ObjectiveTo investigate the role of Ras-GTPase-activating protein SH3 domain-binding protein 2 （G3BP2） in regulating the activation， proliferation， and migration of hepatic stellate cells （HSCs）. MethodsThe mouse HSCs （JS-1 cell line） were treated with 5 μg/L transforming growth factor-beta 1（TGF-β1） for 24 hours to establish an HSC activation and proliferation model. A G3BP2 knockdown system was constructed using siRNA interference technology. The experiment was divided into four groups： Control， TGF-β1 treatment， TGF-β1+si-NC， and TGF-β1+ G3BP2-siRNA. The expression levels of key fibrosis indicators， including type I collagen （Collagen I）， α-smooth muscle actin （α-SMA）， and G3BP2， were detected by Western blot and RT-qPCR. Cell proliferation activity was assessed using the CCK-8 proliferation assay kit and EdU fluorescence labeling technology. Cell migration ability was analyzed by scratch wound healing assay and Transwell migration assay. The formation level of stress granules was quantified by immunofluorescence microscopy to investigate the effects of G3BP2 on stress granule formation in activated HSCs. ResultsStimulation with TGF-β1 upregulated the expression of G3BP2 in JS-1 cells （RT-qPCR： P0.000 1； Western blot： P0.000 1）， while a downward trend in its expression was observed in the G3BP2‑silenced group （RT-qPCR： P0.01； Western blot： P0.000 1）. Compared with the control group， the TGF-β1 group exhibited increased protein expression levels of α-SMA and Collagen I （RT-qPCR： both P0.01； Western blot： P0.01 and P0.05， respectively）， concomitant with an increased number of stress granules and enhanced cell proliferation and migration capacity （all P0.001）. The experimental results demonstrated that G3BP2 knockout effectively reversed the aforementioned phenotypes， with the G3BP2-silenced group showing reduced expression of fibrotic markers （all P0.01）， decreased stress granule formation （P0.01）， and reduced cell proliferation and migration capacity （all P0.05）， compared to the negative control group. ConclusionG3BP2 enhances the activation， proliferation， and migration of HSCs by promoting the formation of stress granules， thereby accelerating the pathological progression of liver fibrosis. This suggests that stress granules may serve as important regulators in controlling the activation， proliferation， and migration of HSCs.

Objective: To explore the association between mammalian sterile 20-like kinase 2(MST2) gene polymorphism and haplotype and the risk of colorectal cancer, rectal cancer, and colon cancer in the Han population in Baotou area by case-control association study. Methods: A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination pop-ulation were collected, and 2 mL of peripheral blood was taken for subsequent gene genotyping. Single nucleotide polymorphisms(SNPs) of MST2 gene were screened according to the genetic polymorphism data of Chinese Han population provided by the NCBI-Hapmap database. Gene genotyping was performed by Taqman method. Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer, colon cancer, and rectal cancer under codominant, dominant, overdominant, and recessive genetic models. Results: Five SNPs of MST2 gene were screened, namely rs11783149, rs10955176, rs7827435, rs4075986, rs3019295. Among them, SNP rs4075986 was associated with the risk of colorectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=2.473(1.844-3.316) could increase the risk of colorectal cancer. Compared with the rs4075986 GG genotype, carrying the AG+AA genotype [OR(95%CI)=2.475(1.844-3.323) could increase the risk of colorectal cancer. SNP rs4075986 and rs3019295 were associated with the risk of rectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=3.411(2.387-4.874)] could increase the risk of rectal cancer. Compared with the rs3019295 GG+AA genotype, carrying the AG genotype [OR(95%CI)=0.706(0.501-0.996)] could reduce the risk of rectal cancer. SNP rs11783149 and rs4075986 were associated with the risk of colon cancer. Compared with the rs11783149 CC genotype, carrying the TT [OR(95%CI)=10.883(1.186-99.862)] and CT [OR(95%CI)=1.665(1.036-2.675)] genotype could increase the risk of colon cancer, respectively. Compared with the rs4075986 GG genotype, the AG+AA genotype [OR(95%CI)=1.824(1.262-2.638)] could increase the risk of colon cancer. Conclusion MST2 gene SNP rs3019295 AG genotype may be protective factor for rectal cancer. SNP rs11783149 CT and TT genotypes maybe risk factors for colon cancer. SNP rs4075986 AG and AG+AA genotypes may be a common risk factors for colorectal cancer, rectal cancer and colon cancer.

