic therapy (CDT). This capability stems from their intrinsic enzyme-like catalytic activity or potent thioredoxin reductase (TrxR) inhibitory function, which disrupts the intracellular redox homeostasis and effectively activates downstream apoptotic pathways.(3) Direct therapeutic agents are characterized by their energy conversion capabilities: they can either convert absorbed light into heat to directly kill cancer cells, or transfer that photon energy to surrounding oxygen molecules to generate cytotoxic reactive oxygen species (ROS), leading to cell apoptosis or necrosis. (4) Potent radiosensitizers that enhance radiotherapy efficacy by enhancing localized radiation dose and promoting ROS generation. This review systematically summarizes the recent advances in Au NCs as intelligent delivery systems, direct chemotherapeutic agents, phototherapeutic agents, and efficient radiosensitizers in tumor treatment, elucidating how Au NCs overcome traditional therapeutic limitations through synergistic strategy. It establishes a robust theoretical foundation for next-generation nanotheranostic platforms. However, the translation of laboratory findings into functional clinical technologies confronts three significant challenges. First, although researchers can synthesize atomically precise Au NCs, achieving large-scale production of batches with completely consistent structure, size, and surface chemistry remains extremely challenging. To effectively control the final synthetic product, a deep understanding of the characteristics and formation mechanisms of Au NCs is essential. The traditional “trial-and-error” experimental approach faces inherent limitations when dealing with vast combinations of variables, which is time-consuming, labor-intensive, and struggles with systematic exploration and reproducibility. Machine learning has emerged as a powerful tool to bridge fundamental research and clinical application, which can guide experiments in reverse by predicting synthesis success through data mining and multi-variable analysis. In the future, we anticipate to achieve precise prediction and on-demand design of Au NCs’ structure and properties. Secondly, a systematic framework for evaluating the in vivo pharmacokinetics and long-term toxicity of Au NCs is absent. To address this gap, it is crucial to develop advanced imaging methodologies and integrated theranostic platforms. Au NCs, serving as both a therapeutic core and a highly promising photoluminescent material, are key to constructing such platforms through integration with other agents. These multifunctional systems are designed to achieve optimal synergistic therapy by combining multiple treatment modalities. Finally, the investigation of Au NCs is still largely confined to preclinical cellular and animal studies. Progress necessitates comprehensive clinical research to rigorously assess their safety and efficacy across a range of human cancer models, thereby ensuring broad clinical applicability. In summary, Au NCs-based platforms hold immense promise for translation into clinical anticancer therapy.

Objective To identify genetic regulators of ionizing radiation(IR)sensitivity through clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9(Cas9)genome-wide screening.Methods A specialized single guide RNA(sgRNA)library was developed targeting 987 stress-response regulatory genes identified through Kyoto Encyclopedia of Genes and Genomes(KEGG),Reactome and gene ontology(GO)databases,followed by construction of sgRNA plasmids and packaging into a lentiviral library.Using colon adenocarcinoma Caco-2 cells as a model system,the Cas9-stable transgenic line was established via lentiviral transduction and antibiotic selection.Library-transduced cells underwent puromycin selection,followed by γ-irradiation(dose optimized via preliminary experiments).Post-irradiation phenotypic selection was conducted after 14 days,with subsequent next-generation sequencing of surviving cell populations to identify enriched/depleted sgRNAs.Candidate genes were functionally validated through orthogonal assays:cell counting kit-8(CCK-8)proliferation analysis,clonogenic survival assays and flow cytometric quantification of reactive oxygen species(ROS)and apoptotic markers.Results The optimized screening platform identified 281 radiation response genes(165 radiosensitive and 116 radioprotective candidates).Functional validation revealed Bcl2-associated athanogene 3(BAG3)knockdown significantly enhanced radioresistance.Proliferation was increased 1.2-1.5 fold,clonogenic survival improved 1.5-2.0 fold,and ROS was reduced by 13％-25％coupled with 32％-73％apoptosis attenuation compared to control groups.Conclusion The integrated CRISPR/Cas9 screening platform effectively identifies novel radiation response regulators,as evidenced by the discovery of BAG3 as a critical radiosensitivity determinant.This high-throughput functional genomics approach provides a robust methodology for systematically mapping molecular determinants of cellular radiation response,with potential applications in both mechanistic studies and therapeutic target discovery.

