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.

Hepatocellular carcinoma （HCC） often has an insidious onset， and early diagnosis and accurate differential diagnosis are critical for improving the prognosis of patients. Ultrasound remains an important radiological examination for the screening and initial assessment of high-risk populations due to its advantages of convenience， real-time monitoring， repeatability， and suitability for dynamic follow-up. With the development of ultrasound technologies in recent years， the application of ultrasound in HCC has gradually expanded from lesion detection to lesion characterization， differential diagnosis， and prognostic evaluation. With reference to the clinical needs for the early and differential diagnosis of HCC， this article reviews the application value， clinical localization， and limitations of gray-scale ultrasound， Doppler ultrasound， and contrast-enhanced ultrasound in HCC， with a focus on their application in the evaluation and differential diagnosis of small HCC. It highlights that comprehensive evaluation should be performed based on liver background， lesion morphology， blood flow features， enhancement patterns， and dynamic changes during follow-up， so as to improve the early and differential diagnosis of HCC.

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Objective To investigate the effect of 3D technology combined with smartphones in problem-based learning(PBL)for neuroendoscopy.Methods 82 trainees who were enrolled from January 2021 to January 2023 were selected as the research subjects.A randomized controlled trial was conducted,and the subjects were divided into a control group and an experimental group.PBL and 3D technology combined with smartphone-assisted PBL were implemented respectively for two groups of students.The data were analyzed using t-test.Teaching satisfac-tion is evaluated by 2 test.Results The results of the in-operation examination and theoretical examination of the ex-perimental group students were found to be higher than those of the control group students(t=8.630,6.087,P＜0.001),the satisfaction scores of students and teachers showing that the satisfaction of the experimental group was higher than that of the control group(x2=4.213,6.301,7.026,P＜0.01).Conclusion In the PBL of neuroendosco-py,the use of 3D technology combined with smart phones as an auxiliary teaching system can effectively improve students'sense of participation,reduce the difficulty of skull base anatomy learning,and improve students'theo-retical and surgical assessment scores and teaching satisfaction.

Objective:To explore the efficacy and prognosis of hepatectomy via Laennec membrane approach in patients with hepatocellular carcinoma (HCC).Methods:The data of 98 patients with HCC who underwent hepatectomy in the First Affiliated Hospital of Soochow University from January 2016 to December 2022 were retrospectively analyzed, including 76 males and 22 females, aged 61.0 (55.0, 66.0) years. Forty-eight patients treated with Laennec membrane approach hepatectomy were included in the study group and 50 patients treated with traditional approach hepatectomy were included in the control group. The age, gender, combined hypertension and diabetes, aspartate transaminase, alanine transaminase, albumin, total bilirubin, prealbumin, platelet, alpha-fetoprotein, carbohydrate antigen 19-9 and carbohydrate antigen 125 were compared between the two groups. The surgical bleeding, operation time and complications (abdominal bleeding, bile leakage, poor incision healing, etc.) were compared between the two groups. The prognosis of the two groups was compared.Results:There were no significant differences in gender, age, underlying diseases, preoperative biochemical and tumor serological indexes between the two groups (all P>0.05). The operation time of the study group was 180.0 (141.3, 227.3) min, which was lower than that of the control group 221.5 (187.5, 256.3) min ( Z=-0.41, P=0.002). The intraoperative blood loss in the study group was 295.0 (127.5, 350.0) ml, which was lower than that in the control group 300.0 (200.0, 500.0) ml, and the difference was statistically significant ( Z=-1.97, P=0.003). The levels of aspartate transaminase and alanine transaminase 1 week after surgery in the study group were 33.4 (24.0, 43.8) U/L and 64.5 (38.3, 119.1) U/L, respectively, which were lower than those in the control group 41.3 (29.7, 63.0) U/L and 102.8 (50.1, 140.7) U/L, the differences were statistically significant ( Z=-2.09, -2.38, P=0.035, 0.028). Postoperative complications occurred in 8 cases (16.7%) in the study group and 10 cases (20.0%) in the control group, with no significant difference between the two groups ( χ2=0.18, P=0.670). The median overall survival was 16 months in the study group and 18 months in the control group, respectively. There was no significant difference in cumulative survival between the two groups ( χ2=1.41, P=0.130). Conclusion:Laennec membrane approach hepatectomy can not only shorten the operation time and reduce the amount of blood loss, but also promote the recovery of liver function.

