Erythropoietin-producing hepatoma receptor A2 （EphA2） is a member of the erythropoietin-producing hepatoma （Eph） subfamily of receptor tyrosine kinases. As a critical regulator of cancer development and progression， EphA2 can promote tumor initiation， growth， invasion， metastasis， stemness， and angiogenesis by activating or enhancing the oncogenic signaling pathways. High expression of EphA2 in tumor tissues is closely associated with poor prognosis， thus it is a very promising potential target for cancer treatment. This article reviews the molecular mechanisms by which EphA2 promotes cancer development and progression， aiming to provide clues and theoretical basis for EphA2-targeted cancer treatment.

Objective:To investigate the role of O-GlcNAcylation in the regulation of the stability of receptor for activated C kinase 1(Rack1)during SHH-type medulloblastoma(SHH-MB)initiation.Methods:SHH-MB tumors and adjacent tissues were selected from the clinical tu-mor specimen library of the Department of Pathology at The General Hospital of Western Theater Command.Rack1 expression and O-GlcNAcylation(O-GlcNAc)levels in these tumor tissues were analyzed.The human medulloblastoma cell line Daoy was treated with a glyc-osyltransferase(OGT)inhibitor(OSMI-1)and adeglycosyltransferase(OGA)inhibitor(TM-G),and their impact on tumor cell proliferation was assessed using a Cell Counting Kit-8(CCK-8)and immunofluorescence staining.The O-GlcNAc enzyme labeling system co-immunoprecipita-tion(Co-IP)and Western blot were used to correlate Rack1 protein levels with O-GlcNAc levels.The impact of O-GlcNAcon Rack1 stability was confirmed using cycloheximide(CHX)and ubiquitination modification experiments.In a medulloblastoma mouse model with Rack1 knockdown,tumor cell proliferation was detected using a Cell Counting Kit-8(CCK-8),immunofluorescence staining,and a scratch assay.Xenograft tumors were transplanted into immunodeficient mice and SHH signaling was detected by Western blot in the obtained tissue samples(sh-NC and sh-Rack1)to verify the role of Rack1 protein in SHH-MB.Results:Rack1 and O-GlcNAcylation levels were significantly in-creased in SHH-MB tumor samples,and a negative correlation was observed between Rack1 levels and patient survival rates.Treatment of Daoy cells with OGT and TM-G revealed that O-GlcNAc significantly promotes Daoy cell proliferation,while inhibiting O-GlcNAc impedes tu-mor cell proliferation.Molecular experiments have confirmed that O-GlcNAc modification of Rack1 protein can regulate tumor cell stability,thereby promoting tumor cell proliferation.When Rack1 expression was knocked down in Daoy cells,cell proliferation was significantly re-duced relative to control cells.Accordingly,proliferation was significantly inhibited in tumor tissues with Rack1 protein knockdown in mouse models,suggesting that Rack1 can participate in the initiation of SHH-MB by regulating SHH signaling.Conclusions:O-GlcNAcylation particip-ates in SHH-MB initiation by regulating Rack1 stability.

OBJECTIVE To evaluate the operation effect of the drug complaints and reporting system in China， and put forward the suggestions for improving the drug supervision system and enhancing the national drug scientific supervision capacity. METHODS The statistical data of drug supervision from 2012 to 2023 and the complaint data of various provinces and 7 third- party platforms of drug online sales from National 12315 Consumer Complaint Information Disclosure Platform from 2023 to 2024 were collected. The operation effect of drug complaints and reporting system was analyzed from the dimensions of public participation， public satisfaction， case handling efficiency and quality， social effect and risk early warning ability. RESULTS From 2012 to 2019， the acceptance of drug complaints and reporting fluctuated greatly， and the number of drug complaints and reporting cases showed a downward trend as a whole， but the public satisfaction was high and the closure rate continued to increase. From 2023 to 2024， the top five provinces in terms of the number of drug complaints were Guangdong， Henan， Zhejiang， Shandong and Shanghai. Drug complaints in the online platform mainly involved Chinese and Western medicines， traditional Chinese medicines and Chinese herbal medicines sold on the network platforms of Pinduoduo， Jingdong and Taobao. The complaints focused on quality and after-sales service， and there were significant differences in the proportion of mediation agreements in drug complaint cases. From 2021 to 2024， the drug regulatory authorities investigated and dealt with 11 typical cases of online sales violations through complaint and reporting clues. CONCLUSIONS The drug complaints and reporting system in China runs smoothly. It is suggested to further use the data of National 12315 Consumer Complaint Information Disclosure Platform to strengthen the monitoring of key areas and network platforms， and urge enterprises to implement the main responsibility， so as to improve the quality and safety of drugs and ensure the safety of public medication.

ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules（Zhuye Shigaotang） based on fingerprint and determination of index components， and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome. MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography（HPLC）， and the methods for determination of total calcium， orientin， isoorientin， ginsenosides Rg₁， Re and Rb₁ and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group， model group， Zhuye Shigao granules low， medium and high dose groups（9.3， 18.6， 37.2 g·kg^-1·d^-1）， with 10 mice in each group. In addition to the blank group， the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose， while the blank group and model group were given the same volume of normal saline by gavage. Then， the body temperature and organ index of mice in each group were measured， hematoxylin-eosin（HE） staining was used to investigate the lung tissue injury of mice in each group， and enzyme-linked immunosorbent assay（ELISA） was used to detect the changes of tumor necrosis factor-α（TNF-α）， interleukin（IL）-lβ， IL-6， IL-10 levels in serum and lung tissue， as well as immunoglobulin（Ig）A and IgM levels in serum. ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950， and 20 common peaks were calibrated. Seven of them were identified， including peak 11（isoorientin）， peak 12（orientin）， peak 14（apioside liquiritin）， peak 15（liquiritin）， peak 17（apioside isoliquiritin）， peak 19（isoliquiritin） and peak 20（liquiritigenin）. The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows：Total calcium of 9.978-11.294 mg·g^-1， isoorientin of 0.033-0.041 mg·g^-1， orientin of 0.046-0.055 mg·g^-1， ginsenoside Rg₁+ginsenoside Re of 0.748-0.762 mg·g^-1， ginsenoside Rb₁ of 0.151-0.197 mg·g^-1， liquiritin of 1.106-1.366 mg·g^-1， glycyrrhizic acid of 0.904-1.182 mg·g^-1_. Compared with the blank group， the body temperature of mice in the model group was significantly increased， the organ indexes of liver， lung and spleen were significantly decreased， the organ index of thymus was significantly increased， HE staining of lung tissue showed infiltration of inflammatory cells， a small amount of serous exudation was observed in the alveoli， and lung tissue was damaged. After the intervention of Zhuye Shigao granules， the pathological changes were improved compared with the model group. The expression levels of IL-1β， IL-6 and TNF-α were significantly increased， the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased（P<0.01）. Compared with the model group， the body temperature， the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced（P<0.05， P<0.01）. ConclusionIn this study， the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components， and the fingerprint of four herbs（Lophatheri Herba， Ophiopogonis Radix， Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma） in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.

Objective To study the effect of auditory and speech development after cochlear implant(CI)in children with bilateral cochlear nerve deficiency(CND)and its influencing factors.Methods A total of 20 children with bilateral CND were included in the study,of which 5 were implanted bilaterally and 15 unilaterally.CT of the temporal bone showed stenosis of the cochlear aperture in 14 cases and atresia of the cochlear aperture in 6 cases.There were 8 cases accompanied by other inner ear malformations,and 12 cases with no accompanying inner ear mal-formations.MRI of the internal auditory canal showed 1 nerve in 5 cases,2 nerves in 6 cases,3 nerves in 8 cases,and 4 nerves in 1 case.There were 6 cases in which the EABR was not elicited and 14 cases in which it was elicited.The postoperative auditory and speech abilities of the subjects were evaluated using categories of auditory perform-ance(CAP)and speech intelligibility rating(SIR).Results ① The CAP(P＜0.001)and SIR(P＜0.001)scores of the children with stenosis of the cochlea nerve canal were higher than those of the patients with atresia of the cochlea nerve canal.② The more nerve roots in the internal auditory canal,the higher the score of CAP(P=0.003)and SIR(P=0.008).③ CAP score of the children with EABR elicited was higher than that of the children without EABR elicited(P=0.030).The difference in SIR scores was not statistically significant(P=0.14).④The differences in CAP and SIR between those with bilateral CI and unilateral CI,as well as between those with and without other inner ear malformations,were not statistically significant(P＞0.05).Conclusion Children with bi-lateral CND had significant postoperative improvement in auditory function but poor speech development after CI.Postoperative auditory speech ability was related to the condition of the cochlear foramen,the number of nerve roots in the internal auditory canal,and whether or not the EABR was elicited intraoperatively.

