Efficacy of satellite rod revision surgery via a combined anterior and posterior approach for rod fracture after posterior vertebral column resection in patients with severe thoracolumbar kyphosis / 中华创伤杂志

Objective:To investigate the clinical efficacy of satellite rod revision surgery via a combined anterior and posterior approach for rod fracture after posterior vertebral column resection (PVCR) in patients with severe thoracolumbar kyphosis.Methods:A retrospective case series study was conducted on the clinical data of 11 patients with rod fracture after PVCR for severe thoracolumbar kyphosis, who were treated in Henan Provincial People′s Hospital from January 2013 to January 2021. There were 6 males and 5 females, with the age range of 21-62 years [(35.4±13.0)years]. Among them, 4 patients had traumatic kyphosis, 4 presented congenital kyphosis and 3 showed tuberculous kyphosis. All the patients had obvious low back pain. According to the American Spinal Injury Association (ASIA) score, 2 patients were found with grade C, 2 with grade D and 7 with grade E. All the patients underwent revision surgery for internal fixation using satellite rod via a combined anterior and posterior approach. The operation time, intraoperative blood loss and postoperative hospital stay were recorded. The imaging parameters such as kyphosis Cobb angle, scoliosis Cobb angle, distance between C 7 plumb line and central sacral vertical line (C 7-CSVL), and distance between C 7 plumb line and sagittal vertical axis (SVA) were measured preoperatively, at 1 week postoperatively and at latest follow-up. At the same time, the visual analogue scale (VAS), Oswestry dysfunction index (ODI), and simplified Chinese version of the scoliosis research society-22 (SRS-22) questionnaire were used to evaluate the clinical efficacy. At the latest follow-up, the osteotomy fusion was evaluated by Suk criterion and ASIA score was used to evaluate the recovery of neurological function. The complications were also recorded for the patients. Results:All the patients were followed up for 24-84 months [(47.5±16.2)months]. The operation time was 100-220 minutes [(149.4±37.6)minutes], with the intraoperative blood loss of 150-350 ml [(246.3±64.6)ml] and the postoperative hospital stay of 5-8 days [(6.1±1.1)days]. The kyphosis Cobb angles [(18.5±3.2)° and (19.3±2.9)°] and the scoliosis Cobb angles [(11.8±2.2)°, (11.1±2.2)°] at 1 week post-operation and at the latest follow-up were all improved significantly compared with the preoperative ones [(60.4±6.3)°, (21.7±5.5)°] (all P<0.01), with the average correction rates being 69.4% and 45.6%, respectively, with no significant differences between 1 week post-operation and latest follow-up (all P>0.05). The C 7-CSVL was reduced from preoperative (21.2±4.3)mm to (15.7±2.4)mm at 1 week post-operation, and to (15.9±2.2)mm at the latest follow-up (all P<0.01). The SVA was improved from preoperative (51.0±6.8)mm to (16.6±3.6)mm at 1 week post-operation, and to (15.3±3.9)mm at the latest follow-up (all P<0.01). There were no significant differences in C 7-CSVL or SVA at 1 week post-operation or at the latest follow-up (all P>0.05). The VAS [(2.5±0.9)points, (1.9±0.9)points], ODI (20.1±5.4, 18.4±5.2) and SRS-22 [(83.4±5.8)points, (85.0±4.1)points] at 1 week post-operation and at the latest follow-up were significantly improved compared with the preoperative ones [(6.0±1.4)points, 57.2±8.7, (62.0±9.1)points] (all P<0.01), but no significant differences were found between 1 week post-operation and latest follow-up (all P>0.05). At the latest follow-up, the bone grafts achieved osseous fusion in all the patients, and the ASIA grade was improved from grade C to grade D in 2 patients and from grade D to grade E in 2 patients. No complications such as serious neurological or vascular injury occurred during perioperative period. No pseudoarthrosis formation, internal fixation loosening or fracture occurred during follow-up. Conclusion:Satellite rod revision surgery via a combined anterior and posterior approach for rod fracture after PVCR in patients with severe thoracolumbar kyphosis has the advantages of less trauma and faster convalescence, excellent results of deformity correction, significant pain relief, functional improvement, and fewer complications.

