Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.

The oral and maxillofacial region is a highly complex area composed of multiple tissue types and bears various critical functions of the human body. Diseases in this region pose significant diagnostic and management challenges; therefore, exploring new strategies for early diagnosis, targeted treatment, and tissue reconstruction is key to improving patient prognosis and quality of life. Extracellular vesicles are a group of heterogeneous lipid-bilayer membrane structures secreted by most cell types, including exosomes, microvesicles, and apoptotic bodies. Present in various body fluids and tissues, they act as messengers via the transfer of nucleic acids, proteins, and metabolites to recipient cells. To date, studies have revealed the different roles of extracellular vesicles in physiological or pathological processes, as well as applications in disease diagnosis, prognosis, and treatment. The importance and tissue specificity of the dental and maxillofacial tissues indicate that extracellular vesicles derived from this region are promising for further research. This paper reviews the published data on extracellular vesicles derived from cells, body fluids, and tissues in oral and maxillofacial regions, summarizes the latest advances in extracellular vesicles from extensive sources, and concludes with a focus on the current research progress and application prospects of engineered exosomes in oral science.
Humans ; Extracellular Vesicles/physiology* ; Mouth ; Exosomes/physiology*

Important anatomical structures such as mandibular incisive canal,tongue foramen,and mouth floor vessels may be damaged during implant surgery in the mandibular anterior region,which may lead to mouth floor hematoma,asphyxia,pain,paresthesia and other symptoms.In severe cases,this can be life-threatening.The insufficient alveolar bone space and the anatomical variation of blood vessels and nerves in the mandibular anterior region increase the risk of blood vessel and nerve injury during implant surgery.In case of vascular injury,airway control and hemostasis should be performed,and in case of nerve injury,implant removal and early medical treatment should be performed.To avoid vascular and nerve injury during implant surgery in the mandibular anterior region,it is necessary to be familiar with the anatomical structure,take cone-beam computed tomography,design properly before surgery,and use digital technology during surgery to achieve accurate implant placement.This article summarizes the anatomical structure of the mandibular anterior region,discusses the prevention strategies of vascular and nerve injuries in this region,and discusses the treatment methods after the occurrence of vascular and nerve injuries,to provide clinical reference.

The canalis sinuosus,a canal containing the anterior superior alveolar nerve bundle,originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla.It was once regarded as an anatomical variation.However,with the widespread application of cone beam computed tomography(CBCT),the detection rate of canalis sinuosus in the population has increased.The canalis sinuosus exhibits diverse courses,branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region,with the majority traversing the palatal side of the central incisor.The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth and the corresponding soft tissues,and the maxillary sinus mucosa,but also relates to the nasal septum,lateral nasal wall,and parts of the palatal mucosa.To minimize surgical complications,strategies for preventing and treating canalis sinuosus injuries need to be investigated.Preoperatively,CBCT is used to identify the canalis sinuosus and to virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus.Intraoperatively,assessing bleeding and patient comfort,complemented by precision surgical techniques such as the use of implant surgical guide plates.Postoperatively,CBCT is used to examine the relationship between the implant and the canalis sinuosus,and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms.This review summarizes the detection of canalis sinuosus in the population,its anatomical characteristics,and the physiological functions in the anterior maxilla,and discusses strategies for avoiding canalis sinuosus injuries during implant surgery,thereby enhancing clinical awareness and providing references for clinical decision-making.