Objective: To explore the association between single nucleotide polymorphism(SNP) in the arachidonate 15-lipoxygenase(ALOX15) gene and Helicobacter pylori(H. pylori) infection as well as the risk of non-cardia gastric cancer in Baotou Han population, and to provide experimental evidence and data support for the screening of susceptible population for non-cardia gastric cancer. Methods: A total of 458 cases with non-cardia gastric cancer and 460 healthy examination people were collected. The 14C urea breath test(UBT) and enzyme-linked immunosorbent assay(ELISA) were used to detect H. pylori infection in the 460 healthy individuals. The genotypes of ALOX15 rs2619112, rs2619118, rs2664593, rs7220870 were detected by polymerase chain reaction-restriction fragment length polymorphism, and the association of SNP with H. pylori infection as well as the risk of non-cardia gastric cancer was statistically analyzed. Results: The positive rate of H. pylori infection was 42.4%. ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 had no association with H. pylori infection. ALOX15 rs2619112, rs2664593, and rs7220870 were not associated with the risk of non-cardia gastric cancer. Compared with the carriers of(CC + CT) genotype, the carriers of rs2619118 TT genotype had an increased onset risk of non-cardia gastric cancer [OR(95%CI)=1.512(1.110-2.060)]. The haplotype ACCC constructed by ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 could reduce the onset risk of non-cardia gastric cancer. The second-order interaction of ALOX15 rs2619112 and rs2619118 was associated with the risk of non-cardia gastric cancer ( P < 0. 05 ) . Conclusion ALOX15 rs2619112 , rs2619118 , rs2664593 , rs7220870 may not play a major role in H. pylori infection. ALOX15 rs2619118 TT genotype is a risk factor for the development of non⁃cardia gastric cancer. The haplotype ACCC constructed by ALOX15 rs2619112 , rs2619118 , rs2664593 , and rs7220870 reduces the onset risk of non⁃cardia gastric cancer. The interaction of ALOX15 rs2619112 and rs2619118 has a synergistic effect in the development of non⁃cardia gastric cancer.

BACKGROUND:With the development of computer-aided design and computer-aided manufacturing technology,zirconia abutments with a titanium base are widely used in clinic due to its good application advantages,but there are still some problems and a lack of consensus design standards. OBJECTIVE:To review the fabrication methods of Ti-base zirconia abutment,and the effect of abutment connection,emergence design,abutment angle,and bonding on mechanical properties of Ti-base zirconia abutment. METHODS:Relevant literature published from 2010 to 2023 was searched in CNKI and PubMed databases with the search terms"zirconia abutment,titanium base"in Chinese and English,respectively.The search time limit was extended for some classical literature.The relevant literature was obtained through inclusion and exclusion criteria,and 57 eligible documents were included for review. RESULTS AND CONCLUSION:It is recommended that clinicians try to select antirotational titanium bases or rotational titanium bases with a Morse taper connection.Implants should be placed in the correct axial angulation of not more than 15° or with an inclination to the palatal side when using angled zirconia abutments.When a≥30° labial inclination is followed for implant placement,the bite force must be decreased effectively to reduce the risk of mechanical and biological complications of implants,abutments,and prostheses.Ti-base zirconia abutments with a higher gingival height should be selected,and its restorative angle should not exceed 40°.Multilink Hybrid Abutment could be the first choice for extraoral bonding of zirconia abutment to titanium bases.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

