The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [¹⁸F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [¹⁸F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 in vitro and in vivo, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [¹⁸F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [¹⁸F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [¹⁸F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.

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.

ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective:To develop a deep learning-based segmentation model MT-UNet to automatically segment bone metastases and benign bone lesions in bone scintigraphy with SPECT/CT.Methods:A total of 93 patients (48 males and 45 females, age 28-84 years) who underwent bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from June 2023 to December 2023 were enrolled retrospectively in this study, with a total of 184 bone lesions (94 benign lesions and 90 metastatic tumors). The MT-UNet was employed to segment bone lesions in SPECT, CT and SPECT/CT images respectively. Comparative analysis with 8 segmentation models was performed. The training set and validation set were divided by using 5-fold cross-validation and transfer learning was introduced to further enhance the robustness of the model. An additional cohort of 22 patients (15 males and 7 females, age 37-87 years) who received bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from April 2023 to May 2023 were included, comprising 40 bone lesions (22 benign lesions and 18 metastatic tumors) as the test set of MT-UNet. Segmentation performance of different models was assessed using accuracy, sensitivity, specificity, AUC, intersection over union and Dice similarity coefficient (DSC). Delong test was used to compare the segmentation efficacy among different models in the test set.Results:In the validation set, MT-UNet demonstrated DSC of 0.940, 0.962, and 0.963 for SPECT, CT, and SPECT/CT bone lesion segmentation, respectively, which were outperformed other models. Following transfer learning implementation, the SPECT/CT model′s DSC was improved to 0.984. In the test set, MT-UNet maintained comparable segmentation performance to the validation set, with significant AUC differences among the three models ( Z values: from -15.42 to -9.27, all P<0.01). Compared with conventional image interpretation, MT-UNet-based segmentation reduced physician interpretation time from 164min to 102min. Conclusion:MT-UNet has shown good performance in automatic segmentation of bone metastases and benign bone lesions, and is expected to become an important part of SPECT/CT image intelligent diagnosis system for bone metastases.

Objective:To analyze the efficacies of unilateral biportal endoscopy(UBE)and percutaneous endoscopic transforaminal discectomy(PETD)in treatment of lumbar disc herniation(LDH),and to explore the optimal selection of minimally invasive surgical approaches for the The LDH patients.Methods:A retrospective analysis was performed on the clinical data of 64 LDH patients who underwent surgery at Liwan Central Hospital of Guangzhou City in Guangdong Province,between January 2020 and June 2024.The surgical approaches were determined through physician-patient communication,and the patients were divided into UBE group(n=30)and PETD group(n=34).The materials of patients were recorded including gender,age,body mass index(BMI),percentages of affected segments,course of disease,duration of hospitalization,operation duration,intraoperative blood loss,numbers of intraoperative fluoroscopy,total incision length,and time to full weight-bearing(WB).The therapeutic outcomes were evaluated using Oswestry disability index(ODI),Visual Analog Scale(VAS)scores for low back pain and leg pain,MacNab criteria,and spinal canal areas at the affected segment.the postoperative complications of the patients in two groups were analyzed.Results:There were no statistically significant differences in age,gender composition ratio,BMI,course of disease,and percentages of affected segments of the patients between UBE group and PETD group(P＞0.05).Compared with PETD group,the intraoperative blood loss,total incision length,and time to full WB of the patients in UBE group were significantly increase(P＜0.01),while the number of intraoperative fluoroscopy time was decreased(P＜0.01).Compared with pre-operation,the ODI scores and VAS scores for low back and leg pain of the patients at final follow-up in both groups were decreased(P＜0.01),and the spinal canal areas at the affected segments of the patients were increased(P＜0.01).At final follow-up,compared with PETD group,the ODI score and VAS scores for low back and leg pain of patients in UBE group were decreased(P＜0.01),while the spinal canal areas at the affected segments of the patients was increased(P＜0.01).According to MacNab criteria,the percentages of excellent and good had no significant difference between two groups(P＞0.05).The incidence of complication showed no statistical difference between two groups(P＞0.05).Conclusion:Both UBE and PETD yield satisfactory outcomes in the treatment of single-segment LDH.PETD is less invasive and permits earlier time to full WB,whereas UBE provides more extensive decompression and superior long-term efficacy.The surgical approach selection should be individualized based on specific factors in the clinic.

