ABSTRACT
Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.
ABSTRACT
ABSTRACT Background: Among patients with acute ischemic stroke with a mismatch between deficit severity and infarct volume, thrombectomy performed within a 6-24 hours time window has efficacy and safety similar to treatment within 6 hours. However, whether magnetic resonance imaging with T2 diffusion-weighted imaging (DWI) is feasible remains to be validated. Objective: To investigate prognosis among stroke patients receiving endovascular treatment (EVT) within 6 hours and 6-24 hours using non-contrasted computed tomography (NCCT) and DWI. Methods: Overall, 209 anterior-circulation ischemic stroke patients with large-vessel occlusion who underwent EVT were divided into ≤ 6 hours and 6-24 hours groups. Patients presenting symptoms within 6 hours were treated if their NIHSS score was ≥ 7 and ASPECTS score was ≥ 5, whereas those with wake-up stroke (WUS) or presenting symptoms 6-24 hours after last seen well (WUS/late-presenting stroke, LPS) were managed if their NIHSS score was ≥ 7 and ASPECTS score was ≥ 5. Results: The percentages of patients undergoing intracranial stenting and intracranial ballooning without stenting significantly differed between two groups (p < 0.001). Grades 0, 1, 2a and 2b recanalization rates did not differ between the 6 hours and 6-24 hours groups (all p > 0.05). Grade 3 recanalization rate in the 6 hours group was significantly lower than in the 6-24 hours group (p = 0.043). The 3-month Rankin Scale score did not significantly differ between the two groups (p = 0.629). Conclusions: EVT is a safe and effective treatment for patients with WUS and LPS selected through NCCT and DWI-based simple imaging.
RESUMO Antecedentes: Entre pacientes com acidente vascular cerebral isquêmico (AVCI) agudo com divergência entre gravidade do déficit e volume do infarto, a trombectomia em 6 a 24 horas tem eficácia e segurança semelhantes ao tratamento em até 6 horas. Entretanto, a viabilidade da imagem ponderada em T2 com difusão (DWI) da ressonância magnética necessita validação. Objetivo: Investigar o prognóstico de pacientes com AVCI que recebem tratamento endovascular (EVT) em até 6 horas e de 6-24 horas usando tomografia computadorizada sem contraste (NCCT) e DWI. Métodos: Duzentos e nove pacientes com AVCI de circulação anterior submetidos a EVT foram divididos em ≤ 6 horas e 6-24 horas. Pacientes com sintomas até 6 horas foram tratados se NIHSS ≥ 7 e ASPECTS ≥ 5; aqueles com AVCI ao despertar (WUS) ou com sintomas entre 6-24 horas da última vez em que foram vistos bem (WUS/AVC de fase tardia, LPS) foram tratados se NIHSS ≥ 7 e ASPECTS ≥ 5. Resultados: As porcentagens de pacientes submetidos a implante de stent intracraniano e angioplastia intracraniana sem stent diferiram entre os dois grupos (p <0,001). As taxas de recanalização 0, 1, 2a e 2b não diferiram entre 6 horas e 6-24 horas (p> 0,05). A taxa de recanalização de grau 3 no grupo 6 horas foi menor do que 6-24 horas (p = 0,043). Pontuação na Escala Rankin (3 meses) não foi diferente (p = 0,629). Conclusões: EVT é um tratamento seguro e eficaz para pacientes com WUS e LPS selecionados por meio de imagens baseadas em NCCT e DWI.
