High-risk non-muscle invasive bladder cancer (HR-NMIBC) presents a significant therapeutic challenge due to its high recurrence and progression rates, particularly in patients with human epidermal growth factor receptor 2 (HER2) expression who are unresponsive to or ineligible for Bacillus Calmette–Guérin (BCG) therapy. This study aimed to evaluate the efficacy and safety of the HER2-targeted antibody-drug conjugate (ADC), Disitamab Vedotin (RC48), alone or in combination with PD-1 inhibitors, as a systemic bladder-sparing approach in a real-world HR-NMIBC cohort. We conducted a multicenter, retrospective, real-world study involving 32 patients with HR-NMIBC who received RC48 alone (n = 3) or in combination with PD-1 inhibitors (n = 29) between June 2022 and December 2024. Eligibility criteria included BCG-unresponsive (n = 7) or BCG-ineligible (n = 25). Data were collected on demographics, clinical characteristics, treatment responses, and adverse events. The primary endpoint was complete response rate (CRR). Secondary endpoints included event-free survival (EFS), duration of complete response (DoCR), 6-month bladder preservation rate, and safety. At a median follow-up of 13.3 months, the overall CRR was 71.9% (23/32; 95% CI: 53.3%–86.3%). In the BCG-unresponsive and BCG-ineligible subgroups, CRRs were 85.7% (6/7) and 68.0% (17/25), respectively. The median EFS for the overall cohort was 22.1 months (95% CI: 16.7–27.4), with no significant difference between the BCG subgroups (P = 0.98). Among the 23 responders, the median DoCR was 16.9 months (95% CI: 13.1–20.7). Treatment-related adverse events (TRAEs) occurred in 53.1% of patients, primarily Grade 1–2 peripheral neuropathy (21.9%) and rash (21.9%). Grade ≥ 3 TRAEs were rare (6.3%). In this real-world study, RC48-based systemic therapy, particularly in combination with PD-1 inhibitors, demonstrates promising preliminary activity and a manageable safety profile in BCG-unresponsive or BCG-ineligible HR-NMIBC. Large prospective trials are required to confirm long-term durability and the optimal role of this systemic approach.

Abstract The ovary is susceptible to harmful environmental factors. Tumor progression (TP) is an intracorporal harmful environmental factor. It is known that TP could impair adjacent tissues through pro-inflammatory cytokines. However, it is unclear whether and how non-reproductive tumor progression (NRTP) impairs ovarian function. In this study, we used MCA205 (mouse fibrosarcoma) cell-allotransplanted B6 mice as a basic model (M group); meanwhile, we established two popular therapeutic models — PD-1 monoclonal antibody injection in allotransplanted mice (PD-1 group) and whole cancer cell vaccine (WCV) injection in allotransplanted mice (WCV group) — to facilitate the discovery process. As expected, TP in M group decreased ovarian function multifacetedly. Interestingly, WCV injection significantly reversed these abnormalities, whereas PD-1 did not. Next, plasma cytokine microarray characterized CXCL10 with both the biggest increment in M group and best rescue in WCV group. Next, we baited the only CXCL10 receptor, IL18R1, within ovaries. Next, we found that CXCL10 directly bound to IL18R1 to impair ovarian function through three pathways: inducing ovarian fibrosis through p-JNK→p-JUN → COL1A1, promoting primordial follicle overactivation through p-AKT→p-FOXO3A, and increasing ovarian inflammation through p-P65 → IFNγ. We have also preliminarily verified the CXCL10–IL18R1 axis and the upper three downstream pathways in MC38 (mouse colon cancer cells)-allotransplanted and B16F10 (mouse melanoma cells)-allotransplanted B6 mice. Finally, we rescued the decreased ovarian function in the M group by blocking the CXCL10 → IL18R1 pathway with CXCL10 antibody or a CXCL10–IL18R1 interface peptide, CIBB. This study provides mechanical evidence and translational strategies of how NRTP impairs ovarian functions and how to target-protect ovaries under NRTP.