Objective To investigate the effect of lidocaine medicated plaster （LMP） combined with pregabalin （PGB） on patients with postherpetic neuralgia （PHN）, and the impact on serum pain mediators. Methods 108 PHN patients admitted in our hospital from January 2024 to December 2024 were selected and grouped according to the time point of receiving treatment, 54 PHN patients treated with PGB from January 2024 to June 2024 were included in the PGB group, and 54 PHN patients treated with LMP on top of the PGB group from July 2024 to December 2024 were included in the PGB+LMP group. Comparisons were made between the two groups in terms of pain score, serum pain mediator levels, dosage of PGB, and incidence of adverse reactions. Results After 4 weeks of treatment, both groups showed a decrease in Pain Rating Index scores （sensory score and affective score）, Present Pain Intensity score, Visual Analog Scale score, and total score. Meanwhile, above scores of the PGB+LMP group were lower than those of the PGB group （P<0.05）. After 4 weeks of treatment, the levels of substance P（SP） and neuropeptide Y （NPY） in both groups were lower than those before treatment, while serum 5-hydroxytryptamine （5-HT） levels were higher than those before treatment. Moreover, the levels of SP and NPY were lower, and 5-HT level was higher in the PGB+LMP group than in the PGB group （P<0.05）. The dosages of PGB in the PGB+LMP group at T1, T, T3 and T4 were significantly lower than those in the PGB group （P<0.05）. The incidence of adverse reactions was 1.85%（1/54） in the PGB+LMP group. Compared to 5.56%（3/54） in the PGB group, and the difference was not statistically significant （P>0.05）. Conclusion LMP combined with PGB was effective in the treatment of patients with PHN, which could effectively alleviate pain and lower the levels of serum pain mediators, with good safety.

Objective : To investigate the role of single nucleotide polymorphisms(SNP) of glutathione peroxidase 4(GPX4) gene in the risk of non-cardia gastric cancer. Methods: A total of 1 031 samples were selected, including 506 normal examiners and 525 patients with non-cardia gastric cancer.GPX4rs4807542, rs713041, rs2074451 and rs3746162 were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Unconditional Logistic regression was used to analyze the relationship between each SNP with the risk of non-cardia gastric cancer under the four genetic models. Results : The CT+TT genotype of rs713041 reduced the risk of non-cardia gastric cancer compared with the CC genotype(OR=0.699, 95%CI: 0.537-0.910). The GT+TT genotype of rs2074451 reduced the risk of non-cardia gastric cancer compared with the GG genotype(OR=0.681,95%CI: 0.520-0.893). The G-C-G-C haplotype, constructed by the four SNPs ofGPX4, was related to an increased risk of non-cardia gastric cancer(OR=1.262, 95%CI: 1.035-1.539), and G-T-T-C haplotype was related to a decreased risk of non-cardia gastric cancer(OR=0.784, 95%CI: 0.656-0.937). The fourth-order interaction ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 played a synergistic effect in the risk of non-cardia gastric cancer(P<0.05). Conclusion GPX4rs713041 and rs2074451 are related to non-cardia gastric cancer susceptibility. The G-C-G-C haplotype composed ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 is a risk factor for non-cardia gastric cancer, while the G-T-T-C haplotype is a protective factor. The interaction betweenGPX4rs4807542, rs713041, rs2074451 and rs3746162 is closely connected with the occurrence of non-cardia gastric cancer.