Genetic analysis of a gonadal-mosaicism BMD family with prenatal diagnosis and PGT-M / 中华检验医学杂志

Objective:To identify the pathogenic characteristics of a suspected gonadal mosaicism Becker muscular dystrophy (BMD) family, and provide provide basis for pregnancy selection of similar families.Methods:A BMD family admitted to Hunan Jiahui Genetics Hospital from June 2012 to September 2019 was systematically reviewed. The medical history and family history of the proband were checked, and multiplex ligation-dependent probe amplification was used to detect the deletion/duplication of 79 exons of the Duchenne muscular dystrophy (DMD) gene in the proband, fetuses, and parents. Moreover, potential variants were verified by combining PCR amplification, short tandom repeat polymorphic linkage analysis, and real-time fluorescence quantitative PCR. High-quality embryos are screened for transplantation after preimplantation genetic testing for monogenic (PGT-M). And amniotic fluid was collected in the second trimester for prenatal diagnostic verification.Results:According to the phenotype analysis of the proband, the initial clinical diagnosis was BMD, and the exon 45-50 deletion in DMD gene was detected. The mutation was not detected in the mother′s peripheral blood, but when she was pregnant again, the prenatal diagnosis showed that the fetus had the same deletion mutation as the proband. Neither of two vitro embryos tested by PGT-M has the deletion mutation, then single embryo transfer was performed nor was pregnancy successful. After confirmation of prenatal diagnosis during pregnancy, a normal baby girl was born by full-term cesarean section.Conclusions:This BMD family was a family with two consecutive BMD homodeletion mutations, and the mutation of the DMD gene was not detected in the peripheral blood of the proband′s mother and two embryonic cells, suggesting that the mother may be a gonad chimeric carrier of this deletion mutation. The combined application of prenatal diagnosis and PGT-M provides a reference approach to effectively avoid the birth of similar children.

Risk factors of bone cement leakage after percutaneous vertebroplasty for osteoporotic vertebral compression fracture / 中华创伤杂志

Objective:To investigate the risk factors of bone cement leakage after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).Methods:A multi-center, large-sample, case-control study was carried out to analyze the clinical data of 2 273 OVCF patients (2 689 vertebrae) undergone PVP at four hospitals between May 2018 and October 2021, including 994 males and 1 279 females, with the age of 52-91 years [(69.1±3.1)years]. Of all, 581 patients (604 vertebrae) were allocated to leakage group and 1 692 patients (2 085 vertebrae) to no leakage group according to the occurrence of bone cement leakage. The gender, age, fracture sites, vertebral compression degree, endplate integrity of fractured vertebrae, surgical segments, surgical approaches and bone cement injection volume were recorded. Univariate analysis was used to investigate the correlation between those indicators with bone cement leakage. Multivariate Logistic regression analysis was used to identify the independent risk factors for bone cement leakage.Results:Univariate analysis showed that gender, age, fracture sites, vertebral compression degree, bone cement injection volume were related to bone cement leakage after PVP ( P<0.05 or 0.01), but no correlation was found in the endplate integrity of fractured vertebrae, surgical segments and surgical approaches (all P>0.05). Multivariate Logistic regression analysis showed that fracture sites ( OR=1.68, 95% CI 1.11-2.55, P<0.05), vertebral compression degree more than 40% ( OR=1.98, 95% CI 1.29-3.02, P<0.01), bone cement injection volume greater than or equal to 5.5 ml ( OR=1.55, 95% CI 1.07-2.26, P<0.05) were significantly associated with bone cement leakage after PVP. Conclusion:Thoracic vertebral fracture, vertebral compression degree more than 40% and bone cement injection volume greater than or equal to 5.5 ml are independent risk factors for bone cement leakage after PVP in OVCF.

