Objective To evaluate the efficacy and safety of intraoperative pleural irrigation with Nocardia rubra cell-wall skeleton (N-CWS) for reducing pleural effusion drainage after radical surgery for lung cancer. Methods A retrospective analysis was conducted on the clinical data of lung cancer patients who underwent lobectomy and mediastinal lymph node dissection at the First Affiliated Hospital of Xiamen University between December 2024 and May 2025. Patients were divided into a control group and an irrigation group based on the intraoperative use of N-CWS. Patients in the irrigation group received pleural irrigation with 800 μg of N-CWS diluted in 10 mL of normal saline. The following outcomes were compared between the two groups: pleural effusion drainage volume at 0-24 h, 24-48 h, and 48-72 h postoperatively, degree of air leak, chest tube duration, postoperative length of stay, and the incidence of adverse events (fever, chest pain, and nausea and vomiting). Results A total of 245 patients were included (97 males, 148 females) with a mean age of (61.28±6.26) years, with 205 in the control group and 40 in the irrigation group. Compared to the control group, the irrigation group showed significantly lower pleural effusion drainage volumes at 0-24 h, 24-48 h, and 48-72 h, as well as shorter chest tube duration and postoperative length of stay (all P<0.05). There was no statistical difference in the degree of postoperative air leak (P=0.661). No significant differences were observed between the two groups regarding the highest body temperature within 72 h post-surgery (P=0.130), fever grade (P=0.196), severity of chest pain (P=0.105), or the incidence of nausea and vomiting (P=0.376). Conclusion Intraoperative pleural irrigation with N-CWS in patients undergoing lobectomy and mediastinal lymph node dissection for lung cancer can significantly reduce postoperative pleural effusion drainage volume, shorten chest tube duration and length of hospital stay. The procedure is safe and feasible.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood. METHODS: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons. RESULTS: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions. CONCLUSIONS This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery.
Animals ; Robotic Surgical Procedures/methods* ; Laparoscopy/methods*

Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Objective To investigate the relationship between primary pulmonary mucinous adenocarcinoma (PPMA) mass type and pneumonia type and their difference in malignant degree, and to analyze the role of clinical manifestations and CT features in the diagnosis of this disease. Methods The clinical data of PPMA patients admitted in the First Affiliated Hospital of Xiamen University from May 2011 to March 2022 were retrospectively analyzed. According to CT features, they were divided into a mass type group and a pneumonia type group. The clinical manifestations, CT features and the degree of malignancy between the two groups were analyzed and compared. Results A total of 57 PPMA patients were enrolled. There were 17 males and 40 females, with an average age of (53.82±10.65) years, and 28 (49%) patients had reversed hato-like sign. There were 42 patients in the mass type group and 15 patients in the pneumonia type group. PPMA often occurs in both lower lungs, with clinical manifestations mainly of coughing and expectorating white mucoid sputum. There were statistical differences between the two groups in the maximum diameter of tumor (P<0.001), boundary condition (P<0.001) and pleural indentation sign (P=0.019). There was no statistical difference between the two groups in Ki-67 index (P>0.05). Conclusion There is no statistical difference in the degree of malignancy between the two types of PPMA. Considering their clinical manifestations and differences in imaging features, it is supported that the pneumonia type is just a progression of the mass type. CT can present various manifestations, among which the reversed hato-like sign is expected to become an important imaging feature. Combined with a high proportion of solid components, pleural indentation sign, and vacuole sign, reversed hato-like sign can play a significant role in the diagnosis of PPMA.

ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

Objective To discuss the main pathological types and imaging characteristics of pulmonary nodules that are highly suspected to be malignant in clinical practice but are pathologically confirmed to be benign. Methods A retrospective analysis was performed on the clinical data of patients with pulmonary nodules who were initially highly suspected of malignancy but were subsequently pathologically confirmed to be benign. These patients were treated at the First Affiliated Hospital of Xiamen University from December 2020 to April 2023. Based on the outcomes of preoperative discussions, the patients were categorized into a benign group and a suspicious malignancy group. The clinical data and imaging characteristics of both groups were compared. Results A total of 232 patients were included in the study, comprising 112 males and 120 females, with a mean age of (50.7±12.0) years. Among these, 127 patients were classified into the benign group, while 105 patients were categorized into the suspicious malignancy group. No statistically significant differences were observed between the two groups regarding age, gender, symptoms, smoking history, or tumor history (P>0.05). However, significant differences were noted in nodule density, CT values, margins, shapes, and malignant signs (P＜0.05). Further analysis revealed that in the suspicious malignancy group, solid nodules were predominantly characterized by collagen nodules and fibrous tissue hyperplasia (33.3%), followed by tuberculosis (20.4%) and fungal infections (18.5%). In contrast, non-solid nodules were primarily composed of collagen nodules and fibrous tissue hyperplasia (41.2%) and atypical adenomatous hyperplasia (17.7%). Conclusion Benign pulmonary nodules that are suspected to be malignant are pathologically characterized by the presence of collagen nodules, fibrous tissue hyperplasia, tuberculosis, atypical adenomatous hyperplasia, and fungal infections. Radiologically, these nodules typically present as non-solid lesions and may exhibit features suggestive of malignancy, including spiculation, lobulation, cavitation, and pleural retraction.

OBJECTIVE To explore the relationship between peripheral blood interferon γ(IFN-γ)/interleukin-4(IL-4)and the short-term prognosis of children with Mycoplasma pneumoniae pneumonia(MPP),and to analyze the influencing factors for the short-term prognosis of children with MPP.METHODS A total of 170 children with MPP admitted to the hospital from Jan.2021 to Jan.2024 were selected(MPP group).Based on the condition 28 days after treatment,they were divided into a poor prognosis group(n=49)and a good prognosis group(n=121).Clinical data of the children were collected,and the levels of peripheral blood interleukin-4(IL-4)and inter-feron-γ(IFN-γ)were measured to calculate the IFN-γ/IL-4 ratio.Multivariate Logistic regression model was used to analyze the factors affecting the short-term prognosis of children with MPP.RESULTS In the poor prognosis group,the duration of antibiotic use,the proportion of pleural effusion,the proportion of extrapulmonary compli-cations,and the levels of peripheral blood IL-4 and IFN-γ were higher than those in the good prognosis group,while the IFN-γ/IL-4 ratio was lower than that in the good prognosis group(P＜0.05).Logistic regression re-sults showed that persistent fever,prolonged antibiotic use and the occurrence of extrapulmonary complications were risk factors for the short-term prognosis of children with MPP(P＜0.05),and a high IFN-γ/IL-4 ratio was a protective factor(P＜0.05).CONCLUSION Persistent fever,prolonged antibiotic use and extrapulmonary com-plications are risk factors for the short-term prognosis of children with MPP,and high IFN-γ/IL-4 values is a pro-tective factor.