Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.

Objective:To evaluate the efficacy and safety of sintilimab combined with bevacizumab in the second-line treatment of malignant pleural mesothelioma(MPM).Methods:This was a longitudinal study. Patients with MPM who had progressed after first-line treatment and were admitted to the Day-Care Outpatient Department of Medical Oncology, Ningguo People′s Hospital from February 2019 to February 2022 were included. General clinical data of the patients were collected at baseline. The patients were treated with the second-line treatment regimen of sintilimab (200 mg)+bevacizumab (15 mg/kg) on a 21-day cycle. Enhanced CT scans were performed every 3 cycles to evaluate the efficacy until tumor progression or death. Follow-up period ended in December 2023. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and the best response of each patient was recorded. The objective response rate (ORR) and disease control rate (DCR) were calculated. Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), ranging from grade Ⅰto Ⅳ. Kaplan-Meier survival curves were used to analyze PFS and OS, and survival times were expressed as median values.Results:A total of 23 MPM patients were included, with the mean age of (55.04±13.27)years, 15 males, 8 females, 19 cases of epithelial type and 4 cases of non-epithelial type. The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0-1 in 12 patients and 2 in 11 patients. There were 17 smokers and 6 non-smokers, 12 cases with PD-L1 positive and 11 cases with PD-L1 negative, and 6 cases with anti-angiogenic drugs and 17 cases without using anti-angiogenic drugs in the first-line treatment. Of the 23 patients, 1 achieved complete response (CR), 9 achieved partial response (PR), 7 had stable disease (SD), and 6 had progressive disease (PD). The ORR and DCR of the enrolled patients were 43.5% (10/23) and 73.9% (17/23), respectively. Kaplan-Meier survival analysis showed that the PFS of the enrolled patients was 7.50 (95% CI: 5.47-9.54) months, and the OS was 12.50 (95% CI: 1.07-23.93) months. The most common adverse reactions related to the treatment of sintilimab combined with bevacizumab were hypertension (14 cases (60.9%)), fatigue (10 cases (43.5%)), decreased appetite (8 cases (34.8%)), proteinuria (6 cases (26.1%)), pruritus (5 cases (21.7%)), constipation (4 cases (17.4%)) and nausea (3 cases (13.0%)), etc. Only 9 patients had grade Ⅲ adverse reactions (8 cases of hypertension and 1 case of nausea), and only 1 patient had grade Ⅳ adverse reaction (hypertension). Conclusion:Sintilimab combined with bevacizumab has some therapeutic effects on progressive MPM, and the adverse reactions are relatively mild.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective:To investigate the diagnostic and differential diagnostic values of midbrain morphological measurements at the mammillary body level on axial cranial MRI in progressive supranuclear palsy (PSP).Methods:This cross-sectional study included 50 patients with clinically diagnosed, probable or possible PSP, admitted to Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2023 to December 2024. Additionally, 44 patients with Parkinson's disease (PD), 30 patients with multiple system atrophy-cerebellar type (MSA-C), and 35 gender- and age-matched healthy controls recruited from the community were chosen. The following midbrain morphological parameters on axial cranial MRI were measured in all participants: distance from the interpeduncular fossa to the aqueduct (IF-AQ), distance from the lateral mesencephalic sulcus to the interpeduncular cistern (LS-IC), distance between the bilateral lateral mesencephalic sulci (D-BMS), cerebral peduncle angle (CPA), distance between the medial aspects of the cerebral peduncles (D-MP), and distance from the line connecting the highest points of the cerebral peduncle to the interpeduncular fossa (PP-IF). Differences in these measurements among the 4 groups were compared, and the diagnostic and differential diagnostic performances of each parameter in PSP was evaluated using receiver operating characteristic (ROC) curve.Results:The PSP group exhibited significantly shorter IF-AQ, LS-IC, and D-BMS distances compared with the other 3 groups ( P<0.05). (1) ROC curve analysis of PSP group versus non-PSP group (MSA-C patients, PD patients, and healthy controls) showed that IF-AQ had an area under the curve (AUC) of 0.977 (95% CI: 0.959-0.995, P<0.001), and at a cutoff of 10.895 mm, IF-AQ demonstrated a sensitivity of 96.0% and a specificity of 89.9% for diagnosing PSP; LS-IC had an AUC of 0.917 (95% CI: 0.868-0.966, P<0.001), and at a cutoff of 10.82 mm, LS-IC demonstrated a sensitivity of 82.0% and a specificity of 89.0% for diagnosing PSP; D-BMS had an AUC of 0.785 (95% CI: 0.704-0.866, P<0.001), and at a cutoff of 20.01 mm, D-BMS demonstrated a sensitivity of 66.0% and a specificity of 83.5% for diagnosing PSP. (2) In distinguishing PSP from MSA-C, IF-AQ achieved an AUC of 0.939 (95% CI: 0.889-0.988, P<0.001), with a sensitivity of 84.0% and a specificity of 90.0% at a cutoff of 10.385 mm; LS-IC achieved an AUC of 0.846 (95% CI: 0.756-0.936, P<0.001), with a sensitivity of 80.0% and a specificity of 76.7% at a cutoff of 10.710 mm; D-BMS achieved an AUC of 0.696 (95% CI: 0.578-0.813, P<0.001), with a sensitivity of 60.0% and a specificity of 80.0% at a cutoff of 19.810 mm. (3) In discriminating PSP from PD, IF-AQ yielded an AUC of 0.986 (95% CI: 0.970-1.000, P<0.001), with a sensitivity of 96.0% and a specificity of 89.2% at a cutoff of 10.955 mm; LS-IC achieved an AUC of 0.937 (95% CI: 0.885-0.988, P<0.001), with a sensitivity of 82.0% and a specificity of 95.5% at a cutoff of 10.820 mm; D-BMS had an AUC of 0.825 (95% CI: 0.740-0.909, P<0.001), with a sensitivity of 60.0% and a specificity of 95.5% at a cutoff of 19.820 mm. Conclusion:IF-AQ, LS-IC, and D-BMS distances on axial cranial MRI at the mamillary body level can diagnose and differentiate PSP to a certain extent, with IF-AQ enjoying the best efficacy.