Dormant cancer stem cells (CSCs) are the root cause of the drug resistance and metastatic processes of malignant tumors, but an in-depth analysis of their biological mechanisms is needed. Dormant CSCs are in the G0 phase of the cell cycle and are characterized by enhanced autophagic activity, a stable genomic structure and strong plasticity. Recently, several new specific markers of dormant CSCs, such as p27, CD13, QSOX1, Survivin, GPD1 and BEX2, have been identified, which offer hope for targeted therapy. In addition, epigenetic modifications such as DNA methylation and histone modifications have been reported to regulate the transition between the quiescent and proliferative states of dormant CSCs. From a clinical perspective, keeping cancer stem cells in a dormant state is helpful for preventing tumor recurrence and metastasis. To this end, clarifying the potential mechanisms and molecular regulation of cancer stem cell dormancy is vital. Here, in this review, we examine recent significant findings regarding tumor stem cell dormancy in both experimental and human disease models, emphasizing the underlying molecular mechanisms, regulatory processes, experimental models, and prospective research directions aimed at advancing this field and enhancing clinical translation.

Gastric signet ring cell carcinoma (GSRCC) is a special type of gastric cancer common in young women. Diffuse gastric cancer (DGC) begins with intramucosal lesions comprising differentiated GSRCC cells. Genetically, GSRCC and DGC are clonally identical, with their morphology influenced by extracellular Wnt signaling. Interestingly, Wnt activation facilitates the transition of indolent GSRCC cells into more invasive DGC cells, indicating the high plasticity of GSRCC cells. With respect to its cellular origin, GSRCC may originate from MUC5AC-/MUC6- pre-pit cells in the proliferative area of the gastric gland. Importantly, the tumor immune microenvironment (TIM) of GSRCC has unique characteristics. Compared with that of non-GSRCC, the TIM of GSRCC seems to be in a relatively "quiescent" state, and CD4+ and CD8+ T cells are difficult to activate. Moreover, compared with non-GSRCC patients, GSRCC patients have significantly greater Treg infiltration and significantly fewer CD8+ T effector cells. This immune "quiescent" state may explain the poor response to immunotherapy in patients with GSRCC. Notably, the depletion of CXCL13 derived from exhausted CD8+ T cells (CD8-Tex) and the absence of mature tertiary lymphoid structures are key reasons for the low response to immunotherapy in patients with GSRCC. Therefore, for patients with GSRCC, enhancing the ability of CD8-Tex cells to produce CXCL13 may be the key to improving the immune therapy response. In this review, we explore recent key findings on GSRCC, focusing on molecular mechanisms, immune regulation, and prospective research directions to improve clinical applications.

Chemoresistance to cisplatin is a major contributor to the progression of head and neck squamous cell carcinoma (HNSCC); however, the mechanisms underlying cisplatin resistance in HNSCC remain incompletely understood. Dysregulation of metabolite transport between mitochondria and the cytoplasm, mediated by solute carrier family 25 (SLC25), is closely associated with tumor progression. Solute carrier family 25 member 1 (SLC25A1) promotes malignant phenotypes in various cancers; however, its role in HNSCC remains unexplored. Here, we demonstrate that SLC25A1 is overexpressed in HNSCC and is closely associated with poor prognosis. SLC25A1 upregulation promotes cisplatin resistance in HNSCC cells. Moreover, SLC25A1 enhances cisplatin resistance in HNSCC cells by inducing cellular senescence. Mechanistically, SLC25A1 upregulates the expression of RANBP1, CDC45, and PES1 through histone H3 lysine 27 acetylation-mediated transcriptional activation. Furthermore, SLC25A1 interacts with HSPD1, a mitochondrial chaperonin protein, via its C-terminal region to increase citrate transport and cytosolic acetyl-CoA levels. Treatment with CTPI-2, a specific inhibitor of SLC25A1, exhibits therapeutic effects against cisplatin-resistant HNSCC. These findings establish SLC25A1 as a key regulator of cisplatin resistance in HNSCC, suggesting that it serves as both a predictive biomarker and a potential therapeutic target in chemoresistant HNSCC. From a translational perspective, these results support CTPI-2 as a promising therapeutic agent for overcoming cisplatin resistance.

