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 expression levels of serum microRNA-15a(miR-15a),microRNA-195-5p(miR-195-5p),and microRNA-33(miR-33)in pregnant women with gestational diabetes mellitus(GDM)and to explore their associations with maternal and neonatal outcomes.Methods The research subjects were selected from 208 patients with GDM who completed delivery at our hospital between September 2021 and October 2024.Based on maternal pregnancy outcomes,the subjects were categorized into either the poor maternal outcome group or the good maternal outcome group.Similarly,they were classified into the poor perinatal outcome group and the good perinatal outcome group according to perinatal outcomes.Clinical data and serum levels of fasting plasma glucose(FPG),miR-15a,miR-195-5p,and miR-33 were collected and compared between groups with different maternal and perinatal outcomes.Multivariate logistic regression analysis was conducted to identify risk factors associated with adverse maternal and perinatal outcomes among GDM patients.Additionally,the predictive value of these biomarkers for adverse maternal and perinatal outcomes was evaluated using receiver operating characteristic(ROC)curve analysis.Results Among 208 patients with GDM,81 experienced adverse maternal pregnancy outcomes(38.94％).Of the 192 newborns,51 cases were associated with adverse perinatal outcomes,resulting in an incidence rate of 26.56％.Multivariate logistic regression analysis revealed that a high insulin resistance index(OR=2.197),poor glycemic control(OR=2.482),a history of adverse pregnancy or childbirth(OR=2.838),elevated FPG levels(OR=1.910),increased serum expression of miR-15a(OR=1.988),miR-195-5p(OR=2.273),and miR-33(OR=2.479)were independent risk factors for adverse maternal pregnancy outcomes in GDM patients(P<0.05).The area under the receiver operating characteristic curve(AUC)for the combined detection of miR-15a,miR-195-5p,and miR-33 was higher than that of FPG alone in predicting maternal pregnancy outcomes,with the combined detection showing the highest AUC(P<0.05).Similarly,multivariate logistic regression results also indicated that elevated levels of the aforementioned biomarkers—insulin resistance index(OR=2.155),poor glycemic control(OR=2.408),history of adverse pregnancy or childbirth(OR=2.838),FPG(OR=2.018),miR-15a(OR=2.197),miR-195-5p(OR=2.246),and miR-33(OR=3.043)—were independent risk factors for adverse perinatal outcomes in GDM patients(P<0.05).The AUC for combined detection of miR-15a,miR-195-5p,and miR-33 was significantly higher than that of FPG alone in predicting perinatal outcomes,with the combination yielding the highest predictive accuracy(P<0.05).Conclusions Patients with GDM are at increased risk of adverse maternal and perinatal outcomes.Elevated insulin resistance index,poor glycemic control,a history of adverse pregnancy or childbirth,and increased serum levels of miR-15a,miR-195-5p,and miR-33 were identified as independent risk factors for adverse pregnancy outcomes in individuals with gestational diabetes.The individual measurement of miR-15a,miR-195-5p,and miR-33,as well as their combined detection,demonstrated greater predictive value for pregnancy outcomes in GDM patients compared to FPG alone,with the combined detection showing the highest predictive accuracy.

Objective:To investigate the role of adenosine triphosphatase phospholipid transporter 10a(ATP10a)methylation assay in the triage of atypical squamous cell of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesions(LSIL)in cervical cytology.Methods:188 patients with cervical exfolia-ted cells of ASC-US and LSIL were selected,and High-risk human papilloma virus(HR-HPV)typing and cervical biopsy results of the patients were collected at the same time.The cervical biopsy pathology results were used as the gold standard,and they were divided into inflammation,LSIL,high grade squamous intraepithelial lesions(HSIL)and cervical squamous cell carcinoma(SCC).Classify inflammation and LSIL as LSIL-group,HSIL and SCC as HSIL+group to compare the efficacy of ATP10a methylation and HR-HPV testing for diagnosis of HSIL+in this population(including HSIL and SCC).Results:The methylation detection value of ATP10a in the inflam-mation,LSIL,HSIL,and SCC patients were 19.035(16.478,20.823),13.446(5.890,20.674),10.336(4.733,17.336),4.223(1.713,7.754),respectively.The methylation detection value of ATP10a in the LSIL-group was 17.812(10.787,20.686),while that in the HSIL+group was 7.251(3.170,14.194).There was a statistically sig-nificant difference between the groups(Z=-5.824,P＜0.001).The proportion of HR-HPV positivity in the LSIL-group was 70.9％,which was lower than that of the HSIL+group(88.2％),and the difference was statistically significant(Z=-2.887,P=0.004).The specificity,negative predictive value(NPV),and area under the receiver operating characteristic(ROC)curve(AUC)of ATP10A methylation diagnosis of HSIL+(66.0％,79.1％,and 0.747)were higher than those of HR-HPV detection(29.1％,50.7％,0.587).Sensitivity and positive predictive value(PPV)(78.8％and 65.7％)were lower than those of HR-HPV testing(88.2％and 75.0％).when using ATP10a methylation instead of HR-HPV detection for triage of cytological abnormalities(ASC-US,LSIL),the col-poscopy referral rate could be reduced to 54.3％.In the ASC-US population,the AUC(0.683)for the diagnosis of HSIL+by ATP10a methylation test was higher than that of HR-HPV test(0.599),and the difference was statisti-cally significant(P=0.028).In the LSIL population,the AUC(0.828)for the diagnosis of HSIL+by ATP10a methylation test was still higher than that of HR-HPV test(0.563),and the difference was statistically significant(P=0.005).Conclusions:ATP10a methylation levels increased with the severity of cervical lesions,and the di-agnostic efficacy of ATP10a methylation detection for the severity of cervical lesions may not be lower than HR-HPV typing.