Subject(s)
Brain Ischemia , Brain Ischemia/diagnostic imaging , Stroke/therapy , Stroke/diagnostic imaging , Endovascular Procedures , Ischemic Stroke , Treatment Outcome , Thrombectomy , Diffusion Magnetic Resonance ImagingABSTRACT
Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,
ABSTRACT
Objective The aim of the study is to investigate the therapeutic efficacy of next-generation anaplastic lynphoma kinase-tyrosine kinase inhibitor (ALK-TKI) in advanced non-small cell lung cancer (NSCLC).Methods The clinical data and outcomes of 22 patients with advanced non-small cell lung cancer who received the next generation of ALK-TKI from 2014 to 2017 in our hospital were retrospectively analyzed.Results 22 patients were included for survival analysis with 15 males and 7 females.The median age was 48 and all of them were adenocarcinoma patients.There were 12,2,7 and 1 patients received ceritinib,alectinib,brigatinib and lorlatinib,respectively.A total of 14 patients could be evaluated,including complete response (CR) in 2 cases,partial response (PR) in 3 cases,stable disease (SD) in 6 cases,progressive disease (PD) in 3 cases.The ORR and DCR were 35.7％ and 78.6％,respectively.The median progression free survival (PFS) of the 22 NSCLC patients was 8.7 months.Progression pattern can be analyzed in 17 patients.Among them,10 patients underwent primary progression (lung),occurring at the leading frequency (accounting for 58.8％) and followed by central nerve system (CNS) progression (accounting for 29.4％).Conclusions Next-generation ALK-TKI provide a reasonable choice for crizotinib-resistant patients.Primary progression (lung) is the leading cause for treatment failure.Multi-disciplinary integration may provide a potential choice for prolonging administration of next-generation ALK-TKI.
ABSTRACT
Objective To investigate the diagnostic value of High-Sensitive Troponin T(hs-TnT)in acute myocardial infarction(AMI). Methods One hundred and sixty nine patients with serum hs-TnT concentration≥0.014 μg/L in early hospitalization were enrolled in this study.The ROC curve was used to compare the concentra-tion of hs-TnT with four heart enzyme(CK,CK-MB,LDH,AST)on the diagnostic efficacy to AMI. The differ-ence of hs-TnT in different clinical data groups were investigated using Mann-Whitney U rank test.Then the correla-tion between hs-TnT and Gensini score of Coronary angiography was investigated using the Spearman rank correla-tion test.Results The concentration of hs-TnT in patients with chest pain was significantly higher than that in non-AMI group(P<0.05).The AUC of each ROC curve was hs-TnT(0.806)>CK-MB(0.792)>CK(0.780)>AST (0.704)> LDH(0.684). The optimal diagnostic point of hs-TnT was 0.152 ug/L(sensitivity 0.659,specificity 0.894,Yuden index 0.553).There was a positive correlation between hs-TnT and Gensini scores in men,age>65 years old and the chest tightness group(P < 0.05). Conclusion The hs-TnT is better than four heart enzyme in early diagnosis of AMI and benefit early treatment of AMI.
ABSTRACT
Objective:To research the anti-dysmenorrhea effect of different extracts of Rupixiao granules. Methods:The anti-dys-menorrhea effect of different extracts of Rupixiao granules was studied by writhing test induced by oxytocin in mice. Results:Compared with the model group, the extracts of Rupixiao granules could reduce the writhing times induced by oxytocin significantly (P0. 05). Conclusion:The water-soluble parts of Rupixiao granules have significant anti-dysmenor-rhea effect.
ABSTRACT
Objective To study effects of Rupixiao granules on contraction of uterus of mice in vitro. Methods Mouse model with isolated uterine contraction was established. The mice pretreated with estradiol benzoate were sacrificed and then the uteri were taken out. The normal contractions were recorded by the biological function system. Effects of 10, 20, 30, 40, 50, 60 mg.mL-1 Rupixiao granules on spontaneous and oxytocin-induced (5 U.L-1) uterine contractions were recorded,inhibition of Rupixiao granules on mean constriction amplitude,constriction frequency and contraction activity of pitocin-pretreated uterus was observed and the inhibition rates were calculated. Results Compared with the baselines, the amplitude, frequency, activity of spontaneous uterine contraction were significantly down-regulated by Rupixiao solution at a range of 10-60 mg.mL-1 ,as well as it could inhibit oxytocin-induced spasmodic contraction of isolated uterus at 10-50 mg . mL-1 ( P<0. 01 ) . Conclusion The Rupixiao granules inhibits spontaneous contraction of isolated mouse uteri and oxytocin-induced spasm of uterine smooth muscle in vitro.