Immune checkpoint inhibitors (ICIs) demonstrate therapeutic benefits in advanced hepatocellular carcinoma (HCC), yet most patients exhibit limited responses to anti-PD-1 therapy and the molecular basis underlying this resistance remains largely undefined. Here, we identified the circular RNA SPECC1 (circSPECC1) as a regulator of antigen presentation and a crucial factor influencing the efficacy of anti-PD-1 therapy. circSPECC1 was significantly elevated in tumor tissues of HCC patients showing resistance to anti-PD-1 therapy and correlated with diminished intratumoral CD8+ T-cell infiltration. Elevated circSPECC1 levels facilitated tumor progression and impaired the therapeutic efficacy of anti-PD-1 treatment. Overexpression of circSPECC1 in cancer cells suppressed the proliferation and cytotoxic activity of CD8+ T cells both in vitro and in vivo. Mechanistically, circSPECC1 bound to the peptide-loading complex (PLC) chaperone ERP57 and disrupted its interaction with TAPBP (TAP binding Protein), thereby destabilizing PLC integrity. This aberrant interaction redirected MHC-I toward ER-associated degradation (ERAD), suppressing surface antigen presentation and impairing CD8+ T-cell activation. Importantly, targeted silencing of circSPECC1 using a PEG-PEI-folate nanosystem encapsulating si-circSPECC1 significantly restored sensitivity both murine and patient-derived xenograft HCC models to PD-1 blockade. In summary, these findings uncover a novel circRNA-guided ERAD of MHC-I mechanism that impairs antitumor immunity and highlight circSPECC1 as a promising therapeutic target to overcome immunotherapy resistance.

Background:The prognosis for patients with ultra high-risk gestational trophoblastic neoplasia (GTN) is significantly worse, and there is currently no consensus regarding the optimal treatment strategies for this specific patient population. Objectives:This study aims to investigate the clinical characteristics, treatment responses, outcomes, and prognostic risk factors in ultra high-risk GTN patients with an International Federation of Gynecology and Obstetrics (FIGO) score of 13 or higher. Design:Retrospective study. Methods:Medical records of 36 GTN patients with FIGO score ⩾ 13, treated at the first affiliated hospital of Zhengzhou University, China, from January 2015 to June 2024, were retrospectively reviewed. Chi-square tests, univariate analysis, and Kaplan-Meier survival analysis were employed for data analysis. Results:Etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) was the most commonly used chemotherapy regimen (17/36, 47.2%). Twenty-one patients responded well to the initial chemotherapy regimen and achieved complete remission (CR). One patient was switched to salvage chemotherapy due to resistance to the initial regimen and subsequently achieved CR. Four patients experienced relapse; of these, three attained CR. The median follow-up time was 46 months (range 12-85 months). The CR rate was 69.4% (25/36). A total of 20 patients (55.6%) received adjuvant treatments, including surgery and radiotherapy. Stage IV disease, liver metastases, uncommon distant metastatic sites, and ⩾3 metastatic sites were significant predictors of mortality. Conclusion:In our study, the overall CR rate for ultra high-risk GTN patients with FIGO score ⩾ 13 was 69.4%. Five patients (45.5%) experienced early mortality. All patients with brain metastases who received chemotherapy in conjunction with whole-brain or stereotactic radiotherapy achieved CR. Immune checkpoint inhibitors demonstrated potential efficacy in treating chemotherapy-resistant GTN.

Metachronous colorectal liver metastases (CRLM) had been the main cause of death in most colorectal cancer (CRC) patients after curative surgery. However, the clinical impact of the pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) on metachronous CRLM remains unclear, the present study aims to clarify this issue. This study retrospectively enrolled in 2155 CRC patients who underwent curative surgery at the Sixth Affiliated Hospital of Sun Yat-sen University from 2017 to 2018, including 300 cases with MASLD and 1855 cases of Control group. Cox regression and Kaplan–Meier curves were constructed to evaluate the influencing factors and cumulative incidence of recurrence (CIR) of metachronous CRLM. The pre-existing MASLD was an independent risk factor for metachronous CRLM in TNM stage 0–II CRC patients (HR, 2.696; 95