Objective:To observe the improving effect of acupuncture and Tuina(Chinese therapeutic massage)combined with Ba Duan Jin(Eight-brocade Exercise)on motor function in patients with Parkinson disease(PD)in the early and middle stages.Methods:Seventy patients with early-or middle-stage PD were randomly divided into a control group and an observation group,with 35 patients in each group.The control group was given conventional treatment such as oral levodopa hydrochloride tablets;the observation group was treated with acupuncture,Tuina,and Ba Duan Jin in addition to the control group's treatment.Acupuncture and Tuina were administered twice a week,and Ba Duan Jin was performed five times a week.Each course of treatment lasted 4 weeks,and a total of 3 courses were completed.The changes in the unified Parkinson disease rating scale Ⅲ(UPDRS Ⅲ)score,Berg balance scale(BBS)score,15-meter walking speed,and 6-minute walk distance were compared between the two groups.Results:The total effective rate in the observation group was 93.6%,which was significantly higher than 45.7%in the control group(P<0.01).After 4,8,and 12 weeks of treatment,the UPDRS Ⅲ score in the observation group was significantly lower than the previous score(P<0.05);the BBS score was significantly higher than the previous score(P<0.05),and the 6-minute walk distance also significantly increased compared to the previous result(P<0.05).After 8 and 12 weeks of treatment,the 15-meter walking speed in the observation group was significantly higher than that before treatment and the previous measurement(P<0.05).In comparison with the control group,the observation group showed significantly lower UPDRS Ⅲ scores after 8 and 12 weeks of treatment(P<0.05).Additionally,after 4,8,and 12 weeks of treatment,the observation group had significantly higher BBS scores,15-meter walking speed,and the 6-minute walk distance than the control group(P<0.05).There were no significant differences in the above indicators before and after treatment in the control group(P>0.05).Conclusion:The addition of acupuncture,Tuina,and Ba Duan Jin to Western medication treatment can effectively improve motor function,balance ability,and walking ability in patients with early-or middle-stage PD.

Klebsiella pneumoniae,as a clinically prevalent opportunistic pathogen,ranks as the second most com-monly detected pathogen in clinical isolates in China.The extensive clinical use of carbapenem antibiotics has led to a high global detection rate of carbapenem-resistant K.pneumoniae(CRKP).Characterized by complex resist-ance mechanisms and diverse evolutionary pathways,CRKP infections pose significant challenges in prevention and treatment,with high associated mortality rates,creating substantial obstacles for clinical anti-infective therapy.In recent years,the emergence and global spread of carbapenem-resistant hypervirulent K.pneumoniae(CR-hvKP)have escalated into a major public health threat.Notably,hypervirulent K.pneumoniae isolates carry-ing carbapenem resistance genes are rapidly disseminating worldwide,causing fatal infections even in immunocom-petent individuals.This article systematically reviews the latest research advances on the resistance mechanisms,evolutionary pathways,adaptive changes,and clinical management strategies of CR-hvKP,aiming to deepen un-derstanding of this"superbug"and provide a theoretical foundation for clinical prevention and control.

Objective To evaluate the efficacy of vitamin AD combined with step-up therapy in children with asthma and its impact on humoral immunity,pulmonary function and recurrence.Meth-ods A total of 94 children with asthma were enrolled,and randomly divided into study group(n=47)and control group(n=47)using random number table method.The control group adopted the step-up treatment plan on the basis of conventional treatment,while the study group was treated with vitamin AD on the basis of the control group.The clinical efficacy,pulmonary function indicators[forced vital capacity(FVC),forced expiratory volume in one second(FEV,),FEV1/FVC and peak expiratory flow rate(PEF)]and humoral immunefunction[immunoglobulin G(IgG),immuno-globulin A(IgA),immunoglobulin M(IgM)and immunoglobulin E(IgE)]after treatment were compared between the two groups.The recurrence rateand safety of the two groups after treatment were compared.Results The total effective rate of clinical efficacy in the study group was 93.62％,which was significantly higher than 78.72％in the control group(P＜0.05).After treatment,FVC,FEV1,FEV1/FVC and PEF levels were significantly higher in both groups compared to pre-treatment values,and the study group showed significantly better improvement than the control group(P＜0.05).After treatment,serum IgG and IgA levels in the study group were significantly higher than those in the control group,whereas IgM and IgE levels were significantly lower(P＜0.05).At 12 months after treatment,the recurrence rate in the study group was 4.26％(2/47),which was sig-nificantly lower than 19.15％(9/47)in the control group(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Vitamin AD combined with step-up therapy effectively alleviates clinical symptoms,modulates humoral immune balance,improves pulmonary function,and reduces recurrence rates in children with asthma,and has high safety.

