AIM: To explore the clinical therapeutic effect of teprotumumab combined with glucocorticoid pulse therapy for thyroid-associated ophthalmopathy(TAO), and its impacts on thyroid function, levels of inflammatory factors, and adverse reactions in patients. METHODS: Active TAO patients admitted to the Ophthalmology Department were enrolled and randomly divide into the steroid group and the combined group. Then the steroid group was treated with glucocorticoid pulse therapy, while the combined group was combined with intravenous infusion of teprotumumab on the basis of the steroid group. The clinical therapeutic effect, the CAS, OSDI, M-C-TAO-QOL scores, ocular sign indicators(fissure width, proptosis), levels of inflammatory factors(TNF-α, CRP, IL-17), thyroid function(TSH, FT3, FT4)before and after treatment, and occurrence of adverse reactions were compared between two groups.RESULTS:Totally 96 TAO patients(192 eyes)were included, with 48 cases(96 eyes)in each group. In the combined group, there were 17 males and 31 females, with an average age of 51.85±3.53 y; in the steroid group, there were 14 males and 34 females, with an average age of 51.26±3.84 y. The total effective rate of the combined group(94%)was higher than that of the steroid group(79%)(P<0.05). After treatment, the CAS score, OSDI score, fissure width, proptosis, levels of TNF-α, CRP, and IL-17 in the combined group were all lower than those in the steroid group, and the M-C-TAO-QOL score was higher than that in the steroid group(P<0.05). However, there was no difference in thyroid function indicators and adverse reactions between two groups after treatment(P>0.05). CONCLUSION: The combination of teprotumumab and glucocorticoid pulse therapy for TAO has a prominent therapeutic effect. Meantime, it can more effectively control ocular inflammation, improve ocular signs and quality of life of patients, and has no obvious adverse effect on thyroid function, with controllable safety.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals ; Humans ; Autophagy/drug effects* ; Reishi/chemistry* ; Mice ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Neoplasms/genetics* ; Hepatoblastoma/genetics* ; Polysaccharides/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Male ; Cell Proliferation/drug effects* ; Hep G2 Cells

Objective:To analyze the transcriptomic features of breast cancer and its lymph node metastasis using single-cell RNA sequencing, to identify potential biomarkers for breast cancer.Methods:The GSE180286 single-cell RNA sequencing dataset was used to examine the transcriptomic characteristics of breast cancer and its lymph node metastasis. Following quality control, dimensionality reduction, clustering, and cell annotation of single-cell data, genes associated with breast cancer were identified. Dotplot, FeaturePlot, and other analytical methods were applied to investigate the expression profiles of target genes ( ALOX15B, FAAH, HDGF, KLF5, TLE3, TNS1) across different cell types and to assess their activity in immune and metabolic pathways. Statistical analysis was performed using the bilateral Student′s t-test. Results:ALOX15B, FAAH, HDGF, KLF5, TLE3, and TNS1 were differentially expressed across various cell types in breast cancer. ALOX15B was specifically expressed in macrophages and involved in immune responses, particularly with high activity in complement and inflammatory response pathways. HDGF was primarily expressed in epithelial cells and closely associated with breast cancer proliferation, migration, and angiogenesis. FAAH, KLF5, TLE3, and TNS1 were also closely related to the onset and progression of breast cancer. Co-expression analysis revealed relationships between these genes and breast cancer regulatory genes such as BRCA1 and BRCA2. Conclusions:This study identified 6 breast cancer-specific expressed potential biomarkers, and revealed their expression characteristics in different cell types and their differential activity in immune-metabolism-related pathways. These findings provide potential targets for understanding the molecular mechanisms of breast cancer and developing new therapeutic strategies.

Non-coding RNAs(ncRNAs),encompassing microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs),have emerged as critical regulators of gene expression and cellular function.In alcohol-associated liver disease(ALD),chronic alcohol consumption disrupts the expression and function of ncRNAs in the liver and circulation,contributing to the disease's pathogenesis and progression.Dysregulated ncRNAs influence key pathways involved in hepatocyte injury,lipid metabolism,inflam-mation,and hepatic stellate cell(HSC)activation,thereby exacerbating steatosis,inflammation,and fibrosis.Furthermore,extracellular vesicles play a pivotal role in mediating ncRNA-driven intercellular communication,amplifying liver damage and fibrosis.This review provides a comprehensive overview of the multifaceted roles of ncRNAs in ALD,with a focus on their mechanistic contributions to disease development and progression.Additionally,we discuss the potential of ncRNAs as diagnostic biomarkers and therapeutic targets,emphasizing their translational relevance in addressing the burden of ALD.