Gasdermin D (GSDMD)-induced pyroptosis is associated with inflammatory disease. However, the role of GSDMD in acute pancreatitis (AP) is not yet fully elucidated. This study reveals that GSDMD serves two distinct functions in pancreatic acinar cells and macrophages. In acinar cells, GSDMD inhibits the synthesis of pancreatic enzyme by downregulating the expression of Prss1, Pnlip, and Amy1 via the inhibition of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 (RPS6)/eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) pathway. Moreover, GSDMD induces pancreatic acinar cells to express mucin 1 (MUC1) by activating the nuclear factor kappa-B (NF-κB) pathway, which forms a barrier that prevents digestive enzyme-mediated digestion. However, GSDMD promotes the secretion of inflammatory cytokines by macrophages during AP. In addition, GSDMD increases the infiltration of macrophages and neutrophils in AP and increases the proportion of Th1 and Th17 lymphocyte subsets in peripheral blood. However, in general, the harmful effect of GSDMD in AP outweighs its beneficial effect, and GSDMD knockout can effectively alleviate AP. These findings indicate that GSDMD may be a potential target for the treatment of AP; however, its dual effects need to be comprehensively considered.

Nutritional literacy is a crucial determinant of healthy dietary behaviors, particularly for older adults who face increased risks of malnutrition and chronic diseases. This study integrates Nutbeam's health literacy framework and the COM-B model (Capability, Opportunity, Motivation-Behavior) to explore factors influencing nutritional literacy and dietary behaviors among older adults in China. A qualitative study was conducted with 20 participants aged 60 years or older, recruited using purposive sampling from Jiangsu Province. Semi-structured interviews were conducted from October to November 2024. Data were analyzed thematically following Braun and Clarke's framework, using NVivo software for data organization. Functional nutritional literacy relied on trusted sources such as healthcare providers and family, but participants faced challenges with food labels and online information. Interactive literacy was fostered through family discussions and community programs, though generational gaps and health limitations posed barriers. The COM-B model highlighted capabilities in dietary adjustments, limited access to affordable healthy foods, and strong motivation driven by health goals and family encouragement as determinants of dietary behavior. Improving functional, interactive, and critical nutritional literacy through tailored interventions is vital. Policies to enhance digital inclusion, lower healthy food costs, and strengthen community resources can support healthier dietary behaviors and contribute to successful aging.

Introduction Blinatumomab, a bispecific antibody targeting CD3/CD19, can significantly improve the complete remission (CR) rate, measurable residual disease (MRD) clearance, and survival in patients with relapsed and refractory (R/R) or newly diagnosed B-ALL, especially those with MRD-positive (MRD+) disease. Although clinical studies and guidelines recommend administering blinatumomab in a 28-day cycle, prospective studies have shown that a 14-day short course of blinatumomab combined with low-dose chemotherapy for first-line treatment is not significantly different from the standard cycle in terms of early efficacy. However, the clinical efficacy of short-course blinatumomab remains not fully understood. AIMS To compare the differences in CR rate, MRD negative rate, and survival outcomes between the 14-day and >14-day courses of blinatumomab in B-ALL patients. To assess the clinical benefit for patients receiving a shortened 14-day course of blinatumomab. METHODS: This multicenter retrospective study was conducted from March 2022 to July 2025 on patients with B-ALL who had detectable leukemia burden, defined as being at least MRD-positive, after one cycle of standard chemotherapy or those who were relapsed or refractory. These patients were treated with blinatumomab as reinduction therapy and were divided into two cohorts: those with a treatment duration of ≤14 days (12-14 days) and those with a treatment duration of >14 days. The outcomes assessed included CR rate, MRD-negative rate, overall survival (OS), and progression-free survival (PFS), with comparisons made between the two cohorts. Hematopoietic toxicity, cytokine response syndrome (CRS), and infections were also evaluated. RESULTS: A total of 119 B-ALL patients with detectable leukemia burden were analyzed, including those with high leukemia burden (>50% blast cells) (n = 36), intermediate burden (5-50%) (n = 35), and low burden (≤5% and MRD+) (n = 48). These patients received either ≤14 days (12-14) (n = 50) or >14 days of blinatumomab (n = 61), including 21 days (15-21 days) (n = 30) and 28 days (22-28 days) (n=31). Cohort analysis revealed no significant differences in CR/CRi rates (76.67% vs. 76.19%, P = 0.99) and MRD-negative rates (66.67% vs. 73.81%, P = 0.602) between the two cohorts of ≤14 days and >14 days of blinatumomab for reinduction therapy in patients with medium-to-high leukemia burden. Similarly, there was no significant difference in the MRD-negative rate (89.47% vs. 90%) between the two cohorts in patients with MRD-positive status prior to blinatumomab. The MRD-negative rate in patients with medium-to-high leukemia burden was significantly lower than in those with a low burden (70.83% vs. 89.74%, P = 0.03). For patients who had not achieved CR/CRi or MRD negativity after 14 days of blinatumomab (n = 37), extending treatment to 21 or 28 days did not significantly increase the CR/CRi rate or MRD negativity rate. Notably, in high-load patients (n = 17) who received >14 days of blinatumomab treatment, the CR/CRi rate and MRD-negative rate were 70.59% (12/17) and 88.24% (15/17), respectively, which were slightly higher than those at 14 days (both CR rate and MRD-negative rates were 64.71% (11/17)). However, the differences were not statistically significant (both P values were > 0.05). For MRD+ patients (n = 9), the MRD-negative rate at 14 days was 77.78% (7/9), which remained unchanged at 21 days. With a median follow-up of 21.47 months, the median progression-free survival (PFS) in the 14-day cohort was 9.90 months, compared to 9.33 months in the >14-day cohort. The 1-year PFS rates were 46.6% (95% CI 36.2-60.1) and 46.4% (95% CI 34.7-62.2), respectively, with no significant differences observed between the two cohorts. Regarding toxicity, there were no significant differences in the incidence and severity of CRS between the two cohorts. Lymphocyte depletion was more pronounced in the >14-day cohort, with an infection rate of 49.27% (34/69), which was significantly higher than the 28% (14/50) in the ≤14-day cohort (P = 0.0036). However, there was no significant difference in infections of grade ≥ 3. CONCLUSIONS: Recognizing the limits of a retrospective comparison, a 14-day course of blinatumomab yields response rates and survival outcomes similar to the standard course, particularly in patients with a low leukemia burden. Patients with high tumor burden may benefit from more than 14 days of treatment.

