1.Molecular Mechanism Mediated by HIF-1α/HO-1 Signaling Pathway of Guizhi Fulingwan in Suppressing Ferroptosis in Endometriosis
Li TANG ; Yi ZHANG ; Lulu WU ; Yingying LIANG ; Wenying GONG ; Quanning TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):1-11
		                        		
		                        			
		                        			ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan (GFW) inhibits ferroptosis in endometriosis (EMT) through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 (HIF-1α/HO-1) signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT, including core targets. Functional enrichment analysis was conducted to explore the biological processes, molecular functions, cellular components, and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley (SD) rats were randomly divided into five groups: sham-operated, model, positive control (dienogest at 0.2 mg·kg-1), low-dose GFW (2.5 g·kg-1), and high-dose GFW (5 g·kg-1). After modeling, the rats received their respective treatment by oral gavage for 28 consecutive days, while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin (HE) staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction (Real-time PCR) and Western blot were conducted to assess mRNA and protein expression of HIF-1α, HO-1, glutathione peroxidase 4 (GPX4), spermidine/spermine N1-acetyltransferase (SAT1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Tissue levels of malondialdehyde (MDA), glutathione (GSH), and ferrous iron (Fe²⁺) were quantified using commercial assay kits. Serum levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) were measured via enzyme-linked immunosorbent assay (ELISA). ResultsFive ferroptosis-related biomarkers in EMT were identified: ALOX12, CHAC1, SAT1, AST1, and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment, with FOS, JUN, HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group, the model group exhibited significant increases in both mRNA and protein expression of HIF-1α, HO-1, and PTGS2, as well as elevated tissue levels of Fe²⁺ and MDA. Conversely, GSH levels and the expression of GPX4 and SAT1 were markedly reduced, and serum levels of IL-6 and TGF-β1 levels were significantly higher (P<0.01). Compared with the model group, all GFW-treated groups showed significant downregulation of HIF-1α and HO-1, reduced Fe²⁺ levels, and downregulated expression of MDA, PTGS2, IL-6, and TGF-β1. Meanwhile, GSH, GPX4, and SAT1 expression levels were significantly increased (P<0.05, P<0.01), effectively ameliorating iron overload and oxidative stress, thereby demonstrating therapeutic efficacy in EMT, with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation, providing a novel theoretical foundation for the clinical application of GFW in EMT treatment. 
		                        		
		                        		
		                        		
		                        	
2.Research progress of HGF/c-Met signaling pathway in oral squamous cell carcinoma
SHI Jiafan ; GONG Lingling ; SUN Mingze ; LIU Lulu ; ZHANG Huilin ; LI Ming
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(8):709-718
		                        		
		                        			
		                        			Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.
		                        		
		                        		
		                        		
		                        	
3.Aromatic Substances and Their Clinical Application: A Review
Yundan GUO ; Lulu WANG ; Zhili ZHANG ; Chen GUO ; Zhihong PI ; Wei GONG ; Zongping WU ; Dayu WANG ; Tianle GAO ; Cai TIE ; Yuan LIN ; Jiandong JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):264-272
		                        		
		                        			
		                        			Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules, such as limonene, linalool, linalool acetate, geraniol, and citronellol. These chemicals have been extensively studied and shown to have a variety of functions, including reducing anxiety, relieving depression, promoting sleep, and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled, they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier, thereby exerting effects on the central nervous system. Currently, the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However, the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances, including plant extracts and natural small molecule compounds, in antibacterial and antiviral fields and the regulation of nervous system activity. As a result, a deeper understanding of aromatherapy was achieved. At the same time, the potential of these aromatic substances for drug development was thoroughly explored, providing important references and insights for possible future drug research and application. 
		                        		
		                        		
		                        		
		                        	
4.Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy.
Siqin HE ; Lulu WANG ; Dongxu WU ; Fan TONG ; Huan ZHAO ; Hanmei LI ; Tao GONG ; Huile GAO ; Yang ZHOU
Acta Pharmaceutica Sinica B 2024;14(2):765-780
		                        		
		                        			
		                        			A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.
		                        		
		                        		
		                        		
		                        	
5.Finite element analysis of three-dimensional frame screws and minimally invasive plate for fixation of Sanders Ⅲ calcaneal fractures
Dewei KONG ; Chao SONG ; Liang WU ; Ming WU ; Lulu GONG ; Jiaqi WANG ; Hongyuan PAN ; Xinbin FAN ; Yan ZHANG
Chinese Journal of Tissue Engineering Research 2024;33(33):5289-5294
		                        		
