Objective To study the expression of N6-methyladenosine(m6A)methyltransferase-like protein 16(METTL16),Ankyrin repeat and SOCS box containing protein 4(ASB13)in elderly breast cancer tissues and their relationship with clinicopathological features and prognosis.Methods 124 elderly patients with breast cancer diagnosed and treated in the Zibo 148 Hospital from January 2019 to January 2021 were selected.Immunohistochemistry(IHC)was used to detect the expression of METTL16 and ASB13 proteins in tissues.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression of METTL16 mRNA and ASB13 mRNA in tissues.Pearson correlation was used for correlation analysis.Survival analysis used Kaplan-Meier curves and Log Rank tests to compare the prognostic differences among patients with different METTL16 and ASB13 expression levels.COX regression analysis was used to analyze the prognostic factors of elderly patients with breast cancer.Results The positive rate of METTL16 in cancer tissue(70.97%)was higher than that in adjacent tissues(8.06%),while the positive rate of ASB13(22.58%)was lower than that in adjacent tissues(72.58%),the differences were statistically significant(χ2=102.642,62.146,all P<0.001).METTL16 mRNA,Snail mRNA and N-cadherin(N-cd)mRNA were higher in cancer tissues than in adjacent tissues,while ASB13 mRNA was lower in adjacent tissues,the differences were statistically significant(t=40.498～48.624,all P<0.001).METTL16 mRNA was positively correlated with Snail mRNA and N-cd mRNA in cancer tissue(r=0.712,0.669,all P<0.001),while ASB13 mRNA was negatively correlated with Snail mRNA and N-cd mRNA(r=-0.734,-0.759,all P<0.001).Compared with TNM stage Ⅰ-Ⅱ and patients with high to medium differentiation,patients with TNM stage Ⅲ and low differentiation had higher positive rate of METTL16 in cancer tissue and lower positive rate of ASB13,the differences were statistically significant(χ2=5.340～10.370,all P<0.05).The 3-year progression free survival rate(73.86%)of the METTL16 positive group was lower than that of the METTL16 negative group(88.89%),the 3-year progression free survival rate(92.86%)of the ASB13 positive group was higher than that of the ASB13 negative group(73.96%),and the differences were statistically significant(Log Rank χ2=4.483,4.882,all P<0.005).METTL16 positive,TNM stage Ⅲ,poor differentiation were risk factors affecting the prognosis of elderly breast cancer,and ASB13 positive was protective factors(Wald χ2=5.056～9.267,all P<0.001).Conclusion METTL16 expression is up-regulated and ASB13 expression is down-regulated in elderly breast cancer,both of which are related to the expression of invasion and metastasis genes,and are new prognostic markers for elderly breast cancer.

Objective To study the expression of N6-methyladenosine(m6A)methyltransferase-like protein 16(METTL16),Ankyrin repeat and SOCS box containing protein 4(ASB13)in elderly breast cancer tissues and their relationship with clinicopathological features and prognosis.Methods 124 elderly patients with breast cancer diagnosed and treated in the Zibo 148 Hospital from January 2019 to January 2021 were selected.Immunohistochemistry(IHC)was used to detect the expression of METTL16 and ASB13 proteins in tissues.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression of METTL16 mRNA and ASB13 mRNA in tissues.Pearson correlation was used for correlation analysis.Survival analysis used Kaplan-Meier curves and Log Rank tests to compare the prognostic differences among patients with different METTL16 and ASB13 expression levels.COX regression analysis was used to analyze the prognostic factors of elderly patients with breast cancer.Results The positive rate of METTL16 in cancer tissue(70.97%)was higher than that in adjacent tissues(8.06%),while the positive rate of ASB13(22.58%)was lower than that in adjacent tissues(72.58%),the differences were statistically significant(χ2=102.642,62.146,all P<0.001).METTL16 mRNA,Snail mRNA and N-cadherin(N-cd)mRNA were higher in cancer tissues than in adjacent tissues,while ASB13 mRNA was lower in adjacent tissues,the differences were statistically significant(t=40.498～48.624,all P<0.001).METTL16 mRNA was positively correlated with Snail mRNA and N-cd mRNA in cancer tissue(r=0.712,0.669,all P<0.001),while ASB13 mRNA was negatively correlated with Snail mRNA and N-cd mRNA(r=-0.734,-0.759,all P<0.001).Compared with TNM stage Ⅰ-Ⅱ and patients with high to medium differentiation,patients with TNM stage Ⅲ and low differentiation had higher positive rate of METTL16 in cancer tissue and lower positive rate of ASB13,the differences were statistically significant(χ2=5.340～10.370,all P<0.05).The 3-year progression free survival rate(73.86%)of the METTL16 positive group was lower than that of the METTL16 negative group(88.89%),the 3-year progression free survival rate(92.86%)of the ASB13 positive group was higher than that of the ASB13 negative group(73.96%),and the differences were statistically significant(Log Rank χ2=4.483,4.882,all P<0.005).METTL16 positive,TNM stage Ⅲ,poor differentiation were risk factors affecting the prognosis of elderly breast cancer,and ASB13 positive was protective factors(Wald χ2=5.056～9.267,all P<0.001).Conclusion METTL16 expression is up-regulated and ASB13 expression is down-regulated in elderly breast cancer,both of which are related to the expression of invasion and metastasis genes,and are new prognostic markers for elderly breast cancer.