Objective To study the effect of auditory and speech development after cochlear implant(CI)in children with bilateral cochlear nerve deficiency(CND)and its influencing factors.Methods A total of 20 children with bilateral CND were included in the study,of which 5 were implanted bilaterally and 15 unilaterally.CT of the temporal bone showed stenosis of the cochlear aperture in 14 cases and atresia of the cochlear aperture in 6 cases.There were 8 cases accompanied by other inner ear malformations,and 12 cases with no accompanying inner ear mal-formations.MRI of the internal auditory canal showed 1 nerve in 5 cases,2 nerves in 6 cases,3 nerves in 8 cases,and 4 nerves in 1 case.There were 6 cases in which the EABR was not elicited and 14 cases in which it was elicited.The postoperative auditory and speech abilities of the subjects were evaluated using categories of auditory perform-ance(CAP)and speech intelligibility rating(SIR).Results ① The CAP(P＜0.001)and SIR(P＜0.001)scores of the children with stenosis of the cochlea nerve canal were higher than those of the patients with atresia of the cochlea nerve canal.② The more nerve roots in the internal auditory canal,the higher the score of CAP(P=0.003)and SIR(P=0.008).③ CAP score of the children with EABR elicited was higher than that of the children without EABR elicited(P=0.030).The difference in SIR scores was not statistically significant(P=0.14).④The differences in CAP and SIR between those with bilateral CI and unilateral CI,as well as between those with and without other inner ear malformations,were not statistically significant(P＞0.05).Conclusion Children with bi-lateral CND had significant postoperative improvement in auditory function but poor speech development after CI.Postoperative auditory speech ability was related to the condition of the cochlear foramen,the number of nerve roots in the internal auditory canal,and whether or not the EABR was elicited intraoperatively.

Objective:To investigate the role of O-GlcNAcylation in the regulation of the stability of receptor for activated C kinase 1(Rack1)during SHH-type medulloblastoma(SHH-MB)initiation.Methods:SHH-MB tumors and adjacent tissues were selected from the clinical tu-mor specimen library of the Department of Pathology at The General Hospital of Western Theater Command.Rack1 expression and O-GlcNAcylation(O-GlcNAc)levels in these tumor tissues were analyzed.The human medulloblastoma cell line Daoy was treated with a glyc-osyltransferase(OGT)inhibitor(OSMI-1)and adeglycosyltransferase(OGA)inhibitor(TM-G),and their impact on tumor cell proliferation was assessed using a Cell Counting Kit-8(CCK-8)and immunofluorescence staining.The O-GlcNAc enzyme labeling system co-immunoprecipita-tion(Co-IP)and Western blot were used to correlate Rack1 protein levels with O-GlcNAc levels.The impact of O-GlcNAcon Rack1 stability was confirmed using cycloheximide(CHX)and ubiquitination modification experiments.In a medulloblastoma mouse model with Rack1 knockdown,tumor cell proliferation was detected using a Cell Counting Kit-8(CCK-8),immunofluorescence staining,and a scratch assay.Xenograft tumors were transplanted into immunodeficient mice and SHH signaling was detected by Western blot in the obtained tissue samples(sh-NC and sh-Rack1)to verify the role of Rack1 protein in SHH-MB.Results:Rack1 and O-GlcNAcylation levels were significantly in-creased in SHH-MB tumor samples,and a negative correlation was observed between Rack1 levels and patient survival rates.Treatment of Daoy cells with OGT and TM-G revealed that O-GlcNAc significantly promotes Daoy cell proliferation,while inhibiting O-GlcNAc impedes tu-mor cell proliferation.Molecular experiments have confirmed that O-GlcNAc modification of Rack1 protein can regulate tumor cell stability,thereby promoting tumor cell proliferation.When Rack1 expression was knocked down in Daoy cells,cell proliferation was significantly re-duced relative to control cells.Accordingly,proliferation was significantly inhibited in tumor tissues with Rack1 protein knockdown in mouse models,suggesting that Rack1 can participate in the initiation of SHH-MB by regulating SHH signaling.Conclusions:O-GlcNAcylation particip-ates in SHH-MB initiation by regulating Rack1 stability.