		                        			
		                        			BACKGROUND:Satisfactory clinical results have been achieved in the treatment of Sanders Ⅲ calcaneal fractures by percutaneous compression fixation with three-dimensional frame screws.However,whether the stability of minimally invasive plate internal fixation can be achieved in terms of biomechanics,and the advantages and disadvantages after comparison are still unknown. OBJECTIVE:To investigate the fixation effect of different internal fixation devices on Sanders Ⅲ calcaneal fractures by finite element analysis. METHODS:A finite element model of Sanders Ⅲ calcaneal fracture was made based on CT data of a 26-year-old healthy male volunteer.The calcaneal fracture models were fixed by minimally invasive three-dimensional frame screws and minimally invasive Y-plate.The longitudinal loads of 350 and 700 N were applied respectively.The displacement and stress distribution of the two models were analyzed,and the stability of each model was compared. RESULTS AND CONCLUSION:(1)The peak stress of bone block and implant in the minimally invasive three-dimensional frame screw model was significantly lower than that in the minimally invasive minimally invasive plate model.The average stress of bone block and implant in the three-dimensional frame screw model was also significantly lower than that in the minimally invasive plate model.(2)The maximum displacement of the two models was located at the medial side of the articular surface of the posterior talus,and the maximum displacement of the three-dimensional frame screw model was smaller than that of the minimally invasive plate model.(3)The longitudinal displacement between the anterior fragment and the medial fragment of the minimally invasive plate model was smaller,and the transverse and vertical displacement between the medial fragment and the middle fragment of the three-dimensional group screw model was smaller.(4)It is concluded that both of the two internal fixation models can provide satisfactory fixation effect.The three-dimensional frame screw model can provide better transverse and vertical stability with more uniform stress distribution and smaller comprehensive displacement of bone fragments,while the minimally invasive plate has more advantages in maintaining longitudinal stability.
		                        		
		                        		
		                        		
		                        	
6.Application and reflection on smart Party building management platform under the new situations
Lifang MIN ; Lulu HU ; Jun XU ; Huijun GONG
Modern Hospital 2024;24(2):181-183,186
		                        		
		                        			
		                        			To date,the information technology develops rapidly and the dawn of digital era comes just around the cor-ner.Under these new situations,smart Party building management platforms stand as a new impetus,energizing the Party build-ing efforts with robust capabilities for data storage,analysis,automatic computation,and administration.These platforms provide comprehensive data support that enhances the precision and efficiency of Party building.This leads to an invigorated process of continuous innovation and high-quality development within the Party building.This article delves into the practical application of the current unit's smart party building management platform,examining the challenges encountered during its operation.It also posits several reflections and strategic responses aimed at elevating the scientific management standards of party building.
		                        		
		                        		
		                        		
		                        	
7.Finite element analysis of effect of proximal fibular fracture on knee joint stress in an extended state
Jiaqi WANG ; Jiangan TANG ; Guohua HUANG ; Dece KONG ; Yiding ZHAO ; Lulu GONG ; Hongyuan PAN ; Dewei KONG ; Yue LIU ; Tieyi YANG
Chinese Journal of Tissue Engineering Research 2024;28(30):4757-4762
		                        		
		                        			
		                        			BACKGROUND:The traditional view is that proximal fibular fractures do not require fixation.Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint,and its mechanism of action is worth studying. OBJECTIVE:To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS:Finite element method was used to conduct simulated biomechanical experiments.A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data,and four proximal fibular shapes were simulated(Model A:intact,Model B:1 cm fracture below the fibular head,Model C:1 cm tip defect fracture from the proximal end of the fibula to the distal end,and Model D:2 cm bone defect from the proximal end of the fibula).A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION:(1)In Model A,the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment,while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment.The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle,and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle.(2)Compared to Model A,there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C.(3)Compared to Model A,the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage(14.9%),medial condyle of femoral cartilage(13.6%),and medial meniscus(6.6%).The maximum first principal stress increase amplitude was the medial meniscus(11.06%),the medial tibial cartilage(8.65%),and the medial condyle of the femoral cartilage(7.46%).The maximum equivalent stress increase amplitude of the ligament was as follows:popliteal arch ligament(33.2%)>anterior cruciate ligament(21.3%)>fibular collateral ligament(17%)>posterior cruciate ligament(14.3%)>anterior lateral collateral ligament(13.2%)>medial collateral ligament(10.1%).(4)Compared to Model A,the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage(19.5%),femoral cartilage medial condyle(17.9%),and medial meniscus(9.9%).The maximum first principal stress in sequence was the medial meniscus(14.04%),the medial tibial cartilage(13.03%),and the medial condyle of the femoral cartilage(11.37%).The increasing trend of maximum equivalent stress in ligaments was as follows:anterior cruciate ligament(25.2%)>posterior cruciate ligament(18.9%)>medial collateral ligament(18.5%)>anterior lateral collateral ligament(12.7%).(5)It is suggested that when the knee joint is extended,a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage,anterior cruciate ligament,and posterior lateral ligament complex.
		                        		
