Background Silicosis is a fatal form of pulmonary fibrosis caused by the inhalation of silica dust. Although the underlying pathogenesis remains unclear, and the macrophage-mediated immune response plays a central role in its development. Objective To investigate the expression, functional role, and upstream regulatory mechanism of C-C motif chemokine ligand 22 (CCL22) in silica-induced pulmonary fibrosis. Methods Through bioinformatics analysis, we identified CCL22 as a potential key factor in pulmonary fibrosis. We established in vitro models by stimulating human monocytic leukemia cells (THP-1) and peripheral blood mononuclear cell-derived macrophages (PBMC-m) with crystalline silica (CS). The regulation of CCL22 expression by CS was validated using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Subsequently, a conditioned co-culture system comprising macrophages and lung epithelial cells (BEAS-2B) was developed to evaluate the effects of CCL22 on lung epithelial cell function. Furthermore, the molecular mechanisms underlying CS-induced CCL22 secretion by macrophages were investigated using bioinformatics analysis, Western blot, specific inhibitors, qRT-PCR, and ELISA. Results Bioinformatics analysis identified CCL22 as a key upregulated molecule in pulmonary fibrosis. In vitro experiments confirmed that CS treatment significantly enhanced CCL22 mRNA transcription and protein secretion in THP-1 and PBMC-m cells (P<0. 0001). In the co-culture system, supernatant from CS-stimulated macrophages with stable CCL22 knockdown significantly inhibited the scratch-healing ability and fibrotic process of BEAS-2B cells, and reversed the epithelial-mesenchymal transition (EMT) phenotype compared to the control group. Mechanism studies found that, compared to other transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB), the inhibition of of specific protein 1 (SP1) most significantly attenuated the CS-induced upregulation of CCL22. Furthermore, pathway inhibition experiments demonstrated that inhibiting extracellular signal-regulated kinase (ERK) reduced both CCL22 expression and p-SP1. Conversely, SP1 intervention did not affect ERK activation. Conclusion CS promotes CCL22 secretion by macrophages through the Raf/ERK-Sp1 signaling pathway, thereby driving fibrotic changes in pulmonary epithelial cells.

ObjectiveTo explore the molecular mechanism through which modified Guizhi Fulingwan （MGZFLW） promotes apoptosis and inhibits prostate cancer through the miR-34a-5p/δ-like protein 1 （DLL1）/Notch signaling pathway based on the traditional Chinese medicine theory of Yang transforming Qi while Yin constituting form. MethodsThe optimal intervention conditions of MGZFLW-containing serum and docetaxel （DXT） were screened by the cell counting kit-8 （CCK-8） method. Human prostate cancer cells （PC-3） were allocated into blank， MGZFLW （10%）， and DXT （30 nmol·L^-1） groups. The effects of MGZFLW-containing serum on the migration and proliferation of PC-3 cells were evaluated by cell scratch and colony formation assays， and the apoptosis of PC-3 cells was detected by terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） assay. The cells were transfected with miR-34a-5p mimics and miR-34a-5p inhibitor. The mRNA levels of miR-34a-5p， DLL1， Notch1 and its downstream effector factors Notch1 intracellular domain （NICD1）， Hes family basic helix-loop-helix transcription factor 1 （Hes1）， and hairy/enhancer-of-split related with YRPW motif 1 （Hey1） were determined by Real-time PCR. The protein levels of DLL1， Notch1， NICD1， Hes1， and Hey1 were determined by a WES fully automatic protein system. The effect of miR-34a-5p on the DLL1-mediated Notch pathway was evaluated based on the results. Further， after MGZFLW-containing serum intervention， the expression of DLL1 and Notch1 was detected by the immunofluorescence （IF） assay， and the mRNA and protein levels of miR-34a-5p/DLL1/Notch pathway-related molecules were quantified by Real-time PCR and the WES fully automatic protein system， respectively， to explore the regulatory effect of MGZFLW-containing serum on the miR-34a-5p/DLL1/Notch pathway. ResultsMGZFLW-containing serum inhibited the viability， migration， and proliferation and promote the apoptosis of PC-3 cells （P<0.01）. The overexpression of miR-34a-5p down-regulated the mRNA and protein levels of key molecules in the DLL1/Notch signaling pathway and promoted cell apoptosis （P<0.01）， while inhibition of miR-34a-5p had the opposite effects. MGZFLW-containing serum reversed the activation of the DLL1/Notch pathway and the inhibition of apoptosis caused by miR-34a-5p inhibition， up-regulated the expression of miR-34a-5p， and down-regulated the expression of related molecules in this pathway （P<0.01）. ConclusionMGZFLW can up-regulate the expression of miR-34a-5p to inhibit the DLL1/Notch signaling pathway and promote the apoptosis of prostate cancer cells， thereby inhibiting prostate cancer. This study provides experimental evidence for clarifying the molecular mechanism of the anti-prostate cancer effect of this formula.

