Objective:To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins(WTAP)on the cell biological properties of esophageal squamous cell carcinoma(ESCC)cells.Methods:31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected.The esophageal cancer cells KYSE30,KYSE410,KYSE150,KYSE510,TE-1,and normal human esophageal epithelial cells HET-1A were routinely cultured.Transfection reagents were used to transfect si-NC,si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells.The cells were divided into si-NC,si-WTAP#1 and si-WTAP#2 groups.The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay.CCK-8 assay,clone formation assay,and scratch healing assay,Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation,migration,invasion and apoptosis.WB assay was used to detect the expressions of WTAP,MAP3K9,EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP;immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues,immunoprecipitation of methylated RNA(MeRIP)-qPCR assay to detect the level of MAP3K9 m6A in ESCC cells,actinomycin D assay to detect the stability of mRNA of MAP3K9,and database data to analyze the expression,target genes,functional enrichment,and interacting RNA of WTAP.Results:WTAP was highly expressed in ESCC tissues and cells(P<0.05 or P<0.01 or P<0.001)and correlated with the degree of differentiation(P<0.01);the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells(P<0.01 or P<0.001);the knockdown of WTAP significantly inhibited the proliferation,migration and invasion of KYSE150 and KYSE510 cells(P<0.05 or P<0.01 or P<0.001),and promoted the apoptosis of KYSE150 and KYSE510 cells(P<0.05 or P<0.01).Knockdown of WTAP resulted in a significant decrease in the m6A level of MAP3K9(P<0.05),and its mRNA expression level and mRNA stability were both significantly reduced(P<0.05).Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway;the expression levels of MAP3K9,p-ERK,N-cadherin,and MMP9 were significantly reduced(P<0.05 or P<0.01),and the expression level of E-cadherin was significantly elevated(P<0.05 or P<0.01)in the KYSE150 and KYSE510 cells after knockdown of WTAP.Conclusions:WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation.It promotes the stability of MAP3K9 mRNA through m6A modification,activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.

Objective:To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins(WTAP)on the cell biological properties of esophageal squamous cell carcinoma(ESCC)cells.Methods:31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected.The esophageal cancer cells KYSE30,KYSE410,KYSE150,KYSE510,TE-1,and normal human esophageal epithelial cells HET-1A were routinely cultured.Transfection reagents were used to transfect si-NC,si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells.The cells were divided into si-NC,si-WTAP#1 and si-WTAP#2 groups.The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay.CCK-8 assay,clone formation assay,and scratch healing assay,Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation,migration,invasion and apoptosis.WB assay was used to detect the expressions of WTAP,MAP3K9,EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP;immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues,immunoprecipitation of methylated RNA(MeRIP)-qPCR assay to detect the level of MAP3K9 m6A in ESCC cells,actinomycin D assay to detect the stability of mRNA of MAP3K9,and database data to analyze the expression,target genes,functional enrichment,and interacting RNA of WTAP.Results:WTAP was highly expressed in ESCC tissues and cells(P<0.05 or P<0.01 or P<0.001)and correlated with the degree of differentiation(P<0.01);the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells(P<0.01 or P<0.001);the knockdown of WTAP significantly inhibited the proliferation,migration and invasion of KYSE150 and KYSE510 cells(P<0.05 or P<0.01 or P<0.001),and promoted the apoptosis of KYSE150 and KYSE510 cells(P<0.05 or P<0.01).Knockdown of WTAP resulted in a significant decrease in the m6A level of MAP3K9(P<0.05),and its mRNA expression level and mRNA stability were both significantly reduced(P<0.05).Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway;the expression levels of MAP3K9,p-ERK,N-cadherin,and MMP9 were significantly reduced(P<0.05 or P<0.01),and the expression level of E-cadherin was significantly elevated(P<0.05 or P<0.01)in the KYSE150 and KYSE510 cells after knockdown of WTAP.Conclusions:WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation.It promotes the stability of MAP3K9 mRNA through m6A modification,activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.