Objective To evaluate the prognosis and fertility of patients with stage II-IV borderline ovarian tumors who underwent fertility-sparing surgery. Methods This retrospective single-institution study included patients under the age of 40 years with stage II-IV borderline ovarian tumors at the First Affiliated Hospital of Zhengzhou University between January 2007 and March 2023. Disease-free survival was the main outcome. The association of disease-free survival was assessed using the Kaplan‒Meier and Cox proportional hazards methods. Results A total of 144 patients were included in this study. Based on whether fertility-sparing surgery was performed, the patients were categorized into two groups, fertility-sparing surgery group with 96 cases (66.67%) and radical surgery group with 48 cases (33.3%). There were differences between the two groups in terms of age (27.36±6.42 vs 34.67±5.43, p<0.001), pregnancy history (53.1% (51/96) vs 81.2% (39 /48), p=0.001), maximum tumor diameter (103.00 (76.25, 148.25) vs 88.50 (60.25, 124.75), p=0.011), involvement of bilateral ovaries (45.83% (44/96) vs 66.67% (32/48), p=0.018), and whether postoperative adjuvant chemotherapy (15.6% (15/96) vs 31.2% (15/48), p=0.030). The median follow-up time from primary cytoreduction were 67.0 months (IQR: 44.0-101.75). At the end of the observation period, 32 cases (22.2%) recurred. There were 3 (2.1%) death and 2 cases (1.4%) of survival with tumor. Fertility-sparing surgery, incompleteness of cytoreduction, micropapillary subtype, FIGO Ⅲ stage, invasive implants were independent risk factors for poor disease-free survival through the multivariable Cox proportional hazard regression analysis. Among patients with fertility intentions (41 cases), 34 cases (82.9%) had successful pregnancies. Twenty-nine cases (70.7%) had successful births, and 3 cases were pregnant at the time of this study completion. Conclusions Fertility-sparing surgery may be feasible and considered for patients who lack the other significant risk factors identified for disease-free survival including incompleteness of cytoreduction, micropapillary subtype, FIGO Ⅲ stage, invasive implants.