Eighty patients(American Society of AnesthesiologistsⅠ-Ⅱ)scheduled for elective unilateral inguinal hernia surgery with spinal anesthesia between January and June 2016 were randomized into two groups with 40 in each group.Patients were intravenously injected with normal saline (5 ml) in control group or hydromorphone 5 μg/kg (diluted to 5 ml) in intervention group after spinal anesthesia.Tympanic temperature and the incidence of shrivering were measured before and after spinal anesthesia at predetermined intervals.Side effects during surgery and the first 48 h after surgery were recorded.Rescue drug tramadol 0.5 mg/kg was given intravenously to patients with grade ≥2 shivering for more than 5 min duration.Tympanic temperature decreased significantly compared to the baseline from 20 min in control group and from 10 min in intervention group after spinal blocking(P<0.05),while there were no significant differences in tympanic temperature at the same time points between two groups(P>0.05).The incidence of shivering was significantly lower in intervention group [17.5%(7/40)] than that in control group [47.5%(19/40),χ2=8.205,P=0.004].The incidence of nausea and vomiting was 5.0%(2/40)in intervention group and 0.0% (0/40) in control group (χ2=2.051,P=0.494).The incidence of sedation was not significantly different between control group [0.0%(0/40)] and intervention group[10.0%(4/10),χ2=4.211,P=0.116].The use of rescue tramadol was more frequently in control group [32.5%(13/40)] than that in intervention group [7.5%(3/40),χ2=7.812,P=0.01].The results indicate that intravenous hydromorphone can significantly attenuate the incidence of shivering after spinal anesthesia for inguinal herniorrhaphy repair surgery with minimum side effects.

CYP2D6 genetic polymorphism results in individual difference of therapeutic effect and adverse reaction of related drugs this article made an overview for that.

Objective:To explore therapeutic effect of bisoprolol with CYP2D6 and CYP3A4 gene targeting therapy for hypertension .Methods :A total of 100 cases with essential hypertension (EH) were selected ,among them 20 ca-ses were randomly chosen to receive routine medication (bisoprolol 5 mg/d ,routine treatment group ) ,the other 80 patients were equally divided into group A (CYP2D6*10) and group B (CYP3A4*1G) .According to detection results of CYP2D6*10 and CYP3A4*1G gene polymorphism ,they were dived into group ACC (n=13) ,group ACT (n=14) ,group ATT (n=10) ,group BCC (n=21) ,group BCT (n=17) and group BTT (n=0) .Bisoprolol dosage was adjusted according to genotypes :group ACC and group BCC received 10 mg/d ,group ACT and group BCT received 5 mg/d ,group ATT and group BTT received 2.5 mg/d .Blood drug concentration ,blood pressure and heart rate were compared among above groups after two weeks .Relationship between plasma concentration of bisoprolol and gene polymorphism of drug metabolism enzyme was evaluated .Results:Comparison between related groups with same bi-soprolol dosage :there were no significant difference in blood drug concentration ,heart rate and blood pressure be-tween ACT and routine treatment group , P>0.05 all;compared with routine treatment group ,there was significant rise in blood drug concentration [ (33.5 ± 19.1) ng/ml vs .(50.13 ± 23.21) ng/ml] ,significant reduction in heart rate [ (71.4 ± 5.16) times/min vs .(66.5 ± 6.04) times/min] and blood pressure [ (127.22 ± 10.44/82.4 ± 7.27) mmHg vs .(119.48 ± 11.97/71.2 ± 10.30) mmHg] in BCT group , P<0.05 all .Conclusion:Because gene possesses polymorphism ,therapeutic effect of bisoprolol treating hypertension is differing ;the gene targeting therapy may significantly improve therapeutic effect for hypertension .

Objective: To study the relationship between CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension. Methods: A total of 60 patients with essential hypertension (EH) received metoprolol 47.5mg/d for 3d. After 3d the plasma metoprolol concentration after oral 2h was measured. Polymorphism of CYP2D6*10 gene was detected by PCR-RFLP. According to results of gene detection, the patients were divided into CC genotype group (wild type homozygote, fast metabolism type, n=14), CT genotype group (heterozygous mutation, intermediate metabolism type, n=25) and TT genotype group (homozygous mutation, slow metabolism, n=19). Metoprolol dosage was adjusted according to CYP2D6*10 genotype. After one week, plasma concentration of metoprolol after oral 2h was measured again, and mean heart rate and blood pressure were measured before and after gene-directed therapy. Results: Before gene-directed therapy, compared with CC and CT group there was significant increase in plasma concentration of metoprolol [(26.57±19.40) ng/ml vs. (23.88±12.86) ng/ml vs. (64.74±32.94) ng/ml, P<0.01] in TT group; compared with TT group, there were significant rise in mean systolic blood pressure [mSBP, (132.84±13.40) mmHg vs. (144.14±14.28) mmHg], mean diastolic blood pressure [mDBP, (76.95±9.07) mmHg vs. (81.36±7.33) mmHg] and mean heart rate [mHR, (69.13±11.83) times/min vs. (76.66±7.33) times/min] in CC group, P<0.05 all. After gene-directed therapy, there were no significant difference in plasma concentration of metoprolol, mSBP, mDBP and mHR among all groups, P>0.05 all; Compared with before gene-directed therapy, there was significant increase in plasma concentration of metoprolol, and significant decrease in mSBP, mDBP and mHR in CC group (P<0.05). There were no significant difference in blood pressure and heart rate between before and after treatment in CT group and TT group (P>0.05). Conclusion: CYP2D6*10 gene polymorphism affects metoprolol metabolism and its therapeutic effect on hypertension, gene-directed therapy can significantly improve drug therapeutic effect and reach ideal therapeutic goal in short time.