Objective To construct a nomogram model for prediction of constipation risk in adult patients with cardiovascular disease (CVD). Methods A total of 780 adult patients with CVD admitted to Zhongshan Hospital, Fudan University from June 15, 2025 to August 15, 2025 were prospectively enrolled and randomly divided into a training set and a validation set at a 7∶3 ratio. Risk factors for constipation were identified using the least absolute shrinkage and selection operator (LASSO) and Firth logistic regressions, and a nomogram model was subsequently constructed in the training set. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the discrimination ability of the model. Calibration curve and decision curve analysis (DCA) were used to assess calibration and clinical applicability. The value of model was evaluated in the validation set. Results Among 780 adult patients with CVD, 391 patients (50.1%) developed constipation. Eleven variables were selected by LASSO regression and Firth logistic regression, and a nomogram model was constructed. The ROC curve showed that the AUCs of the model to predict constipation in adult patients with CVD in training and validation sets were 0.881 and 0.883, respectively. Calibration curves and DCA demonstrated good calibration and predictive performance of the model in training and validation sets. Conclusions The nomogram model based on LASSO-Firth logistic regression demonstrates good predictive performance and may serve as a useful tool for identifying adult patients with CVD at high risk of constipation.

Objective: To explore the association between daytime light exposure intensity and duration and objectively assessed sleep parameters among primary school students, so as to provide a scientific basis for understanding the impact of light exposure on children s sleep quality. Methods: From October 2023 to May 2024, a total of 741 primary school students in grades 2 to 3 were recruited from two primary schools in Chuzhou City, Anhui Province. Participants were required to wear an illuminance meter and an actigraph concurrently for 5 consecutive days to simultaneously collect 24 hour light exposure, sleep parameters, and physical activity data. Objective sleep parameters included total sleep time, sleep efficiency, sleep onset latency, wake after sleep onset, and sleep fragmentation index. Generalized linear model was applied to analyze the associations of average daytime (overall, morning, afternoon) light exposure intensity and exposure duration at different illuminance thresholds with various sleep parameters among primary school students. Results: The mean values of total sleep duration, sleep efficiency, sleep latency, wake time after sleep onset and sleep fragmentation index were (465.70±40.27)min, (83.22±5.16)%, (17.40±8.31)min, (75.97±26.81)min and (26.23±6.20), respectively. Generalized linear model showed that the average daytime light exposure intensity and duration of exposure ≥1 000 lx were positively correlated only with total sleep duration ( β =0.94, 8.51, both P <0.05). Morning light exposure intensity was associated with higher sleep efficiency ( β =0.11), longer total sleep duration ( β =0.80), shorter sleep latency ( β = -0.20 ), shorter wake time after sleep onset ( β =-0.57) and lower sleep fragmentation index ( β =-0.11) (all P <0.05). The duration of morning light exposure at ≥1 000 lx also improved childrens sleep efficiency, total sleep duration, sleep onset latency, wake time after sleep onset and sleep fragmentation index ( β =1.74, 13.91, -4.43, -11.04, -2.01, all P <0.05). Conclusions There is a significant association between morning light exposure intensity, exposure duration ≥1 000 lx, and multiple objective sleep parameters among primary school students. Increasing morning outdoor activities or high illuminance indoor light exposure could serve as feasible intervention strategies to improve the sleep of primary school students.

ObjectiveTo observe the clinical efficacy of modified Yuejuwan in the treatment of thyroid cysts after microwave ablation. MethodsA total of 90 patients with thyroid cysts who met the inclusion criteria and treated in the First Affiliated Hospital of Hebei University of Chinese Medicine from September 2022 to December 2023 were randomly assigned to either the control group or the observation group， with 45 patients in each group. The control group received conventional postoperative drug treatment and was followed up regularly. The observation group was additionally administrated with modified Yuejuwan for one month and followed up regularly. The alterations in volume， thyroid function parameters ［thyroid-stimulating hormone （TSH）， free triiodothyronine （FT₃）， and free thyroxine （FT₄）］， quality of life scores， and clinical efficacy were monitored and compared between the two groups. Additionally， the safety profile was appraised. ResultsAfter treatment， both the observation group and the control group showed a reduction in cyst volume （P<0.05）， and the observation group exhibited a more significant reduction in cyst volume than the control group （P<0.05）. After treatment， both the observation group and the control group showed a decrease in TSH level and increases in FT₃ and FT₄ levels （P<0.05）， and the changes were more significant in the observation group （P<0.05）. In addition， both groups exhibited elevations in the quality of life scores （P<0.05）. Moreover， the observation group showed more increments in physiological， psychological， and social scores than the control group （P<0.05）. The total response rate of the observation group was higher than that of the control group （Z=-2.516， P<0.05）. The incidence of adverse reactions was similar between the two groups， with no statistically significant difference. ConclusionModified Yuejuwan is effective in the treatment of thyroid cysts after microwave ablation. It can promote the absorption of cysts， improve the thyroid function and quality of life， and has high safety.

