Uremic pruritus is one of the skin complications that perplex patients with end-stage renal disease undergoing hemodialysis or peritoneal dialysis. Because the specific pathogenesis is not clear, there is no unified treatment plan in the world. In August 2021, the US Food and Drug Administration approved the use of difelikefalin (under the trade name Korsuva) for the treatment of moderate to severe pruritus associated with chronic kidney disease in adult patients undergoing hemodialysis. Studies have shown that difelikefalin can remarkably reduce the intensity of pruritus and improve sleep and pruritus-related quality of life. The recommended dose of difelikefalin is 0.5 μg/kg, and difelikefalin is well tolerated and has high safety. This paper reviews the pharmacological effects, pharmacokinetics, clinical efficacy and safety of difelikefalin.

Objective To investigate the correlation between vitamin A,E,D and folic acid levels and concomitant preeclampsia(PE)in patients with gestational diabetes mellitus(GDM).Methods A total of 108 patients with GDM complicated with PE were used as the PE group,and another 108 GDM patients without PE were used as the GDM group.A total of 108 normal pregnant women with normal pregnancy test were used as the normal control group.The general information and vitamin A,E,D and folic acid levels were compared between the three groups.According to the severity of the disease,the PE group was subdivided into the mild-moderate PE group(62 cases)and the severe PE group(46 cases),and vitamin A,E,D and folic acid levels were compared between these two groups.Results Systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),fasting insulin(FINS)were increased in turn in the normal control group,the GDM group and the PE groups(P＜0.05),and vitamins A,E,D and folic acid levels were decreased in turn(P＜0.05).Triglyceride,total cholesterol and glycated haemoglobin were higher in the PE group than those in the GDM group and the normal control,and high density lipoprotein(HDL)cholesterol was lower than that in the GDM group and the normal control group(P＜0.05).Vitamin A,vitamin E,vitamin D and folic acid levels were lower in the severe PE group than those in the mild to moderate PE group(P＜0.05).Higher levels of vitamin A,vitamin E,vitamin D and folate were protective factors for GDM patients with severe PE.Folic acid showed higher predictive efficacy and specificity in single indicator analysis.Vitamin A showed high predictive specificity.The combined prediction of four indicators for severe PE in GDM patients was more effective than each individual indicator.Conclusion Serum vitamin A,E,D and folate levels are significantly lower in patients with GDM complicated with PE,and the combination of all four may improve the predictive value of severe PE complicated with GDM.

OBJECTIVETo investigate the expression of TMEMl6A in the colon of intractable functional constipation patients and its clinical implications.

METHODSA total of 30 patients with intractable chronic functional constipation were selected as trial group (full thickness tissue of sigmoid colon), 30 patients with colon cancer as control group (distant tissues at least 5 cm away from cancer). Tissues from two groups were collected in our hospital from February 2012 to June 2014 and confirmed by pathological diagnosis. Immunofluorescence staining, RT-PCR and Western blot were performed to detect the mRNA and protein expression of TMEM16A and c-kit in colon.

RESULTSTMEM16A and c-kit protein expressions were observed in similar sites of colon tissues in two groups. Expressions of TMEM16A and C-kit in colon tissues detected by immunofluorescence, RT-PCR, and Western blotting were significantly lower in trial group than those in control group (TMEM16A: mean A 1.84±0.25 vs. 3.65±0.32, P<0.05, gray intensity ratio 0.66±0.07 vs. 1.04±0.17, P<0.05, relative mRNA 0.41±0.05 vs. 1.00, P<0.05; c-kit: mean A 3.38±0.24 vs. 5.06±0.31, gray intensity ratio 0.64±0.06 vs. 0.98±0.09, relative mRNA 0.18±0.08 vs. 1.00, all P<0.05).

CONCLUSIONSTMEM16A expression in colon tissues of intractable functional constipation patients is significantly lower and may adjust the movement of colonic smooth muscle by regulating the c-kit expression. TMEMl6A may be used as a new candidate target for diagnosis and treatment of intractable functional constipation.

Anoctamin-1 ; Blotting, Western ; Chloride Channels ; Colon, Sigmoid ; Colonic Neoplasms ; Constipation ; Humans ; Muscle, Smooth ; Neoplasm Proteins ; Proteomics ; Proto-Oncogene Proteins c-kit ; RNA, Messenger

OBJECTIVETo establish an innovative rat model of slow transit constipation by selective chemical ablation of the colon enteric plexus.

METHODSSprague Dawley rats, 5-6 weeks old, were randomly divided into normal control group, sham operation group, treatment group I, II, III, IIII. The normal control group did not receive treatment. Rats in the sham operation group and the treatment groups received abdominal operation under anesthesia, and the gauze containing 0.9% normal saline, 0.05%, 0.1%, 0.25%, 0.5% benzalkonium chloride (BAC) was applied into colon for 30 minutes. Two weeks after operation, the number of feces, fecal dry weight in 24 h and gastrointestinal transit time were recorded, then hematoxylin-eosin (HE) staining, immunohistochemistry, ELISA were used for the evaluation of colonic pathology, enteric plexus, Interstitial cells of Cajal and neurotransmitters 5-hydroxytryptamine(5-HT).

RESULTSCompared to the normal control group and the sham operation group, the gastrointestinal transit time was significantly prolonged and fecal dry weight was lower in the treatment group II, III (all P<0.05). HE and immunohistochemical staining showed varying degrees of pathological changes in the treatment groups and in line with the pathological changes of slow transit constipation. 5-HT concentration reduced significantly in treatment group III compared to other groups (P<0.01).

CONCLUSIONThe animal model of STC is successfully established by applying 0.25% BAC selective chemical ablation of the colon enteric plexus. This model is simple, stable, and is more in line with pathological changes of slow transit constipation.

Animals ; Autonomic Pathways ; Constipation ; Disease Models, Animal ; Gastrointestinal Transit ; Immunohistochemistry ; Interstitial Cells of Cajal ; Rats ; Rats, Sprague-Dawley

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.