In recent years,there has been a significant rise in the incidence of peripheral nerve injury(PNI),highlighting the urgent need for effective treatment strategies.The inflammation and pain hypersensitivity associated with PNI greatly diminish patients'quality of life.Although there are promising treatment approaches for nerve injury,the com-plex pathological mechanisms underlying neuropathic pain caused by PNI present significant challenges for clinical manage-ment.Extensive research has established that the development of neuropathic pain is closely linked to nerve conduction and related signaling molecules.Among these,P2X4 receptor(P2X4R),an ATP-dependent ion channel,is involved in nerve signal transmission and associated pathways-plays a crucial role in the progression of neuropathic pain.This article offers a comprehensive overview of the function and distribution of P2X4R,investigates its pathological mechanisms in PNI-induced neuropathic pain,and elucidates its relationship with peripheral neuropathic pain disorders.Through this explo-ration,we aim to provide valuable insights that could inform the development of novel clinical strategies for pain management.

Background and purpose:Polo-like kinase 4(PLK4)is a cell cycle regulatory protein,which is closely related to the occurrence and development of a variety of malignant tumors.The aim of this study was to investigate the role of PLK4 in the proliferation,invasion and apoptosis of oral squamous cell carcinoma(OSCC).Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)and the University of Alabama at Birmingham Cancer Data Analysis Portal(UALCAN)were used to analyze the expression of PLK4 in head and neck squamous cell carcinoma and surrounding normal tissues.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot were employed to evaluate the mRNA and protein expression of PLK4 in OSCC cells.We further analyzed PLK4,phosphoinositide 3-kinase(PI3K),phosphorylated phosphoinositide 3-kinase(p-PI3K),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),survivin,and cyclin D1 protein expression.The effects of PLK4 on cell proliferation,apoptosis and invasion were analyzed by cell counting kit-8(CCK-8)assay,flow cytometry and transwell assay.In addition,12 4-week-old SPF BALB/c female nude mice were divided into sh-NC group(n=6)and sh-PLK4 group(n=6)by random number table method.The sh-NC/sh-PLK4 cells were injected into the right anterior armpit of nude mice for subcutaneous tumor formation.The body weight,tumor volume and tumor weight of the two groups of nude mice were observed,and the stripped tumor tissues were analyzed by H-E staining.The animal experiments were approved by the Animal Experiment Center of Shandong Second Medical University(No:2024SDL840).Results:The results of GEPIA2 and UALCAN online databases showed that PLK4 was highly expressed in OSCC compared with normal tissues.In addition,PLK4 was highly expressed in OSCC cell lines(HN6,Cal-27,SCC-4,SCC-9,SCC-25)compared with oral mucosal epithelial cells(P＜0.05).Western blot results showed that the expression levels of PI3K/AKT signaling pathway proteins p-PI3K,p-AKT,cyclin D1 and survivin were decreased after PLK4 knockdown and increased after PLK4 overexpression in OSCC cells(P＜0.05).The cell proliferation activity and the number of transmembrane cells were positively correlated with the decrease and increase of PLK4 expression(P＜0.05),while the cell apoptotic rate was negatively correlated(P＜0.05),indicating that cell proliferation and apoptosis were both affected.In addition,compared with the sh-NC group,the tumor volume and weight of the nude mice in the sh-PLK4 group were decreased(P＜0.05),while there was no significant difference in the body weight of the nude mice between the two groups(P＞0.05).Moreover,the nuclear atypia of tumor tissues in sh-PLK4 group was lower than that in sh-NC group(P＜0.05).Conclusion:PLK4 can regulate the invasion,proliferation and apoptosis of OSCC cells,potentially through the activation of PI3K/AKT signaling pathway.

Aging is characterized by a gradual deterioration of the physiological integrity of cells,tissues,and or-gans,resulting in a decrease in the body's physiological functions and an acceleration of the onset of age-related diseases,ultimately leading to death.The aging of the liver,which is a critical metabolic organ,is closely linked to various chronic liver diseases,such as hepatitis,liver fibrosis,and cirrhosis,and it ex-acerbates their prognosis and is a primary risk factor for their development at all stages.Therefore,a comprehensive understanding of the causes,mechanisms,and potential therapeutic targets associated with liver aging holds significant clinical importance for delaying or potentially reversing liver aging and for treating chronic liver diseases.Stem cells,which are potential anti-aging agents,present a promising and effective alternative for managing liver aging.In this review,we systematically assess the driving factors,characteristics,and underlying mechanisms of liver aging.We then discuss the current status of the use of stem cells to mitigate liver senescence and address related liver diseases.The review reveals that a stem cell-based approach represents a promising therapeutic strategy for combating liver aging and associated diseases.

