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Mutations of NKX2-5 largely contribute to congenital heart diseases (CHDs), especially atrial septal defect (ASD). We identified a novel heterozygous splicing mutation c.335-1G > A in NKX2-5 gene in an ASD family via whole exome sequencing (WES) and linkage analysis. Utilizing the human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) as a disease model, we showed that haploinsufficiency of NKX2-5 contributed to aberrant orchestration of apoptosis and proliferation in ASD patient-derived hiPSC-CMs. RNA-seq profiling and dual-luciferase reporter assay revealed that NKX2-5 acts upstream of PYK2 via miR-19a and miR-19b (miR-19a/b) to regulate cardiomyocyte apoptosis. Meanwhile, miR-19a/b are also downstream mediators of NKX2-5 during cardiomyocyte proliferation. The novel splicing mutation c.335-1G > A in NKX2-5 and its potential pathogenic roles in ASD were demonstrated. Our work provides clues not only for deep understanding of NKX2-5 in cardia development, but also for better knowledge in the molecular mechanisms of CHDs.
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Comunicação Interatrial , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Humanos , Fatores de Transcrição/genética , Proteína Homeobox Nkx-2.5/genética , Quinase 2 de Adesão Focal/genética , Proteínas de Homeodomínio/genética , Comunicação Interatrial/genética , Mutação/genética , MicroRNAs/genéticaRESUMO
Objective To evaluate the safety and effectiveness of drug-eluting stents (DES)implanted in the main branch(MB)of the coronary artery combined with drug-coated balloon(DCB)inflation in the side branch(SB)in patients with coronary bifurcation lesions.Methods A total of 68 patients with true coronary bifurcation lesions(Medina 1,1,1;1,0,1;0,1,1) admitted into our hospital from June 2017 to June 2018 were enrolled in this single center observation study.Patients were treated with DES MB implantation and DCB SB inflation,and were followed up and assessed with quantitative coronary angiography(CAG)at 6 months after PCI.The primary endpoints were late lumen loss(LLL)of MB and SB at 6 months after PCI.Results DES was implanted in MB in 68 patients.DCB was used in SB in 67 patients,and DES was implanted in SB in 1 patient due to TIMI 1 flow in SB after predilation.The rate of residual stenosis was (8.9 ± 5.6) % in MB and (19.7 ± 6.2)% in SB immediately after PCI.Of 68 patients,type A dissection occurred in 7 cases and type B dissection in 5 cases in MB immediately after PCI.Overall 64 patients were followed up and assessed with quantitative CAG at 6 months after PCI.The LLL of MB was (0.25±0.31)mm and the LLL of SB was-(0.12±0.38)mm.All patients' SB dissection disappeared,and 1 patient died due to cerebral hemorrhage at 2 months after PCI.The 30-day main adverse cardiac events(MACE)was 0,and 6-month MACE was 5.97%,in which 2 cases had angina pectoris at about 3 months after PCI,with CAG showing in-stent restenosis(ISR)in the left anterior descending coronary artery(LAD)and good SB.DCB was used to treat ISR.LAD was good when assessed with CAG at 6 months during follow-up.Myocardial infarction occurred in 2 cases at about 4 months after PCI,but not in the target-vessel.Conclusions DES MB implantation combined with DCB SB inflation is safe and effective in treating coronary bifurcations lesions.
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[Objective] To research the construction and optimization of natural language processing model for unstructured medical records,and using the model to extract structured data from medical records of stroke patients in Jiangxi Medical Big Data Platform.[Methods] According to the actual needs of clinical research,a stroke specialist entity annotation system and named entity annotation corpus were constructed based on 500 hospital admission records of stroke patients,which randomly selected between 2011 to 2016 from the Jiangxi provincial medical big data platform.The corpus is used to construct a named entity extraction model based on CRF and RUTA rules,and the recognition accuracy is improved by adjusting RUTA rules and parameters.[Results] Accuracy rate of extraction model was 0.960,recall rate was 0.916 and F-score was 0.939.The extraction model was used to extract 264 580 entities and 1 161 077 entity relation from 10 295 stroke patients' admission records of the medical big data platform.[Conclusions] The constructed natural language extraction model has a high recognition accuracy,which can accurately obtain valuable scientific research data of patients' past history,life history and clinical manifestations from a large number of unstructured medical records and effectively improve the clinical research efficiency and scientific research level of cerebrovascular diseases.