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.

Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Objective To investigate the expression levels of serum microRNA-15a(miR-15a),microRNA-195-5p(miR-195-5p),and microRNA-33(miR-33)in pregnant women with gestational diabetes mellitus(GDM)and to explore their associations with maternal and neonatal outcomes.Methods The research subjects were selected from 208 patients with GDM who completed delivery at our hospital between September 2021 and October 2024.Based on maternal pregnancy outcomes,the subjects were categorized into either the poor maternal outcome group or the good maternal outcome group.Similarly,they were classified into the poor perinatal outcome group and the good perinatal outcome group according to perinatal outcomes.Clinical data and serum levels of fasting plasma glucose(FPG),miR-15a,miR-195-5p,and miR-33 were collected and compared between groups with different maternal and perinatal outcomes.Multivariate logistic regression analysis was conducted to identify risk factors associated with adverse maternal and perinatal outcomes among GDM patients.Additionally,the predictive value of these biomarkers for adverse maternal and perinatal outcomes was evaluated using receiver operating characteristic(ROC)curve analysis.Results Among 208 patients with GDM,81 experienced adverse maternal pregnancy outcomes(38.94％).Of the 192 newborns,51 cases were associated with adverse perinatal outcomes,resulting in an incidence rate of 26.56％.Multivariate logistic regression analysis revealed that a high insulin resistance index(OR=2.197),poor glycemic control(OR=2.482),a history of adverse pregnancy or childbirth(OR=2.838),elevated FPG levels(OR=1.910),increased serum expression of miR-15a(OR=1.988),miR-195-5p(OR=2.273),and miR-33(OR=2.479)were independent risk factors for adverse maternal pregnancy outcomes in GDM patients(P<0.05).The area under the receiver operating characteristic curve(AUC)for the combined detection of miR-15a,miR-195-5p,and miR-33 was higher than that of FPG alone in predicting maternal pregnancy outcomes,with the combined detection showing the highest AUC(P<0.05).Similarly,multivariate logistic regression results also indicated that elevated levels of the aforementioned biomarkers—insulin resistance index(OR=2.155),poor glycemic control(OR=2.408),history of adverse pregnancy or childbirth(OR=2.838),FPG(OR=2.018),miR-15a(OR=2.197),miR-195-5p(OR=2.246),and miR-33(OR=3.043)—were independent risk factors for adverse perinatal outcomes in GDM patients(P<0.05).The AUC for combined detection of miR-15a,miR-195-5p,and miR-33 was significantly higher than that of FPG alone in predicting perinatal outcomes,with the combination yielding the highest predictive accuracy(P<0.05).Conclusions Patients with GDM are at increased risk of adverse maternal and perinatal outcomes.Elevated insulin resistance index,poor glycemic control,a history of adverse pregnancy or childbirth,and increased serum levels of miR-15a,miR-195-5p,and miR-33 were identified as independent risk factors for adverse pregnancy outcomes in individuals with gestational diabetes.The individual measurement of miR-15a,miR-195-5p,and miR-33,as well as their combined detection,demonstrated greater predictive value for pregnancy outcomes in GDM patients compared to FPG alone,with the combined detection showing the highest predictive accuracy.