ABSTRACT
Objective:To investigate the anti-inflammatory and analgesic effects of Rupixiao granules. Methods:Activity of Rupixi-ao granules against xylene-induced ear edema in mice was measured to evaluate the anti-inflammatory effect, while the analgesic effect was evaluated by acetic acid induced writhing test and hot plate test in mice. Results:Compared with the control group, Rupixiao gran-ules groups (1. 0, 2. 0 and 4. 0 g·kg·d-1) could significantly inhibit ear swelling in mice(P<0. 05 or 0. 001), and reduce the acetic acid induced writhing times(P<0. 01 or 0. 001). Rupixiao granules at medium and high dose could significantly increase the pain thresh-old of mice in the hot plate test. Conclusion:Rupixiao granules exhibit significant anti-inflammatory and analgesic activities.
ABSTRACT
Objective To explore the action mechanism of shenxiong glucose injection in treatment of acute spinal cord injury(SCI) through observing its effects on the recovery of motor function and the expression of aquaporin-4(AQP-4) in SCI rats.Methods Totally 90 healthy,aduh,Sprague-Dawley rats were randomly divided into a sham operation group (n=30),aSCI group (n=30) and a drug group (n=30).The SCI rat models in both the SCI group and the drup group were established aecording to the modified Allen's method,while the sham operation group was only given laminectomy.After the operation,the drug group was given intraperitoneal shenxiong glucose injection of 30 rnl/kg a day,while the other two groups were injected in the same way with normal saline.The neural function recovery,the pathological changes after SCI and the expressions of AQP-4 were observed 1,3,7,14 and 21 d after the operation using the Tarlov score,the hematoxylin and eosin staining,as well as immunofluorescence techniques and Western blotting.And the correlation of Tarlov scores with AQP-4 expressions was analyzed.Results No significant changes in Tarlov scores were observed in the sham operation group (P ＞ 0.05),while in the SCI group and the drug group,postoperative Tarlov scores decreased significantly.The hindlimb nerve function recovered to some degree with time in the SCI group and drug group.At 3,7,14 and 21 days after the operation,the Tarlov scores in the drug group were significantly higher than the SCI group (P ＜ 0.05).The drug group showed less severe pathological changes,with more residual neurons still visible of nucleoli than the SCI group 21 days after the operation.Compared with the sham operation group,the expression levels of AQP-4 were significantly higher in the SCI group and drug group at all the time points (P ＜ 0.05).However,the expression levels of AQP-4 in the drug group were significantly lower than the SCI group accordingly (P ＜ 0.05).The Tarlov scores were found to be significantly and negatively related to the AQP-4 protein expression levels 3 days(r =-0.523,P =0.003),7 days(r =-0.437,P=0.016),14 days(r=-0.417,P=0.022) and 21 days(r=-0.377,P=0.040)after the operation.Conclusion Injecting shenxiong with glucose can effectively promote the recovery of motor function after SCI,at least in rats.And its mechanism may be that the development of spinal cord edema is prevented and the secondary spinal cord injury alleviated by restraining the expressions of AQ P-4 in the injured areas.
ABSTRACT
Objective To investigate clinical efficacy of different ventilator parameters on acute left heart failure.Methods One hundred and nineteen patients with acute left heart failure were randomly divided into A,B,C,D group.Patients in A,B,C,D groups were treated separately with higher air pressure,high pressure,medium pressure or low pressure respectively.In each group,clinical efficacy,heart rate (HR),arterial partial pressure of oxygen (PaO2),pulse oxygen saturation (SpO2),partial pressure of carbon dioxide (PaCO2) and pH were measured.Results There were significant differences among the four groups in terms of HR,PaO2,SpO2,PaCO2 and pH (F =32.21,29.46,12.34,36.47,18.38 ; P ＜ 0.05).Compared with that in A,C and D group,the levels of HR,PaO2,SpO2,PaCO2 and pH in B group were significant difference (P ＜ 0.05).Meanwhile those indices in B group were difference among before and after treatment (t =12.25,13.46,8.75,9.83,2.58 ;P ＜ 0.05).The efficacy rates of four groups were significant different (x2 =0.97,P =0.012),and in B group was 93.1％,higher than that of other 3 groups(71.0％,65.6％,51.8％ ;P ＜0.05).Condusion The ventilator parameters(10-15 cmH2O,55％-75％ FiO2 at beginning and later revised the FiO2 to 30％-40％) was proved to be worthy in treating acute left heart failure.
