Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

Objective To investigate the feasibility of selectively omitting ureteral stent placement after ureteroscopic lithotripsy(URL).Methods A total of 118 patients with distal ureteral calculi undergoing URL from 2021 to 2024 were enrolled.Patients were divided into a control group(indwelling ureteral stent for 2 weeks,n=86)and an observation group(no ureteral stent placement,n=32).General data,operation time,hospital stay,and total medical costs were compared between the two groups.Patients were followed 2 weeks postoperatively for assessment of flank pain visual analogue scale(VAS)scores,bladder irritation symptoms,hematuria,and incidence of urinary tract infection.Hydronephrosis was evaluated by ultrasonography 3 months after surgery.Results There was no significant difference in the general information and operation time between the two groups(P>0.05).The length of hospital stay and total treatment cost in the observa-tion group were significantly lower than those in the control group(P<0.05).Two weeks after surgery,the VAS scores of low back pain on the affected side and occurrence rates of bladder irritation symptoms,hematu-ria,and urinary tract infection in the observation group were significantly lower than those in the control group(P<0.01).Three months after operation,no hydronephrosis was observed in both groups.Conclusion It is safe and feasible to avoid indwelling ureteral stent after URL in appropriate cases.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma.Methods:This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis.Results:A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups ( P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group ( P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ 2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ 2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death ( P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion:The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.