Objective To investigate the efficacy of Yiqi Wenyang Sanjie Decoction in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution,and to observe its effect on serum inflammatory factors and immune function.Methods From January 2020 to June 2024,a total of 106 patients with pulmonary ground glass nodules and yang-deficiency constitution admitted to the Department of Respiratory Medicine and Preventive Treatment of Disease Center of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine were selected.The patients were randomly divided into control group and Chinese medicine group by random number table method,with 53 cases in each group.The patients in the control group were only given follow-up without any intervention,and the patients in the Chinese medicine group were treated with Yiqi Wenyang Sanjie Decoction for 3 months.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,maximum diameter of pulmonary ground glass nodules,serum levels of inflammatory factors of interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α),and levels of immune function indicators of peripheral blood CD3+,CD4+cell percentage and CD4+/CD8+ratio.After treatment,the efficacy and safety of the two groups were evaluated.Results(1)During the trial,5 cases fell off from the control group and 3 cases fell off from the Chinese medicine group.A total of 98 cases were eventually included,and 48 cases were in the control group and 50 cases were in the Chinese medicine group.(2)After 3 months of treatment,the total effective rate of the Chinese medicine group was 46.00%(23/50),and that of the control group was 10.42%(5/48).The intergroup comparison(tested by chi-square test)showed that the efficacy of the Chinese medicine group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group were lowered(P＜0.05),while the TCM syndrome score and the maximum diameter showed no obvious changes compared with those at enrollment(P＞0.05);the intergroup comparison showed that the reduction of TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the levels of serum inflammatory factors of IL-6,IL-17A and TNF-α in the Chinese medicine group were significantly lowered compared with those at enrollment(P＜0.05),while there was no significant change in serum IL-6,IL-17A and TNF-α levels of the control group(P＞0.05);the intergroup comparison showed that the decrease of serum IL-6,IL-17A and TNF-α levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the percentage of T lymphocyte subset CD4+and the ratio of CD4+/CD8+in the Chinese medicine group were significantly increased compared with those at enrollment(P＜0.05),while there was no significant change in the percentage of CD3+,CD4+cells and the ratio of CD4+/CD8+of the control group and in the percentage of CD3+cells of the Chinese medicine group(P＞0.05).The intergroup comparison showed that the increase of CD4+percentage and CD4+/CD8+ratio in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(6)There were no obvious adverse reactions occurring in the Chinese medicine group during the treatment,showing relatively high safety.Conclusion Yiqi Wenyang Sanjie Decoction exerts certain effect in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution.It can effectively promote the reduction of nodules,relieve clinical symptoms,decrease serum levels of inflammatory factors,improve immune function,and has good safety.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography(PET/CT)remains limited.This investigation involved the synthesis of[18F]AlF-NOTA-PCP2,which is a novel peptide-based radiolabeled tracer that targets PD-L1,and evaluated its imaging capabilities in orthotopic glioblastoma(GBM)models.Using this tracer,we could noninvasively monitor radiation-induced PD-L1 changes in GBM.[18F]AlF-NOTA-PCP2 exhibited high radiochemical purity(＞95％)and stability up to 4 h after synthesis.It demonstrated specific,high-affinity binding to PD-L1 in vitro and in vivo,with a dissociation constant of 0.24 nM.PET/CT imaging,integrated with contrast-enhanced magnetic resonance imaging,revealed significant accumulation of[18F]AlF-NOTA-PCP2 in orthotopic tumors,correlating with blood-brain barrier disruption.After radiotherapy(15 Gy),[18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51％±0.73％to 12.04％±1.43％,indicating enhanced PD-L1 expression consistent with immunohisto-chemistry findings.Fractionated radiation(5 Gy × 3)further amplified PD-L1 upregulation(13.9％±1.54％ID/cc)compared with a single dose(11.48％±1.05％ID/cc).Taken together,[18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.

In the field of healthcare service,it is crucial to optimize medical innovation services by combining the preferences of health service providers and demanders(i.e.,stakeholders).The best-worst scaling(BWS)method is a recently developed stated preference method for assessing preferences with distinctive advantages.Nevertheless,there is a lack of a comprehensive introduction to stakeholder preference assessment using BWS,thus constraining its applications and promotion.This paper introduces the process of using BWS to assess service providers'preferences for the Shared Medical Appointment for diabetes(SMART),an integrated healthcare service of medicine and health management,in the hope of providing reference for researchers for promoting the use of BWS in implementation research.