BACKGROUND:As an essential trace element for body growth and development,copper participates in many processes such as redox process,energy generation,signal transduction and bone metabolism.The imbalance of copper homeostasis in diabetic patients will lead to the increase of oxidative stress and the impairment of antioxidant mechanism,which stimulate the production of inflammatory mediators and inflammatory factors,and thus lead to cytotoxicity and body damage.In recent years,the role of copper in diabetes has gradually attracted attention,and some studies have confirmed that copper plays a key regulatory role in the pathological process of diabetes.OBJECTIVE:To summarize the current progress in the role of copper in systemic complications of diabetes and provide some theoretical reference for its future research and treatment.METHODS:The first author searched PubMed,Web of Science,CNKI and WanFang databases for literature related to the role of copper in systemic complications of diabetes.The search terms were"copper,Cu,diabetes,diabetic complications,diabetic cardiomyopathy,diabetic nephropathy,diabetic retinopathy,diabetic osteoporosis,diabetic periodontitis"in English and Chinese,respectively.After screening,95 articles were included in the review.RESULTS AND CONCLUSION:(1)Copper is involved in the occurrence and development of diabetic complications and most of the damage caused by copper to the body is due to interference with the body's redox level.(2)In diabetic cardiomyopathy,increased Cu2+in the corpuscular circulation and impaired uptake of copper ions by cardiomyocytes,the accumulation of redox-active Cu2+and ceruloplasmin outside the cardiomyocyte induces copper oxidative stress in cardiomyocytes,leading to acute cardiac impairment.(3)In diabetic nephropathy,the toxic effect of excessive copper leads cause granular degeneration and vacuolar degeneration of renal tubular epithelial cells and proximal tubular necrosis,eventually leading to chronic or acute renal failure.(4)Excessive copper in diabetic patients can produce reactive oxygen species and directly or indirectly affect the function of copper protein with antioxidant function,thus damaging retinal cells.(5)In patients with diabetic osteoporosis,accumulated copper induces lipid peroxidation and interferes with bone metabolism.Copper acts on osteoblasts mainly through inhibition of superoxide dismutase,glutathione peroxidase,and alkaline phosphatase activities.(6)Excessive copper exacerbates inflammatory changes in periodontal tissue by promoting inflammatory responses.

Radiation‐induced lung injury (RILI) is one of the common and serious complications in chest cancer patients after undergoing radiotherapy. In recent years, gut microbiota has garnered attention as a research hotspot. Multiple studies found that it has preventive and therapeutic effects on RILI. It can exert its effects through various mechanisms including the regulation of the immune system, the gut‐lung axis and its own metabolites, etc. In this article, the mechanism of RILI was elucidated and the protective mechanism of gut microbiota against RILI was comprehensively analyzed, providing new insights for the prevention and treatment of RILI in clinical practice and offering new methods to improve patient prognosis and enhance the quality of life.

Background and purpose:The microphthalmia-associated transcription factor(MITF)plays a complex role in melanoma pathogenesis and progression.It is known to regulate multiple processes both in melanocytes and melanoma cells.While numerous studies have explored MITF in cutaneous melanoma(CM),research in acral melanoma(AM)is still limited.This study retrospectively analyzed the correlation between MITF expression and clinical,pathological characteristics and prognosis in AM patients,providing a basis for prognosis evaluation and personalized treatment plan formulation for patients.Methods:Patients who underwent primary resection of AM at Fudan University Shanghai Cancer Center from March 2008 to February 2022 were included.All surgical samples were diagnosed by clinical histopathology and used to construct the tissue microarray(TMA).This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:2203-ZZK-69-3).Cutting complete tissue microarray and evaluating MITF expression levels by immunohistochemistry(IHC)staining were carried out.The results were independently assessed and scored by three pathologists.Clinical and pathological data were collected from the hospital's electronic medical record system,and each patient's data was matched to their corresponding tissue sample on the chip.Patients were stratified into two groups based on MITF expression levels.Statistical analyses were performed to assess differences in clinical,pathological characteristics and survival outcomes between these two groups.Results:A total of 137 AM patients were included.MITF expression was significantly associated with T stage,N stage,American Joint Committee on Cancer(AJCC)stage,clark level,sentinel lymph node status,and presence of ulceration.Among these,N stage and ulceration were independent risk factors for high expression of MITF after adjusting for confounding factors.Survival analysis showed that AM patients with high MITF expression or higher T stage were associated with shorter disease-free survival(DFS).Patients with high MITF expression showed no significant difference in overall survival(OS)between observation or cytokine therapy and adjuvant immune checkpoint inhibitor(ICI)therapy,whereas those with low MITF expression derived significant survival benefits from ICI treatment.Conclusion:A higher N stage or the presence of ulceration indicates high MITF expression in tumor cells,with high MITF levels serving as a warning signal for early recurrence,metastasis,and even death.Patients with low MITF expression could receive improved OS with early adjuvant ICI therapy.MITF could not only serve as an auxiliary diagnostic marker for melanoma but also provide a basis for clinical prognosis assessment and the formulation of personalized treatment plans.