Correlation Research of Plasma Glucose, Blood Pressure Level and TCM Syndromes in Shanghai Community Residents / 世界科学技术-中医药现代化

Objectives: The purpose of this study is to understand the relationships among plasma glucose, blood pressure level and Traditional Chinese Medicine (TCM) syndromes in Shanghai community residents, and provide a theoretical basis for the prevention of community chronic disease based on TCM syndrome differentiation.Methods: Residents above35 years old will attend the Type 2 Diabetes Mellitus (T2 DM) risk assessment at Community Health Center. By distributing questionnaires and performing glucose testing, we screened the residents at high risk of T2 DM, and conducted a physical examination of them. Further, a body constitution questionnaire was required to be completed by the residents. Results: In total, 933 residents were screened. The plasma glucose and blood pressure levels related to age, waist circumference, hip circumference, body mass index (BMI) and waist-to-height ratio (WHtR) . Residents with increasing blood pressure have an increased risk of T2 DM (P ＜ 0.01) . Total 529 questionnaires were completed, and 129 subjects (24.4％) have single TCM syndromes, 75 subjects (14.2％) have at least two TCM syndromes and 325 subjects (61.4％) have no TCM syndromes. Conclusion: Plasma glucose and blood pressure are associated and interacted with several physical indexes. TCM syndromes distribution was found no significant change among subjects with different plasma glucose and blood pressure.

Risk factors for mortality in patients with severe fever with thrombocytopenia syndrome / 中华传染病杂志

Objective To analyze the clinical features and risk factors for mortality of patients with severe fever with thrombocytopenia syndrome (SFTS) in Zhoushan, the eastern coastal of China with high incidence of severe fever with thrambocytopenia syndrome bunyavirus infection, to provide reference for reducing the mortality rate of SFTS.Methods Clinical data of 107 cases of SFTS from Zhoushan Hospital during June 2011 to June 2016 were retrospectively analyzed.According to the prognosis, patients were divided into survival group and death group.The clinical features and the laboratory results were analyzed with a case-control method to analyze the prognostic factors.Normal distribution data were compared with the independent t test.Kolmogorov-Smirnov Z test were used in data with skewness distribution.Categorical data were analyze by chi-square test.The related risk factors were analyzed with the receiver-operating characteristic (ROC) curve and multivariate unconditioned logistics regression analysis.Results Seventeen cases among 107 STFs patients died, yielding the mortality rate of 15.9%.The proportion of patients suffering from two or more underlying diseases, with disorders of consciousness, activated partial thromboplastin time (APTT), the level of creatine kinase (CK), lactate dehydrogenase (LDH) as well as sepsis-related or sequential organ failure assessment (SOFA) score in death group were all significantly higher than those in the survival group (all P73.45 s, SOFA scores >9 were the independent risk factors for mortality of SFTS (OR=6.947, 8.459 and 11.770, respectively, all P<0.05).Conclusion Ca2+, APTT and SOFA score are the independent risk factors for prognosis of SFTS, which provide reference for prognostic evaluation of SFTS.

Surface Electromyography Studies of Pharyngeal Swallowing in Healthy Middle-aged and Old People / 中国康复理论与实践

Objective To observe the character of amplitude of myoelectric activity with surface electromyography (sEMG) on pharyn-geal swallowing in healthy middle-aged and elderly people. Methods From January, 2015 to January, 2016, 78 healthy subjects were separat-ed into middle-aged group (38~60 years old, n=38) and elderly group (61~82 years old, n=40). The amplitudes of sEMG activity of related muscles under different swallowing modes were recorded by sEMG technique and analysis system. The root mean square (RMS) was ana-lyzed. Results There was significant difference in RMS among different swallowing modes (F>105.120, P0.05). There was no difference between two groups in both muscles under relax and dry swallow (t0.05), and was different under water swallow and continuous drinking (t>2.700, P<0.05). Conclusion sEMG could be used for analyzing the characteristics of amplitude of myoelectric activity in healthy mid-dle-aged and elderly people during pharyngeal swallowing in different swallowing modes, that can be used to evaluate and screen swallow-ing and dysphagia in clinic.

Influence of Baduanjin on mild cognitive impairment in elderly diabetic patients / 中国实用护理杂志

Objective To explore the influence of Chinese Qigong--Baduanjin on mild cognitive impairment (MCI) in elderly diabetic patients.Methods A total of 78 elderly type 2 diabetic patients complicated with MCI were divided into intervention group and control group by random digits table method.The control group with 41 patients was received routine treatment and discharged guidance after discharging from hospital.The intervention group with 37 patients was received Baduanjin exercise for 12 months based on the routine treatment in control group.Montreal Cognitive Assessment (MoCA) and Activity of Daily Living (ADL) scores in two groups were compared before intervention and 1,3,6,9 and 12 months after intervention.Results In intervention group,MoCA scores were significantly increased at different times after intervention compared with those before intervention,F=72.782,the differences were statistically significant,P＜0.05.At the same time,MoCA scores were all significantly higher in intervention group than those in control group,F=2.231,2.972,4.362,5.085,5.373,the differences were statistically significant,P＜ 0.05.In intervention group,ADL scores had significantly improved since 6 months after intervention compared with those before intervention,F=93.126,the differences were statistically significant,P＜0.05,and compared with those in control group,the scores were significantly higher since 6 months after intervention,F=3.853,4.561,7.162,the differences were statistically significant,P＜0.05.Conclusion Chinese Qigong--Baduanjin in treatment of elderly diabetic patients complicated with MCI can delay the MCI progress and improve ADL of the patients.

