A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Objective: To investigate the characteristics and trend of stroke incidence in Yixing City, Jiangsu Province from 2016 to 2023, so as to provide the reference for formulating prevention and control strategies of stroke. Methods: Data of stroke case in Yixing City from 2016 to 2023 were collected from the National Health Information Platform of Yixing City, including sex, age, time of onset, and diagnostic subtypes. Crude incidence was standardized using the data from the 2010 Chinese National Population Census to analyze the characteristics of stroke incidence. The incidence trend of stroke was analyzed by average annual percent change (AAPC). Results: A total of 54 157 stroke cases were reported in Yixing City from 2016 to 2023, with a crude incidence of 629.52/100 000 and a standardized incidence of 299.50/100 000, showing an upward trend (AAPC=9.744% and 5.955%, both P<0.05). The crude and standardized incidence of stroke in males were significantly higher than those in females (695.30/100 000 vs. 565.79/100 000, 328.73/100 000 vs. 270.71/100 000, both P<0.05). Stroke incidence exhibited an age-dependent increase (P<0.05), peaking in the ≥60 years age group (1 820.43/100 000). The crude and standardized incidence of ischemic stroke (555.46/100 000 and 262.26/100 000) were significantly higher than those of hemorrhagic stroke (52.80/100 000 and 28.03/100 000, both P<0.05). From 2016 to 2023, the standardized incidences of stroke in males, females, the 0-<40 years age group, the 40-<60 years age group, the ≥60 years age group, and ischemic stroke all showed an upward trend (AAPC=6.692%, 4.925%, 5.607%, 5.777%, 5.698%, and 8.481%, respectively, all P<0.05). No significant temporal trend was observed for hemorrhagic stroke incidence (P>0.05). Conclusions The incidence of stroke among residents in Yixing City showed an upward trend from 2016 to 2023, with males and elderly individuals being high-risk populations. Ischemic stroke emerged as the predominant subtype, while a concerning trend of increasing stroke incidence among younger adults was observed.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective To explore the current situation and influencing factors that affect stroke specialist nurses in Henan Province and provide a reference for targeted interventions.Methods A total of 140 stroke specialist nurses from over 103 general hospitals in Henan Province were selected to participate the study with the convenience sampling method,between March and November 2022.General data questionnaire and the core competence evaluation questionnaire of stroke specialist nurses in Henan Province were employed for the investigation.Influencing factors were analysed by binary Logistic regression.Results A total of 134 specialist nurses responded to the survey.The findings revealed that the total score of core competence in the stroke specialist nurses was 279.5(257.0,306.0).Among the dimensions of core competence,the clinical thinking ability scored the highest at 4.4(4.0,4.9),while professional development ability scored the lowest at 3.7(3.4,4.0).Cluster analysis categorised that the scores＜250 were of a low score group(n=26)and those≥250 were of a high score group(n=108).Binary Logistic regression analysis indicated that education level,years working as a stroke specialist nurse,and the working experience in the stoke fast track team of A&E were the factors that influenced the core competence of the stroke specialist nurses in Henan Province(all P＜0.05).Conclusions This study has found that the core competence of stroke specialist nurses in Henan Province is at an acceptable level.Education,years working as a stroke specialist nurse and the working experience in the fast track team of A&E are the primary factors which influence core competence.Nursing managers should devise supportive programs to target the influencing factors and to improve the core competence of the stroke specialist nurses.

Objective To screen and analyze the differentially expressed genes(DEGs)in basal cell carcinoma(BCC)of the eyelid using RNA sequencing technology.Methods Six patients who underwent extended resection and primary eyelid reconstruction for BCC of the eyelid in Hebei Eye Hospital from July to November 2021 were selected.Part of the excised cancer tissues and the adjacent normal tissues trimmed during the repair of the defect were sampled for the study.The library construction for sequencing was performed using RNA sequencing technology.The threshold for DEGs was set using the DESeq2 software:P＜0.05 and|log2(foldchange)|＞1,to identify DEGs.Gene Ontology(GO)and Kyo-to Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using the clusterProfiler software,and the biological significance of these DEGs was further analyzed.Results DESeq2 software was used to analyze the differential expression between cancer tissues and adjacent tissues,and 1 317 DEGs were screened out.In the cancer tis-sues of the 6 patients,906 DEGs were up-regulated,and 411 DEGs were down-regulated.GO enrichment analysis showed that the top 30 up-regulated DEGs were mainly concentrated in humoral immune response,immunoglobulin complex,B cell receptor signaling pathway,extracellular matrix,antigen binding,and receptor modulator activity,and the top 10 down-regulated genes were mainly related to epidermal development in biological process,cell composition,and molecular func-tion.KEGG pathway analysis revealed that DEGs were mainly enriched in the melanogenesis signaling pathway,WNT sig-naling pathway,and immune-related signaling pathway,and there were 8 related gene pathways.According to the signifi-cance of gene up-regulation,the core genes identified finally were FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2.Conclusion The occurrence of BCC is closely related to the interaction and synergy of various pathways.Among the highly expressed genes,the up-regulation of FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2 expression in the tissues of patients with BCC of the eyelid is the most significant,which is closely related to the occurrence and development of BCC of the eyelid.

Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) can influence the incidence, outcome, and recurrence risk of ischemic stroke independently of traditional risk factors. This article reviews the relationship, related mechanisms, and treatment decisions between NAFLD and ischemic stroke, in order to provide reference for clinical diagnosis and treatment decisions.

Objectives:To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication.Methods:A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed.Results:Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients ( P=0.007), which was related to tumor site ( P=0.032), tumor size ( P=0.029) and TP53 wild-type ( P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb ( P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions:PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.

BACKGROUND:The application of orthodontic force triggers autophagy in the periodontal tissue via diverse signaling pathways,augmenting or attenuating the activity of relevant cell types such as periodontal ligament cells,osteocytes,osteoclasts,and osteoblasts,thus facilitating the process of periodontal remodeling. OBJECTIVE:To review the research progress in orthodontic force mediated autophagy in periodontal tissue and its impact on orthodontic tooth movement. METHODS:The PubMed,Web of Science,China Biology Medicine disc and CNKI were searched for literature published from 2010 to 2023 to summarize the progress in orthodontics-related autophagy.And 76 papers were finally included in the analysis and discussion. RESULTS AND CONCLUSION:Orthodontic force can trigger a series of biochemical signal changes through periodontal mechanical receptors and aseptic inflammation they cause,leading to autophagy in periodontal tissue.Subsequently,autophagy generates corresponding feedback through cascaded amplified signaling pathways such as Phosphoinositide 3-kinase/protein kinase B,Hippo,and mitogen-activated protein kinase pathways,promoting periodontal tissue remodeling and ultimately achieving tooth movement and stability.Orthodontic force-induced autophagy can differentially regulate bone resorption on the tooth pressure side and bone formation on the tension side.Related targets have good prospects in the clinical application of orthodontic treatment.Orthodontics and autophagy have complex mechanisms.However,existing research has only focused on exploring the role of autophagy in orthodontic tooth movement.Further exploration is needed to investigate the mutual regulatory effects between autophagy and orthodontic tooth movement,as well as the interactions between upstream mechanical receptors and signaling pathways involved in related pathways.