Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

BACKGROUND:Interleukin-8 is an important cytokine that has been found to play an important role in bone regeneration through multiple pathways. OBJECTIVE:To comprehensively review the action mechanism of interleukin-8 effects on bone regeneration to provide ideas for the following studies on interleukin-8. METHODS:By searching the China National Knowledge Infrastructure database for articles published from January 1999 to February 2023 and PubMed database for articles published from January 1985 to February 2023 reporting the role of interleukin-8 in bone-associated cells and vascularisation.Chinese and English search terms were"interleukin-8,bone repair,bone metabolism,mesenchymal stem cells,osteoblasts,osteoclasts,vascularization".The initial review yielded 508 articles in English and Chinese,and a total of 51 articles were included for review and analysis according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:According to the existing research,interleukin-8 can promote bone cell regeneration and assist bone healing through multiple pathways,which is mainly divided into three aspects:(1)Promote the proliferation and differentiation of bone cells such as mesenchymal stem cells and osteoblasts,and promote the development of cells in the direction of promoting bone healing;(2)interleukin-8 can promote angiogenesis and provide sufficient nutrition and oxygen for bone tissue,thus further improving the quality and stability of bone healing.(3)The appearance of interleukin-8 facilitates the expression of hypoxia-inducible factor-1α,vascular endothelial growth factor,and matrix metalloproteinase,which can create a microenvironment conducive to bone regeneration,thus promoting the regeneration and repair of bone tissue.In summary,interleukin-8 plays an important role in bone healing by promoting osteoblast proliferation and differentiation,facilitating angiogenesis and improving the mechanical properties of bone regeneration,as well as influencing bone metabolism through osteoclasts,mesenchymal stem cells,and other action sites.

Objective To study the expression levels of serum complement C1q/tumor necrosis factor-related protein 6(CTRP6)in women in early pregnancy and to explore its relationship with gestational diabetes mellitus(GDM).Methods Women at the Second Affiliated Hospital of Zhengzhou University from March 2021 to March 2022 were prospectively and consecutively selected from 10 to 13 weeks gestation for outpatient obstetric check-ups.The age,height,weight,and time of last menstruation of pregnant women were collected,and the levels of total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS)and CTRP6 were measured in early pregnancy,and the pre-pregnancy body mass index(BMI),baseline BMI,prenatal BMI,and homeostatic model assessment of insulin resistance(HOMA-IR)were calculated.All pregnant women underwent a 75g oral glucose tolerance test at 24-28 weeks of gestation and were divided into GDM group and normal glucose tolerance(NGT)group according to the test results.The clinical data and laboratory indexes of the two groups in early pregnancy were compared,and the correlation between serum CTRP6 and various indexes in early pregnancy and its relationship with GDM were analyzed.Results A total of 213 maternal cases were enrolled,and 203 cases were completed for follow-up.Among them,52 mothers were diagnosed with GDM,with a GDM prevalence rate of 25.62%.Serum CTRP6,age,pre-pregnancy BMI,baseline BMI,antenatal BMI,TC,LDL,FPG,HbA1c,FINS,and HOMA-IR were higher in GDM group compared to NGT group,with a statistically significant difference(P<0.05).CTRP6 in early pregnancy was positively correlated with age,pre-pregnancy BMI,baseline BMI,prenatal BMI,TG,LDL,FPG,HbA1c,FINS,HOMA-IR,and negatively correlated with HDL(P<0.05).After correcting for age,BMI,glycolipid metabolism index and HOMA-IR,CTRP6 in early pregnancy remained an independent factor in the development of GDM.Conclusion Elevated serum CTRP6 in early pregnancy is associated with GDM and is an independent risk factor for GDM.

This paper systematically analyzed the ancient monographs of acupuncture and moxibustion and comprehensive medical books from pre-Qin to 1911， and extracted the data according to the etiology and pathogenesis， treatment principles and methods， acupoint selection， needling and moxibustion， and taboos of needling and moxibustion. The pathogenesis of migraine in ancient books and documents is summarized as "the causes are diverse， and phlegm-dampness is the majority". For treatment， the features include "needling has a sequence， and the root and the branch should be treated separately" and "focusing on tonifying deficiency and drain excess". It is also obtained of the rich ideas of acupoints selection， extensive application records of moxibustion， unique application of bloodletting therapy and clear explanation of acupuncture and moxibustion taboos. All mentioned above is expected to enrich the ideas and methods of modern migraine treatment and improve the clinical effects.

Objective To analyze the effect of neurofeedback training based on early start Denver model(ESDM)on children with autism spectrum disorder(ASD). Methods From August,2020 to May,2024,a total of 60 children with ASD from Hangzhou Children's Hospital were randomly divided into control group(n=30)and observation group(n=30).The control group received ESDM intervention,while the observation group received neurofeedback training in addition,for six months.They were assessed with Autism Treatment Evaluation Checklist(ATEC)and Psycho-Educational Profile-3rd Edition(PEP-3). Results After treatment,the score of ATEC was lower in the observation group than in the control group(t=3.545,P<0.05),the scores of cognition(t=2.236,P=0.029),emotional expression(t=2.293,P=0.025)and problem be-havior(Z=2.099,P=0.036)were higher in the observation group than in the control group.The score differenc-es of ATEC(Z=3.620,P<0.001),and cognition(Z=2.920,P<0.05)and problem behaviors(Z=4.209,P<0.05)of PEP-3 before and after intervention were higher in the observation group than in the control group. Conclusion Combination of neurofeedback training could improve the effect of ESDM on ASD.

