The benefit of postoperative adjuvant therapy for patients with resectable esophageal squamous cell carcinoma (ESCC) is not yet supported by high-level evidence. This review analyzes the role of adjuvant therapy by examining the discrepancy between clinical needs and guidelines, its historical evolution, recent advances in high-risk factors, and future outlooks. We provide a detailed discussion of high-risk factors used for patient selection, including lymph node positivity, and for node-negative patients, features such as tumor length, location, T stage, extent of lymph node dissection, differentiation, vascular and neural invasion, laboratory indices, and molecular markers. The goal is to inform the development of individualized precision treatment strategies for resectable ESCC.

With the maturation of proteomics technologies in recent years, proteomics has made significant achievements in early detection of major diseases, disease classification, drug target discovery, and other fields. To explore the important role of proteomics, especially proteomics-based cutting-edge lifeomics technologies, in promoting the development of precision laboratory medicine and to discuss the opportunities and challenges faced during the clinical translation of innovative outcomes, the National Center for Protein Sciences-Beijing invited renowned experts and scholars in laboratory medicine, lifeomics, and precision medicine. The discussions revolved around the collaborative development of laboratory medicine and lifeomics, the future trends of new technologies in clinical laboratory testing, the innovation and development of lifeomics in laboratory medicine, the translational application of proteomics technologies in laboratory medicine, and the opportunities and challenges in the industrialization of proteomics achievements. All participants agreed that proteomics provides new directions and opportunities for precision diagnosis and treatment of diseases. However, close collaboration between academia, hospitals and industry is required. Additionally, challenges such as clinical applicability of equipment, standardization of detection methods and data, cost and quality control, talent cultivation, and the industrialization pathway need to be addressed.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective:Age-related cataract is the most common type of adult cataract and a leading cause of blindness.Currently,there are few reports on the establishment of animal models for age-related cataract.During the experimental breeding of Microtus fortis(M.fortis),we first observed that M.fortis aged 12 to 15 months could naturally develop cataracts.This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M.fortis. Methods:The 12-month-old healthy M.fortis were served as a control group and 12-month-old cataractous M.fortis were served as an experimental group.The lens transparency was observed using the slit-lamp biomicroscope.Hematoxylin and eosin staining was used to detect pathological changes in the lens.Biochemical detection methods were applied to detect blood routine,blood glucose levels,the serum activities of superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in both groups.Finally,real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. Results:Compared with the control group,the lens of cataract M.fortis showed severely visible opacity,the structure of lens was destroyed seriously,and some pathological damage,such as swelling,degeneration/necrosis,calcification,hyperplasia,and fiber liquefaction were found in lens epithelial cells(LECs).The fibrous structure was disorganized and irregularly distributed with morgagnian globules(MGs)aggregated in the degenerated lens fibers.There was no statistically significant difference in blood glucose levels between the experimental and control groups(P＞0.05).However,white blood cell(WBC)count(P＜0.05),lymphocyte count(P＜0.01),and lymphocyte ratio(P＜0.05)were significantly decreased,while neutrophil percentage(P＜0.05)and monocyte ratio(P＜0.01)were significantly increased.The serum activities of SOD and GSH-Px(both P＜0.05)were both reduced.The mRNAs of cataract-related genes,including CRYAA,CRYBA1,CRYBB3,Bsfp1,GJA3,CRYBA2,MIP,HspB1,DNase2B,and GJA8,were significantly downregultaed in the lenses of the experimental group(all P＜0.05). Conclusion:There are significant differences in lens pathological changes,peroxidase levels,and cataract-related gene expression between cataract and healthy M.fortis.The developed cataract spontaneously in M.fortis is closely related to age,the cataract M.fortis might be an ideal animal model for the research of age-related cataract.

