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Objective:To observe any effect of repeated transcranial magnetic stimulation (rTMS) in the treatment of diabetic peripheral neuropathic pain (DPNP).Methods:Eighty-six persons with type 2 diabetes mellitus and DPNP were randomly divided into an observation group and a control group, each of 43. Both groups were given basic treatment to control plasma glucose and blood pressure, while the observation group was additionally provided with daily 10Hz rTMS of the primary motor cortex (M1 area) of the non-dominant hand 5 days a week for 4 weeks. Before and after the treatment, pain in both groups was evaluated using a visual analog scale (VAS) and the Patient′s Global Impression Change scale (PGIC). The motor conduction velocity (MCV) and sensory conduction velocity of the median and the common peroneal nerves were also tested.Results:After treatment, the average VAS pain rating and PGIC score of the observation group were significantly lower than the control group′s averages and those before treatment. The observation group′s treatment effectiveness rate (79.07%) was then much better than that of the control group (23.26%). After the treatment, the average MCV of the median and common peroneal nerves of the observation group (47.65±1.94 m/s and 46.98±3.26 m/s, respectively) were significantly faster than before treatment, and those of the control group.Conclusions:rTMS based on routine intervention can significantly relieve DPNP and promote the recovery of injured nerves, bettering diabetics′ physical condition and life quality.
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OBJECTIVE@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*METHODS@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*RESULTS@#Gene sequencing has identified a homozygous c.985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c.1459_1467del9 (p.D487_F489del) and c.1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c.985_987delTACinsAA(Y329Kfs) mutation.@*CONCLUSION@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c.985_987delTACinsAA(Y329Kfs) is the most common. The c.1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.
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Female , Humans , Male , Adrenal Hyperplasia, Congenital , Genetics , Exons , Mutation , Pedigree , Steroid 17-alpha-Hydroxylase , GeneticsABSTRACT
Objective@#To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD).@*Methods@#Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees.@*Results@#Gene sequencing has identified a homozygous c. 985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c. 1459_1467del9 (p.D487_F489del) and c. 1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c. 985_987delTACinsAA(Y329Kfs) mutation.@*Conclusion@#Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c. 985_987delTACinsAA(Y329Kfs) is the most common. The c. 1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.
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OBJECTIVE@#To explore the genotype-phenotype correlation among 18 patients with 21-hydroxylase deficiency (21-OHD).@*METHODS@#PCR-Sanger sequencing was used to analyze the 10 exons and flanking regions of the CYP21A2 gene among the 18 patients and 20 healthy controls.@*RESULTS@#Seventeen patients had variants of the CYP21A2 gene. Eight patients (44.4%, 8/18) carried homozygous variants including p.Ile 173Asn (62.5%, 5/8), p.Pro31Leu (25.0%, 2/8), and IVS2-13A/C>G (12.5%, 1/8), respectively. Six patients (33.3%, 6/18) carried compound heterozygous variant, among which IVS2-13 A>G+p.Ile 173Asn were most common (50.0%). 94.4% (34/36) of the variant were pathogenic, with the most common variants being p.Ile173Asn (41.7%), IVS2-13A/C>G (19.4%), and p.Ile173Asn (7.5%). No variant was identified among the 20 healthy controls.@*CONCLUSION@#The majority of 21-OHD patients carried CYP21A2 gene variants in homozygous or compound heterozygous forms, among which the p.Ile173Asn was the most common one. There is a strong correlation between the genotypes and clinical phenotypes.