AIM:To understand the efficacy and safety of amikacin(AMK)for the treatment of car-bapenem-resistant Klebsiella pneumoniae pneu-moniae(CRKP)in preterm infants and to establish a management process for the use of amikacin in preterm infants.METHODS:CRKP-infected preterm infants treated with amikacin between January 2019 and December 2021 were retrospectively ana-lyzed,and parametric data paired t-tests were used to assess the efficacy and safety of amikacin for the included infectious and safety indicators,and to es-tablish a management process for amikacin use in preterm infants.RESULTS:Eight cases of CRKP in-fection were included,with the main diagnosis of pneumonia and sepsis.eight preterm infants were screened for the AMK ototoxicity gene mitochon-drial gene MT-RNR1(MT-RNR1 1494C＞T and MT-RNR11555A＞G)before amikacin treatment,and none of them were found to have the gene variant.after receiving amikacin sulphate injection treat-ment for 7 days,the indicators of infectivity were improved,and was statistically significant(P＜0.01).No clinical ototoxicity or nephrotoxicity was ob-served in the children before or after treatment.CONCLUSION:Aminoglycosides are still the main antibiotics used for the empirical treatment of sus-pected infections in preterm infants,especially drug-resistant bacterial infections.Despite the risk of ototoxicity and nephrotoxicity,we provide man-agement procedures and recommendations for neonatal treatment with amikacin to reduce the risk of ototoxicity and nephrotoxicity in AMK.

AIM:To understand the efficacy and safety of amikacin(AMK)for the treatment of car-bapenem-resistant Klebsiella pneumoniae pneu-moniae(CRKP)in preterm infants and to establish a management process for the use of amikacin in preterm infants.METHODS:CRKP-infected preterm infants treated with amikacin between January 2019 and December 2021 were retrospectively ana-lyzed,and parametric data paired t-tests were used to assess the efficacy and safety of amikacin for the included infectious and safety indicators,and to es-tablish a management process for amikacin use in preterm infants.RESULTS:Eight cases of CRKP in-fection were included,with the main diagnosis of pneumonia and sepsis.eight preterm infants were screened for the AMK ototoxicity gene mitochon-drial gene MT-RNR1(MT-RNR1 1494C＞T and MT-RNR11555A＞G)before amikacin treatment,and none of them were found to have the gene variant.after receiving amikacin sulphate injection treat-ment for 7 days,the indicators of infectivity were improved,and was statistically significant(P＜0.01).No clinical ototoxicity or nephrotoxicity was ob-served in the children before or after treatment.CONCLUSION:Aminoglycosides are still the main antibiotics used for the empirical treatment of sus-pected infections in preterm infants,especially drug-resistant bacterial infections.Despite the risk of ototoxicity and nephrotoxicity,we provide man-agement procedures and recommendations for neonatal treatment with amikacin to reduce the risk of ototoxicity and nephrotoxicity in AMK.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective To investigate the mechanism of anti-epileptic effect of the curcumin .Methods The SD rats were injected intraperitoneally with pentylenetetrazol kindling 25 .0 mg/kg to induce a rat epilepsy model .All of the treatments were performed once a day continuously for 28 days .The rats in blank group and model group received 5 ml of normal saline .The rats in the high and low curcumin group were given 200 mg/kg and 100 mg/kg of curcumin once a day ,respectively .The rats in the sodium valproate (VPA) group were given 400 mg/kg of VPA once a day by gavage .After treatment ,the seizures level was recorded by using the Racine′s six point grading scale ,and the expression of IL-2 and IL-6 of hippocampus were detected by the enzyme linked immunoassay (ELISA) .Results The seizures level was reduced by curcumin in epileptic rats .The ex-pressions of IL-2 and IL-6 of the model group were significantly higher than those of the blank group (P<0 .05) ,while those rats of the anti-epileptic groups ,including high dose group and low dose group ,were lower than those rats of the model group (P<0 .05) .When compared with the curcumin low dose group ,the expression of IL-2 and IL-6 of curcumin high dose group is lower (P< 0 .05) .There was no significant difference between the high dose curcumin group and VPA group (P>0 .05) . Conclusion The curcumin can reduce the seizure level in rats ,it shows some anti-epileptic effets and dose-dependently ,which may be through down-regulating the expression of IL-2 and IL-6 in hippocampus .

Objective To observe the effect of hot compress with medicinal salt pack in preventing PICC-associated mechanical phlebitis.Method Totally 200 inpatients undergone PICC intubation were randomized into a treatment group and a control group, 100 cases in each group. After PICC intubation, the treatment group was intervened by hot compress with medicinal salt pack, while the control group was by hot compress with warm wet towel. The occurrence of mechanical phlebitis was observed at different time points and compared between the two groups. Result The occurrence rate of mechanical phlebitis was 9.0% in the treatment group versus 26.0% in the control group, and the difference was statistically significant (P<0.05). In the treatment group, the occurrence rate of mechanical phlebitis was respectively 6.0% and 3.0% when treatment≤72 h and>72 h, versus 16.0% and 10.0% in the control group, and the differences were statistically significant (P<0.05). Conclusion Hot compress with medicinal salt pack can effectively reduce the occurrence of PICC-associated mechanical phlebitis.