Objective To prepare neutrophil-responsive luminescent nanomicelles based on self-luminating compound,luminol,and investigate their imaging capability for a mouse burn model at early stage of inflammation.Methods Hexachlorotripolyphosphazene(HCCP)was utilized as the skeleton material to synthesize amphiphilic LHP luminescence materials through chemical synthesis of luminol and polyethylene glycol(PEG).The chemical structure of LHP was characterized using infrared spectrum and nuclear magnetic hydrogen spectrum.Nanomicelle LHP NM was formed by self-assembly of LHP in deionized water,and then its particle size and potential were measured.Transmission electron microscopy(TEM)was applied to observe the morphology of nanomicelles.Optical fiber spectrometer,weak luminescence measuring instrument,and small animal living imager were employed to evaluate the spectroscopic properties,chemiluminescence rules,and in vitro luminescence imaging ability of the nanomicelles.After that,female Balb/c mice were subjected to scalding with hot water at temperatures of 70℃,80℃,and 90℃,respectively to establish a mouse burn model ranging from degree Ⅰ to degree Ⅱ burns.The depth of skin scalds in the model mice was determined through HE staining,while the expression levels of TNF-α,IL-1β,IL-6 and myeloperoxidase(MPO)in the scalded skin tissues were assessed with fluorescence quantitative qPCR.The changes in reactive oxygen species(ROS)levels over time and burn depth in the skin tissues were determined with ROS detection kit.Additionally,the neutrophils within the skin tissues of model mice were labeled with FITC-Ly6G antibody to count the neutrophil number.Finally,a small animal imaging system was utilized to examine the imaging capability of nanomicelle LHP NM in a mouse burn model to analyze the correlation between luminous intensity and number of recruited neutrophil in order to evaluate the effectiveness of luminous nanomicelles for monitoring early inflammatory response and diagnosing burn depth in a mouse burn model.Results Nuclear magnetic resonance(NMR)spectroscopy confirmed the bonding of approximately 5 luminol units and a polyethylene glycol(PEG)chain to 1 HCCP molecule.TEM and particle size determination results demonstrated that the prepared nanomicelles were spherical,hollow structures in a diameter of around 120 nm.In vitro luminescence experiments revealed that the nanomicelles exhibited high brightness and sustained chemiluminescence under varying concentrations of ROS and MPO levels,with luminescence intensity dependent on both ROS level and nanomicelle concentration.The in vitro cellular experiments demonstrated that the nanomicelles exhibited neutrophil-responsive imaging capability.The luminescence intensity was positively correlated with both the number of neutrophils and the dose of LHP NM,with a linear correlation coefficient(r)of 0.98 and 0.99,respectively.In vivo animal study revealed a significant increase(P<0.05)in the count of neutrophils and ROS level in the skin tissue of burned and scalded mice.Notably,at the time point of 24 h,compared to the 80℃and 70℃treatment groups,the number of recruited neutrophils was increased by 86.4％,and the luminescent imaging intensity rose by 71.5％.These findings indicated that the severity of burns was correlated with the extent of neutrophil recruitment in the injured area,and LHP NM could effectively achieve neutrophil-responsive imaging in model mice.The changes in imaging intensity were closely associated with the number of neutrophils and the level of ROS in the injured skin tissue.Conclusion The neutrophil-responsive luminescent nanomicelle LHP NM is successful prepared,and the nanomicelles enable responsive imaging of skin damage in mouse burn model.The luminescence intensity accurately reflects the neutrophil infiltration and ROS level,allowing for real-time monitoring of early inflammatory responses in mouse burn model.Additionally,this study provides methods and strategies for diagnosing burn depth.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.