Subject(s)
Humans , Adrenal Hyperplasia, Congenital , Genetics , Genotype , Mutation , Phenotype , Steroid 21-Hydroxylase , GeneticsABSTRACT
Objective To investigate the change of CD35 expression on neutrophils in the peripheral blood and the relationship between the change and disease activity in patient with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV).Methods Forty untreated patients with active MPO-AAV(patient group)and forty healthy volunteers (control group) were enrolled into this study,and Bermingham vasculitis activity score (BVAS) for every patient was recorded.Flow cytometry (FCM) was employed to detect the CD35 and MPO expression on the neurtrophil,and enzyme linked immunosorbent assay (ELISA) was taken to test the levels of autoantibody against MPO-Antineutrophil cytoplasmic antibody (MPO-ANCA),fragment a from the activated complement factor B (Ba) and MPO in peripheral blood from both group.All test results were compared between the 2 groups by t test,Non-parametric test,Spearman correlation analysis.In addition,the relations among the laboratory results and the relationship between BVAS and the laboratory results were analyzed respectively.Results Compared with the control group,the expression level,which was represented as mean flourscence indensity (MFI),of CD35 and neutrophil membrane MPO on peripheral blood neutrophils was significantly increased [(2 014±968) vs (1 454±511),t=3.024,P=0.002 and (709±244) vs (580±158),t=2.806,P＜0.01,respectively],and the MPO expression level in neutrophils was significantly lower [(1 525±1 033) vs (3 196±2 126),t=-4.468,P＜0.01].Ba and MPO levels in serum of the patient group was significantly higher than that in the control group [37.89(26.17,63.14) μg/L vs 27.99(18.64,46.52) μg/L,Z=-2.521,P=0.012 and 546.16(450.55,729.96) U/L vs 327.93(279.02,365.10) U/L,Z=7.121,P＜0.01,respectively].In patient group,the expression level of CD35 had a significant positive relationship with peripheral blood neutrophil count (r=0.573,P＜0.01),serum Ba (r=0.433,P=0.005) and BVAS (r=0.368,P=0.020),respectively,whereas,there was a negative correlation between the MPO expressed on the neutrophils and that in the neutrophils (r=-0.458,P=0.003),and a positive relationship between MPO-ANCA and BVAS (r=0.351,P=0.026).Conclusion There is significant increased expression of CD35 on the neutrophil of patient with MPO-AAV,which might protect the neutrophil from destruction by the activated complement alternative pathway,and more neutrophils consequently contribute to the MPO-AAV pathogenesis.Inhibition of CD35 expression might become one of the potential new pathways for the treatment of MPO-AAV.
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Objective To investigate the effect and its underlying mechanism of Linagliptin on mild cognitive impairment (MCI) in elderly type 2 diabetes mellitus (T2DM) patients.Methods Montreal Cognitive Assessment(MoCA)scale was used to prospectively screen T2DM patients for MCI in our hospital from December 2016 to June 2017,and a total of 98 elderly T2DM patients with MCI were recruited.They were randomly divided into the linagliptin group(Linagliptin + metformin,n=50)and the non-linagliptin group(gliclazide + metformin,n =48).Serum fasting plasma glucose (FPG),glycosylated hemoglobin(HbAlc),blood lipids and amyloid β-protein 1-42 (Aβ1-42) levels were determined,and MoCA score and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated,and were compared between the two groups before and after 24 weeks of treatment.Results In the linagliptin group,serum FPG,HbA1c,HOMA-IR,Aβ1-42 levels were significantly decreased and MoCA score was increased after 24 weeks of treatment as compared with pre-treatment [(7.29± 1.00) mmol/L vs.(9.16 ± 1.60) mmol/L,(7.19 ± 0.99) ％ vs.(9.36 ± 1.07) ％,(3.05 ± 1.12) vs.(4.05±1.30),(0.463±0.093)g/L vs.(0.528±0.110)g/L,(24.48± 1.18) vs.(23.22± 1.37),all P＜0.05].In the non-linagliptin group as control,FPG and HbA1c levels were decreased after 24 weeks of treatment as compared with pre-treatment[(7.23±1.09)mmol/L vs.(9.20± 1.75) mmol/L,(7.23±1.03)％ vs.(9.69± 1.18)％,both P ＜ 0.05],while there was no significant difference in HOMA IR,Aβ1-42 level and MoCA score[(3.95 ± 1.00) vs.(4.19± 1.13),(0.517± 0.113)g/L vs.(0.526±0.119)g/L,(23.21±1.18) vs.(23.00±1.32),all P＞0.05].It is worth to pay close attention to the key discovery of this paper that HOMA-IR and Aβ1-42 levels were significantly lower and MoCA score was significantly higher in the linagliptin group than in the non-linagliptin group after 24 weeks of treatment(all P＜0.05).Conclusions Linagliptin as one of DPP-4 enzyme inhibitors can improve the cognitive function in elderly patients with T2DM,which might be relevant to reducing serum Aβ level and improving HOMA-IR.DPP-4 enzyme inhibitor may be a good option for treatment of mild cognitive dysfunction in T2DM patients in the future.
