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We report a case of type A insulin resistance syndrome. A 16-year-old girl with BMI of 19.1 kg/m 2 presented with primary amenorrhea and hyperglycemia for two years. Baseline HbA 1C was 10.8%, along with severe hyperinsulinemia, increased total testosterone and free androgen index(FAI). Ultrasonography showed polycystic ovaries. Next generation sequencing identified a novel and de novo heterozygous missense mutation of Trp1220Gly in the insulin receptor gene. Short-term intensive insulin pump treatment was initiated, followed by insulin glargine, pioglitazone and acarbose combination regiment. Fasting blood glucose and insulin levels decreased significantly, but post-load hyperglycemia and hyperinsulinemia remained unsatisfactory. HbA 1C dropped to 7.6% at 1-year follow up. Patients with polycystic ovarian syndrome who are adolescent-onset and with lean body type should be taken into account of type A insulin resistance syndrome. Currently, there is no standardized treatment protocol, and therapy should be individualized based on the specific gene mutation of each patient.
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SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.
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Guidance and reference are provided for protocol designer. The classification of laser medical devices are introduced. The key points such as the selection of control group, evaluation indicators and method, criteria of inclusion and exclusion, and application of blinded, etc. are discussed, and the importance of management of defects in medical device is emphasized.
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Clinical Trial Protocols as Topic , Equipment and Supplies , Lasers , Research DesignABSTRACT
Objective To investigate the relationship between Fibroscan? data controlled attenuation parameter(CAP), liver stiffness measurement(LSM), and the risk of metabolic syndrome(MS). Methods A total of 817 subjects in this year's staffs physical checkup screening for fatty liver were recruited. Questionnaires were filled, anthropometries including neck and waist circumferences were collected, and fasting glucose, lipid profiles, insulin, adiponectin levels were measured, CAP and LSM were recorded using FibroScan? . The subjects were divided into MS and control groups. Clinical characteristic parameters were compared, and independent predictors for MS were analyzed. Results There were 231 subjects(28.3％) in the MS group and 586(71.7％) in the control group. As compared to the controls, MS group had significantly higher CAP, LSM, neck circumference, and fasting insulin levels[(277±48vs237±44)dB/m,(4.9±2.2vs4.1±1.0)kPa,(37.1±3.3vs34.1±3.0)cm,(9.3±4.7vs5.7± 2.9)μIU/ml, all P<0.01], whereas adiponectin levels were lower [(10.6 ± 8.8 vs 18.7 ± 14.9) ng/ml, P<0.01] . With the accumulation of MS components, CAP and LSM increased. When CAP and LSM were divided into quartiles, the number of MS components increased with increasing quartiles, along with proportions and odds ratios for the occurrence of MS, and CAP showed a stronger correlation with MS than LSM. Binary Logistic regression analysis revealed that CAP, age, neck circumference, adiponectin, and fasting insulin levels were independent predictors for MS. Even with no MS component, subjects with CAP≥248 dB/m had elevated body mass index, neck and waist circumference, waist to hip ratio, increased fasting insulin, triglyceride, uric acid and reduced adiponectin levels. Conclusion CAP showed a close relationship with MS. Increased CAP was associated with increased body weight, dyslipidemia, elevated uric acid, and fasting insulin, whereas reduced adiponectin even before the occurrence of MS.
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Objective To compare the clinical effect of minimal invasive drilling cranium from frontal part and craniotomy from temporal in the treatment of patients with cerebral hemorrhage in basal ganglia.Methods From August 2011 to August 2017,126 cases with cerebral hemorrhage in basal ganglia in the People's Hospital of Meishan were divided into observation group and control group,with 63 cases in each group.The observation group was treated by minimal invasive drilling cranium,and the control group was treated by craniotomy.The clinical treatment effect,operation indicators (operation time,amount of intraoperative bleeding,operation cost,discharge time) and nervous function recovery were analyzed.Results The operation time,amount of intraoperative bleeding,operation cost,discharge time of observation group were (31.6 ± 10.3) min,(20.9 ±5.8)mL,(2.1 ± 1.0) thousand CNY,(15.3 ± 0.9) d,respectively,which were better than those of the control group [(214.2 ± 46.8) min,(94.1 ± 56.2) mL,(15.0 ±4.8) thousand CNY,(21.4 ±0.4)d] (t =13.56,11.94,19.65,8.39,all P ＜0.05).The effective rate and the nerve function score between the two groups had no statistically significant differences (all P ＞ 0.05).Conclusion The minimal invasive drilling cranium from frontal part has advantages of small surgical trauma,short operation time,less bleeding in the operation,low death rate,less cost of operation,short hospitalization time and good drainage effect,and thus it is worthy of clinical application.