ABSTRACT
Objective To investigate the relationship of plasma homocysteine with the genotype distribution of MTHFR and MTRR among Chinese Han women in Xiangtan. Methods MTHFR C677T, A1298C and MTRR A66G geno?typing was analyzed to detect the distribution of gene polymorphisms among 1 701 women from Xiangtan city then the data were compared with the rest of the Han women in Zibo, Zhengzhou, Yantai, Zhenjiang, Songzi, Huizhou, Qionghai. Plasma Hcy levels from 110 patients were measured and analyzed the correlation with gene polymorphisms. Results The frequency of MTHFR C677T genotype and allele frequencies in Xiangtan is 12.6%which is higher than Huizhou (10.9%) and Qionghai (6.1%) but lower than Zibo (43.6%), Zhengzhou (36.8%), Yantai (32.2%), Zhenjiang (21.8%) with statistically significant dif?ference (P<0.05). There is no significant different in MTHFR C677T between Xiangtan and Songzi. The frequency of MTH?FR A1298C genotype and allele frequencies in Xiangtan is 4.8%which is lower than Qionghai(7.1%)but higher than Zibo (1.4%),Zhengzhou(2.4%), Yantai(1.8%), Zhenjiang(3.5%)and Songzi(2.6%)with statistically significant difference. The frenquency of MTRR A66G genotype and allele frequencies in Xiangtan is 6.8%which is higher than Zibo (4.8%) but lower than Qionghai (9.3%) with statistically signifcant difference. Plasma Hcy concentration correlate with MTHFR C677T, Hcy concentration in TT population is higher than that in CT and CC population(μmol/L:8.52±2.01 vs 5.94±1.47 vs 5.71± 0.18);Plasma Hcy concentration also correlate with MTHFR A1298C and Hcy concentration in CC population is higher than AA and AC population(μmol/L:9.83 ± 2.26 vs 6.35 ± 2.13 vs 5.55 ± 1.75);Plasma Hcy concentration does not correlate with MTRR A66G. Conclusion The gene polymorphism of MTHFR C677T, A1298C and MTRR A66G among the Han women in Xiangtan was statistically different from other selected regions of China. Mutation in MTHFR C 677T and A1298C were associated with elevated plasma levels of Hcy.
ABSTRACT
Objective To analyze the clinical infection distribution and drug resistance status of 442 strains of Escherichia coli to provide the basise for the treatment of Escherichia coli infection and the control of nosocomial infection.Methods The clinically submitted various kinds of specimens during 2013 were performed the bacterial culture and identification.The susceptibility of Escherichia coli to commonly used bacterial drugs were detected by adopting the MIC method.The data were analyzed by WHO-NET V5.5 and SPSS V13.0 softwares.Results 442 strains of Escherichia coli were isolated from the middle urine and secretion. The detection rate of ESBLs-producing Escherichia coli was 61.3%.442 strains of Escherichia coli had the high resistance to peni-cillins,cephalosporins and fluoroquinolones,better sensitivity toβ-lactam/β-lactamase inhibitor compounds and highest sensitivity to carbapenems.ESBLs-producing Escherichia coli had the higher resistance to commonly used antibacterial drugs than non-ESBLs-producing Escherichia coli .Conclusion The drug resistance of Escherichia coli is severe.ESBLs-producing Escherichia coli are u-sually resistant to many different types of antimicrobial drugs.Carbapenems are the first choice to treatment of severe infections of Escherichia coli .