Effect of surface electromyographic biofeedback on the pharyngeal phase activities in patients with dysphagia after stroke / 中国脑血管病杂志

Objective To observe the effect of surface electromyographic biofeedback on the pharyngeal phase activities in patients with dysphagia after stroke. Methods Seventy-six consecutive patients with pharyngeal dysphagia after stroke admitted to the departments of rehabilitation and neurology,brain hospital affiliated to nanjing medical university from August 2014 to February 2015 were enrolled retrospectively. After excluding 40 patients,the remaining 36 patients were divided into either a conventional training group (n =19)or a biofeedback group (n =17)by using the random number table. The patients of the conventional training group received swallowing function training only,while those of the biofeedback group also received the surface electromyographic biofeedback treatment on the basis of the therapy program of the conventional training group. The patients of both groups were treated 6 times a week for 4 weeks. The assessment of swallowing angiography,the digital measurement and analysis were performed before and after treatment. The outcome measures included the degree of openness of upper esophageal sphincter (UES),0pharyngeal transit time (PTT),and the maximum displacement of the hyoid bone (HmaxD). Results (1)The proportions of UES complete opening of the conventional training group before and after training were 26. 3% (5 / 19)and 47. 4% (9 / 19)respectively. There was significant difference between before and after training (χ2 = 5. 08, P =0.020). The proportions of UES complete opening of the biofeedback group before and after training were 47.1% (8/ 17)and 82.4% (14/ 17)respectively. There was significant difference between before training and after training (χ2 =11.46,P = 0. 001). There was no significant difference in the degrees of UES complete opening before training between the conventional training group and the biofeedback group (P >0. 05). There was significant difference in the degree of UES complete opening after training between the 2 groups (χ2 =4. 63,P = 0. 040). (2)PTT of the conventional training group before and after training was 0.24 ±0.07 and 0.19 ±0.06 s respectively. PTT of the biofeedback before and after training was 0.23 ±0.06 and 0. 15 ± 0. 05 s. There was significant difference between before training and after training (F = 154. 50,P = 0. 000). There was no significant difference in PTT before training between the conventional training group and the biofeedback group (P > 0. 05). There was significant difference in PTT after training between the 2 groups (F =4.66,P = 0. 038). (3)The HmaxD distances of the conventional training group before and after training were 0. 5 ± 0. 4 and 0. 9 ± 0. 4 cm respectively,the PTT of the biofeedback training before and after training was 0. 6 ± 0. 4 and 1. 3 ± 0. 6 cm respectively. There was significant difference between before training and after training (F = 137. 56,P = 0. 000). There was no significant difference in the HmaxD distance of the conventional training group and the biofeedback training group before training (P > 0. 05). There was significant difference in the HmaxD distance after training between the 2 groups (F = 4. 29,P = 0. 033). Conclusion The surface electromyographic biofeedback therapy in combination with the conventional swallowing training for the treatment of dysphagia after stroke has the synergistic efficacy.

Phenotype-genotype correlation analysis of 12 cases with Angelman/Prader-Willi syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genotype-phenotype correlation in patients with Angelman syndrome/Prader-Willi syndrome (AS/PWS) and assess the application value of high-resolution single nucleotide polymorphism microarrays (SNP array) for such diseases.</p><p><b>METHODS</b>Twelve AS/PWS patients were diagnosed through SNP array, fluorescence in situ hybridization (FISH) and karyotype analysis. Clinical characteristics were analyzed.</p><p><b>RESULTS</b>Deletions ranging from 4.8 Mb to 7.0 Mb on chromosome 15q11.2-13 were detected in 11 patients. Uniparental disomy (UPD) was detected in only 1 patient. Patients with deletions could be divided into 2 groups, including 7 cases with class I and 4 with class II. The two groups however had no significant phenotypic difference. The UPD patient had relatively better development and language ability. Deletions of 6 patients were confirmed by FISH to be of de novo in origin. The risk to their sibs was determined to be less than 1%.</p><p><b>CONCLUSION</b>The phenotypic differences between AS/PWS patients with class I and class II deletion need to be further studied. SNP array is useful in detecting and distinguishing of patients with deletion or UPD. This method may be applied for studying the genotype-phenotype association and the mechanism underlying AS/PWS.</p>