Endometrial mesonephric-like adenocarcinoma (MLA) is a rare subtype of uterine corpus endometrial carcinoma (UCEC) first described in 2016. The clinicopathological features, treatment options, and prognosis of endometrial MLA remain poorly understood. In this study, we retrospectively analyzed the clinicopathological characteristics, molecular features, treatment regimens, and outcomes of 11 patients diagnosed with endometrial MLA. The most prevalent symptom observed was postmenopausal bleeding. Notably, 78% (7 out of 9) of patients were diagnosed at advanced FIGO stages (II-IV), with four cases presenting with distant metastasis upon initial examination. Multivisceral metastases were identified in three cases, with lung metastases being the most common, occurring in 45% of patients. The median progression-free survival (PFS) was 16 months (95% confidence intervals: 6-26). All tumors tested negative for progesterone receptors (PR), while 91% of patients (10 out of 11) were negative for estrogen receptors (ER). Most patients exhibited positive immunohistochemical staining for "mesonephric-like" markers, including GATA-binding protein 3 (GATA-3), thyroid transcription factor-1 (TTF-1), and CD10. Furthermore, 91% of patients showed a wild-type p53 immunostaining pattern. Among the 11 patients, five underwent KRAS mutation testing, revealing KRAS mutations in all tested individuals (p.G12D in 2/5, p.G12A in 1/5, p.G12V in 1/5, and p.G13D in 1/5). These findings indicate that 78% of endometrial MLA patients were diagnosed at an advanced stage and suggest that this subtype may exhibit more aggressive behavior compared to endometrial endometrioid carcinoma. The consistent presence of KRAS mutations in patients who underwent testing highlights the potential role of KRAS in the initiation and progression of endometrial MLA, positioning it as a promising therapeutic target.

Pelvic organ prolapse (POP) is a common gynecological disease caused by pathological defects, lesions, or mechanical weakening of the support structures of the pelvic floor. However, its pathogenesis is unclear. Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules, which are thought to play an important role on skeletal muscle development by regulating gene expression. In this study, five pairs of peripheral blood samples from control and POP groups were used for circRNA sequencing analysis to obtain differential expression profiles. A total of 75 differentially expressed circRNAs (DEcircRNAs) were identified (fold change >2.0, P < 0.05). Furthermore, RT-qPCR confirmed that the expression levels of two circRNAs (hsa_circ_0067962 and hsa_circ_0057051) were significantly lower in the POP group. The two validated DEcircRNAs were abundantly involved in the collagen catabolic process. The circRNA-miRNA-mRNA network of two DEcircRNAs comprised nine mRNAs, which indicated that hsa_circ_0067962 and hsa_circ_0057051 may be involved in the pathogenesis of POP by regulating these nine mRNAs.

Background:Acute pancreatitis (AP) is a common gastrointestinal disease. Systemic inflammatory response syndrome (SIRS), a severe complication of AP, increases the risk of organ failure and progression to severe AP (SAP). Gut microbiota dysbiosis is linked to AP pathogenesis. The aim of this study is to investigate the gut microbiota characteristics of AP patients and their association with SIRS and organ failure. Methods:Rectal swabs from 19 healthy controls (HC) and 88 AP patients (stratified into non_SIRS, SIRS, low/med/high_sequential organ failure assessment (SOFA) groups) were analyzed using 16S rRNA gene sequencing. Microbiota diversity, composition, and function were evaluated, and random forest diagnostic models were constructed. Results:Compared with HC, AP (SIRS/non_SIRS) patients had altered clinical indices, reduced gut microbial richness and diversity. As SOFA scores increased, the high_SOFA group exhibited further reductions in richness and diversity. Barplots analysis showed that there were differences in the mainly dominant microbiota between HC and AP (SIRS/non_SIRS) patients. Some differentially abundant genera such as Faecalibacterium, Parabacteroides, Megasphaera, and Fusicatenibacter may be closely associated with the occurrence of AP, development of SIRS, and severity of organ failure. Furthermore, functional pathways like L-isoleucine biosynthesis, lysine biosynthesis, AMPK signaling, and glycogen biosynthesis may also play significant roles in diseases. The random forest models constructed for distinguishing between HC and non_SIRS, as well as for distinguishing between HC and SIRS, showed extremely diagnostic accuracy. Conclusion:Gut microbiota dysbiosis is correlated with the occurrence of AP, development of SIRS, and severity of organ failure. Specific microbiota taxa and functional pathways may serve as potential therapeutic targets or diagnostic biomarkers for AP, providing a microbial perspective for personalized management of this disease.