Objective To investigate the clinical significance of the expression of antioxidant 1 copper chaperone protein(ATOX1)in hepatocellular carcinoma(HCC)and its relationship with tumor proliferation,migration and invasion.Methods The expression of ATOX1 mRNA in HCC cancer tissue and normal liver tissue was analyzed using the Human Genome Atlas database.Immunohistochemical experiment was used to detect the expression of ATOX1 in 15 cases of HCC cancer tissue and adjacent tissue.Human HCC cell lines Hep3B and HepG2 were divided into the control group(NC),the ATOX1 knockdown group 1(si-ATOX1#1)and the ATOX1 knockdown group 2(si-ATOX1#2).The effects of ATOX1 knockdown on the malignant biological behavior of HCC cells were observed through CCK-8 cell proliferation experiment,scratch experiment and Transwell invasion experiments.A nude mouse xenograft tumor model was constructed to analyze the effect of ATOX1 knockdown on the quality and volume of transplanted tumors.Western blot assay was used to detect the relationship between ATOX1 and JAK2/STAT3 pathway protein expression.Results Bioinformatics analysis showed that expression of ATOX1 mRNA in HCC cancer tissue was higher than that in adjacent normal tissue(P＜0.05).The immunohistochemical staining results showed that the positive rate of ATOX1 protein was higher in HCC cancer tissue than that in adjacent tissue(93.33%vs.13.33%,P＜0.01).In vitro experimental results showed that siRNA knockdown of ATOX1 protein expression in Hep3B and HepG2 cells significantly reduced the proliferation,migration and invasion abilities of cancer cells(P＜0.05).In vivo experiments in mice showed that the volume and weight of subcutaneous xenograft tumors were significantly smaller in the sh-ATOX1 group than those in the sh-con group(P＜0.05).The expression levels of JAK2/STAT3 pathway-related proteins p-JAK2,p-STAT3,CyclinD1 and MMP2 were significantly lower in the subcutaneous transplanted tumor tissue of the sh-ATOX1 group than that of the sh-con group(P＜0.05).Conclusion ATOX1 can promote the proliferation,migration and invasion of HCC through JAK2/STAT3 pathway,which can potentially become a potential tumor marker and therapeutic target.

Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell(ADMSC)exosomes(Exo)on adverse ventricular remodeling after myocardial infarction(MI).Methods The chan-ges of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed.MI rats were in-jected with an equal volume of normal saline,adipose derived mesenchymal stem cell exosomes(MSC-Exo)or fibroblast exosomes(MEF-Exo)via a tail vein.The expression of autophagy related 16 like protein 1(ATG16L1),autophagy re-lated protein 7(ATG7)and NOD-like receptor protein 3(NLRP3),inflammatory response,the degree of myocardial fi-brosis,and the cardiac function were observed in different groups.Results After treatment with H2O2 on cardiac fi-broblasts,the expressions of ATG16L1 and ATG7 were significantly decreased(P＜0.001),NLRP3 was significantly in-creased(P＜0.001),and the levels of inflammatory cytokines interleukin-1β(IL-1β)and IL-18 were significantly elevated(P＜0.001).After MI rats were intervened with MSC-Exo,the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated(P＜0.001),NLRP3 was significantly down-regulated(P＜0.001),serum IL-1β and IL-18 levels were significantly decreased(P＜0.001),fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced(P＜0.001),myocardial fibrosis was significantly relieved(P＜0.001),and cardiac function was sig-nificantly improved(P＜0.001).Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.

Objective:To investigate the effects of Apelin-13 regulatory peptide on neuronal cell pyroptosis in mice modeled with cerebral ischemia-reperfusion(I/R).Methods:We prepared a mouse cerebral I/R model using middle cerebral artery embolization and Reperfusion(MCAO/R).The HT22 cell injury model was prepared by the oxygen glu-cose deprivation/reoxygenation(OGD/R),and Apelin-13 treatment was also given.Neurological function was assessed by neurological deficit score;hematoxylin-eosin(HE)staining and Nissl staining were used to observe the morphologic changes of the infarcted area of the mice;and 2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;The expression of NOD-like receptor thermoprotein structural domain-related protein 3(NLRP3),gasdermin D(GSDMD),caspase-1,apoptosis-associated speck-like protein(ASC),interleukin 1β(IL-1β),and interleukin 18(IL-18)in brain tissues from infarcted areas or HT22 cells was detected by Western Blot,and IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA)in serum of mice and culture supema-tants;The cell viability and cell damage of HT22 were detected by CCK-8 kit and lactate dehydrogenase(LDH)assay kit,respectively;caspase-1 activity was measured by caspase-1 activity kit in HT22 cells;and the expression of caspase-1 and GSDMD was observed by immunofluorescence staining in HT22 cells.Results:Apelin-13 significantly improved neurological function and cerebral infarct volume in I/R mice,and attenuated pathological damage in the in-farcted area.It also reduced the serum levels of IL-1β and IL-18.In addition,Apelin-13 reduced the expression of mol-ecules such as NLRP3,GSDMD,caspase-1,IL-1β,and IL-18 in the cerebral infarct area of mice.In vitro experiments showed that Apelin-13 significantly increased the viability of OGD/R-treated HT22 cells,decreased caspase-1 activity,and reduced the LDH content,as well as decreased the expression of molecules such as NLRP3,GSDMD,caspase-1,IL-1β,IL-18,and so on,in OGD/R-treated HT22 cells.Conclusion:Apelin-13 inhibits pyroptosis through the NL-RP3/caspase-1/GSDMD pathway in cerebral ischemia/reperfusion mice and thus exerts neuroprotective effects.