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Objective To investigate the risk factors of pancreatic cancer in Wenzhou area.Methods A case control study was conducted on 220 cases with pancreatic cancer and 220 matched controls using conditional logistic regression analysis.Results Univariate analysis showed BMI ＞ 30 kg/m2,smoking,reproductive history,diabetes,cholecystitis,chronic pancreatitis,history of appendectomy,history of partial gastrectomy,history of cancer and familial history of cancer were associated with pancreatic cancer,while multivariate conditional logistic regression analysis showed that the risk factors of pancreatic cancer included smoking (OR =3.624,95％ CI i.474 ～ 8.907),BMI ＞ 30 kg/m2 (OR =1.789,95％ CI 1.030 ～ 3.108),diabetes (OR =3.191,95％ CI 1.094 ～ 9.309),chronic pancreatitis (OR =4.972,95％ CI 1.593 ～ 14.898),and cholecystitis (OR =2.289,95 ％ CI 1.024 ～5.116).Conclusions BMI ＞ 30 kg/m2,smoking and diabetes are risk factors for pancreatic cancer in Wenzhou area.
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ObjectiveTo assess the recent effect of the invasiveness and transsphenoidal microsurgical operation in the treatment of growth hormone-secreting adenom tumor.MethodsThe data of 22 patients with growth hormone(GH) adenomas were collected.All patients were tested preoperative GH level and that within the first 3 days,30 days following surgery.The invasiveness of pituitary adenomas was judged according to Hardy's classification scheme modified by Wilson.ResultsThere were 22 patients with GH-secreting pituitary adenomas,8 males and 14 females,11 patients with invasive adenomas and 11 patients with noninvasive adenomas.The remission rate between the patients with invasive adenomas and the patients with non-invasive adenomas had no statistically significant difference (P ＞ 0.05 ).The postoperative remission rate of patients with GH values ≤ 50μg/L was no significantly lower than that of ＞ 50μg/L( P ＞ 0.05).ConclusionThe recent effects of operation were not significantly different with the invasiveness of tumor.
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of slow anti-epileptic drug (AED) taper protocol and a rescue benzodiazepine protocol in video-electroencephalography (video-EEG) monitoring for presurgical evaluation of epilepsy.</p><p><b>METHODS</b>Sixty-two of 109 patients with refractory focal epilepsy underwent pre-surgical video-EEG monitoring with a slow AEDs taper protocol and a rescue benzodiazepine protocol. Seizures were recorded by video-EEG in 56 patients. The time to the first seizure, duration of monitoring, incidence of 4-h and 24-h seizure clustering, secondarily generalized tonic-clonic seizures (sGTCS), status epilepticus, falls and cardiac asystole were evaluated.</p><p><b>RESULTS</b>A total of 191 seizures were recorded in the 56 cases, and the diagnostic efficiency of video-EEG was 90.3%. The mean time to the first seizure was 2.4 days and the time to conclude video-EEG monitoring averaged 6.8 days. Eight (12.9%) patients had 4-h clusters and 24 (38.7%) had 24-h clusters. Seizure clusters were more frequent in extra temporal epilepsy than in temporal lobe epilepsy. While 19 sGTCS were recorded in 15 patients (26.8%), status epilepticus did not occur and no seizure was complicated by cardiac asystole. Epileptic falls with no significant injuries occurred in 4 patients.</p><p><b>CONCLUSION</b>Seizure clustering is common during presurgical video-EEG monitoring, but serious adverse events are rare with a slow AED tapering and a rescue benzodiazepine protocols. These two protocols are effective and save in presurgical video-EEG monitoring for refractory focal epilepsy.</p>
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Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Anticonvulsants , Therapeutic Uses , Electroencephalography , Methods , Epilepsy , Diagnosis , Drug Therapy , Monitoring, Physiologic , Methods , Substance Withdrawal Syndrome , Diagnosis , Video RecordingABSTRACT