Objective:To explore the spatial correlation between gray matter volume (GMV) changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia (FES) .Methods:Fifty-four FES patients(FES group) and fifty-nine healthy controls (HC group) were selected from June 2014 to May 2020 in the Psychiatry Department of Renmin Hospital of Wuhan University. Structural magnetic resonance imaging (sMRI) was conducted on all subjects. Differences of GMV were compared across 400 cortical regions and 32 subcortical regions. Based on the positron emission tomography(PET) data from Neuromaps, which provides the density of 19 different neurotransmitter receptors and transporters, Spearman correlation analysis was performed to evaluate the spatial correlation between GMV changes and neurotransmitter systems.Results:Compared to the HC group, FES group exhibited significant GMV reductions in widespread cortical (90/400) and subcortical (6/32) regions (all FDR-corrected P<0.05). The effect size of GMV reduction (Cohen’s d) showed significant positive correlations with the density of 5-hydroxytryptamine 1a(5HT1a) ( r=0.400, Pspin=0.002), γ-aminobutyric acid type A receptor(GABA A)( r=0.307, Pspin=0.002), and metabotropic glutamate receptor 5(mGluR5) ( r=0.275, Pspin=0.020) receptors (all FDR-corrected P<0.05). Conclusion:GMV reductions in a wide range of brain regions existed in patients with FES. There are significant correlations between 5HT1a, GABA A and mGluR5 receptors and gray matter reduction in patients with FES. The disorder of these neurotransmitter receptors may be the potential neurobiological mechanism of gray matter structural abnormalities in the early stage of schizophrenia.

Background and purpose:Polo-like kinase 4(PLK4)is a cell cycle regulatory protein,which is closely related to the occurrence and development of a variety of malignant tumors.The aim of this study was to investigate the role of PLK4 in the proliferation,invasion and apoptosis of oral squamous cell carcinoma(OSCC).Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)and the University of Alabama at Birmingham Cancer Data Analysis Portal(UALCAN)were used to analyze the expression of PLK4 in head and neck squamous cell carcinoma and surrounding normal tissues.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot were employed to evaluate the mRNA and protein expression of PLK4 in OSCC cells.We further analyzed PLK4,phosphoinositide 3-kinase(PI3K),phosphorylated phosphoinositide 3-kinase(p-PI3K),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),survivin,and cyclin D1 protein expression.The effects of PLK4 on cell proliferation,apoptosis and invasion were analyzed by cell counting kit-8(CCK-8)assay,flow cytometry and transwell assay.In addition,12 4-week-old SPF BALB/c female nude mice were divided into sh-NC group(n=6)and sh-PLK4 group(n=6)by random number table method.The sh-NC/sh-PLK4 cells were injected into the right anterior armpit of nude mice for subcutaneous tumor formation.The body weight,tumor volume and tumor weight of the two groups of nude mice were observed,and the stripped tumor tissues were analyzed by H-E staining.The animal experiments were approved by the Animal Experiment Center of Shandong Second Medical University(No:2024SDL840).Results:The results of GEPIA2 and UALCAN online databases showed that PLK4 was highly expressed in OSCC compared with normal tissues.In addition,PLK4 was highly expressed in OSCC cell lines(HN6,Cal-27,SCC-4,SCC-9,SCC-25)compared with oral mucosal epithelial cells(P＜0.05).Western blot results showed that the expression levels of PI3K/AKT signaling pathway proteins p-PI3K,p-AKT,cyclin D1 and survivin were decreased after PLK4 knockdown and increased after PLK4 overexpression in OSCC cells(P＜0.05).The cell proliferation activity and the number of transmembrane cells were positively correlated with the decrease and increase of PLK4 expression(P＜0.05),while the cell apoptotic rate was negatively correlated(P＜0.05),indicating that cell proliferation and apoptosis were both affected.In addition,compared with the sh-NC group,the tumor volume and weight of the nude mice in the sh-PLK4 group were decreased(P＜0.05),while there was no significant difference in the body weight of the nude mice between the two groups(P＞0.05).Moreover,the nuclear atypia of tumor tissues in sh-PLK4 group was lower than that in sh-NC group(P＜0.05).Conclusion:PLK4 can regulate the invasion,proliferation and apoptosis of OSCC cells,potentially through the activation of PI3K/AKT signaling pathway.