Occupational pneumoconiosis remains the most common occupational disease in China, with occupational mineral dust exposure being its primary causative factor. Although national standards for online monitoring and early warning systems of coal mine dust concentrations have been established, national occupational health standards for rapid and online monitoring of dust concentration and particle size distribution in other industries are still limited. Among dust concentration sensor technologies, the light scattering method is the preferred choice for online dust monitoring owing to its wide measurement range and low cost. The beta-ray absorption method is mature but highly sensitive to humidity. The electrostatic induction method offers high sensitivity, simple structure, and low maintenance costs but exhibits high errors in low-concentration dust monitoring. The tapered element oscillating microbalance method is highly sensitive but costly. Multi-sensor data fusion technology can improve monitoring reliability, however, mature domestic products are not yet available. For monitoring dust particle size distribution, sieving and sedimentation methods are cumbersome. The aerodynamic method shows broad prospects in the online monitoring of respirable dust but has obvious measurement errors for larger dust particles. The use of optical measurement method is limited by dust morphology and is not suitable for monitoring coal dust particle size distribution. The electrical mobility method is primarily applicable to submicron dust. Future research should focus on promoting the application of monitoring technology for respirable dust particle size distribution in online monitoring of industrial dust. By integrating Internet of Things, data mining, and artificial intelligence technologies, along with multi-sensor data fusion and numerical simulation, dust concentration prediction models can be established to achieve accurate dust concentration monitoring and early warning of exceedances. The advancements of technologies will provide scientific support for the assessment of industrial dust hazards and the prevention and control of occupational pneumoconiosis.

Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

Objective To investigate the expression level and clinical application value of circular RNA hsa_circ_0001766 in gastric cancer(GC)tissues and serum of patients with GC.Methods The PCR amplification products from GES-1 cells of normal gastric mucosa were analyzed for the cyclic sites of hsa_circ_0001766 by the Sanger sequencing technique.The expression levels of hsa_circ_0001766 in GES-1 cells treated or untreated with RNase R(RNase R)were detected by real-time fluorescence quantitative PCR(qRT-PCR).The expression levels of hsa_circ_0001766 in GC and adjacent tissues of 73 GC patients and serum samples of 34 GC patients were also detected by qRT-PCR.The receiver operating characteristics(ROC)curve was used to evaluate the clinical diag-nostic value of hsa_circ_0001766 in GC.The correlations between hsa_circ_0001766 and clinicopathological parameters in GC patients were also analyzed.Results There was cyclic sites in hsa_circ_0001766 and RNase R had no significant impact on the expression lev-el of hsa_circ_0001766 in GES-1 cells(t=1.678,P=0.169).Compared with adjacent tissues,the expression levels of hsa_circ_0001766 in GC tissues were significantly up-regulated(U=1 360,P<0.001).Compared with healthy controls,the expres-sion levels of hsa_circ_0001766 in serum of GC patients were significantly up-regulated(U=375,P<0.001).The area under the ROC curve(AUCROC),sensitivity,and specificity of hsa_circ_0001766 in GC tissues for diagnosing GC were 0.759(95％CI:0.682-0.837,P<0.000 1),79.45％,and 68.49％,respectively.The AUCROC,sensitivity,and specificity of serum hsa_circ_0001766 in diagnosing GC were 0.773(95％CI:0.662-0.884,P<0.000 1),73.53％,and 72.12％,respectively.The expression levels of hsa_circ_0001766 in GC tissues were correlated with lymph node metastasis(x2=5.509,P=0.019)and TNM staging(x2=5.161,P=0.023).The 3-year survival rate of GC patients with high expression of hsa_circ_0001766 in GC tissues was significantly lower than that with low ex-pression(x2=3.700,P=0.037).Conclusion The hsa_circ_0001766 in GC tissues and serum of GC patients is highly expressed,and its change in the expression level is of great significance for the diagnosis and prognostic evaluation of GC patients.

Objective To identify risk factors associated with lymphatic leakage after laparoscopic radical prostatectomy(LRP)and to develop a machine learning-based nomogram for predicting such outcomes to support clinical prevention strategies.Methods We retrospectively analyzed perioperative data from 248 patients who underwent radical prostatectomy for prostate cancer between January 2020 and January 2024.Independent risk factors were identified through univariate and multivariate logistic regression analyses.A predictive model was developed,and its diagnostic performance was assessed by the area under the receiver operating characteristic curve(AUC).Five-fold cross-validation was performed to evaluate the model's generalizability.A nomogram was subsequently constructed to facilitate individualized risk quantification.Results Among the 248 patients,89(35.9%)developed lymphatic leakage,while 159(64.1%)did not.Independent risk factors for lymphatic leakage included intraopera-tive lymph node dissection(OR=5.415,95%CI:2.167～13.532,P<0.001),intraoperative plasma transfusion(OR=2.952,95%CI:1.524～5.718,P=0.001),and postoperative fasting duration of≥2 days(OR=1.412,95%CI:1.089～1.829,P=0.009).The predictive model showed good discrimination and calibration(AUC=0.711,95%CI:0.647～0.776,P<0.001;sensitivity:0.764;specificity:0.597).Model robustness was confirmed through five-fold cross-validation(training set AUC=0.822;test set AUC=0.829).The nomogram provided a clinically useful tool for quantifying individual risk of lymphatic leakage.Conclusions Intraoperative lymph node dissection,plasma transfusion,and postoperative fasting lasting≥2 days are independent risk factors for lymphatic leakage following radical prostatectomy.The validated predictive model demonstrates favorable clinical utility.