BACKGROUND:The regeneration and remodeling of Achilles tendon rupture after surgery are difficulties in clinical treatment.Tissue engineering hydrogels afford the possibility on the healing of postoperative Achilles tendon. OBJECTIVE:To investigate the effect of tannic acid modified interpenetrating network hydrogel on tissue regeneration and remodeling of ruptured Achilles tendon in rats. METHODS:(1)The interpenetrating network hydrogel was prepared under the blue light and the immersion of CaSO4 solution.The micromorphology,mechanical properties,adhesion properties,in vitro drug release properties,and biocompatibility of hydrogels were characterized.(2)Thirty Sprague-Dawley rats were randomly divided into sham operation group,operation group,and hydrogel group,with 10 rats in each group.The animal model of Achilles tendon rupture was established in the latter two groups.In the operation group,the ruptured Achilles tendon was sutured using the modified Kessler method.In the hydrogel group,the ruptured Achilles tendon was repaired by the same method,and the tannic acid modified interpenetrating network hydrogel patch was completely wrapped around the joint of the broken end.Four weeks after the operation,imaging examination,histological evaluation,biomechanical test,and the level test of inflammatory factors were performed. RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that tannic acid modified interpenetrating network hydrogels had porous microstructure with pore size of 3-10 μm,and the hydrogels had good in vitro drug release properties,adhesion strength and tensile strength.CCK-8 assay and live/dead staining showed that the hydrogel had no significant effect on the proliferation activity of rat bone marrow mesenchymal stem cells,and had good biocompatibility.(2)MRI imaging showed that compared with the operation group,the Achilles tendon in the hydrogel group showed uniform low signal,the thickness of the anteroposterior diameter of the Achilles tendon was reduced,and the boundary between the Achilles tendon and the surrounding tissue was more clear,and the performance was more similar to that of the sham operation group.Hematoxylin-eosin staining and Masson staining showed that the tendon fibers in the operation group were arranged in a loose and chaotic manner,with increased cell density and disordered arrangement,accompanied by obvious inflammatory cell infiltration,and intratendinous ossification appeared in some areas.In the hydrogel group,the tendon fibers were arranged in an orderly manner;the cell density was reduced and arranged orderly;the inflammatory cell infiltration was significantly reduced.The tensile strength of Achilles tendon in the operation group was lower than that in the sham operation group(P<0.05).The tensile strength of Achilles tendon in the hydrogel group was higher than that in the operation group(P<0.05).Compared with sham operation group,the mass concentration and mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor α in Achilles tendon of rats were increased in the operation group(P<0.05).Compared with the operation group,the level and mRNA expression of three inflammatory factors were decreased in the hydrogel group.(3)It is concluded that tannic acid modified interpenetrating network hydrogel can inhibit the local inflammatory response and promote the tendon remodeling.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective To understand the epidemiological characteristics of new occupational pneumoconiosis in Zigong City from 2018 to 2022, and to provide the basis for further prevention and treatment of local pneumoconiosis. Methods The information of newly diagnosed and reported cases of pneumoconiosis in Zigong City from 2018 to 2022 was collected through the occupational disease and occupational health information monitoring system, and the characteristics of the distribution of pneumoconiosis in three regions, the composition of diseases and the length of service of exposure to dust were analyzed. Results From 2018 to 2022, the top 3 newly diagnosed pneumoconiosis diseases in Zigong City were silicosis, coal workers' pneumoconiosis and asbestosis. Silicosis cases were mainly distributed in small and medium-sized employers, accounting for 81.41%. Coal workers' pneumoconiosis was mainly distributed in large and medium-sized employers, accounting for 97.24%. Asbestosis mainly distributed in large scale employers, accounting for 96.36%. There was significant difference in dust handling age of different scale employers (H=11.453, P<0.05). The median ages of silicosis, coal workers' pneumoconiosis and other pneumoconiosis were 47.0 years, 52.0 years and 48.2 years, respectively. The median age of dust handling was 3.3 years, 22.0 years and 23.2 years, respectively. The age of onset of coal workers' pneumoconiosis was higher than that of silicosis and other pneumoconiosis (H=72.547, P<0.05), and the age of dust exposure of silicosis was shorter than that of coal workers' pneumoconiosis and other pneumoconiosis (H=10.453, P<0.05). Conclusion The current situation of pneumoconiosis in Zigong City is still severe, with obvious clustering in disease types and industries. Prevention and treatment of pneumoconiosis in key industries should be further strengthened to protect the health rights and interests of workers.