ObjectiveTo investigate the current status of health literacy among type 2 diabetes mellitus patients in Shanghai communities, to analyze its correlation with glycemic and lipid metabolic indicators and quality of life (QoL), and to provide an evidence for the development of effective intervention measures. MethodsA follow⁃up survey was conducted among diabetic patients diagnosed at hospitals above the secondary level from March to June, 2023, who were part of a diabetes cohort study jointly established by Songnan Community in Baoshan District and the Shanghai Institute of Endocrinology. Patients were assessed using a simplified evaluation form for diabetes-related health literacy and a QoL scale, and metabolic indicators such as blood glucose and blood lipids were measured. Pearson correlation coefficients were employed to assess the relationship between health literacy levels and metabolic indicators as well as QoL. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations between patients’ health literacy levels, metabolic status, and QoL. ResultsAmong the 932 diabetic patients surveyed, the health literacy level was low, with an average score of (65.2±13.4) points of which (62.6±13.8) points for males and (67.9±12.5) points for females. The average QoL score was (44.1±9.2) points of which (44.0±9.5) points for males and (44.2±8.9) points for females. The achievement rates of HbA1c, total cholesterol (TC), and triglycerides (TG) were 51.6%, 30.3%, and 64.8%, respectively. The TC achievement rate among male patients (37.6%) was significantly higher than that among females (22.8%). Significant differences in HbA1c achievement rates were observed across age groups, education levels, disease durations, and BMI levels (P<0.05). Similarly, significant differences were found in FPG achievement rates across different age groups, annual household incomes, disease durations, and family histories (P<0.05). No statistically significant differences were noted in TG and HDL-C achievement rates across all variables (P>0.05). However, LDL-C achievement rates were significantly higher in patients without complications compared to those with complications (P<0.05). Health literacy showed a significant negative correlation with psychological dimension, treatment dimension, and QoL scores (r=-0.14, P<0.05). After adjusting for potential confounding factors, a significant association was found between patients’ health literacy levels and QoL, but not with metabolic indicators. ConclusionThere is a significant correlation between health literacy levels and QoL among diabetic patients in community settings. Further exploration is needed to identify factors influencing patients’ QoL and glycemic and lipid metabolic indicators.

Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, organ shortage is a global problem, which limits further development of organ transplantation. Recent research shows that genetically modified pig may become a realistic alternative source of clinical organ transplantation donor. Xenotransplantation may serve as one of the effective measures to resolve the problem of organ shortage. Since 2021, 2 cases of living xenotransplantation and 6 cases of xenotransplantation in brain death recipients have been performed worldwide, and phase Ⅰ clinical trial of xenotransplantation has been launched, and the results have exceeded expectations. Therefore, in this article, recent clinical trial results of xenotransplantation in living and brain death recipients were retrospectively analyzed, and scientific, technical and ethical issues related to clinical research of xenotransplantation were illustrated, hoping to provide reference for clinical research of xenotransplantation in China and promote the development of xenotransplantation in clinical practice.

Objective To investigate the impact of O-linked β-N-acetylglucosamine(O-GlcNAc)modification levels in the amygdala on stress resilience.Methods A restraint stress model was established in male C57BL/6J mice by confining them for 24 hours,followed by by 7days of rest.Behavioral assays,including the tail suspension test,forced swimming test and fear conditioning test,were conducted.Subsequently,the mice were euthanized,and the hippocampus,cortex,and amygdala were isolated.O-GlcNAc modification levels in these brain regions were assessed using enzyme-linked immunosorbent assay(ELISA).Using stereotaxic brain injection techniques,the O-GlcNAcase(OGA)inhibitor,O-GlcNAc transferase(OGT)inhibitor,and OGA and OGT adeno-associated viruses were administered to regulate O-GlcNAc levels in the amygdala before their effects on stress-related behavior were observed.Results The restraint stress group showed significantly increased anxiety,depressive-like behavior,and impaired memory.Concomitantly,O-GlcNAc levels in the amygdala were significantly decreased post-stress and were negatively correlated with behavioral performance.Mice with higher stress resilience exhibited significantly higher levels of O-GlcNAc in the amygdala than more sensitive ones.Upregulation of O-GlcNAc levels in the amygdala via Thiamet-G or adeno-associated virus-O-GlcNAc transferaseinjections increased O-GlcNAc levels,alleviated depressive-like behavior and enhanced stress resilience.In contrast,downregulation of O-GlcNAc levels through OSMI-1 or adeno-associated virus-O-GlcNAcase injections reduced the O-GlcNAc levels,exacerbated depressive-like behavior and reduced resilience to stress.Conclusion O-GlcNAc modification levels in the amygdala play a critical role in regulating stress resilience following restraint stress in mice.