Objective To investigate th effect of PCSK9 inhibitors on early intensive lipid-lowering therapy in patients with symptomatic intracranial atherosclerotic stenosis(ICAS).Method One hundred and thirty-nine symptomatic ICAS patients who attended the Xuzhou Central Hospital from October 2022 to August 2023 were collected.According to the choice of lipid-lowering regimen,they were divided into statin drug group(n=54),PCSK9 inhibitor group(n=42)and combination drug group(n=43).Baseline data,laboratory indices,adverse drug reactions,clinical neurological function scores and endpoint events of the three groups were collected and analyzed.Results There was no statistically significant difference in the clinical data among the three groups before treatment.Compared with pre-treatment,total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels were significantly lower in the three groups after treatment(all P＜0.01),and peripheral blood leukocyte counts were significantly lower in the PCSK9 inhibitor group after treatment(P＜0.05).After treatment,the differences in TC and LDL-C levels and the proportions of LDL-C＜1.8 mmol/L after 2 weeks of medication and LDL-C＜1.4 mmol/L on the 90th day were statistically significant among the three groups(all P＜0.01).Compared with the statin drug group,the differences in TC and LDL-C levels and the proportions of LDL-C＜1.8 mmol/L after 2 weeks and LDL-C＜1.4 mmol/L on the 90th day in the PCSK9 inhibitor group and the combination drug group were statistically significant(all P＜0.05).The differences in the occurrence of endpoint events,the proportion of recurrent AIS or TIA,cardiovascular events,and the time to endpoint events among the three groups were statistically significant on the 180th day after treatment(all P＜0.05).Differences in the occurrence of endpoint events,proportion of cardiovascular sexual events,and time to endpoint events on day 180 after treatment were statistically different in the PCSK9 inhibitor group and the combination drug group compared with the statin drug group(all P＜0.05).There was a statistically significant difference among the survival analysis curves of the three groups,with higher event-free survival in both groups with PCSK9 inhibitors alone or in combination(Log-Rank=13.95,P=0.0009).Conclusion Early intensive lipid lowering with PCSK9 inhibitors is effective and safe in patients with symptomatic ICAS,and can further reduce LDL-C,TC,and white blood cell counts,as well as improve lipid compliance,and significantly reduce the rate of end-point events with a significantly prolonged time to occurrence.

ObjectiveTo examine the protective mechanism of wogonin in SH-SY5Y cells cultured in the conditioned media with lipopolysaccharide （LPS）-induced BV-2 microglia. MethodBV-2 microglia were divided into the blank group， LPS group， low concentration group of wogonin （4 μmol∙L^-1）， medium concentration group of wogonin （8 μmol∙L^-1）， and high concentration group of wogonin （16 μmol∙L^-1）. The LPS group was given 1 mg·L^-1 LPS， and the other three groups were treated with the corresponding concentration of wogonin for 4 h and then given 1 mg·L^-1 LPS. The conditioned media from these groups were used to cultivate SH-SY5Y cells. Cell counting kit-8 （CCK-8） was used to assess the vitality of BV-2 cells in the above groups. The contents of interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α） in the supernatant of BV-2 cells were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of tyrosine hydroxylase （TH） and α-Synuclein （α-Syn） in SH-SY5Y cells was detected by immunohistochemical staining （IHC）. The nuclear transfer and fluorescence expression intensity of nuclear transcription factor-κB p65 （NF-κB p65） protein in SH-SY5Y cells were detected by immunofluorescence staining （IF）. Western blot was used to detect the expression of Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/NF-κB pathway-related proteins in SH-SY5Y cells. ResultThe levels of IL-6 and TNF-α in the supernatant of BV-2 cells in the LPS group were significantly higher than those in the blank group （P<0.01）. Compared with those in the LPS group， the IL-6 content of BV-2 cells in the low concentration group of wogonin was statistically significantly lower （P<0.05）， whereas the IL-6 and TNF-α contents of the medium and high concentration groups of wogonin were statistically lower （P<0.05，P<0.01）. The IL-6 and TNF-α contents in the high concentration group of wogonin decreased most significantly （P<0.01）， and the intervention effect was the best. Compared with that in the blank group， the expression of α-Syn protein in SH-SY5Y cells cultured with conditioned media in the LPS group was significantly increased， and the expression of TH protein was significantly decreased （P<0.05）. Compared with that in the LPS group， α-Syn protein expression in the medium and high concentration groups of wogonin showed a decreasing trend （P<0.05， P<0.01）. TH protein expression was increased in the low， medium， and high concentration groups of wogonin （P<0.05， P<0.01）. Compared with the blank group， NF-κB p65 protein gradually accumulated into the nucleus， and the fluorescence expression intensity was significantly enhanced （P<0.01）. Compared with the LPS group， the NF-κB p65 protein was gradually dispersed outside the nucleus， and the fluorescence expression intensity was gradually weakened in all concentration groups of wogonin. The fluorescence intensity in the high concentration group of wogonin was significantly reduced （P<0.01）. Compared with those in the blank group， the expression levels of TLR4 protein， phosphorylated（p）-NF-κB p65 protein， and MyD88 protein in the LPS group were significantly increased （P<0.05， P<0.01）. Compared with those in the LPS group， the expressions of TLR4 protein， p-NF-κB p65 protein， and MyD88 protein in the medium concentration group of wogonin were all significantly decreased （P<0.05， P<0.01）. The expressions of TLR4 protein， and MyD88 protein in the high concentration group of wogonin were significantly decreased （P<0.05， P<0.01）. ConclusionWogonin may regulate the TLR4/MyD88/NF-κB signaling pathway to inhibit the release of LPS-induced inflammatory factors in BV-2 microglia and protect SH-SY5Y cells， thereby reducing inflammation and achieving neuroprotective effects.

Objective To investigate the impact of femoral prosthesis malposition on internal structural strain in unicompartmental knee arthroplasty for osteoporotic knees. Methods A normal bone knee joint model was constructed based on imaging studies (CT, magnetic resonance imaging) of healthy volunteers, and an osteoporotic knee joint model was constructed by altering the elastic modulus. Finite element models of femoral prosthesis malposition in unicompartmental knee arthroplasty were then established for both normal bone and osteoporotic groups. A vertical static load of 1, 000 N was applied to both models, and the peak strain values and distributions were observed in the medial compartment structures (polyethylene gasket, cancellous bone under tibial prosthesis) and lateral compartment structures (meniscus, tibial cartilage) at various malposition angles of the femoral prosthesis. Results The peak strain values of the polyethylene gasket, cancellous bone under tibial prosthesis, meniscus, and tibial cartilage in the osteoporotic group were higher than those in the normal bone group at different varus and valgus angles. In the osteoporotic group, the peak strain values of the polyethylene gasket and cancellous bone under tibial prosthesis increased with the increase in femoral prosthesis malposition angle, with a greater increase at valgus angles than at varus angles. Similarly, the peak strain values of the meniscus and tibial cartilage increased with the increase in femoral prosthesis malposition angle, but the increase was greater at varus angles than at valgus angles. The strain concentration area of the polyethylene gasket was located in a circular-like area where the femoral prosthesis contacted the gasket, the strain concentration area of the cancellous bone was mainly located in the posterolateral region, the strain concentration area of the meniscus was located near the anterior horn, and the strain concentration area of the tibial cartilage was mainly located in the middle near the intercondylar eminence. Conclusion Osteoporosis may adversely affect the strain on internal structures of the knee joint after unicompartmental knee arthroplasty. Varus malposition of the femoral prosthesis may exacerbate the progression of osteoarthritis in the contralateral compartment (lateral compartment), while valgus malposition may increase the risk of prosthesis loosening and revision surgery.

BACKGROUND: The burden of esophageal cancer varies across different regions of the world. The aim of this study is to analyze the current burden of esophageal cancer in 185 countries in 2022 and to project the trends up to the year 2050. METHODS: We extracted data on primary esophageal cancer cases and deaths from the GLOBOCAN 2022 database, which includes data from 185 countries. Age-standardized incidence rates (ASIR) and mortality rates (ASMR) per 100,000 person-years were calculated by stratifying by Human Development Index (HDI) levels and regions. Considering changes in population size and age structure, we assumed that the risks of incidence and mortality remain constant at the levels of 2022 to forecast the number of new cases and deaths from esophageal cancer globally by 2050. RESULTS: In 2022, an estimated 511,054 people were diagnosed with esophageal cancer globally, and 445,391 died from the disease. The global ASIR and ASMR for esophageal cancer were 5.00 and 4.30 per 100,000, respectively. The highest rates were observed in East Africa (7.60 for incidence, 7.20 for mortality per 100,000), East Asia (7.60 for incidence, 5.90 for mortality per 100,000), Southern Africa (6.30 for incidence, 5.90 for mortality per 100,000), and South Central Asia (5.80 for incidence, 5.50 for mortality per 100,000). Among the 185 countries worldwide, esophageal cancer was among the top five causes of cancer incidence in 18 countries and among the top five causes of cancer mortality in 25 countries. In 2022, China had 224,012 new cases and 187,467 deaths from esophageal cancer, accounting for approximately 43.8% and 42.1% of the global total, respectively, which is higher than the proportion of China's population to the global population (17.9%). ASIR was 8.30 per 100,000, and ASMR was 6.70 per 100,000. The highest burden of esophageal cancer was in high HDI countries, with new cases and deaths accounting for 51.3% and 50.0% of the global total, respectively. The ASIR and ASMR were highest in the high HDI group (6.10 and 5.10 per 100,000, respectively), also exceeding the global averages. There was a trend of decreasing mortality to incidence ratio with increasing HDI, but no correlation was observed between HDI and ASIR or ASMR. In all regions worldwide, the incidence and mortality rates were higher in males than in females (with a male-to-female ASR ratio ranging from 1.10 to 28.7). Compared to 2022, it is projected that by 2050, the number of new esophageal cancer cases will increase by approximately 80.5%, and deaths will increase by 85.4% due to population growth and aging. CONCLUSIONS The burden of esophageal cancer remains heavy. Adopting a healthy lifestyle, including reducing tobacco and alcohol intake, avoiding moldy foods, and increasing intake of fresh fruits and vegetables, can help reduce the risk of stomach and esophageal cancer. In addition, the development and implementation of evidence-based and effective public health policies are critical to reducing the global disease burden of esophageal cancer.
Esophageal Neoplasms/mortality* ; Humans ; Male ; Incidence ; Female ; Middle Aged ; Global Health ; Aged ; Adult