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OBJECTIVE:To compare the efficacy,safety,vascular endothelial growth factor(VEGF)and matrix metallopro-teinase-2 (MMP-2) of docetaxel combined with carboplatin and paclitaxel combined with cisplatin (DDP) in the treatment of ad-vanced ovarian cancer. METHODS:120 patients with advanced ovarian cancer were randomly divided into docetaxel combined with carboplatin group(60 cases)and paclitaxel combined with DDP group(60 cases). Docetaxel combined with carboplatin group received 70 mg/m2 Docetaxel injection,intravenous infusion of 1 h,d1;50 mg/m2 carboplatin injection,intravenous infusion of 1 h,d2. Paclitaxel combined with DDP group received 135 mg/m2 Paclitaxel injection,intravenous infusion of 24 h,d1;30 mg/m2 DDP for injection,intravenous infusion,d3;60 mg/m2 Paclitaxel injection (a maximum of 2.0 m2) by intraperitoneal infusion,d8. 3-week was regarded as 1 treatment course,and it lasted 6 courses. Clinical efficacy,VEGF,MMP-2,progression-free survival, overall survival before and after treatment,mortality rate within 2 years of treatment and the incidence of adverse reactions in 2 groups were compared. RESULTS:There were no significant differences in the objective response rate,disease control rate,mortal-ity rate,incidence of adverse reactions between 2 groups(P>0.05). The progression-free survival in docetaxel combined with car-boplatin group was significantly longer than paclitaxel combined with DDP group,the difference was statistically significant (P0.05). After treat-ment,VEGF and MMP-2 level in 2 groups were significantly lower than before,and VEGF at different time points and MMP-2 level after 4 weeks,8 weeks and 12 weeks of treatment in docetaxel combined with carboplatin group were lower than paclitaxel combined with DDP group,the differences were statistically significant(P<0.05). CONCLUSIONS:Docetaxel combined with car-boplatin and paclitaxel combined with DDP shows similar efficacy and safety in the treatment of advanced ovarian cancer,but docetaxel carboplatin combined with is superior to paclitaxel combined with DDP in reducing VEGF and MMP-2 and improving pro-gression-free survival.
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<p><b>OBJECTIVE</b>To compare the complications associated with mechanical and manual cervical esophagogastric anastomosis following esophagectomy for esophageal cancer.</p><p><b>METHODS</b>From September, 2004 to June, 2007, 227 patients with middle and upper thoracic esophageal cancer underwent cervical esophagogastric anastomosis after esophagectomy. The patients were randomized into two groups and cervical esophagogastric anastomosis was performed using a stapler (n=102) or manually (n=125). The incidence of postoperative complications and operative time were compared between the two groups.</p><p><b>RESULTS</b>In manual anastomosis group, anastomotic leak and anastomotic stricture occurred in 14.4% (18/125) and 8.8.% (11/125) of the patients, significantly higher than the incidences of 2.9% (3/102) and 3.9% (4/102) in the mechanical anastomosis group (P<0.01). Manual anastomosis required a significantly longer operative time than mechanical anastomosis (52∓12 vs 25∓5 min, P<0.01).</p><p><b>CONCLUSION</b>The use of circular mechanical stapler in cervical esophagogastric anastomosis is associated with a lower rate of anastomotic leak and a shorter operative time, and is easy to learn and standardize to reduce the complications of the anastomosis.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anastomose Cirúrgica , Métodos , Fístula Anastomótica , Constrição Patológica , Neoplasias Esofágicas , Cirurgia Geral , Esofagectomia , Métodos , Complicações Pós-Operatórias , Suturas , Resultado do TratamentoRESUMO