Objective:To investigate the role and mechanism of leucine-rich α-2-glycoprotein 1 (LRG1) in the fibrosis of human pterygium fibroblasts (HPFs).Methods:A total of 30 nasal primary pterygium tissues from patients who underwent pterygium excision surgery and 30 nasal normal conjunctival tissues from patients who underwent strabismus correction surgery were collected from the First Affiliated Hospital of Harbin Medical University between January 2022 and March 2023, serving as the pterygium group and normal control group, respectively.LRG1 protein expression in both groups was detected by immunofluorescence staining.The mRNA and protein levels of LRG1 and transforming growth factor-β1 (TGF-β1) were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot.Primary HPFs were cultured from excised pterygium tissues using tissue block adhesion method, and cell morphology was observed.Vmentin and cytokeratin were identified by immunofluorescence staining.HPFs were divided into recombinant human LRG1 (rhLRG1) group and blank control group treated with or without 10 μg/ml rhLRG1 for 24 hours, respectively, and cell migration was evaluated via scratch assay.Additionally, HPFs were divided into blank control group, LRG1 overexpression group and LRG1 knockdown group.HPFs in LRG1 overexpression group and LRG1 knockdown group were transfected with LRG1 overexpression plasmids and small interfering RNA for 24 hours, respectively.TGF-β1 mRNA level was evaluated by qRT-PCR and expression of TGF-β1, fibronectin (FN), type Ⅲ collagen (COL3), and α-smooth muscle actin (α-SMA) proteins were evaluated by Western blot.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (No.2022IIT026).Written informed consent was obtained from each subject.Results:HPFs were successfully isolated, exhibiting spindle-shaped morphology with whorled arrangement, positive identification for vimentin, and negative immunofluorescence staining for cytokeratin.The migration rate of the rhLRG1 group was (83.01±2.56)%, significantly higher than (50.32±4.97)% of the blank control group ( t=9.59, P<0.001).Immunofluorescence staining results showed that compared with normal conjunctival tissue, LRG1 protein was significantly higher expressed in pterygium tissue and was widely distributed in fibrous connective tissue and epithelial layer.Both mRNA and protein levels of LRG1 and TGF-β1 were significantly higher in the pterygium group than in the normal control group (mRNA: t=10.18, 6.15, both P<0.05.protein: t=6.83, 8.79, both P<0.05).In the LRG1 overexpression group, mRNA level of TGF-β1, and protein levels of FN, COL3 and α-SMA were significantly increased compared with the blank control and LRG1 knockdown groups (all P<0.05). Conclusions:LRG1 promotes fibrosis and enhances the migration ability in HPFs, and its mechanism may be associated with the upregulation of the TGF-β1 signaling pathway.

Objective To predict the potential suitable areas and change trend of the medicinal plant Mosla chinensis Maxim;To analyze the main environmental factors affecting the distribution of Mosla chinensis Maxim;To provide scientific strategies for promoting the cultivation of Mosla chinensis Maxim.Methods Based on the actual geographical distribution data and environmental factor data of Mosla chinensis Maxim,MaxEnt model was used to simulate the distribution of potential suitable areas in the current and four climate scenarios in future three periods.The model prediction results were tested for accuracy using the receiver operating characteristic curve method to identify the main environmental factors that affect the potential suitable area distribution of Mosla chinensis Maxim and analyze their distribution,changes and migration trends.Results The accuracy test of the model,indicated high reliability of the results;the main environmental factors affecting the distribution of potential suitable areas for the growth of Mosla chinensis Maxim were the lowest temperature in the coldest month,annual precipitation and temperature seasonality.Under the current climate scenario,the potential suitable areas of Mosla chinensis Maxim were mainly concentrated in Jiangsu,Anhui,Hubei,Chongqing,Zhejiang,Jiangxi,Hunan,Guizhou,Guangdong,Guangxi,Fujian and Taiwan,among which the high suitable areas were mainly in Jiangxi,Hunan,Fujian,Zhejiang,Guangdong,Guangxi and Taiwan.Under the future climate scenario,the geographical distribution pattern of potential suitable areas of Mosla chinensis Maxim will be relatively stable,and the suitable areas will change along the high latitude but the total area decreases.Under the current and future climate scenarios,the centroid and centroid migration trajectories of the potential suitable area of Mosla chinensis Maxim will be in Hunan.Conclusion This study predicted distribution of potential changes in the distribution of suitable growth areas for Mosla chinensis Maxim,which can provide references for the sustainable utilization and promotion of cultivation of Mosla chinensis Maxim resources.

