Immune checkpoint inhibitors (ICIs) are widely used in the treatment of malignant tumors, and their related immune-related adverse events (irAEs) have attracted increasing attention. This study reports the diagnosis and treatment process of a case of immune cystitis in a patient with hepatobiliary tract malignant tumor after treatment with pembrolizumab. The patient was admitted to the hospital due to frequent urination, urgency of urination and dysuria for 1 month. Previous repeated anti-infection treatments were ineffective. Combined with medical history, laboratory tests, imaging findings, cystoscopy and pathological results, the patient was clinically diagnosed with ICIs-associated immune cystitis (Pembrolizumab) ultimately. The patient's symptoms significantly improved after treatment with glucocorticoids. This case reindicates that clinicians need to improve awareness of ICI-related urinary system irAEs. Early identification and timely intervention can significantly improve patient prognosis.

ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

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.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Despite of the widespread use of hydrogen and methane breath test, the variability in testing protocols, gas measurement techniques, and interpretation criteria continues to challenge the reproducibility and comparability across centers, especially in the Asia-Pacific region. The Asian Neurogastroenterology and Motility Association hence presents the first Asian monograph guiding application and interpretation of breath test. The monograph was formulated according to the framework of indications, preparatory process, performance, and interpretation of results, as well as future direction for research.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

ObjectiveTo investigate the clinicopathological features， molecular profile， treatment response， and prognosis of SMARCA4 （BRG-1） and SMARCB1 （INI-1）-deficient undifferentiated tumors of the digestive system， aiming to enhance the understanding of this rare and highly aggressive molecular subtype. MethodsThis study is a single-center retrospective analysis. We included 9 cases of malignant digestive system tumors with loss of BRG-1 expression and 3 cases with loss of INI-1 expression， all pathologically confirmed at Sun Yat-sen University Cancer Center between April 2022 and December 2025. By reviewing clinical data， histological morphology，immunohistochemistry and next-generation sequencing （NGS） results from partial cases， we systematically summarized their clinicopathological and molecular characteristics， treatment strategies， and survival outcomes. Results​ Among the 12 patients， 6 were male and 6 were female， with a median age of 62 （44-70） years. 9 cases exhibited SMARCA4 deficiency， and 3 cases exhibited SMARCB1 deficiency. Tumors originated in the stomach （5 cases）， colon （3 cases）， pancreas （1 case）， with the primary site unknown in 3 cases. The histology predominantly showed undifferentiated carcinoma， with 1 case of poorly differentiated carcinoma. The tumor cells were epithelioid with significant atypia. Epithelial markers （e.g. CKpan） were often lost or markedly decreased， while vimentin could be positive. All 9 cases tested for MMR status were mismatch repair proficient （pMMR）， and the Ki-67 proliferation index was high ［median 80% （60%-90%）］. A discordance was observed between IHC findings and NGS results in the 6 sequenced cases. The NGS profiling revealed frequent co-occurring mutations， including TP53， KRAS， and NRAS， with no germline mutations identified.The median follow-up time was 277 （55-867） days. 9 of the 12 patients presented with stage Ⅳ disease at the time of initial diagnosis. Among 3 newly diagnosed patients without metastasis who received treatment， 2 achieved prolonged recurrence-free survival. Patients with advanced disease at initial diagnosis primarily underwent platinum-based chemotherapy or combination regimens， yet their prognosis was generally poor， with a median overall survival of 60 （45-541） days， ranging from 16 to 867 days. Notably， several patients who received chemotherapy combined with targeted therapy and immunotherapy achieved extended survival. ConclusionSMARCA4/SMARCB1-deficient undifferentiated tumor of the digestive system is a distinct molecular subtype characterized by high aggressiveness and poor prognosis， predominantly affecting middle-aged and elderly individuals. Diagnosis relies on the immunohistochemical loss of BRG-1 or INI-1 proteins. While no standard of care currently exists， treatment often refers to regimens for adenocarcinoma of the primary site. Combined immunotherapy and targeted therapy may offer potential benefits， warranting further validation in large-scale prospective studies.