Objective:To study the differentially expressed genes (DEG) during the differentiation of human induced pluripotent stem cells (hiPSC) and human embryonic stem cells (hESC) into pericytes and endothelial cells, and to identify key molecules and signaling pathways that may regulate this differentiation process.Methods:hiPSC and hESC were selected and expanded using mTeSR medium. A "two-step method" was used to induce the differentiation of hiPSC and hESC into pericytes and endothelial cells. Pericytes were identified using immunofluorescence staining, while endothelial cells were isolated and identified using flow cytometry. Total RNA samples were extracted on days 0, 4, 7, and 10 of differentiation and consistently significant DEGs were screened. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis were performed on the screened DEGs.Results:Both hiPSCs and hESCs successfully differentiated into pericytes and endothelial cells under induction conditions. Transcriptome sequencing results showed that with the extension of differentiation time, the DEGs in hiPSCs and hESCs were significantly upregulated or downregulated, following a generally consistent trend. During the differentiation process, marker genes for pericytes and endothelial cells were significantly upregulated. A total of 491 persistent DEGs were detected in both hiPSC and hESC, with 164 unique to hiPSCs and 335 to hESCs, while 8 DEGs were co-expressed in both cell lines. Among these, SLC30A3, LCK, TNFRSF8, PRDM14, and GLB1L3 showed sustained downregulation, whereas CLEC18C, CLEC18B, and F2RL2 exhibited sustained upregulation. GO enrichment analysis revealed that DEGs with sustained upregulation were primarily enriched in terms related to neurogenesis, differentiation, and developmental proteins, while DEGs with sustained downregulation were enriched in terms related to membrane structure and phospholipid metabolic processes. KEGG pathway analysis showed that upregulated genes were primarily enriched in cancer-related pathways, pluripotency regulatory pathways, the Wnt signaling pathway, and the Hippo signaling pathway, whereas downregulated genes were predominantly enriched in metabolism-related pathways. Conclusions:During the differentiation of hiPSC and hESC into pericytes and endothelial cells, 8 DEGs exhibit sustained specific expression changes. These changes may promote pericyte and endothelial cell differentiation by activating the Wnt and Hippo pathways, inhibiting metabolic pathways, releasing the maintenance of stem cell pluripotency, affecting the cell cycle, and inhibiting cell proliferation.

Objective To explore the relationship between C1q tumor necrosis factor related protein 13(CTRP13)and gestational diabetes mellitus(GDM),and the predictive value of CTRP13 for adverse pregnancy outcomes in GDM patients.Methods A total of 163 pregnant women who underwent prenatal examination in the Second Affiliated Hospital of Zhengzhou University from January to May 2023 were enrolled in GDM group(n=83)and normal glucose tolerance(NGT)group(n=80)according to the results of oral glucose tolerance test at 24-28 weeks of gestation.Collect general information,biochemical data,and adverse pregnancy outcomes from two groups of subjects.Analyze the correlation between serum CTRP13 and glucose and lipid metabolism indicators in GDM pregnant women.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of CTRP13 for adverse pregnancy outcomes in GDM pregnant women.Results The pre pregnancy body mass index,prenatal body mass index,triglycerides,total cholesterol,low density lipoprotein,fasting blood glucose,2-hours plasma glucose,glycosylated hemoglobin,fasting insulin,and homeostasis model assessment of insulin resistanc index in GDM group was significantly higher than those in NGT group,while CTRP13 was significantly lower than that in NGT group(P＜0.05).Serum CTRP13 was negatively correlated with total cholesterol,triglycerides,low density lipoprotein,2-hours plasma glucose,and glycosylated hemoglobin in GDM patients(P＜0.05).The incidence of adverse pregnancy outcomes such as gestational hypertension and premature rupture of membranes in GDM group were significantly higher than those in NGT group(P＜0.05).The area under the curve of serum CTRP13 for predicting adverse pregnancy outcomes in GDM pregnant women was 0.805,with sensitivity and specificity of 75.80％and 76.00％,respectively.Conclusion Serum CTRP13 is associated with glucose and lipid metabolism in GDM pregnant women,and is a potential biomarker for predicting adverse pregnancy outcomes in GDM pregnant women.