As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

Objective To explore the risk factors for the recurrence of autoimmune pancreatitis(AIP),so as to provide a new reference for its clinical treatment.Methods The clinical data of 198 AIP patients admitted to The First Affiliated Hospital of Naval Medical University from 2014 to 2021 were collected,including 164 patients with type 1 AIP and 34 patients with type 2 AIP.Based on the recurrence status of AIP,the patients were categorized into recurrence group(38 cases)and non-recurrence group(160 cases),and differences between the 2 groups were analyzed.Patients with definite duration of glucocorticoid maintenance therapy were further screened,and logistic regression model and Spearman rank correlation analysis were used to analyze the risk factors of AIP recurrence.Results During the follow-up period,19.19％(38/198)of AIP patients experienced a relapse.The 1-,3-,and 5-year cumulative recurrence rates were 6.57％,9.09％,and 12.63％,respectively,with type 1 AIP demonstrating a significantly higher recurrence rate than type 2 AIP(21.95％[36/164]vs 5.88％[2/34],P=0.030).Univariate logistic regression analysis showed that serum low density lipoprotein-cholesterol level(odds ratio[OR]=0.544,95％confidence interval[CI]0.321-0.924,P=0.024)and the duration of glucocorticoid maintenance therapy(OR=0.797,95％CI 0.704-0.902,P＜0.001)were the potential factors of AIP recurrence in 112 patients with definite data on the duration of glucocorticoid maintenance therapy.Multivariate logistic regression analysis showed that the duration of glucocorticoid maintenance therapy was independently associated with AIP recurrence(OR=0.813,95％CI 0.713-0.926,P=0.002).Spearman rank correlation analysis further demonstrated a negative correlation between the duration of glucocorticoid maintenance therapy and AIP recurrence(r=-0.545,P＜0.001).Additionally,receiver operating characteristic curve analysis indicated that the duration of glucocorticoid maintenance therapy had good predictive effect on AIP recurrence,with an area under curve value of 0.873(95％CI 0.800-0.945,P＜0.001).Conclusion Long-term regular glucocorticoid therapy is an independent protective factor against AIP recurrence,and it can significantly reduce the recurrence of AIP.

Spinocerebellar ataxia 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by an abnormal expansion of the CAG/CAA sequence in the TATA-box binding protein ( TBP) gene. According to CAG size range, there are 2 clusters: reduced-penetrance in low-range expansions and full-penetrance in larger expansions. Here, a patient genetically diagnosed with SCA17 and with 43 CAG repeats in the TBP gene, presenting symptoms resembling multiple system atrophy (MSA), is reported. Further review of previously reported cases of SCA17 with a small range of expansions shows the clinical manifestations of SCA17 are highly heterogeneous, of which clinicians need to have sufficient awareness. For patients clinically suspected of having MSA, even if their clinical features and imaging manifestations more strongly support the sporadic neurodegenerative disease, SCA17 should still be considered as one of the differential diagnoses.

Spinocerebellar ataxia 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by an abnormal expansion of the CAG/CAA sequence in the TATA-box binding protein ( TBP) gene. According to CAG size range, there are 2 clusters: reduced-penetrance in low-range expansions and full-penetrance in larger expansions. Here, a patient genetically diagnosed with SCA17 and with 43 CAG repeats in the TBP gene, presenting symptoms resembling multiple system atrophy (MSA), is reported. Further review of previously reported cases of SCA17 with a small range of expansions shows the clinical manifestations of SCA17 are highly heterogeneous, of which clinicians need to have sufficient awareness. For patients clinically suspected of having MSA, even if their clinical features and imaging manifestations more strongly support the sporadic neurodegenerative disease, SCA17 should still be considered as one of the differential diagnoses.

