Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective: To investigate trends in incidence and mortality of colorectal cancer in Nantong City, Jiangsu Province from 2013 to 2022. Methods: Data on incidence and mortality of colorectal cancer from 2013 to 2022 in Nantong City were collected through the Nantong City cancer registry. The crude incidence, crude mortality, average age at onset, and average age at death of colorectal cancer were calculated. Chinese population-standardized incidence, Chinese population-standardized mortality, Chinese population-standardized average age at onset and Chinese population-standardized average age at death were calculated using the age structure of the standard population from the Fifth National Population Census in 2000. Trends in incidence and mortality of lung cancer from 2013 to 2022 were evaluated using average annual percent change (AAPC). Trends in the Chinese population-standardized average age at onset and Chinese population-standardized average age at death of lung cancer from 2013 to 2022 were evaluated using the linear regression model. Results: From 2013 to 2022, the crude incidence and Chinese population-standardized incidence of colorectal cancer in Nantong City increased from 33.63/105 and 16.05/105 to 53.82/105 and 19.62/105, respectively, showing upward trends (AAPC=5.665% and 2.467%, both P<0.05). The crude mortality increased from 15.99/105 in 2013 to 25.65/105 in 2022, also showing an upward trend (AAPC=5.514%, P<0.05), while no statistically significant trend was found in the Chinese population-standardized mortality (P>0.05). The Chinese population-standardized incidence of colorectal cancer showed upward trends in both males and females (AAPC=2.666% and 1.790%, both P<0.05). The Chinese population-standardized mortality showed an upward trend in males (AAPC=1.966%, P<0.05), but no statistically significant trend was found in females (P>0.05). The crude incidence of colorectal cancer in the groups aged 40-<50 years, 50-<60 years, 60-<70 years, 70-<80 years, and ≥80 years showed upward trends (AAPC=4.045%, 2.833%, 2.300%, 1.948%, and 1.775%, all P<0.05), and the crude mortality in the group aged ≥80 years showed an upward trend (AAPC=3.240%, P<0.05). The average age at onset of colorectal cancer increased at an annual average of 0.156 years (P<0.05), while the trend in the Chinese population-standardized average age at onset was not statistically significant (P>0.05). The average age at death and the Chinese population-standardized average age at death increased at an annual average of 0.325 and 0.153 years, respectively (both P<0.05). Conclusions From 2013 to 2022, both the crude incidence and mortality of colorectal cancer in Nantong City showed upward trends. Males and individuals aged ≥40 years faced a higher risk of both incidence and mortality. It is recommended to implement comprehensive prevention and control measures targeting these high-risk populations to reduce the burden of colorectal cancer.

Aim To construct a model of vascular endothelial cell(EC)-specific gene knockout mice of tumor necrosis factor receptor-associated factor 2(Traf2)by using Cre-loxP technolo-gy,thus to provide basis for the research of vascular dysfunction-related diseases related to the regulation of vascular EC activity through TRAF2.Methods The Cre-loxP system was used to construct a mouse model with EC-specific knockout of Traf2 gene(Traf2flox/flox Tek-iCre+).The mouse genotype was identi-fied through PCR and gel electrophoresis.Primary vascular ECs were isolated from the mice using flow cytometry.The knockout efficiency of Traf2 in vascular ECs was validated by Western blot and immunofluorescence.The pathological changes in blood ves-sels and major organs of the mice were examined using hematox-ylin-eosin(HE)staining.The tube-forming ability of primary vascular EC was assessed using Matrigel tube formation.Results The knockout mice met the required genetic criteria.Flow cy-tometry results demonstrated the successful isolation of primary vascular EC,and TRAF2 expression in vascular EC of knockout mice was significantly reduced(P＜0.01).Histological results showed that TRAF2 expression in the vessel of knockout mice decreased,and the morphology had no significant changes in their blood vessels and major organs.The Matrigel tube forma-tion demonstrated that the tube-forming ability of primary vascu-lar EC from knockout mice was reduced.Conclusion Traf2 specific knockout mouse model in vascular ECs is successfully constructed,providing a reliable animal model for research into the regulatory mechanisms of TRAF2 on vascular ECs in vascular dysfunction related diseases.

OBJECTIVE: To explore the improvement effect of rehabilitation nursing based on information-knowledge-belief-behavior (IKAP) theory on urinary incontinence patients after radical prostatectomy. METHODS Sixty-six patients with urinary incontinence who received robot-assisted laparoscopic radical prostatectomy in General Hospital of Eastern Theater Command from January 2021 to January 2023 were selected and divided into control group (n=33) and observation group (n=33) according to random number table method. The patients in the control group were treated with rehabilitation nursing. The patients in the observation group were treated with rehabilitation nursing guided by IKAP theory. The recovery of urinary incontinence, duration of urinary incontinence, subjective well-being, quality of life, psychological and emotional indexes of patients in the two groups were compared. Results： The total effective rate of urinary incontinence recovery in the observation group was significantly higher than that in the control group (90.91% vs 60.61%，P<0.05). The duration of urinary incontinence in the observation group was significantly shorter than that in the control group (［3.36±1.54］d vs ［4.15±1.36］d，P<0.05). And the subjective well-being score in observation group was significantly higher than that in the control group (［19.36±2.69］points vs ［11.65±2.65］points， P<0.05). There was no significant difference in preoperative physical function, social function，and mental health scores between the two groups (P>0.05). And all scores in the observation group were significantly higher than those in the control group after surgery (P<0.05). There was no significant difference in the preoperative SAS and SDS scores between the two groups of patients (P>0.05). And the scores of SAS and SDS in observation group were lower than those of the control group after the operation (P<0.05). Conclusion： Rehabilitation nursing based on IKAP theory can significantly improve urinary incontinence in patients with prostate cancer after surgery, which promotes the recovery of urinary incontinence, shortens the time of urinary incontinence, and improves the subjective well-being and quality of life, as well as reduces the negative impact of negative emotions. Therefore, it can be widely promoted and implemented in clinical practice.
Humans ; Prostatectomy/adverse effects* ; Urinary Incontinence/etiology* ; Male ; Quality of Life ; Rehabilitation Nursing ; Middle Aged ; Aged

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Achieving precise restoration of tooth function and personalized restoration of natural tooth esthetics has always been a significant challenge in direct restorative dentistry. The traditional direct restorative techniques are limited by the subjective operations of dentists, resulting in high technical sensitivity, long operation time, and unpredictable restoration results, making it difficult to meet patients' personalized demands for restoration outcomes. An innovative flowable resin injection technique was introduced in this study. By combining digital design with personalized restoration guides, this technique achieves precise and personalized tooth restoration, thus revolutionizing the traditio-nal paradigm of direct tooth restoration. Specifically, this technique is guided by the patient's subjective aesthetic needs. It utilizes digital technology to pre-design the restoration result and creates a personalized restoration guide. During clinical operation, the dentist needs to only precisely inject the flowable resin into the guide, allowing for rapid completion of the restoration, thereby significantly reducing the operation time and improving the precision and predictability of the restoration. The perfect combination of digital design and flowable resin injection not only significantly improves the precision and predictability of direct tooth restoration but also remarkably shortens the clinical operation time and reduces the requirements for the dentist's technical level, making it widely applicable to the restoration of various tooth defects. Thus, it improves patient satisfaction and reduces the workload of dentists. This innovative restoration technique is expected to become a new productive force in future clinical direct adhesive restorations.
Humans ; Dental Restoration, Permanent/methods* ; Esthetics, Dental ; Composite Resins ; Computer-Aided Design ; Injections