Objective:To investigate the role of adenosine triphosphatase phospholipid transporter 10a(ATP10a)methylation assay in the triage of atypical squamous cell of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesions(LSIL)in cervical cytology.Methods:188 patients with cervical exfolia-ted cells of ASC-US and LSIL were selected,and High-risk human papilloma virus(HR-HPV)typing and cervical biopsy results of the patients were collected at the same time.The cervical biopsy pathology results were used as the gold standard,and they were divided into inflammation,LSIL,high grade squamous intraepithelial lesions(HSIL)and cervical squamous cell carcinoma(SCC).Classify inflammation and LSIL as LSIL-group,HSIL and SCC as HSIL+group to compare the efficacy of ATP10a methylation and HR-HPV testing for diagnosis of HSIL+in this population(including HSIL and SCC).Results:The methylation detection value of ATP10a in the inflam-mation,LSIL,HSIL,and SCC patients were 19.035(16.478,20.823),13.446(5.890,20.674),10.336(4.733,17.336),4.223(1.713,7.754),respectively.The methylation detection value of ATP10a in the LSIL-group was 17.812(10.787,20.686),while that in the HSIL+group was 7.251(3.170,14.194).There was a statistically sig-nificant difference between the groups(Z=-5.824,P＜0.001).The proportion of HR-HPV positivity in the LSIL-group was 70.9％,which was lower than that of the HSIL+group(88.2％),and the difference was statistically significant(Z=-2.887,P=0.004).The specificity,negative predictive value(NPV),and area under the receiver operating characteristic(ROC)curve(AUC)of ATP10A methylation diagnosis of HSIL+(66.0％,79.1％,and 0.747)were higher than those of HR-HPV detection(29.1％,50.7％,0.587).Sensitivity and positive predictive value(PPV)(78.8％and 65.7％)were lower than those of HR-HPV testing(88.2％and 75.0％).when using ATP10a methylation instead of HR-HPV detection for triage of cytological abnormalities(ASC-US,LSIL),the col-poscopy referral rate could be reduced to 54.3％.In the ASC-US population,the AUC(0.683)for the diagnosis of HSIL+by ATP10a methylation test was higher than that of HR-HPV test(0.599),and the difference was statisti-cally significant(P=0.028).In the LSIL population,the AUC(0.828)for the diagnosis of HSIL+by ATP10a methylation test was still higher than that of HR-HPV test(0.563),and the difference was statistically significant(P=0.005).Conclusions:ATP10a methylation levels increased with the severity of cervical lesions,and the di-agnostic efficacy of ATP10a methylation detection for the severity of cervical lesions may not be lower than HR-HPV typing.

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.

Gastric cancer （GC） is one of the most common cancers in the world， with hidden symptoms， complex pathogenesis， high morbidity， high mortality， and poor prognosis. As one of the classical apoptosis pathways， mitochondrial apoptosis has been widely described in the apoptosis escape by GC cells. Mitochondrial apoptosis can regulate the proliferation， invasion， and metastasis of GC cells via oxidative stress， cell cycle， mitochondrial membrane potential， mitochondrial translocation and other mechanisms， and it is one of the potential targets of traditional Chinese medicine （TCM） intervention to restore the mitochondrial function in GC. The theory of spleen-mitochondria in correlation explains that spleen deficiency and cancer toxin are the root causes of mitochondrial apoptosis. Accordingly， the TCM treatment should follow the basic principle of invigorating spleen to restore healthy Qi and removing cancer toxin to eliminate the root cause. Mitochondrial apoptosis can be promoted by inhibiting oxidative stress， promoting cell cycle arrest， and reducing mitochondrial membrane potential. This therapy can improve the energy metabolism， restore the mitochondrial structure and function， and prevent the occurrence and development of GC， with mild side effects and low drug resistance. However， the mechanism of mitochondrial apoptosis in GC and the target of TCM intervention in GC have not been systematically reviewed. Therefore， this paper systematically summarized the effects of mitochondrial apoptosis on the occurrence and development of GC and the role of TCM in the treatment of GC by intervening in mitochondrial apoptosis， aiming to provide a theoretical reference for the treatment and further research of GC.

This study analyzed the outcome index and related design elements of randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） in the treatment of children with tic disorder （TD） in the past ten years， so as to provide a basis for the construction of the core index set of TCM in the treatment of children with TD. Eight databases were searched， including four English databases （PubMed， Web of Science， Embase， and Cochrane Library） and four Chinese databases， including China National Knowledge Infrastructure （CNKI）， Wanfang Database， VIP Database， and China Biology Medicine disc （CBMdisc）， as well as ClinicalTrials.gov and China Clinical Trial Registry. The search time was limited to from January 1， 2013 to October 29， 2023. RCTs on the TD in children treated with TCM were collected. Two researchers independently conducted literature screening， data extraction， and literature quality evaluation and summarized clinical outcome indexes and related trial design elements through qualitative analysis. A total of 67 RCTs were included， including 63 outcome indexes， with a total frequency of 348 times. The related outcome indexes could be divided into six categories： 12 symptom/sign indexes with a frequency of 134 （38.5%）， seven TCM symptom/syndrome indexes with a frequency of 31 （8.9%）， 33 physical and chemical examination indexes with a frequency of 97 （27.9%）， four safety indexes with a frequency of 67 （19.3%）， three long-term prognostic indexes with a frequency of 14 （4.0%）， and one kind of quality-of-life evaluation index （0.3%）. Currently， the RCTs research design of TCM in the treatment of TD in children has not yet formed a unified standard， and there are many problems in the quality of methodology， which reduces the authenticity and reliability of clinical conclusions. There are problems with clinical outcome indexes， such as significant quantity differences， unclear primary and secondary outcome indexes， unreasonable alternative indexes， non-standard TCM syndrome types and TCM evaluation indexes， lack of economic evaluation indexes， and less attention to long-term prognostic indexes and safety indexes. It is suggested that the researchers should design a more rigorous trial scheme and reasonably design the outcome index which is in line with the clinical trial efficacy evaluation of TCM， so as to construct the core index set with the characteristics of TCM for the treatment TD in children.