Objective:This study aimed to explore the status of radiological Kashin-Beck disease (KBD) among school-aged children in Chamdo City, Tibet, through a 3-year monitoring survey, providing epidemiological evidence for prevention and control strategies.Methods:The target areas for this study were Luolong, Bianba, and Basu counties in Chamdo City, Tibet Autonomous Region, identified as having the most severe historical cases of KBD. Children aged 7-12 years attending school were enrolled as study subjects. Anteroposterior X-ray films of the right-hand were taken, and radiological diagnoses were made based on the "Diagnosis of Kashin-Beck Disease" criteria (WS/T 207-2010). Two experienced researchers independently reviewed the X-rays, and intra- and inter-group consistency were assessed using weighted Kappa values and percentage agreement. Cross-sectional surveys were conducted in 2017 and 2020 to describe the X-ray detection rates of KBD, and logistic regression analysis was employed to construct a predictive model of risk factors for radiological KBD cases.Results:In 2017, a total of 5,711 children aged 7-12 years in Chamdo City, Tibet, participated in the baseline cross-sectional survey (average age 9.2 years, 48.0% female), with 28 cases of radiological KBD. The age- and gender-standardized prevalence rate was 0.527%. In 2020, 6,771 participants (average age 9.3 years, 49.5% female) underwent a second cross-sectional survey, with 9 cases of radiological KBD and a standardized prevalence rate of 0.134%. Logistic regression analysis indicated that older age [ OR=2.439, 95% CI(1.299, 4.580), P=0.006] and female gender [ OR=8.157, 95% CI(1.016, 65.528), P=0.048] were independent risk factors for radiological KBD cases. Conversely, higher residential altitude, under the premise of Tibet's high altitude, was a protective factor [ OR=0.995, 95% CI(0.990, 0.999), P=0.032). Conclusion:The radiographically positive detection rate of KBD among school-aged children in Chamdo City, Tibet Autonomous Region, is at an extremely low level and showing a declining trend, reaching the historical standard in 2020. Considering the absence of positive signs in affected children, it suggests that local KBD has been effectively eliminated.

Objective·To explore the effects and possible molecular mechanisms of nanoplastics(NPs)on severe asthma.Methods·A mouse model of severe asthma was established by using house dust mite(HDM)and lipopolysaccharide(LPS)co-stimulation.Polystyrene nanoplastics(PS-NPs)were instilled into the severe asthma mice's airways.Subsequently,bronchoalveolar lavage fluid(BALF)was collected and lung tissue sections were prepared.Flow cytometry,hematoxylin-eosin(H-E)staining,periodic acid-Schiff(PAS)staining,immunohistochemistry,and terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,were used to observe the effects of PS-NPs on airway inflammation,mucus secretion,alveolar structure,and the proliferation and apoptosis of alveolar type Ⅱ epithelial cells(AT2 cells)in severe asthma mice.The CCK-8 assay and Annexin Ⅴ/PI double staining were performed to evaluate the effects of PS-NPs on the proliferation and apoptosis of the mouse AT2 cell line MLE-12.DNA damage in AT2 cells caused by PS-NPs was detected by using anti-γ-H2A.X immunofluorescence staining.The expression of genes in the ATR/Chk1/p53 signaling pathway was detected by real-time fluorescent quantitative polymerase chain reaction(qPCR),Western blotting,Tyramide signal amplification(TSA)multiplex immunofluorescence staining,and immunofluorescence co-localization,respectively.The ATR-specific inhibitor Ceralasertib(AZD6738)was administrated to MLE-12 cells in combination with PS-NPs to evaluate the recovery effect on cell proliferation and apoptosis.Results·Flow cytometry revealed that exposure to PS-NPs increased the total number of inflammatory cells and the number of each type of inflammatory cells in the BALF of mice with severe asthma,with a predominance of neutrophils.H-E and PAS staining showed significant increase in airway inflammatory cell infiltration and mucus secretion,as well as disruption of alveolar structure.In vitro,the CCK-8 assay demonstrated significant,dose-dependent inhibition of MLE-12 cell proliferation by PS-NPs.The Annexin V/PI double staining assay indicated a higher apoptosis rate of(56.20±3.84)%in PS-NP-exposed cells compared to(23.22±2.52)%in the control group.Immunofluorescence staining demonstrated that PS-NPs were phagocytosed by MLE-12 cells and localized around the nucleus.TUNEL staining confirmed enhanced apoptosis in AT2 cells in vivo.The immunofluorescence assay revealed that compared to the control group,the expression of the DNA damage marker γ-H2A.X increased in the experimental group.qPCR,Western blotting,and TSA multiplex staining results showed that PS-NP-induced elevated expression of mRNA and proteins was related to the ATR/Chk1/p53 pathway in MLE-12 cells.Moreover,immunofluorescence co-localization also confirmed the induction of ATR and p53 proteins in AT2 cells in vivo.The ATR-specific inhibitor Ceralasertib partially restored the PS-NP-induced inhibition of cell proliferation and enhancement of apoptosis in MLE-12 cells.Conclusion·NPs exposure leads to DNA damage in AT2 cells,activating the ATR/Chk1/p53 signaling pathway and exacerbating airway inflammation and alveolar damage in mice with severe asthma.