Objective To study clinical characteristics,causes of misdignosis and diagnostic and therapeutic methods for primary hyperparathyroidism (PHPT).Methods Retrospective analysis was done for 51 patients of PHPT,47 confirmed by biopsy after surgical operation and 4 without operation diagnosed based on their serum levels of calcium,alkaline phosphatase ( ALP),intact parathyroid hormone ( iPTH ),and computed tomography (CT) or 99mtechnetium sestamibi (99mTcMIB1) imaging at the First Affiliated Hospital of Sun Yat-sen University,Guangzhou during June 1997 to November 2010.Results Bone-related complications were the most common clinical manifestation,accounting for 51％ (26/51 ) of the cases,and adenoma,a benign,enlarged and hyperactive parathyroid gland,in 34 of 47 cases ( 72％ ).In orthotopic lesions,the right inferior was affected in 19 of 46 cases (41％),followed by the left inferior in 13 cases (28％),while 5 of 51 cases (10％) with ectopic parathyroid gland.PHPT was easily misdiagnosed as urolithiasis,rheumatic disease,primary osteoporosis,etc,accounting for 92％ of the cases in our study.Preoperative serum levels of calcium,ALP and iPTH in the patients varied with their clinical type and pathological classification,the highest in patients with urolithiasis-bone-related complications [ (3.22 ±0.35) mmol/L,(1455 ± 1091 ) U/L and (1669 ± 515 ) ng/L,respectively ] and in patients with parathyroid carcinoma [ (3.46 ± 0.40) mmol/L,( 1410 ± 426) U/L and ( 1861 ± 768) ng/L,respectively ].Sensibility of preoperative localization diagnosis using ultrasonography,CT and 99mTcMIBI was 88％ (35/40),97％ (30/31) and 97％ (31/32),respectively.Conclusions PHPT is frequently misdiagnosed as other diseases.Measurement of serum calcium should be included in routine physical examinations,supplemented with measurement of serum ALP and iPTH,as well as medical imaging,which can help avoid misdiagnosis.CT combined with 99mTcMIBI imaging can improve accuracy of preoperative localization diagnosis.
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Objective A previously reported female diagnosed with type A insulin resistance syndrome bearing a heterozygous missense mutation of R1174W in the insulin receptor gene was followed for 7 years since the age of 16 years. Methods Five-hour oral glucose tolerance tests (OGTT) were done on baseline, the 3rd, 6th and 7th year respectively, with serum insulin and C-peptide measured at the same time points. Areas under of curve (AUC) of glucose, insulin and C-peptide were compared between the years.Acute insulin response (AIR) was determined at baseline and the 7th year. The dose response were insulin secretion rates at each time point during OGTT being plotted over the corresponding glucose levels, and the slopes of which quantified the insulin secretion responding to glucose. Results The follow up data showed that the glucose metabolism of the subject did not deteriorate over time with yearly glycosylated hemoglobin A1c (HbAlc) being normal (4.6%-5.5%), and hyperinsulinemic hypoglycemia was a persistent phenomenon observed at 4-5 hours post-load. The fasting and AUCs of serum insulin and C-peptide tended to decline without simultaneously increase of those of plasma glucose. The AIR decreased by 56% as compared to baseline. The dose response curves shifted downward as years went by. Conclusions It supports that with the alleviation of physiological insulin resistance after puberty, the gross hyperinsulinemia tends to ameliorate, and β-cell secretion does not deteriorate over time as glucose homeostasis maintains.
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Objective To explore the relationship between NAT2 genetic polymorphism and the risk of colorectal cancer. Methods A hospital-based case-control study was conducted and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect its genotypes.Results The frequency of NAT2 slow genotype was 19.58% in cases with colorectal cancer compared.with increased the risk for developing colorectal cancer and their OR were 2.16(95% CI:1.31～3.54).Conclusion The results suggest that NAT2 genetic polymorphism is associated with colorectal canoer susceptibility.People with NAT2 slow genotype have higher coloreetal cancer risk.