Effect of cognitive-behavioral intervention on mental state and quality of life in elderly patients with coronary heart disease / 中华全科医师杂志

Ninety elderly patients with coronary heart disease were randomly divided into 2 groups:in study group (n = 45) the cognitive-behavioral intervention as well as conventional medical treatment were performed and in control group ( n = 45 ) only conventional treatment was given. Short Form-36 ( SF-36),symptom checklist 90(SCL-90), Hamilton anxiety scale( HAMA), Hamilton depression scale( HAMD)were evaluated before and after intervention, the serum total cholesterol (TC), triglyceride (TG)and body mass index (BMI)were measured, the smoking and drinking behaviors were recorded. After 6-month of intervention the smoking [(0. 6 ± 0. 2)cigarettes/d] and drinking [(10. 1 ± 2. 3)g/d] behaviors, the scores of SF-36 (85 ± 16), SCL-90 (104 ±4), HAMA (10 ±4) and HAMD (12 ±3), the systolic blood pressure [( 123 ± 11 ) mm Hg ( 1 mm Hg = 0. 133 kPa)], diastolic blood pressure [(77 ± 5 ) mm Hg], the fasting blood glucose [(4. 2 ± 2. 6 ) mmol/L] and BMI ( 22.5 ± 0. 5 ) in study group were significantly improved compared to control group ( P ＜ 0. 01 ). The results indicate that cognitive-behavioral intervention can improve the mental state and quality of life in elderly patients with coronary heart disease.

Effects of behavioral intervention on mental health and quality of life of inpatients with coronary heart disease / 中华行为医学与脑科学杂志

Objective To explore the effects of behavioral intervention on mental heath and quality of life of inpatients with coronary heart disease. Methods Eighty cases with coronary heart disease were randomly divid-ed into intervention group(n=40) and the drug treatment group(n=40). SF-36,SCL-90,EPQ,HAMA,HAMD were applied to assess the mental health state and quality of life. Results After 6-months, the score of SF-36,SCL-90,EPQ,HAMA, HAMD,and N score of EPQ in intervention group were more significantly proved than the drug treatment group SF-36:(84.7±16.2)vs(68.3±10.6); P <0.01; SCL-90:(83.5±4.2)vs(148.6±3.2)], P<0.05;EPQ-N:(43.8±4.2)vs(52.8±3.1), P<0.01;HAMA:(10.4±3.4)vs(15.1±5.1), P <0.01; HAMD: (11.4±3.8) vs (17.9±4.6), P< 0.01). Conclustion Behavioral intervention effectively im-proves mental state and quality of life of patients with coronary heart disease.

High-speed apolipoprotein E genotyping by hybridization probes and melting curves / 中华检验医学杂志

Objective To establish a high speed and effective real-time PCR assay to analyze apolipoprotein E(apoE)genotyping in Chinese population using hybridization probes and melting curves. Methods Lightcycler was used to analyzed two codons'polymorphism after condition was optimized. The persons elder than 60 years including 133 patients with abdominal fat and 108 healthy elder were selected. The detection probes were labeled with L-Cred 640 and LC-Red 705 at 5'end covers codons 112 and 158 with the corresponding anchor probes labeled with fluorescein at 3'ends.A 265-bp fragment of the apoE gene was amplified from human genomic DNA to produce FRET.Depending on the various types of base-pair mismatch in the heteroduplex,wild type and mutant type were differentiated.Results The peaks represented the sequence-specific melting points(Tm) and each genetype showed perfect peak.E2/3 and E3/4 in abdominal fat group were much more common allele than health persons(x2=4.210.P＜0.004,x2=6·328,P＜0.012).The frequencies of abdominal fat group was E2/3(27.8%),E3/4(24.8%),E3/3(42.1%),E2/4(2.3%),E4/4(2.2%)and E2/2(0.8%).The frequencies of healthy controls were E2/3(16.7%),E3/4(12%),E3/3(68.5%),E2/4(1.9%),E4/4(O%)and E2/2(0.9%).It showed high agreement as compared with DNA sequencing analysis The expression of apoE in abdominal fat group (101.5±73.6)was up-regulated than the healthy group(50.6±27.1,P＜0.01).Conclusions Apolipoprotein E genotyping method by melting curve is faster and simpler than other technique. It can prevent the cross-contaminated and is suitable to be applied in clinical diagnosis.There was significant difference between the two groups.There was positive relationship between the elder's abdominal fat and apoE gene polymorphism. The genotyping of E3/4.E2/3 or E4/4 had the important role in the elder's abdominal fat on genetic susceptibility.