Objective To explore the value of computer-aided measurement of the mass-based consolidation-to-tumor ratio(CTRmass)in predicting preoperative clinical stage IA lung adenocarcinoma invasion.Methods A total of 56 patients with stage IA lung adenocarcinoma were retrospectively selected from Linfen Central Hospital and the National Lung Screening Trial(NLST)database(project number NLST-1053),and all of them were confirmed by pathology.Computer-aided software was used to automatically cal-culate parameters such as the volume-based consolidation-to-tumor ratio(CTRvol),CTRmass,average CT value,and maximum axial diameter,and its correlation with pathological results was analyzed.Results When the CTRmass≥30.95％,it indicated that lung nodules were more likely to be invasive adenocarcinoma(IAC).Conclusion CTRmass,based on computer-aided software measure-ment,can be used as one of the important indicators to evaluate the preoperative invasion of clinical stage IA lung adenocarcinoma,guiding the selection of surgical methods,and obtaining better curative effects.

Objective To grasp the main environmental factors affecting the growth of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao;To predict the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province;To provide references for the rational distribution of the resources in Shanxi Province.Methods This study utilized the sample point longitude and latitude information collected in the"Fourth Survey of Chinese Materia Medica Resources"database in Shanxi Province.The data were supplemented by searching the China Digital Herbarium and retrieving related literature records.347 sample points distribution data and environmental factors were added to the MaxEnt model.The main environmental factors and contribution rates affecting the geographical distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao were screened out.The ArcGIS software was used to divide the ecological suitable area of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province.Results The area under the ROC curve of the established MaxEnt model was 0.909,indicating that the model prediction results were accurate.The model screened 19 environmental factors.Among them,climate factor was the most important environmental factor,followed by biological factor and topographic factor,and soil factor had the least influence.The potential suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province were mainly distributed in the northern mountainous areas,presenting a trend of gradually decreasing suitability levels from north to south.Under the current climate conditions,the most suitable area for Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province was 15 424 km2,the suitable area was 19 856 km2,the sub suitable area was 59 436 km2,and the unsuitable area was 61 894 km2.Conclusion Based on MaxEnt model and ArcGIS software,this study predicts the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province,which has certain reference value for the protection and rational distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao resources in Shanxi Province.

Objective To establish ecological suitability zone of Forsythia suspensa(Thunb.)Vahl in Shanxi Province;To study the quality regionalization of Forsythia suspensa(Thunb.)Vahl from different producing areas in Shanxi Province;To provide reference for reasonable planting and wild tending of Forsythia suspensa(Thunb.)Vahl.Methods Maximum entropy(MaxEnt)model and ArcGIS software were used to study the ecological suitability of Forsythia suspensa(Thunb.)Vahl in Shanxi Province;By screening the main environmental factors and combining them with the content of forsythoside and forsythoside A in Forsythia suspensa(Thunb.)Vahl of different regions,a quality zoning of Forsythia suspensa Thunb.Vahl medicinal materials in Shanxi Province based on forsythoside,forsythoside A and environmental factors was constructed.Results The ecological suitable areas of Forsythia suspensa Thunb.Vahl in Shanxi Province were mainly distributed in the southern part of Shanxi Province,mainly in Linfen,Yuncheng,Changzhi,and Jincheng.The general contents of forsythoside and forsythoside A in the Forsythia suspensa(Thunb.)Vahl medicinal material were gradually reduced from southern part to northern part of Shanxi Province.The comprehensive quality was high in southern part of Shanxi Province,mainly in Linfen,Changzhi,Yuncheng and Jincheng.Conclusion The results of this study are consistent with the actual survey.The southern part of Shanxi province is a suitable planting area for high quality Forsythia suspensa(Thunb.)Vahl,which provides a reference for the standardized planting and wild tending of Forsythia suspensa(Thunb.)Vahl.