ABSTRACT
Objective To evaluate the role of membrane-bound complement regulatory protein expression in spinal cord dorsal horn in the development of neuropathic pain (NP) in rats.Methods Forty-eight male Sprague-Dawley rats,weighing 200-250 g,in which intrathecal catheters were successfully implanted without complications,were randomly divided into 4 groups (n =12 each):sham operation group (group S),group NP,normal saline group (group NS) and minocycline group (group M).NP was induced by chronic constrictive injury of the sciatic nerve in NP,NS and M groups.Minocycline 50 μg was injected intrathecally once a day for 7 consecutive days starting from 1 day before ligation of the sciatic nerve in M group,while the equal volume of normal saline was given in stead of minocycline in NS group.Mechanical pain threshold and thermal pain threshold were measured at 1 day before ligation of the sciatic nerve (baseline,T0) and 1,3,7 days after ligation of the sciatic nerve (T1-3).Then the rats were sacrificed at T3 and the lumbar segment (L4,5) of spinal cord was removed for determination of the expression of CD46,CD55,CD59 protein and mRNA in the dorsal horn of spinal cord by Western-blot and RT-PCR,respectively.Results Compared with S group,mechanical pain threshold and thermal pain threshold were significantly decreased at T1-3 and the expression of CD46,CD55 and CD59 protein and RNA was down-regulated at T3 in NP,NS and M groups (P ＜ 0.05).Compared with groups NS and NP,mechanical pain threshold and thermal pain threshold were significantly increased at T2.3 and the expression of CD46,CD55 and CD59 protein and RNA was up-regulated at T3 in M group (P ＜ 0.05).Conclusion The down-regulated expression of membrane-bound complement regulatory proteins in spinal cord dorsal horn and abnormal activation of the complement are involved in the development of NP in rats.
ABSTRACT
ObjectiveTo observe the affection of cilostazol combined with valsartan in treating patients with early diabetic nephropathy on serum homocysteine and cystatin C,MethodsNinety-six cases with early diabetic nephropathy were divided into two groups by random digits table method with 48 cases each:observation group was treated with cilostazol and valsartan,control group was treated with valsartan alone.The effect and the levels of 24 h urinary albumin,serum homocysteine and cystatin C before and after treatment in two groups were compared.ResultsThe total effective rate in observation group [85.4％(41/48) ] was significantly higher than that in control group [66.7％(32/48) ](P ＜ 0.05 ).The levels of 24 h urinary albumin,serum homocysteine and cystatin C were significantly decreased after treatment of three weeks in observation group and control group [ (125.48±13.76) mg,(9.25±3.52)p mol/L,(7.82±2.14) mg/L and (168.38±15.43) mg,(13.72±4.23) μ mol/L,(9.57±2.85) mg/L vs.(279.31±21.52) mg,(18.52±6.14) μ mol/L,( 13.25±3.79) mg/L and (275.24±19.31 ) mg,( 18.48±6.12) μ mol/L,( 13.19±3.76)mg/L](P＜ 0.05).And the levels of 24 h urinary albumin,serum homocysteine and cystatin C after treatment of three weeks in observation group were obviously lower than those in control group(P ＜ 0.05).Conclusions Cilostazol combined with valsartan in treating patients with early diabetic nephropathy can improve clinical effect obviously,degrade the level of urinary albumin,homocysteine and cystatin C.Therefore,it deserves to be applied in clinic.
ABSTRACT
Objective To explore the relevant factors of diabetic retinopathy(DR).Methods 400 patients with type 2 diabetes were selected,and the relevant factors with DR of type 2 diabetes were analyzed.Results The incidence of DR in type 2 diabetes was 49.0％.In type 2 diabetes when diabetes duration＞15 years,the incidence of DR was 84.7％,duration＜5-year incidence rate was 30.0％ respectively,there were significant differences(P＜0.05).Incidence rate in lower blood glucose group and poor glycemic control group were 38.1％ and 68.5％ respectively,and there was statistically difference(P＜0.05),and in normal blood pressure and well control group,the incidence rates were 44.1％ and 41.2％,which were significantly better than 80.0％ of poorly controlled hypertension group.Conclusion Duration of diabetes,glycemic control level,blood pressure,exercise,and regular schedule were related factors of DR.The most important thing of DR treatment and prevention was to control blood glucose.