Objective:To search for potential synergistic drugs that can enhance the inhibitory effect of lenvatinib on the proliferation of hepatocellular carcinoma cells by compound screening and explore the underlying molecular mechanisms.Methods:The impact of lenvatinib on the proliferation of Huh7 cells was detected using CCK-8 assay and long-term cell proliferation assays.The potential synergistic drugs for lenvatinib in Huh7 cells was screened using an FDA-approved compound library.Subsequently,the inhibitory effect of lenvatinib combined with zinc pyrithione on the proliferation of Huh7 cells was assessed using CCK-8 assay and long-term cell proliferation assay.Furthermore,RNA-sequencing was utilized to investigate the changes in gene expression profiles following the combined action of zinc pyrithione and lenvatinib,exploring the potential molecular mechanisms.The impact of combination therapy on signaling pathways was investigated through Gene Set Enrichment Analysis(GSEA)and Gene Ontology Analysis(GO).Results:Lenvatinib exerts dose-dependent inhibition on the proliferation of Huh7 in vitro(IC50 value=0.190 μmol/L).Screening of compound libraries identified zinc pyrithione as a compound that synergistically promotes the inhibition of Huh7 cell proliferation by lenvatinib.This result was further validated through CCK-8 assay(P<0.05)and long-term cell proliferation experiments.Compared to treatment with lenvatinib alone,the combination treatment of zinc pyrithione and lenvatinib upregulated signaling pathways related to oxidative stress response,apoptosis,and cellular responses to copper ions in Huh7 cells,with Gene Set Enrichment Analysis(GSEA)showing significant enrichment of the oxidative phosphorylation pathway.Conclusion:Lenvatinib can inhibit the proliferation of Huh7 cells in vitro,while Zinc Pyrithione can synergize with lenvatinib to exert a more significant inhibitory effect on the Huh7 cells.The molecular mechanism of this synergistic effect may involve generation of a large amount of reactive oxygen species(ROS)to induce apoptosis of liver cancer cells through oxidative stress response,as well as promoting the death of hepatocellular carcinoma cells by disrupting copper homeostasis.

Objective:To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC).Methods:Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups.Results:The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ 2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ 2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ 2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ 2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ 2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ 2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ 2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group ( P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ 2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ 2=6.247, P=0.012). Conclusion:EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Pancreatic cystic neoplasm(PCN)is a category of pancreatic tumors with significant heterogeneity.In recent years,the detection rate of PCN has been increasing,and it has gradually become a concern of clinicians.Endoscopic ultrasound(EUS)can be close to the pancreas for scanning and biopsy,and it has certain advantages in the diagnosis and treatment of PCN.This review mainly summarizes the latest progress of EUS in the diagnosis and treatment of PCN.Cyst fluid molecular markers,such as Kirsten rat sarcoma viral oncogene homolog,GNAS complex locus,Von Hippel-Lindau tumor suppressor gene,as well as emerging endoscopic technologies such as EUS-guided needle based confocal laser endomicroscopy and through-the-needle biopsy,have all showed the potential to significantly improve the diagnostic accuracy of PCN.EUS-guided ablation is an emerging minimally invasive treatment technique for PCN,with the efficacy and safety of chemical ablation being supported by a substantial amount of research.

Objective:To explore the accuracy of a multi-task model based on vision Transformer for analyzing the three-dimensional (3D) upper airway and its subregions, and to evaluate its clinical applicability.Methods:According to the inclusion and exclusion criteria, cone-beam CT (CBCT) data of 10 patients [4 males and 6 females, (20.8±2.7) years] who had their first visit to the Department of Orthodontics in the Hospital of Stomatology, Wuhan University from January 2012 to January 2020 were retrospectively selected. The 3D slicer software was used to segment the upper airway and pharyngeal airway and measure their volumes as the gold standard. The Dolphin 3D software was used to segment the pharyngeal airway and its subregions and measure their volumes as the gold standard. A multi-task model based on vision Transformer developed by the research team for automatic segmentation and volume measurement of the upper airway and its subregions. All the measurements were conducted by the same attending physician. The Bland-Altman analysis and intraclass correlation coefficient ( ICC) were used to evaluate the consistency between the multi-task network and the gold standard in the upper airway segmentation and volume measurements, and the paired t test was used to compare the differences between the multi-tasking model and the gold standard. Results:The mean volume deviation of the upper airway segmented by multi-task model and 3D Slicer was -979.6 mm 3, and the ICC was 0.97. The mean volume deviation of the pharyngeal airway, nasopharynx, velopharynx, glossopharynx and hypopharynx segmented by multi-task network and Dolphin 3D were 2 069.5, -950.1, -823.6, -813.9 and 4 003.4 mm 3, respectively. In addition, ICC in pharyngeal airway, nasopharynx, velopharynx, glossopharynx and hypopharynx were 0.97, 0.94, 0.96, 0.96 and 0.69, respectively. Conclusions:The multi-task model based on vision Transformer produced different errors in the segmentation of 3D upper airway and its subregions. The segmentation of the nasopharynx, velopharynx and glossopharynx was in good agreement with the gold standard, while the segmentation of hypopharynx was poor, suggesting that the robustness and generalization of this model should be further enhanced.

Objective:To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC).Methods:Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups.Results:The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ 2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ 2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ 2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ 2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ 2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ 2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ 2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group ( P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ 2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ 2=6.247, P=0.012). Conclusion:EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.