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

BACKGROUND:Free vascularized fibular grafting is an effective hip preservation treatment for femoral head osteonecrosis,but its influencing factors are still controversial. OBJECTIVE:To explore the clinical efficacy of free vascularized fibular grafting for femoral head osteonecrosis,and the influence of the etiology and severity of femoral head osteonecrosis on its efficacy. METHODS:Clinical data and clinical efficacy scores of preoperative and postoperative hip joints in 63 patients with femoral head osteonecrosis(73 cases of hip)were enrolled.The subjects were divided into three groups by the etiological classification criteria of femoral head osteonecrosis,including glucocorticoid-associated,alcohol-associated,and idiopathic groups,and also were divided into three groups by the Ficat classification system,including Ficat Ⅱ,Ficat Ⅲ and Ficat Ⅳ groups.The effects of etiological classification and lesion degree on the clinical efficacy of free vascularized fibular grafting for femoral head osteonecrosis were analyzed. RESULTS AND CONCLUSION:(1)The visual analog scale scores in all periods after free vascularized fibular grafting for femoral head osteonecrosis were significantly decreased compared with preoperative data(P<0.001),and Harris scores were significantly increased compared with preoperative data(P<0.001).(2)In the glucocorticoid-associated,alcohol-associated,and idiopathic groups,except the glucocorticoid-associated group,postoperative Harris scores were significantly increased 2 and 3 years after surgery in other groups compared with preoperative data(P<0.05).(3)In the three groups of Ficat Ⅱ,Ficat Ⅲ,and Ficat Ⅳ,the postoperative Harris scores of Ficat Ⅱ and Ficat Ⅲ groups were significantly increased compared with preoperative data(P<0.05),while the difference was not significant in the Ficat Ⅳ group between the preoperative and postoperative data(P>0.05).(4)These results indicate that the clinical effect of free vascularized fibular grafting for the femoral head osteonecrosis is significant,which can reduce hip pain and improve hip joint function.It may not be affected by the etiology,but by the severity of the femoral head osteonecrosis.

BACKGROUND:At present,the treatment of infected bone defects has the problems of long course of disease,poor treatment effect and high cost.The osteogenic effect of personalized bone replacement materials in clinical treatment is limited.Therefore,a 3D-printed bone graft material with both good osteogenic effect and antibacterial effect is urgently needed for clinical treatment. OBJECTIVE:To summarize the research status of 3D-printed scaffolds loaded with antimicrobial agents for the treatment of infected bone defects. METHODS:PubMed,Web of Science,Elsevier,and CNKI databases from January 2010 to June 2022 were searched for related articles.The Chinese search terms were"bone defect,3D printing,scaffold material,antibacterial,animal experiments,in vitro experiments".English search terms were"bone defect,3D printing,scaffold,antibiosis,animal experiment,in vitro".Finally,60 articles were included for review and analysis. RESULTS AND CONCLUSION:The 3D scaffolds made of titanium,magnesium,tantalum and other metals and their alloys have certain osteogenic properties,but do not have antibacterial function.Hydroxyapatite and other bioceramic materials have good biocompatibility and are prone to be degraded,whereas due to the lack of strength,they are usually combined with artificial polymer materials to form composite materials,which respectively mimic the inorganic and organic components in natural bone,and play their respective excellent functions.Antibiotics,silver/copper nanoparticles,antimicrobial peptides,gallium and other antibacterial agents play an antibacterial role by destroying bacterial cell membrane,producing reactive oxygen species to interfere with bacterial DNA replication,inhibiting iron absorption and other mechanisms.As a result,the 3D-printed scaffold has both antibacterial and osteogenic effects.However,there are still some problems such as drug resistance and difficult to control effective concentrations.3D-printed scaffolds are often loaded with antibacterial agents by loading drug-loaded microspheres on scaffolds,preparing antibacterial coating on the scaffold surface,and participating in joint 3D printing with drugs.The loading mode of antibacterial coating prepared on the scaffold surface is the most widely used,and its antibacterial effect is more stable.Nonetheless,the selection of the most suitable loading mode for antibacterial agents needs to be further discussed and summarized.It is a future research prospect to optimize the mechanical properties of composite scaffolds and prepare biomimetic bone scaffolds so that the degradation rate is consistent with the bone reconstruction rate in infected bone defects.The ideal antibacterial agents may play a role through a variety of antibacterial mechanisms,thus being expected to play a good antibacterial effect through low antibacterial concentration,which should be a hot spot of anti-bone infection research.After loading antibacterial agents on the surface of the scaffold,antibacterial agents can"intelligently"react to the local microenvironment,achieving controlled release,and regulating the osteogenesis,vascularization and immune response of the microenvironment,which is the focus of current research.

Objective To investigate the effects of epithelial transformation sequence 2(ECT2)and p33ING1 on the metastatic activity of esophageal squamous cell carcinoma(ESCC)cells.Methods The expressions of ECT2 and p33ING1 in esophageal squamous cell carcinoma tissues and adjacent tissues were detected by immunohistochemistry and Western blotting.Human esophageal squamous carcinoma cell line KYSE140 cells were divided into 4 groups:blank group,negative control(pcDNA 3.1 NC)group,overexpression group(pcDNA 3.1 ECT2)and inhibited expression group(si ECT2).MTT assay and cell colony formation assay were used to study the proliferation and growth ability of cells,Transwell assay and scratch assay used to study the invasion and migration ability of cells,and flow cytometry used to detect apoptosis and cell cycle,Western blotting used to detect the effect of ECT2 on p33ING1 protein.Results ECT2 expression increased and p33ING1 expression decreased in esophageal squamous cell carcinoma tissues.Overexpression of ECT2 significantly increased the growth,colony formation,migration and invasion abilities of KYSE140 cells,and decreased the apoptosis rate and p33ING1 expression of KYSE140 cells.In addition,inhibition of ECT2 expression could reverse the above changes.Conclusion The high expression of ECT2 can promote the growth and metastasis of esophageal squamous cell carcinoma KYSE140 cells and inhibit their apoptosis.The mechanism may be related to the inhibition of p33ING1 expression by ECT2.