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Objective To explore the relationship between visfatin and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods A perspective study involving 75 hospitalized T2DM patients were divided into groups with(MCI,n=35)and without (NMCI,n =40)mild cognitive impairment.Another 30 non-diabetic patients were chosen as normal control(NC).Fasting plasma levels of glucose (FPG),insulin (FINS),lipid,glycosylated hemoglobin (HbAlc),HOMA-IR and visfatin were measured and calculated.Results The serum visfatin level was higher in MCI(28.81±3.32)μg/L than in NMCI(20.69±3.40)μg/L and NC(19.06±2.35)μg/L (F=96.491,P＜ 0.01).Visfatin was negatively correlated with Montreal Cognitive Assessment (MoCA) total score (MoCA-TS) (r =-0.646,P ＜ 0.01),but positively correlated with course of disease,waist hip ratio,FPG,HbAlc,FINS,HOMA-IR and triglyceride (r=0.282,0.276,0.318,0.496,0.339,0.433,0.309,P＜0.05 or P＜0.01).MoCA-TS was negatively correlated with course of disease,HbAlc,HOMA-IR,triglyceride,total cholesterol,low density lipoprotein cholesterol (r =-0.582,-0.365,-0.234,-0.330,0.277,-0.238,P＜0.05 or P＜0.01),but positively correlated with high density lipoprotein cholesterol(r=0.290,P＜0.05).Higher values of visfatin(OR =3.246,P＜0.01),HbAlc(OR=2.308,P＜0.01)and course of disease(OR=1.634,P＜0.05)were the risk factors for MCI.Conclusions The elevated visfatin level might be a risk factor for MCI in T2DM patients.
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Objective To investigate cartilage oligomeric matrix protein( COMP) gene mutation in a three-generation pedigree with two cases of pseudoachondroplasia, and to definitize genotype-phenotype correlation. Methods The clinical data and peripheral blood were collected from the patients with pseudoachondroplasia and their family members. All the 19 exons and their flanking sequences of COMP gene in two patients and three unaffected family numbers and 50 unrelated individuals were analyzed by PCR amplification and direct sequencing. Results The proband, a 6-year-old girl presented with typical clinical features of pseudoachondroplasia, including disproportionate short limb dwarfism, staggering gait, double genu varus deformity, and wider clinical and imaging long bone metaphysis. The 33-year-old father showed a similar manifestation including disproportionate short limb dwarfism and double genu varus deformity, and was performed correcting operation on lower limbs for double genu varus at the age of 10 years. DNA sequencing analysis of the COMP gene revealed a del mutation ( c. 1417 1419delGAC)in exon 13 in two patients with pseudoachondroplasia, but not in the other unaffected members from the pedrgree and 50 control subjects. Conclusion A del mutation c. 1417 1419delGAC of COMP gene may contribute to the disease in the pedigree.
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Objective Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis(AAV)is a systemic necrotizing small-vessel vasculitis, and myeloperoxidase(MPO) is one of the main antigens that ANCA can recognize.This study was to investigate the clinical significance of MPO, activated complement C5a fragment and ceruloplasmin ( Cp) in the peripheral blood of patients with MPO-ANCA associated vasculitis ( MPO-AAV) in active phase by observing their changes. Methods 132 MPO-AAV patients at active stage were selected as the patient group, while the control group was made up of 30 healthy controls.Peri-nuclear ANCA (p-ANCA) and MPO-ANCA in the patient group were detected by IIF and ELISA, respectively.The levels of MPO, Cp and C5a in both groups were tested by ELISA.The Birmingham vasculitis activity score (BVAS) of every patient was calculated.In the patient group, the relationship among MPO, Cp, C5a and MPO-ANCA were analysed, and the association between BVAS and each of them was also explored. Results The levels of MPO, CP, C5a in the patient group were significantly higher than those in the health control group [MPO:400.7(333.5~506.1) vs 286.9(225.5~329.1)IU/L, P<0.001;C5a:336.7 (277.6~403.5) vs 236.8 (204.2~304.1) ng/mL, P<0.001;Cp:481.1 (387.9~535.9) vs 326.9 (177.1~405.5) ng/mL,P<0.001].The associations between MPO and Cp, C5a and MPO, C5a and Cp in the patient group were statistically significant ( r=0.663, P<0.001;r=0.792, P<0.001;r=0.637, P<0.001, respectively).No significant correlation was found in MPO-ANCA and any of these indexes.MPO-ANCA had a positive association with the total BVAS, the kidney BVAS, and the lung BVAS ( r=0.247, P=0.004;r=0.339,P<0.001 and r=0.191, P=0.028, respec-tively) .p-ANCA had a positive correlation with the kidney BVAS ( r=0.208, P=0.017) while C5a had a negative correlation with the kidney BVAS ( r=-0.207, P=0.018) . Conclusion The levels of MPO, Cp and C5a increased significantly in the peripheral blood of MPO-AAV patients in active phase.The complex interactions among MPO, Cp, C5a and ANCA might influence the clinical damage in MPO-AAV.Notablely, the influence from MPO-ANCA might be most obvious while C5a might affect renal damage more markedly.