The aim of this study was to investigate the utility of serum soluble B7-H3 (sB7-H3) as a diagnostic marker for early-stage nonsmall cell lung cancer (NSCLC) and its potential for evaluating the prognosis of patients with advanced-stage NSCLC. In this study, an ELISA was employed to detect the expression levels of sB7-H3 in a cohort of patients diagnosed with NSCLC ( n = 122) and a control group ( n = 42) during the same observation period. Comparative analyses were conducted to ascertain the variations in sB7-H3 concentrations between the NSCLC cohort and the healthy control group, as well as across pathological types and the presence and absence of lymph node metastasis. (1) The concentration of sB7-H3 in patients diagnosed with NSCLC exhibited a statistically significant increase compared to that observed in the healthy control group ( P < 0.05). Elevated expression levels of sB7-H3 demonstrated a significant correlation with pathological type, lymph node metastasis, tumor, node and metastasis stage and programmed cell death ligand (PD-L1) expression ( P < 0.05). (2) The diagnostic utility of sB7-H3 for the diagnosis of NSCLC and the heightened expression of PD-L1 demonstrated high levels of sensitivity and specificity. (3) Elevated levels of sB7-H3 emerged as an independent risk factor impacting the overall survival of patients diagnosed with advanced NSCLC. The findings of this study suggest that sB7-H3 holds promise as a diagnostic tool for early-stage NSCLC. The elevated expression of sB7-H3 appears to serve as a reliable indicator for assessing the prognosis of patients diagnosed with advanced NSCLC.

Background: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack of structural support. Methods: This study explored the combined use of gene transfection and dermal substitutes to improve wound healing. We used the DGTM (genes: DNP63A, GRHL2, TFAP2A, and MYC) factors to transfect adipose-derived stem cells (ADSCs), inducing their differentiation into keratinocytes. These transfected ADSCs were then incorporated into Pelnac® dermal substitutes to enhance vascularization and cellular proliferation for better healing outcomes. Results: Gene transfer using DGTM factors successfully induced keratinocyte differentiation in ADSCs. The application of these differentiated cells with Pelnac® dermal substitute to dermal wounds in mice resulted in the formation of skin tissue with a normal epidermal layer and proper collagen organization. This method alleviates the tediousness of the multiple transfection steps in previous protocols and the safety issues caused by using viral transfection reagents directly on the wound. Additionally, the inclusion of dermal substitutes addressed the lack of collagen and elastic fibers, promoting the formation of tissue resembling healthy skin rather than scar tissue. Conclusion: Integrating DGTM factor-transfected ADSCs with dermal substitutes represents a novel strategy for enhancing the healing of full-thickness wounds. Further research and clinical trials are warranted to optimize and validate this innovative approach for broader clinical applications.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, a significant proportion of gastric cancer (GC) patients do not respond to this therapy. Consequently, there is an urgent need to elucidate the mechanisms underlying resistance to ICIs and identify robust biomarkers capable of predicting the response to ICIs at treatment initiation.Methods: In this study, we collected GC tissues from 28 patients prior to the administration of anti-programmed death 1 (PD-1) immunotherapy and conducted protein quantification using high-resolution mass spectrometry (MS). Subsequently, we analyzed differences in protein expression, pathways, and the tumor microenvironment (TME) between responders and non-responders. Furthermore, we explored the potential of these differences as predictive indicators. Finally, using machine learning algorithms, we screened for biomarkers and constructed a predictive model.Results: Our proteomics-based analysis revealed that low activity in the complement and coagulation cascades pathway (CCCP) and a high abundance of activated CD8 T cells are positive signals corresponding to ICIs. By using machine learning, we successfully identified a set of 10 protein biomarkers, and the constructed model demonstrated excellent performance in predicting the response in an independent validation set (N = 14; area under the curve [AUC] = 0.959).Conclusion: In summary, our proteomic analyses unveiled unique potential biomarkers for predicting the response to PD-1 inhibitor immunotherapy in GC patients, which may provide the impetus for precision immunotherapy.

Abstract Background Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. Methods We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. Results The median age of the patients was 55.0 (39.0–64.0) years, and the median tumor size was 40.0 (33.0–60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3–81.0) months. Unfortunately, 2 patients died from the disease. Conclusion NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery.