[摘 要] 目的：探讨胃肝样腺癌（HAS）的临床病理特征与免疫微环境异质性，筛选预后标志物，阐释其高侵袭性与疗效差的机制，为精准诊疗策略提供理论依据。方法:​​ 回顾性收集2013年1月至2025年5月期间海军军医大学第一附属医院与第二附属医院收治的65例HAS患者的临床信息及病理资料。采用免疫组织化学技术检测HAS​​肝样分化标志物、神经内分泌标志物​​等分子表达情况，通过Kaplan-Meier生存分析法明确与预后相关的靶点。利用多色免疫荧光技术鉴定肿瘤区域内免疫细胞亚群分布情况，以阐明其免疫微环境特征。结果：65例患者中，男性54例（83.1%），女性11例（16.9%），中位年龄68岁。肿瘤好发于贲门（40%），其次为胃窦（32.3%）和胃体（27.7%）。中位随访时间23.18个月，15例患者死亡，46例生存，4例失访。HAS的胃镜及手术标本大体观呈灰白色实性质硬肿物，镜下可见中低分化胃腺癌与肝细胞癌（HCC）样分化区交错分布。表达神经内分泌相关分子的HAS患者呈现出更多的淋巴结转移数量及更短的总生存期。免疫微环境解析显示，HAS总体缺乏免疫细胞浸润，呈现“冷肿瘤”特征；免疫细胞主要聚集于胃癌腺体周围区域，而在HCC样分化区域罕见淋巴细胞浸润。结论：HAS侵袭性强，根治性手术是主要治疗手段；神经内分泌转化提示不良预后，是个体化治疗的关键标志；免疫细胞浸润缺乏，可能是其免疫治疗响应不佳的原因。

BACKGROUND:Collagen combined with microneedling therapy has gradually become an important means of improving skin photoaging.OBJECTIVE:To summarize and explore the main mechanism and clinical application status of collagen combined with microneedle therapy.METHODS:PubMed,China National Knowledge Infrastructure,and ScienceDirect databases were searched for Chinese and English literature published before August 2024.Chinese and English search terms were"ultraviolet radiation,photoaging,collagen,microneedling,clinical applications."Finally,74 articles were included for summary.RESULTS AND CONCLUSION:Collagen treats skin photoaging through mechanisms such as inhibiting matrix metalloproteinase expression,retaining skin moisture,and reducing melanin formation.Microneedles can better promote the penetration of collagen into deep layers of the skin,breaking down the skin's barrier and increasing the absorption rate.Collagen combined with microneedles has various beneficial effects for treating skin photoaging,such as whitening,anti-wrinkle,improving skin elasticity,shrinking pores,and repairing skin barriers.It also has the advantages of easy operation,significant effects,and high safety.Currently,the research on collagen combined with microneedling therapy is still in its early stages,and achieving clinical application may become a key research direction in the future.The clinical application of collagen combined with microneedles for the treatment of photoaging still faces many challenges,such as exploring the optimal mechanical structure and materials of microneedles,selecting appropriate microneedle types,and insufficient clinical evidence that collagen combined with microneedles can further delay the treatment of skin photoaging.

BACKGROUND:Collagen combined with microneedling therapy has gradually become an important means of improving skin photoaging.OBJECTIVE:To summarize and explore the main mechanism and clinical application status of collagen combined with microneedle therapy.METHODS:PubMed,China National Knowledge Infrastructure,and ScienceDirect databases were searched for Chinese and English literature published before August 2024.Chinese and English search terms were"ultraviolet radiation,photoaging,collagen,microneedling,clinical applications."Finally,74 articles were included for summary.RESULTS AND CONCLUSION:Collagen treats skin photoaging through mechanisms such as inhibiting matrix metalloproteinase expression,retaining skin moisture,and reducing melanin formation.Microneedles can better promote the penetration of collagen into deep layers of the skin,breaking down the skin's barrier and increasing the absorption rate.Collagen combined with microneedles has various beneficial effects for treating skin photoaging,such as whitening,anti-wrinkle,improving skin elasticity,shrinking pores,and repairing skin barriers.It also has the advantages of easy operation,significant effects,and high safety.Currently,the research on collagen combined with microneedling therapy is still in its early stages,and achieving clinical application may become a key research direction in the future.The clinical application of collagen combined with microneedles for the treatment of photoaging still faces many challenges,such as exploring the optimal mechanical structure and materials of microneedles,selecting appropriate microneedle types,and insufficient clinical evidence that collagen combined with microneedles can further delay the treatment of skin photoaging.

Objective To explore the distribution characteristics of allergen positivity rates and related influencing factors among children with allergic rhinitis in Shanxi Province, and to provide a scientific basis for the prevention, diagnosis, and treatment of allergic rhinitis in children in this area. Methods A total of 1 376 pediatric patients from Shanxi Province, who visited the Department of Otolaryngology of Shanxi Children's Hospital and underwent serum-specific immunoglobulin E (IgE) testing between March 2024 and March 2025, were selected. The positive rates of common allergens were analyzed, and the sensitization differences of allergens among different age cohorts were compared. The risk factors influencing the occurrence of allergic rhinitis in children were explored. Results The test results showed that 1,258 cases were positive for inhalant allergens, with a positive rate of 91.42%, while 855 cases tested positive for ingested allergens, with a positive rate of 62.14%. The top four inhalant allergens with the highest positive rates were Artemisia (38.01%), short ragweed (33.94%), willow/beech/oak/walnut (23.26%), and cat dander (18.82%). The top four ingested allergens with the highest positive rates were milk (24.56%), egg white (22.89%), peanut/soybean (22.60%), and cashew/pistachio/hazelnut/almond/walnut (18.60%). Among the inhalant allergens in children aged ≤ 16 years old, household dust mites had the highest sensitivity, followed by dust mites. Chicken protein and pistachios/cashews/almonds/hazelnuts/walnuts were more common among food allergens in children aged ≤ 5 years old, while milk and egg white were more common among food allergens in children aged 6-16 years old. The results of the multivariate logistic regression analysis showed that urban residence (OR=1.260, 95%CI: 1.009-1.574), a meat-based diet (OR=1.525, 95%CI: 1.218-1.908), presence of smoking/passive smoking (OR=2.033, 95%CI: 1.625-2.543), history of asthma (OR=4.122, 95%CI: 2.655-6.400), history of allergies (OR=2.016, 95%CI: 1.568-2.592), comorbid adenoid hypertrophy (OR=2.248, 95%CI: 1.529-3.304), and parental allergic rhinitis (OR=1.723, 95%CI: 1.298-2.289) were risk factors for allergic rhinitis in children. Conclusion The allergen spectrum of allergic rhinitis in children in Shanxi region is predominantly inhalant. Mugwort, short ragweed, willow/beech/oak/walnut, and cat dander are the main inhalant allergens, while milk, egg white, peanut/soybean, and cashew/pistachio/hazelnut/almond/walnut are the primary ingested allergens. The allergen positivity rate exhibits characteristic changes with age. Factors such as residing in urban areas, a meat-based diet, and a history of asthma are influential factors in the prevalence of allergic rhinitis among children in the Shanxi region.

ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

A traditional Chinese medicine (TCM) monomer is a bioactive compound extracted from Chinese herbal medicines possessing determined biological activity and pharmacological effects, and has gained much attention for treating neuronal diseases. However, the application of TCM monomers is limited by their low solubility and poor ability to cross the blood-brain barrier (BBB). Exosomes are small extracellular vesicles (EVs) ranging in size from 30 to 150 nm in diameter and can be used as drug delivery carriers that directly target cells or tissues with unique advantages, including low toxicity, low immunogenicity, high stability in blood, and the ability to cross the BBB. This review discusses the biogenesis, components, stability, surface modification, isolation technology, advantages, and disadvantages of exosomes as drug carriers and compares exosomes and other similar drug delivery systems. Furthermore, exosome-encapsulated TCM monomers exert neuroprotective roles, such as anti-inflammation, anti-apoptosis, anti-mitophagy, and anti-oxidation, in various neuronal diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and cerebral ischemia and reperfusion (CI/R) injury, as well as anti-drug resistance, anti-tumorigenesis, anti-angiogenesis, and promotion of apoptosis in brain tumors, providing more inspiration to promote the development of an exosome-based delivery tool in targeted therapy for neuronal diseases.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Objective:The prediction model of postoperative recurrence of ovarian endometriosis cyst(OEM)was constructed to provide a reference for evaluating postoperative recurrence of OEM patients.Methods:The clinical,pathological and follow-up data of 342 patients who underwent the initial laparoscopic ovarian cystectomy for OEM at The Second Hospital of Hebei Medical University from January 1,2017 to October 31,2021 were retro-spectively analyzed.Based on univariate and multivariate Cox regression analysis,the relevant factors affecting OEM recurrence were identified.According to the results of multivariate analysis,a nomogram was drawn.The C index and receiver operating characteristic(ROC)curve were used to test the efficiency of the prediction model.Results:The 2-year recurrence rate of OEM patients was 20.4%and the 5-year recurrence rate was 35.2%.Uni-variate and multivariate Cox regression analysis showed that menstrual cycle(HR 0.916,95%CI 0.860-0.976,P=0.006),delivery≥1(HR 0.376,95%CI 0.171-0.827,P=0.015),CA125≥100 U/ml(HR 1.790,95%CI 1.167-2.746,P=0.008),total cyst diameter≥10 cm(HR 2.254,95%CI 1.318-3.854,P=0.003),and postoperative medications(HR 0.434,95%CI 0.292-0.644,P=0.000)were associated with OEM recurrence and were included in the no-mogram prediction model.The C-index of the nomogram prediction model was 0.710(95%CI 0.665-0.754),and the area under the curve(AUC)of the ROC for OEM patients with recurrence at 2 years after surgery was 0.786 and 0.708 at 5 years.Conclusions:In this study,we developed a nomogram to predict the probability of recur-rence at 2 years and 5 years for OEM patients under 45 years who underwent conservative surgery,which has i-deal predictive performance and helps clinicians to screen high-risk patients,and thus give high-risk OEM patients additional attention and intervention.