Objective To investigate the effects of strength training and flexibility training on the strategy of crossing obstacles for the elderly women and the risk of tripping over obstacles.Methods Twenty five elderly women were randomly divided into strength training group(n=13)and flexibility training group(n=12),and received corresponding intervention training for 12 weeks.The kinematics data of obstacle crossing were collected using an infrared three-dimensional(3D)motion capture system before and after training.Results Both strength training and flexibility training could significantly improve the gait speed(P=0.033),stride length(P=0.020)and toe distance(P=0.014)during 25 cm obstacle crossing.The interactive effect of training and time was significant for the crossing height(15 cm:P=0.025;25 cm:P=0.019).The interactive effect of training and time was significant for the margin of stability(MOS)in the internal-external direction during 25 cm obstacle crossing(P<0.05).The minimum MOS in the first single support period(P=0.046)and the MOS at the time when the toe crossed directly above the obstacle(P=0.043)in strength training group were significantly increased.Conclusions Both strength training and flexibility training can improve the spatiotemporal characteristics of the elderly women during obstacle crossing.Compared with flexibility,muscle strength is the most important reason that restricts the crossing height of the elderly women.Strength training can effectively reduce the risk of tripping over obstacles by improving the crossing height and dynamic stability of elderly women.

In July 2024,the Diagnosis Related Groups(DRG)2.0 is released based on the Notice from the National Healthcare Security Administration on Issuing the DRG 2.0 and Deepening the Relevant Work.Compared with DRG 1.1,version 2.0 was established based on a wider range of suggestions regarding the Adjacent Diagnosis Related Groups(ADRG),Major Comorbidity or Complication(MCC),and Comorbidity or Complication(CC)from various institutions.A list of disease diagnoses and surgical operations that are not used as grouping rules was compiled,and grouping efficacy was further improved by upgrading the algorithms for MCC and CC with the help of AI.Meanwhile,it is necessary to pay more attention to the number of cases of ADRG,the better methods to list the MCC/CC,the suggestions of various doctors and continuously standardize the data and update the grouping scheme of DRG.

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway plays a crucial role in the regulation of renal fibrosis by participating in inflammatory response,oxidative stress and autophagy.Paeoniflorin exhibits remarkable efficacy in treating myocardial and liver fibrosis.This article provides a comprehensive review on the research progress of paeoniflora in preventing and treating renal fibrosis through modulation of the PI3K/Akt/mTOR signaling pathway,offering novel insights for traditional Chinese medicine-based approaches to prevent and treat renal fibrosis.

OBJECTIVES: To investigate the risk factors of overall postoperative complications in elderly patients undergoing gastrointestinal surgeries. METHODS: This study was conducted among a total of 1388 elderly patients, who underwent elective gastrointestinal surgeries at 17 centers across China between April, 2020 and April, 2022. The primary outcome was the incidence of postoperative complications within 30 days, including procedure-related, neuropsychiatric, respiratory, cardiovascular, and gastrointestinal complications as well as acute kidney injury. Baseline characteristics, preoperative psychological and functional status, intraoperative anesthesia and surgical factors, intraoperative medication, use of nerve block, and postoperative analgesia methods were compared between the patients experiencing one or more postoperative complications and those without complications. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for postoperative complications. The relationship between postoperative acute pain and each type of complication were explored. RESULTS: The incidence of overall postoperative complications was 50.8% (705/1388) in these patients. Multivariate analysis showed that age (OR: 1.026; 95% CI: 1.006-1.046), prognostic nutritional index (OR: 0.998; 95% CI: 0.997-1.000), preoperative EuroQol-5 dimensions score (OR: 0.094; 95% CI: 0.018-0.500), blood loss (OR: 1.002; 95% CI: 1.001-1.003), and acute postoperative pain (OR: 1.308; 95% CI: 1.033-1.657) were significantly associated with the occurrence of postoperative complications. Specifically, patients experiencing severe postoperative pain had a significantly higher incidence of neuropsychiatric (27.2% vs 19.8%), procedure-related (17.3% vs 10.2%), and cardiovascular complications (3.6% vs 1.7%). CONCLUSIONS An advanced age, a low preoperative nutritional index, a poor quality of life score, a greater volume of intraoperative blood loss, and acute postoperative pain are independent risk factors for postoperative complications in elderly patients undergoing gastrointestinal surgeries. There is a significant association between acute postoperative pain and multi-system complications.
Humans ; Postoperative Complications/etiology* ; Aged ; Risk Factors ; Digestive System Surgical Procedures/adverse effects* ; Male ; Female ; China/epidemiology* ; Pain, Postoperative/epidemiology* ; Incidence ; Aged, 80 and over

Phototherapy plays a significant role in vitiligo treatment.Narrow-band ultraviolet B(NB-UVB)remains the first-line phototherapy for non-segmental vitiligo in clinical practice.In recent years,visible light has emerged as a novel therapeutic approach for vitiligo.Studies indicate that helium-neon laser demonstrates superior efficacy in segmental vitiligo,blue light is more effective for localized vitiligo,and NB-UVB is better suited for generalized or extensive vitiligo.Different phototherapy modalities exhibit distinct mechanisms of action,involving multiple biological proteins and signaling pathways in melanocyte activation and repigmentation.This review sum-marizes recent advances in phototherapy for vitiligo treatment.