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

ObjectiveTo investigate the effect of baicalein （BAI） on SH-SY5Y cell injury in lipopolysaccharide （LPS）-activated BV-2 cells conditioned medium and its mechanism. MethodThe BV-2 cells were activated with 1 mg∙L^-1 of LPS to establish the conditioned medium of the LPS group， and a blank group and groups of BAI with low， medium， and high concentrations （4， 8， 16 μmol∙L^-1） were established. SH-SY5Y cells were cultured with the conditioned medium of each group. The cell viability of BV-2 cells in each group after the intervention was determined by cell counting kit-8 （CCK-8）. The content of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the supernatant of BV-2 cells in each group was determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of α-synuclein （α-syn） and tyrosine hydroxylase （TH） in SH-SY5Y cells was observed by immunohistochemical （IHC） staining， and the nuclear transfer of nuclear factor kappa-B p65 protein （NF-κB p65， p65） in SH-SY5Y cells was observed by immunofluorescence （IF）. The protein expression of Toll-like receptor 4（TLR4）， p65， phosphorylated p65 （p-p65）， and Myeloid differentiation factor 88 （MyD88） in SH-SY5Y cells was observed by Western blot. ResultAs compared with the blank group， the viability of BV-2 cells in the LPS group was significantly decreased （P<0.01）， and the content of TNF-α， IL-6， and IL-1β in the cell supernatant was significantly increased （P<0.01）. As compared with the LPS group， the cell viability was significantly increased in groups of BAI with low， medium， and high concentrations （P<0.01）， and TNF-α in the cell supernatant was significantly decreased （P<0.01）. The content of IL-6 in the cell supernatant was decreased in the BAI group with high concentration （P<0.05）， and the content of IL-1β in the cell supernatant was significantly decreased in the BAI groups with medium and high concentrations （P<0.01）. The results of conditioned medium cultured SH-SY5Y cells showed that as compared with the blank group， the protein expression of p65 in the LPS group entered into the nucleus and accumulated， and the protein expression of TH was significantly decreased （P<0.01）， while that of α-syn， TLR4， MyD88， and p-p65 was increased （P<0.05， P<0.01）. Compared with the LPS group， the protein expression of p65 in SH-SY5Y cells in BAI groups with low， medium， and high concentrations gradually dispersed into the cytoplasm and had the enhanced protein expression of TH （P<0.01） but the lowered protein expression of α-syn （P<0.01）. The protein expression of TLR4， MyD88， and p-p65 was decreased in the BAI group with high concentration （P<0.05， P<0.01）， the protein expression of p-p65 and MyD88 was decreased in the BAI group with medium concentration， and the protein expression of MyD88 was decreased in the BAI group with low concentration （P<0.05）. There was no significant difference in the protein expression of p65 among groups. ConclusionBAI can inhibit the activation of BV-2 cells， thereby inhibiting the inflammatory response caused by LPS and further inhibiting the damage of inflammation to SH-SY5Y cells. The mechanism may be related to the regulation of the TLR4/MyD88/NF-κB signaling pathway and reduction of the inflammatory response， thus playing a neuroprotective role.