Objective:To explore the spatial correlation between gray matter volume (GMV) changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia (FES) .Methods:Fifty-four FES patients(FES group) and fifty-nine healthy controls (HC group) were selected from June 2014 to May 2020 in the Psychiatry Department of Renmin Hospital of Wuhan University. Structural magnetic resonance imaging (sMRI) was conducted on all subjects. Differences of GMV were compared across 400 cortical regions and 32 subcortical regions. Based on the positron emission tomography(PET) data from Neuromaps, which provides the density of 19 different neurotransmitter receptors and transporters, Spearman correlation analysis was performed to evaluate the spatial correlation between GMV changes and neurotransmitter systems.Results:Compared to the HC group, FES group exhibited significant GMV reductions in widespread cortical (90/400) and subcortical (6/32) regions (all FDR-corrected P<0.05). The effect size of GMV reduction (Cohen’s d) showed significant positive correlations with the density of 5-hydroxytryptamine 1a(5HT1a) ( r=0.400, Pspin=0.002), γ-aminobutyric acid type A receptor(GABA A)( r=0.307, Pspin=0.002), and metabotropic glutamate receptor 5(mGluR5) ( r=0.275, Pspin=0.020) receptors (all FDR-corrected P<0.05). Conclusion:GMV reductions in a wide range of brain regions existed in patients with FES. There are significant correlations between 5HT1a, GABA A and mGluR5 receptors and gray matter reduction in patients with FES. The disorder of these neurotransmitter receptors may be the potential neurobiological mechanism of gray matter structural abnormalities in the early stage of schizophrenia.

Objective:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.

Objective To examine the diagnosis and treatment of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia and improve the awareness of the pathogen in clinical and laboratory practice.Methods A case of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia in Shanghai Children's Hospital was retrospectively analyzed,including diagnosis and treatment details.Similar cases were identified from PubMed,Wanfang Data,VIP,and CNKI databases since database establishment until June 30,2024,using search terms"Enterocytozoon bieneusi".The relevant literature was reviewed.Results This child had acute lymphoblastic leukemia as the underlying disease and was admitted to hospital for antimicrobial treatment due to fever and abdominal discomfort.The case was considered bacterial infection complicated with Enterocytozoon bieneusi infection,confirmed by detection of Klebsiella pneumoniae in blood and detection of Enterocytozoon bieneusi in blood and ascites by metagenomic next-generation sequencing(mNGS).The treatment was switched to tigecycline plus trimethoprim-sulfamethoxazole at a sufficient dose,which resulted in resolution of symptoms.Six months later,the patient suffered from acute lymphoblastic leukemia and bone marrow depression,Enterocytozoon bieneusi disseminated infection,septic shock.Her family gave up treatment and the child died.Literature review indicated that most patients infected with Enterocytozoon bieneusi had underlying conditions such as organ transplantation,AIDS,and leukemia associated with poor immunity.The onset symptoms are diarrhea,abdominal discomfort,and fever.Enterocytozoon bieneusi was detected by using methods such as modified Masson's trichrome stain,fluorescent calcofluor white staining,molecular detection techniques,and immunofluorescence.The patients were treated with drugs such as albendazole,nitazoxanide,fumagillin,and trimethoprim-sulfamethoxazole.Conclusions Enterocytozoon bieneusi is an opportunistic pathogenic fungus that infects immunocompromised patients and can cause abdominal discomfort,diarrhea,fever,and even disseminated infection and death.Conventional laboratory methods cannot culture Enterocytozoon bieneusi.Molecular detection techniques can be used to identify the pathogen early.

Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

Sjogren's syndrome (SS) is a common autoimmune disorder that primarily targets exocrine glands, leading to hallmark manifestations of xerostomia and xerophthalmia, with potential progression to multisystem involvement. The rapid advances in omics technologies-including metabolomics, proteomics, and transcriptomics-have yielded substantial insights into SS pathophysiology. This review consolidates current evidence on omics-derived biomarkers in SS. Studies consistently implicate aberrant glucose metabolism, neutrophil-derived enzyme activity, mitochondrial bioenergetic impairment, ferroptosis, and apoptotic pathways as central to SS development. These findings refine our understanding of disease mechanisms and the heterogeneity of therapeutic responses. Hydroxyproline has emerged as a candidate marker for distinguishing SS from IgG4-related disease, whereas distinct cytokine and chemokine signatures may enable earlier diagnosis. Genomic analyses demonstrate a robust association between expression of the rs11797 locus and SS-related lymphomagenesis, and several genes controlling DNA methylation represent promising therapeutic targets. Collectively, these findings lay the groundwork for personalized risk stratification and intervention in SS. The review concludes by summarizing existing progress and outlining priorities for future omics-based investigations.
Humans ; Sjogren's Syndrome/diagnosis* ; Biomarkers/analysis* ; Metabolomics/methods* ; Proteomics/methods* ; Genomics ; Multiomics