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Objective To investigate the clinical characteristics of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (MPO-AAV) with pulmonary injury and the relationship between pulmonary injury and ANCA against light chain of MPO (LCMPO-ANCA).Methods A total of 195 patients with newly diagnosed primary active MPO-AAV were recruited in this prospective study.Indirect immunofiuorescence assay was used to detect peri-nuclear ANCA (p-ANCA).Immunoblotting and ELISA were used to detect myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA).Clinical features of patients with both positive p-ANCA and MPO-ANCA were collected.Disease activity was evaluated by Birmingham Vasculitis Activity Score-version 3 (BVAS-V3) Recombinant light chain of MPO was used to coat substrate of LCMPO-ANCA by ELISA.The clinical characteristics of pulmonary injury and its correlation with serum levels of p-ANCA,MPO-ANCA and LCMPO-ANCA were explored.Results All 195 patients (64 male and 131 female),consisted of 191 patients (98.0％) with microscopic polyangiitis,3 patients (1.5％) with granulomatosis with polyangiitis,and 1 (0.5％) with eosinophilic granulomatosis with polyangiitis including 64 men and 131 women.Their mean age was (63.2 ±13.5) years old.The level of MPO-ANCA had a positive correlation with general BVAS-V3 (r =0.193,P =0.007) in all patients,and the level of LCMPO-ANCA was positively related with the pulmonary BVAS-V3 (r =0.228,P =0.001).As for multiple systemic damages,the incidence of lung involvement was 60.51％(118/195),which ranked second to renal involvement (71.80％,140/195).The most common pulmonary injuries represented as pulmonary infiltration of 80.51％ (95/118),pleural effusion / pleurisy of 41.53％(49/118),pulmonary nodule or cavity of 22.03％ (26/118).Compared with those without lung involvement,the patients with pulmonary injuries were older [(66.39 ± 10.70) years old vs (58.30 ±15.72) years old;t =4.277,P =0.001],had a shorter course of disease [2.00(1.00,10.50) months vs 3.00(1.00,3.50) months;t =-2.283,P=0.024],and higher scores of general BVAS-V3 (18.21 ±6.08 vs 15.18 ± 5.64;t =3.501,P =0.001).Also,in the patients with pulmonary lesions,the positive rate of LCMPO-ANCA was significantly higher (35.59％ vs 6.49％;x2 =21.569,P ＜ 0.001),and the level of LCMPO-ANCA was significantly higher (0.377 ±0.229 vs 0.285 ±0.079;t =3.399,P =0.001)than those without lung involvement.The pulmonary BVAS-V3 in the patients with LCMPO-ANCA was significantly higher than that in the patients without LCMPO-ANCA (4.34 ± 2.10 vs 2.59 ± 2.52;t =4.301,P ＜ 0.001),whereas the pulmonary BVAS-V3 was not correlated with LCMPO-ANCA (r =0.035,P =0.708) in patients with lung injuries.Conclusion Pulmonary injury was relatively common and insidious in patients with MPO-AAV.To monitor ANCA level is necessary in patients with pulmonary injury.LCMPO-ANCA might play an important role in the pathogenesis of pulmonary lesions in AAV.