Effect of Radix Paeoniae Rubra on intimal proliferation and expression of MKP-1 mRNA after rabbit carotid artery injury / 中华中医药杂志

Objective:To observe the effect of Radix Paeoniae Rubra on intimal proliferation,activating of angiotensin Ⅱ(AgⅡ) and expression of Mitogen-activated protein kinase phosphatase-1(MKP-1) after carotid artery balloon injury in cholesterol-fed rabbits.Methods: Male rabbits were randomly divided into Radix Paeoniae Rubra(PPR) groups: high dose group(75、50、25g.kg-1.d-1;n=8),middle dose group(2g.kg-1.d-1),low dose group(1g.kg-1.d-1;n=8) and control group.Both groups received high fat forage(2% cholesterol + 5% lard).Balloon injury of carotid artery was performed.Carotid artery were harvested at the end of 10 weeks.Expression level of AgⅡwas measured by radioimmunoassay.MKP-1 expression was determined by RT-PCR.Immunohistochemical staining and morphological detection were adopted.Results: Compare with control group,expression of AgⅡ decreased obviously(P

Effect of Radix Paeoniae Bubra on NADPH oxidase p22phox,MCP-1 mRNA expression and neointimal hyperplasia after balloon injury in cholesterol-fed rabbits / 中华中医药杂志

Objective:To observe the effect of Radix Paeoniae Bubra(RPB)on NADPH oxidase p22phox,monocyte chemotactic protein-1(MCP-1)mRNA expression and neointimal hyperplasia after carotid artery balloon injury in cholesterol-fed rabbits.Methods:The rabbit model of carotid balloon injury was established adopting Clowes method,and treated with extract of RPB.Component of neointima and expression of proliferating cell nuclear antigen(PCNA)and macrophage was determined by immunochemical stain.The collagen of typeⅠwas detected by special staining for blood vessels and the area of neointima was measured by image assay system.Expression of NADPH oxidase p22phox mRNA,MCP-1 mRNA was detected by in situ hybridization and transcription-polymerase chain reaction.Results:RPB can attenuate the neointima area and proliferation of collagen typeⅠinduced by balloon-injury,remarkable prevent the formation of restenosi,and down-regulate expression of NADPH oxidase p22 and MCP-1mRNA significantly and decrease the degree of macrophages infiltration especially in vessel wall of injuring carotid artery.Conclusions:RPB inhibited NADPH oxidase P22Phox and MCP-1 mRNA expression,and modestly reduced neointimal hyperplasia,which might be partly attributed to its antioxidant and inflammatory effects.

Analysis of Antidiabetics Used in44Hospitals in Guangdong Region During the Period2000～2003 / 中国药房

OBJECTIVE:To study the current situation and developing trend of the antidiabetics used in Guangdong re?gion.METHODS:The antidiabetics used in44hospitals in Guangdong region during the period2000～2003were analysed concerning the kinds of drug,sum of money for consumption and frequency of drug use.RESULTS:The sum of money for consumption of antidiabetics increased year by year so did its proportion in sum of money for consumption of total drug.Among them,consumption of insulin increased very quickly and oral antidiabetics assumed a tendency of increase as well.CONCLUSI_ ON:The variety of insulin is stable and new oral antidiabetics is going into market occasionally in this region,but frequency of use is primary to sulfonylurea,biguanides and glycosidase-inhibitors.