Objective:To explore the classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography and its impact on their donor sites.Methods:A retrospective analysis was conducted of the data of 67 patients with large soft tissue defects who had been repaired with anterolateral thigh perforator flaps at Department of Orthopaedics, The Hospital Affiliated to The Second Medical University of Shandong, Department of Orthopaedics, The 80th Group Army Hospital of the People's Liberation Army, and Department of Orthopaedics, Weifang Traditional Chinese Medicine Hospital. The patients were divided into 2 groups according to their flaps used: a unilobar group and a bilobar group. In the unilobar group, 36 cases [25 males and 11 females with an age of (40.3±8.3) years] were repaired with a unilobar anterolateral thigh perforator flap from March 2015 to April 2019. In the bilobar group, 31 cases [22 males and 9 females with an age of (38.9±7.4) years] were repaired with a bilobar anterolateral thigh perforator flap from May 2019 to August 2023. Color Doppler ultrasonography was used to classify the bilobar flaps into 4 types according to the different distributions of perforating vessels: common trunk type, separate trunks type, fascia dependent type, and composite mixed type. The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were compared with the intraoperative findings in the bilobar group. One year after operation, recovery rate of donor muscle strength, rate of skin paresthesia, scar length at the donor site, the widest scar width and motor function were compared between the 2 groups.Results:The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were consistent with the intraoperative findings ( P<0.05). There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). One year after operation in the bilobar group, the recovery rate of donor muscle strength was 96.8% (30/31), significantly higher than that in the unilobar group [77.8% (28/36)], the rate of skin paresthesia 6.5% (2/31), significantly lower than that in the unilobar group [27.8% (10/36)], the scar length at the donor site (22.18±5.02) cm, significantly longer than that in unilobar group [(17.35±3.11) cm], the widest scar width (7.26±1.58) mm, significantly narrower than that in the unilobar group [(43.72±9.81) mm], and the scores of Vancouver Scar Assessment Scale and Fugl-Meyer lower limb motor function scale were (1.95±0.57) points and (8.39±2.17) points, respectively, significantly lower than those in the unilobar group [(6.38±1.72) points and (14.02±3.54) points] ( P<0.05). Conclusions:Preoperative classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography may provide guidance for flap harvesting and lobe layout of the flap. Compared to traditional unilobar flaps, bilobar ones may minimize tissue damage at a donor site.

This study investigated the mechanism by which Jianpi Bushen Yiqi Decoction promotes acetylcholine receptor(AChR) clustering in myasthenia gravis through the Agrin/low-density lipoprotein receptor-related protein 4(LRP4)/muscle-specific receptor tyrosine kinases(MuSK) signaling pathway. A total of 114 female C57BL/6J mice were divided into the normal group, modeling group, and solvent control group. The normal group and the solvent control group were immunized with phosphate-buffered saline(PBS), while the modeling group was established as an experimental autoimmune myasthenia gravis(EAMG) model using the murine-derived AChR-α subunit R97-116 peptide fragment. After successful modeling, the mice were randomly assigned to the model group, the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups, and the prednisone group. After four weeks of continuous treatment, muscle strength was assessed using Lennon scores and grip strength tests. Immunofluorescence staining was conducted on differentiated C2C12 myotubes incubated with a drug-containing serum to observe the number of AChR clusters. The integrity of AChR on myofilaments in mouse gastrocnemius muscles was further assessed by immunofluorescence staining. Hematoxylin-Eosin(HE)staining was applied to examine pathological changes in the gastrocnemius muscles of EAMG mice treated with Jianpi Bushen Yiqi Decoction. Western blot was utilized to detect the expression of key proteins in the Agrin/LRP4/MuSK signaling pathway in both C2C12 myotubes and mouse gastrocnemius muscles. The results demonstrated that compared to the model group, the prednisone group exhibited a significant decrease in the body weights of mice, whereas no significant differences in the body weights of mice were observed among the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups. All treatment groups showed significantly improved grip strength and Lennon scores. Additionally, the formula promoted AChR clustering on myotubes and enhanced AChR integrity in gastrocnemius myofilaments and reduced inflammatory infiltration between muscle tissue and fibrous hyperplasia. Furthermore, Jianpi Bushen Yiqi Decoction upregulated the protein expression of AChRα1, Agrin, and p-MuSK in C2C12 myotubes and increased the protein expression of AChRα1, Agrin, MuSK, p-MuSK, LRP4, and docking protein 7(Dok-7)in gastrocnemius tissue. In conclusion, Jianpi Bushen Yiqi Decoction may promote AChR clustering by targeting key proteins in the Agrin/LRP4/MuSK signaling pathway, thereby improving neuromuscular junction function and enhancing muscle strength.
Animals ; Agrin/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Receptors, Cholinergic/genetics* ; Female ; Mice, Inbred C57BL ; Receptor Protein-Tyrosine Kinases/genetics* ; Neuromuscular Junction/metabolism* ; Myasthenia Gravis, Autoimmune, Experimental/physiopathology* ; Humans ; LDL-Receptor Related Proteins