<p><b>OBJECTIVE</b>To summarize our experience with video-assisted thoracoscopic (VATS) removal of esophageal leiomyoma located with endoscopy during operation.</p><p><b>METHODS</b>Between January 2006 and December 2010, 55 patients with esophageal leiomyoma underwent VATS enucleation. The surgical procedure was similar to that of open thoracotomy with intraoperative endoscopic location of the tumor and examination of the mucosal integrity especially for tumors less than 1 cm in diameter.</p><p><b>RESULTS</b>Of the 55 patients undergoing VATS tumor removal, 54 patients completed the procedures smoothly, and 1 patient experienced ventricular fibrillation during the operation to require an open thoracotomy. Endoscopy was used in 38 patients during the operation. VATS enucleation differed significantly from open thoracotomy in the volume of bleeding, postoperative fasting days and postoperative hospital stay (P<0.05). The symptoms were completely relieved after the operation without postoperative complications. The patients were followed up for 8 to 59 months (mean 23.0 months) and no recurrence was found.</p><p><b>CONCLUSION</b>VATS removal of esophageal leiomyomas is minimally invasive, safe and effective and can serve as the primary option for surgical removal of esophageal leiomyomas.</p>
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias Esofágicas , Cirurgia Geral , Gastroscopia , Métodos , Leiomioma , Cirurgia Geral , Cirurgia Torácica Vídeoassistida , Métodos , Toracoscopia , Toracotomia , Resultado do TratamentoRESUMO
Objectives To investigate the adverse effect of manganese exposure on the iron metabolism in peripheral blood of professionally exposed workers. Methods The manganese in air was collected using personal air sampler, and the time weighted average (TWA) concentration of exposure to manganese was then calculated. The subjects were divided into exposure group (n=85) and control group (n=80) based on the exposure doses they received. The concentrations of iron and manganese in the plasma and blood cells of the subjects were determined using flame atomic absorption detector and graphite furnace atomic absorption detector. Serum ferritin, transferrin, transferrin receptor and total iron binding capacity were determined using enzyme linked immunosorbent assay. Results The manganese contents in both plasma and blood cells were much higher in exposure group than in control group (P0.05). It was revealed by linear correlation analysis that no linear correlation existed between the professional exposure time and manganese and iron contents in both plasma and blood cells, serum ferrin, transferrin, transferring receptor and total iron binding capacity (P>0.05). Conclusion The long-term exposure to high dose manganese may result in an imbalance of iron metabolism in the peripheral blood in exposed population, manifesting a decrease of plasma iron and serum transferrin receptors, and an increase of serum transferrin.
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Objective To investigate the p53,Bax,bcl-2 gene in NaAsO2-induced human embryonic lung fibroblasts(HELF)apoptosis.Methods HELF was divided into HELF cells transfected with p53 plasmid(p53 group),HELF cells transfected with PC plasmid(PC group)and normal cultured HELF cells(normal group).The mRNA expression of p53,Bax and bcl-2 gene was detected by real-time PCR,the protein expression of p53,Bax and bcl-2 was assessed by immunohistochemical SABC and the cell apoptosis of HELF was detected by flow cytometry(FCM),in a 