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Objective To analyze the clinical characteristics of vasculitis associated with antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA),and to investigate preliminarily the relationship between MPO-ANCA and the clinical damages.Methods One hundred and thirty-two patients with primary antineutrophil cytoplasmic antibody (ANCA) associated vasculitis,which were diagnosed for the first time,were involved into this prospective study.All the patients had positive laboratory tests for peri-nuclear ANCA (p-ANCA) and MPO-ANCA.The characteristics of their clinical presentations were analyzed.The levels of p-ANCA and MPO-ANCA in the peripheral blood were detected and the relationship between the levels and the damages were explored.T-test and Spearman rank correlation analysis were used for statistical analysis.Results Of the 132 patients from 8 different clinical departments,128 (97.0％) were microscopic polyangiitis (MPA),3 (2.3％) were granulomatosis with polyangiitis (GPA),and 1 (0.7％) was eosinophilic granulomatosis with polyangiitis (EGPA).The mean age was (62±15) years old.The average time between onset of the disease and diagnosis was (10 ±18) months,and only 14 (10.6％) were diagnosed within one month.Among the major organ involvements,the occurrence of renal,lung,joint,heart,peripheral nerve,skin,and central nerve involvement was 72.0％(95 cases),67.4％(89 cases),26.5％(35 cases),19.7％ (26 cases),17.4％(23 cases),10.6％(14 cases) and 9.8％(13 cases),respectively.Lung was more susceptible to be involved among the aged in their early course [(66±11) years,(55±19) years,t=-3.478,P＜0.01; (6±10) months,(18±27) months,t=2.920,P＜0.01],and joint involvement was more common in the younger [(57±18) years vs (64±13) years,t=2.335,P＜0.05] patients.p-ANCA had no relationship with the disease activity or the range of organ involvements(r=0.013,P＞0.05; r=0.087,P＞0.05).MPO-ANCA had a positive association with disease activity but had no significant correlation with the range of organ involvements(r=0.258,P＜0.01; r=0.022,P＞0.05).Conclusion The MPO-ANCA associated vasculitis is not rare in our country.MPA is the most common vasculitis which mainly affects the aged population,and its diagnosis is often delayed due to the lack of characteristic clinical presentations.It is possible that MPO-ANCA may play a pathogenic role in vasculitis,and the various clinical manifestations might be related with the specificities of MPO-ANCA.
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[Summary] The characteristics ot clinical data and relevant inspection (quantitative sensory and electrophysiological studies) in 5 patients hospitalized with acute painful neuropathy following rapid glycaemic control with insulin from 2010 to 2012 in our hospital were analyzed.The results showed that 5 patients were all males,aged 31-49 years,with lower body mass index,and diagnosed as latent autoimmune diabetes of adults (LADA) or type 2 diabetes.Glycaemic control was poor before application of insulin.When insulin was used,the hyperglycemia was rapidly corrected in a short time,with recurrent episodes of hypoglycemia during insulin treatment.The painful neuropathic symptoms appeared within 2-4 weeks after application of insulin,and were relieved partially or completely after 2-6 months.Neuropathic symptoms manifested as tingling and tenderness,with worsening during night and after insulin injection.The neuropathic symptoms were not significantly alleviated after application of neurotrophic drugs such as methycobal,protogen,and prostaglandin.These patients often suffered from severe anxiety.Nerve electromyogram examination showed slowed or normal motor conduction velocity of tibial and fibular nerves,and normal feeling threshold.
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The clinical and genetic data were retrospectively analyzed in a pedigree with pseudohypoparathyroidism type Ⅰ a.Clinically typical Albright hereditary osteodystrophy (AHO),hypocalcemia,hyperphosphatemia,and PTH- and TSH-resistance were manifested in the proband,but not in his brother and parents.The proband's symptom of epilepsy was alleviated by treatment with calcium and vitamin D,which was of no avail in regard to AHO.After GNAS1 genes were sequenced and compared with the GenBank data among the family members,a deletion of c.1107_1108 ( p.Glu370ArgfsX11 ) in exon l3 of GNAS1 gene leading to a frameshift mutation was found in the proband and his mother.It suggested that the GNAS1 gene mutation might be related to the pathogenesis of the disease.