ObjectiveTo observe the clinical efficacy of modified Yuejuwan in the treatment of thyroid cysts after microwave ablation. MethodsA total of 90 patients with thyroid cysts who met the inclusion criteria and treated in the First Affiliated Hospital of Hebei University of Chinese Medicine from September 2022 to December 2023 were randomly assigned to either the control group or the observation group， with 45 patients in each group. The control group received conventional postoperative drug treatment and was followed up regularly. The observation group was additionally administrated with modified Yuejuwan for one month and followed up regularly. The alterations in volume， thyroid function parameters ［thyroid-stimulating hormone （TSH）， free triiodothyronine （FT₃）， and free thyroxine （FT₄）］， quality of life scores， and clinical efficacy were monitored and compared between the two groups. Additionally， the safety profile was appraised. ResultsAfter treatment， both the observation group and the control group showed a reduction in cyst volume （P<0.05）， and the observation group exhibited a more significant reduction in cyst volume than the control group （P<0.05）. After treatment， both the observation group and the control group showed a decrease in TSH level and increases in FT₃ and FT₄ levels （P<0.05）， and the changes were more significant in the observation group （P<0.05）. In addition， both groups exhibited elevations in the quality of life scores （P<0.05）. Moreover， the observation group showed more increments in physiological， psychological， and social scores than the control group （P<0.05）. The total response rate of the observation group was higher than that of the control group （Z=-2.516， P<0.05）. The incidence of adverse reactions was similar between the two groups， with no statistically significant difference. ConclusionModified Yuejuwan is effective in the treatment of thyroid cysts after microwave ablation. It can promote the absorption of cysts， improve the thyroid function and quality of life， and has high safety.

Objective:To evaluate the effect of fiberoptic endoscopic evaluation of swallowing (FEES) on clinical functional outcomes of patients with intensive care unit-acquired swallowing disorders (ICU-ASD).Methods:This retrospective cohort study analyzed clinical data of patients diagnosed with post-extubation dysphagia (PED) in the intensive care unit (ICU) and respiratory intensive care unit (RICU) of the Affiliated Hospital of Inner Mongolia Medical University from February 2020 to February 2025. Patients were categorized into a FEES group of 60 cases [34 males, 26 females, aged 37-80 years (median age 62 years)] and a control group without FEES of 58 cases [32 males, 26 females, aged 39-77 years (median age 61 years)].The patients in two groups received swallowing function and feeding training based on the results of the FEES assessment and the Volume-Viscosity Swallow Test-Clinical Version (VVST-CV), respectively. Clinical functional outcome measures included pneumonia incidence, clinical pulmonary infection score (CPIS), pneumonia severity index (PSI), Functional Oral Intake Scale (FOIS), and dietary method at discharge. χ2 test, Mann-Whitney U test, and Wilcoxon signed-rank test, were employed for statistical analysis of the outcome measures. Results:Compared with the control group, the FEES group had significantly lower aspiration pneumonia incidence at discharge [3.3% (2/60) vs 15.5% (9/58), χ2=5.179, P=0.023]. Regarding dietary methods,a significantly higher proportion of patients in the FEES group achieved complete oral feeding compared with the control group [75.0% (45/60) vs 67.3% (39/58), χ2=8.065, P<0.05]. After training, the FEES group had higher median FOIS scores than the control group (7.00 vs 6.00, Z=-2.370, P=0.018), and lower CPIS scores (2.50 vs 5.00, Z=-2.216, P=0.027) and PSI scores (59.00 vs 73.00, Z=-2.251, P=0.024). Within-group comparisons revealed that FOIS scores significantly improved post-training in both groups (both P<0.001). Conclusion:Early FEES examination for ICU patients with acquired swallowing disorders is associated with a lower incidence of pneumonia, improved swallowing function, and superior clinical functional outcomes.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To explore the influence of intensified blood glucose control on the diaphragmatic function of patients with sepsis in the intensive care unit(ICU).Methods Sixty-six sepsis patients admitted to the ICU of Affiliated Lihuili Hospital of Ningbo University from January to December 2024 were selected and divided into experimental group and control group according to the random number table method,with 33 cases in each group.The experimental group received intensified blood glucose control,while control group received conventional blood glucose control.The diaphragm distance(DD)and diaphragm thickness fraction(DTF)of two groups of patients were continuously measured by bedside ultrasound,and the mechanical ventilation time,weaning outcome and hospital stay were recorded.Results With the prolongation of treatment time and mechanical ventilation time,the DD and DTF of both groups of patients showed an upward trend.There was no statistically significant difference in DD between two groups of patients at different times(P＞0.05).On the 4th and 6th days,the DTF of patients in experimental group was significantly greater than that in control group(P＜0.05).The weaning success rate of patients in experimental group was significantly higher than that in control group(P=0.026).There was no statistically significant difference in mechanical ventilation time,ICU stay time and total hospital stay time between two groups of patients(P＞0.05).There was no statistically significant difference in the incidence of hypoglycemia between two groups of patients(P＞0.05).Conclusion Intensified control of blood glucose can improve diaphragmatic function of patients with sepsis in the ICU,increase the success rate of weaning from the ventilator,and has high safety.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.