		                        		
		                        		
		                        	
8.Characterization of rhinovirus in patients with respiratory tract infection in Mianyang, 2021—2022
Yue GONG ; Ming PAN ; Guo CHEN ; Qinqin SONG ; Yanhai WANG ; Chen GAO ; Zhiqiang XIA ; Lulu WANG ; Qian CHENG ; Kexin ZONG ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2024;38(3):279-285
		                        		
		                        			
		                        			Objective:To understand the prevalence and characteristics of Rhinovirus (HRV) infection in influenza-like Illness (ILIs) patients in Mianyang, Sichuan province, China.Methods:Throat swabs were collected from patients of ILIs in sentinel hospitals in Mianyang during 2021—2022. Real-time fluorescence quantitative PCR was used to detect 16 common pathogens. The VP4/VP2 coding region genes of HRV positive samples were amplified by nest PCR. The phylogeny, consistency and amino acid variation of different serotypes were analyzed and compared with reference sequences from GenBank database.Results:A total of 332 ILIs′ samples were collected with a virus detection rate of 58.73% (195/332) in Mianyang. Among them, 23 samples (23/332) were HRV-positive, and 18 VP4/VP2 sequences of HRV strains were successfully amplified. It was found that 13 HRV serotypes were detected in ILIs samples in Mianyang, which belonged to three genotypes, namely HRV-A (12 strains), HRV-B (5 strains) and HRV-C (1 strain).Conclusions:HRV was one of the pathogens of ILIs cases in Mianyang during 2021—2022, with HRV-A types as the dominant strains.
		                        		
		                        		
		                        		
		                        	
9.Finite Element Analysis of Three-Dimensional Screws and Circular Plates for Treating Sanders Type Ⅲ AB Calcaneal Fracture
Hongyuan PAN ; Dewei KONG ; Yue LIU ; Lulu GONG ; Yiding ZHAO ; Dece KONG ; Jiaqi WANG ; Zhi WANG ; Tieyi YANG ; Xinbin FAN
Journal of Medical Biomechanics 2024;39(3):435-441
		                        		
		                        			
		                        			Objective To investigate the effects of three-dimensional(3D)screws and circular plates on the biomechanical stability of Sanders ABⅢ calcaneal fractures.Methods Calcaneal computed tomography(CT)and magnetic resonance imaging(MRI)data from a 26-year-old volunteer were collected to establish a 3D finite element model of Sanders ⅢAB calcaneal fracture fixed with 3D screws and circular plates.A longitudinal load of 700 N was applied to compare the variations in the stress,displacement of the bone block,and internal fixation in the different models.Results Under 700 N longitudinal loads,the maximum displacement of the bone block and the maximum stress of the bone block and internal fixation were concentrated at the intersection of the posterior talar articular plane internal fixation and fracture line.The overall displacements of the bone blocks in the 3D screw and circular plate models were similar.Compared with the circular plate model,the maximum and average stresses of the bone block and internal fixation in the 3D screw model were lower,and the displacement and stress changes of the 3D screw model were closer to those of the complete calcaneal bone model.Conclusions In the fixation of Sanders ⅢAB calcaneal fractures,both 3D screw and circular plate fixation method can provide good stability.The biomechanical properties of the 3D screws were better than those of the circular plates,which is consistent with the biomechanical characteristics.
		                        		
		                        		
		                        		
		                        	
10.Genetic characterization of coxsackievirus A6 in Mianyang city in 2022
Yue GONG ; Kexin ZONG ; Qian CHENG ; Lulu WANG ; Renhe ZHU ; Qin LUO ; Yanhai WANG ; Guoyong MEI ; Jun HAN ; Qinqin SONG
Chinese Journal of Microbiology and Immunology 2024;44(5):414-422
		                        		
		                        			
		                        			Objective:To investigate the etiology of hand, foot and mouth disease (HFMD) in Mianyang city in 2022, and to analyze the genetic characteristics of coxsackievirus A6.Methods:Pharyngeal swabs were collected from patients with HFMD in Mianyang city in 2022. Real-time fluorescence quantitative PCR was used to detect enteroviruses in the samples. Part of the VP1 gene in enterovirus-positive samples was amplified by nested PCR using enterovirus typing primers to further identify the viral types. The VP1 coding region of all CVA6-positive samples and the whole genome of some samples were amplified and sequenced by PCR. The endemic strain in Mianyang city was analyzed for phylogeny, gene homology, amino acid variation and genetic recombination.Results:A total of 151 pharyngeal swabs were collected, and 104 enterovirus-positive samples were detected by real-time fluorescence quantitative PCR, with an overall detection rate of 68.88% (104/151). The typing results showed that there were 77 cases of CVA6 infection, with a positive rate of 50.99% (77/151). The full-length VP1 genes of 77 CVA6 strains were amplified, sequenced, and successfully spliced, and phylogenetic analysis showed that all 77 strains were of the D3 genotype. There were multiple amino acid variant sites in the prevalent strains in Mianyang city compared with the reference strain. Twenty whole genome sequences were amplified, sequenced, and successfully spliced, and homology analysis showed that the nucleotide homology between the 20 positive sequences ranged from 97.0% to 99.9%. Phylogenetic tree and recombination analysis showed that no recombination occurred in the coding regions of the epidemic strains in this study.Conclusions:The predominant pathogen causing HFMD in Mianyang city in 2022 is CVA6 D3 subtype, which is consistent with the national epidemic in 2022.
		                        		
		                        		
		                        		
		                        	
            

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