Objective: To evaluate the clinical efficacy of digitally guided precision crown lengthening in secondary aesthetic rehabilitation cases, and to provide a clinical reference for digitally guided crown lengthening procedures and secondary aesthetic restorations. Methods: We present a case of a patient with tetracycline-stained teeth, partial detachment of anterior resin veneers, and gingival margin discrepancies. The patient underwent digitally guided precision crown lengthening followed by secondary aesthetic rehabilitation. Multimodal data, including intraoral, facial, and CBCT scans, were integrated to construct a four-dimensional virtual patient model (incorporating teeth, face, bone, and occlusion) for surgical planning and 3D-printed guide fabrication. Secondary aesthetic restoration was performed after achieving stable post-surgical outcomes. Based on this case, we conducted a detailed analysis and reviewed relevant literature on crown lengthening in secondary aesthetic rehabilitation. Results: The gingival contour of the anterior teeth exhibited significant improvement, with enhanced symmetry and stable gingival margin positioning that closely matched the preoperative design. The crown lengthening procedure demonstrated high precision, and the final outcome was aesthetic and functional. Literature review indicated that secondary restorations frequently present challenges such as gingival contour discrepancies and inflammation. Aesthetic crown lengthening in the anterior region should optimize both soft and hard tissue morphology to meet aesthetic standards, with digital technology improving procedural accuracy. Conclusion Precision crown lengthening effectively addresses gingival margin discrepancies in secondary aesthetic rehabilitation, ensuring stable gingival positioning and superior aesthetic outcomes. This approach is particularly suitable for cases with high aesthetic demands.

Objective To explore the mediating role of occupational well-being in the relationship between professional identity and safety behavior among nurses. Methods A total of 1 006 nurses from ten tertiary general hospitals in eight provincial administrative regions were selected as the research subjects using convenient sampling method. Their safety behavior, professional identity and occupational well-being were investigated using Nurse Safety Behavior Scale, Nurse Professional Identity Scale and Occupational Well-being Scale. Structural equation modeling was performed using AMOS 26.0 to examine the mediating effect of occupational well-being in the relationship between professional identity and safety behavior among nurses. Results The scores for safety behavior, professional identity, and occupational well-being were (53.0±6.1), (123.7±21.2) and (90.8±13.1), respectively. Safety behavior was positively correlated with both professional identity and occupational well-being (correlation coefficients were 0.50 and 0.50, respectively, both P<0.01). Professional identity was positively correlated with occupational well-being (correlation coefficient was 0.51, P<0.01). The multiple linear regression analysis results showed that the higher the professional identity and occupational well-being of nurses, the higher the level of safety behavior (both P<0.05). The result of mediating effect shows that the total effect of occupational identity on safety behavior was 0.498 [95% confidence interval (CI) was 0.405-0.576], and occupational well-being played a mediating role between professional identity and safety behavior among nurses with the mediation effect of 0.156 (95%CI was 0.112-0.205), accounting for 31.33% of the total effect. Conclusion The safety behavior of nurses is at a moderate level. Both professional identity and occupational well-being can affect the safety behavior of nurses. Professional identity can increase the safety behavior of nurses by affecting occupational well-being.

As a sub-discipline of field surgery,trauma surgery of naval warfare focuses on the treatment of marine casualties,which is the extension and application of field surgical theories and techniques in the context of naval warfare.Informatization and 3-dimension have been the basic features of modern naval warfare.With the extensive use of high-tech weapons,maritime combat styles and security needs have undergone profound changes.The complexity and diversity of marine trauma injuries have created new opportunities and challenges for the development of trauma surgery.This paper analyzes the marine trauma under the conditions of modern warfare,the characteristics of marine trauma surgical care,and the medical evacuation system of casualty care in naval battle,aiming to promote the research of naval medical support and the development of field surgery.