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Objective To investigate the clinical and renal pathological features in the new rat model induced by anti-human podocyte-protein antibody. Methods The rat model was induced by once intravenous injection of rabbit anti-human podocyte-protein antiserum which was prepared at first. Male Sprague-Dawley rats (n=36) were randomly divided into six groups (6rats in each group): control group (CG), the time points of day 7 group (D7), day 14 group (D14),day 21 group (D21) and day 28 (D28) group after antiserum injection, and day 28 group after the normal rabbit serum injection (NRG). The level of 24 hour proteinuria, the clearance of creatinine,albumin, blood urea nitrogen, triglyceride, cholesterol and serum creatinine were measured. The renal morphology was detected under the light microscope, immunofluorescence microscope, and electron microscope. Results 24-hour proteinuria (mg) was gradually increased, and the level of proteinuria in D28 (48.56±13.80) was significantly higher than that in CG (5.34±2.77, P＜0.01)and NRG (11.32±4.90, P＜0.01). The clearance of creatinine (ml/min) and serum creatinine (μmol/L) in D28 (0.90±0.47, 33.48±9.94) were significantly different from CG (1.68±0.54, P＜0.05;26.03±2.67, P＜0.05), but showed no difference with NRG (1.34±0.87, P＞0.05; 27.40±4.73, P＞0.05). The level of albumin (g/L) was lower in D7, D14, D21, D28 (28.20±0.87, 27.80±1.97,27.42±1.66, 27.77±1.95) than CG (29.98±0.76, P＜0.05). But there was no difference in the level of albumin among the groups after antiserum injection and NRG (28.68±1.18, P＞0.05). The level of blood urea nitrogen, triglyceride, cholesterol showed no difference among the groups (P＞0.05). The renal morphology showed no obvious changes between CG and NRG. Among the groups after antiserum injection, the renal pathological changes under the light microscope were some spikes formation in D28. Immunostained for rabbit IgG in rat glomeruli progressively decreased over the 28 days, while rat IgG progressively increased. The renal section deposition for rat complement 3 reached a maximum at day 21 then decreased afterward. Under the electron microscope, there were immune complexes and foot process fusion at day 14. Conclusions The new rat model induced by anti-human podocyte-protein antibody showing typically clinical and pathological changes of the membranous nephropathy is successfully established.
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Objective To investigate the therapeutic effect and side effect of prourokinase (Pro-uk) on the patients with acute myocardial infarction. Method From May 2004 to May 2005, a total of 68 cases of acute myocardial infarction treated by thrombolytic agents within 6 hours after onset were divided randomly into Pro-uk group ( n = 43) and urokinase (UK) group ( re = 25). In the Pro- uk group, there were 22 eases treated with 50 mg Pro-uk and 21 cases prescribed in 60 mg Pro-uk. The patency of involved coronary artery was evaluated by using selective coronary angiography at 90 minutes after thrombolytic therapy. The incidence of early heart events, bleeding and adverse reaction, were alse observed. Results (1) The total rates of resumed patency of obstructed coronary artery (TIMI grade 2 and 3 flow) were 76.7% in Pro-uk treated patients and 52.2% in UK treated patient ( P = 0. 041). (2) The occurrence of hyporrhea was lowered more significantly in Pro-uk treated patients than in UK treated patients (P = 0.029), but there were no intracranial hemorrhage found in both group. (3) Early cardiac events and adverse reactions were similar between two groups. Conclusions Pro-UK is safe and effective for the patients with acute myocardial infarction.
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Objective To study the effect of pulse pressure(PP)/mean artery pressure(MAP) ratio in evaluating arteriosclerosis.Methods Blood pressures from 200 subjects without cerebrovascular nor cardiovascular disease were obtained and analyzed by different age groups.PP/MAP ratio was calculated for each patient and compared.Results PP/MAP ratio was significantly different in different age groups.Conclusion PP/MAP ratio has clinical significance in evaluating arteriosclerosis and is worthy of further investigation.