Background and purpose:Diffuse large B-cell lymphoma(DLBCL)is subclassified into germinal center B-cell-like(GCB)and non-GCB subtypes,which differ in prognosis and treatment response.However,current distinction still relies on invasive pathological assays.This study developed radiomics and deep-learning models based on multiparametric magnetic resonance imaging(MRI)to non-invasively differentiate the two subtypes preoperatively,thereby reducing dependence on histopathological examination.Methods:This study retrospectively included patients with pathologically confirmed DLBCL diagnosed at Huashan Hospital,Fudan University,and other institutions between March 2013 and December 2024.Using multiparametric MRI data,we developed DLBCL-subtype classification models that combined 4 radiomics-based machine-learning algorithms:support vector machine(SVM),logistic regression(LR),Gaussian process(GP)and Naive Bayes(NB),with 3 deep-learning architectures[densely-connected convolutional networks 121(DenseNet121),residual network 101(ResNet101)and EfficientNet-b5].Additionally,two radiologists with different experience levels independently classified DLBCL on MRI in a blinded fashion.Model and radiologist performance were quantified using the area under the receiver operating characteristic curve(AUC),accuracy(ACC),and F1-score to evaluate their ability to distinguish GCB from non-GCB subtypes.This study was approved by the Ethics Committee of Huashan Hospital of Fudan University(No.KY2024-663),and all patients signed informed consents.Results:A total of 173 patients were enrolled(55 with GCB subtype and 118 with non-GCB subtype).Radiomics and deep learning methods effectively distinguished DLBCL subtypes.Among these,the GP radiomics model(based on T1-CE+T2-FLAIR+ADC sequences)and DenseNet121 deep learning model(based on T1-CE+T2-FLAIR+ADC sequences)demonstrated optimal performance.Both achieved excellent results on the internal validation set(GP:AUC=0.900,ACC=0.896,F1=0.840;DenseNet121:AUC=0.846,ACC=0.854,F1=0.774)and maintained robustness on the external validation set.Furthermore,the classification efficacy of the optimal AI model surpassed that of experienced radiologists(highest physician AUC=0.678).Conclusion:Radiomics and deep-learning models based on multiparametric MRI features can effectively differentiate GCB from non-GCB subtypes of DLBCL.Among them,GP and DenseNet121 exhibit outstanding performance,especially when integrating multi-sequence feature sets for classifying DLBCL subtypes on complex imaging data.

OBJECTIVE: To explore the effectiveness of arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release in the treatment of non-traumatic elbow stiffness. METHODS: The clinical data of 15 patients with non-traumatic elbow stiffness treated with arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release between April 2019 and September 2023 were retrospectively analyzed. There were 6 males and 9 females with an average age of 46 years ranging from 34 to 56 years. The causes included rheumatoid arthritis in 3 cases, gouty arthritis in 2 cases, loose bodies in 3 cases, and elbow osteoarthritis in 7 cases. There were 4 cases with ulnar neuritis and 3 cases with synovial osteochondromatosis. The duration of elbow stiffness ranged from 6 to 18 months, with an average of 10 months. The operation time and intraoperative blood loss were recorded. The effectiveness was evaluated by visual analogue scale (VAS) score, range of elbow motion (maximum flexion, maximum extension, and total flexion and extension), Mayo score, and Hospital for Special Surgery (HSS) elbow score. RESULTS: The operation time was 60-90 minutes, with an average of 65 minutes, and the intraoperative blood loss was 40-100 mL, with an average of 62 mL. All patients were followed up 13-18 months, with an average of 14 months. There was no complication such as vascular and nerve injury, poor wound healing, collateral ligament injury, elbow joint space narrowing, osteophyte proliferation, or loose body formation around the joint. At last follow-up, the elbow range of motion (maximum flexion, maximum extension, and total flexion and extension), VAS score, and Mayo score significantly improved when compared with those before operation ( P<0.05). The HSS elbow score was 85-95, with an average of 92; 12 cases were excellent, 3 cases were good, and the excellent and good rate was 100%. CONCLUSION Arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release is an effective way to treat non-traumatic elbow stiffness, which has the advantages of small trauma, short operation time, and good effectiveness. It can carry out early elbow rehabilitation training and significantly improve elbow function.
Humans ; Male ; Female ; Arthroscopy/methods* ; Adult ; Middle Aged ; Elbow Joint/physiopathology* ; Retrospective Studies ; Range of Motion, Articular ; Treatment Outcome ; Ulnar Nerve/surgery* ; Operative Time

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway plays a crucial role in the regulation of renal fibrosis by participating in inflammatory response,oxidative stress and autophagy.Paeoniflorin exhibits remarkable efficacy in treating myocardial and liver fibrosis.This article provides a comprehensive review on the research progress of paeoniflora in preventing and treating renal fibrosis through modulation of the PI3K/Akt/mTOR signaling pathway,offering novel insights for traditional Chinese medicine-based approaches to prevent and treat renal fibrosis.