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 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.

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

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 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.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

Radiation-induced lung injury is a prevalent side effect of radiotherapy for chest cancer. The "three phases and three methods "is an innovative theory based on the evolution of the core pathogenesis of radiation-induced lung injury. Its formation also considers the understanding of radiation-induced lung injury by ancient and modern medical practitioners, pathological characteristics, clinical manifestations, and the development patterns of radiation-induced lung injury. The "three phases and three methods" refers to the three phases of the course and the three treatment methods. The core pathogenesis of radiation-induced lung injury from the beginning, middle and late stages is heat toxicity, yin deficiency, and blood stasis. Therefore, the course of radiation-induced lung injury is divided into three phases: blazing heat toxin, yin deficiency and heat accumulation, and static blood obstruction. The method of clearing the lung and resolving toxins, enriching yin and venting heat, invigorating blood and dissolving stasis are used respectively. Traditional Chinese medicines commonly used in each phase include Flos Lonicerae, Atrina Glass, heartleaf houttuynia herb, Radix Ophiopogonis, American Ginseng, Forsythiae Fructus, Radix Salviae Miltiorrhizae, Rhizoma Ligustici chuanxiong, Scorpio, etc. This article presents the theoretical origins of the "three phases and three methods" concept by reviewing of ancient literature, inheriting experience, and summarizing disease pathogenesis, as well as elaborating on the academic connotations of the "three phases and three methods". The scientific validity of the "three phases and three methods" is verified by literature, clinical, and basic research. The "three phases and three methods" interprets the core characteristics of each stage of radiation-induced lung injury, improves the traditional Chinese medicine prevention and treatment system for radiation-induced lung injury, and provides theoretical basis for achieving complete process management.