6-well plate and cultured for 48 hours,which was exposed to different doses(0,3,9,15mmol/L)NaAsO2 for 24 hours.Results The p53 gene mRNA expression level of p53 group(0.51±0.29)was lower than that of the normal group and PC group [ (1.00 ± 0.20), (1.32 ± 0.26), all P < 0.05 ]. The p53 protein expression level of p53 group(4.10 ± 1.20) was lower than the PC group and normal group[ (8.00 ± 1.63), (7.90 ± 1.79), allP < 0.05]. In p53 group, PC group, normal group exposed to 0,3,9,15 mmol/L NaAsO2 doses, the apoptotic rate [(0.57 ± 0.28)%, (22.91 ± 4.86)%, (40.05 ± 3.93)%, (44.87 ± 3.58)%; (0.65 ± 0.24)%, (14.09 ± 3.49)%,(20.31 ± 3.66)%, (32.42 ± 3.63)%; (0.56 ± 0.25)%, (12.14 ± 3.70)%, (19.61 ± 3.63)%, (30.43 ± 2.83)%], Bax mRNA expression level[(12.73 ± 3.96), (25.12 ± 6.42), (104.96 ± 26.77), (154.04 ± 30.52); (14.63 ± 3.57),(36.75 ± 3.67), (272.26 ± 66.11), (846.12 ± 243.36); (14.75 ± 5.65), (37.22 ± 11.27), (278.51 ± 37.42),(861.67 ± 369.29) ], Bax protein expression level [ ( 15.07 ± 0.83 ) %, ( 23.79 ± 3.99 ) %, (38.51 ± 1.58 ) %, (53.86 ±1.74)%;(15.43 ± 1.45)%,(36.11 ± 1.37)%, (56.86 ± 1.97)%, (76.09 ± 2.01)%; (15.20 ± 1.03)%,(35.25 ±1.09)%, (55.56 ± 2.17)%, (74.48 ± 2.85)% ] was respectively increased in a dose-dependent manner with the increased concentration of NaAsO2(all P < 0.05). The bel-2 mRNA expression level [ (443.00 ± 244.47), (156.79 ±53.18), (62.13 ± 13.66), (23.10 ± 6.44); (420.55 ± 110.77), (48.15 ± 10.02), (14.91 ± 6.53), (7.54 ± 2.62);(577.75 ± 123.22), (49.68 ± 10.11), (12.41 ± 1.28), (7.22 ± 1.89)], bcl-2 protein expression level[(47.20 ±3.77)%, (41.80 ± 2.94)%, (36.00 ± 2.36)%, (29.00 ± 2.91)%; (45.90 ± 4.15)%, (35.70 ± 2.77)%, (29.80 ±2.78)%, (24.80 ± 2.66)% ; (46.70 ± 3.47)%, (36.20 ± 2.90)%, (30.10 ± 3.21)%, (25.10 ± 2.28)% ] wasdecreased in a dose-dependent manner with the increased concentration of NaAsO2(all P < 0.05 ). In 3,9,15 mmol/L NaAsO2, apoptotic rate of p53 group, mRNA expression of bcl-2, protein expression of bcl-2 was higher than that ofnormal group and PC group, respectively (all P < 0.05), but mRNA expression of Bax, protein expression of Bax was respeetivelylower than that normal group and the PC group(P < 0.05 ). Conclusion p53 gene reduced the apoptosis induced by NaAsO2 in HELF, possibly by changing the apoptosis pathway.
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<p><b>OBJECTIVE</b>To detect the presence of ion channel protein and its role in cell growth and proliferation in human head and neck squamous carcinoma cells (SCC).</p><p><b>METHODS</b>Human head and neck squamous carcinoma SCC-25 cell line was tested with transient receptor potential melastatin 7 (TRPM7) antibody using the method of immunocytochemistry. The role of TRPM7 in cell growth and proliferation was evaluated through its blockade by ion channel blockers and specific siRNA using lactate dehydrogenase (LDH) assay technique.</p><p><b>RESULTS</b>Clear immunoreactivity against TRPM7 was detected in almost all SCC-25 cells tested, whereas no immunoreactivity was observed in negative control. The inhibitory effect of Gd3+, a non-specific ion channel blocker, on cell growth and proliferation was potent. Addition of 10 micromol/L Gd3+ (n = 16) and 100 micromol/L Gd3+ (n = 16) in the culture medium significantly inhibited the growth of SCC-25 cells, as compared with control cells growing in normal medium (t was 4.1414 and 6.2661, P was 0.0256 and 0.0082 respectively). However, the effect of 2-APB was striking. Cell proliferation was almost totally suppressed in the presence of 100 micromol/L 2-APB (t = 13.4493, P = 0.0008, n = 16) compared with cells growing in normal medium. Suppression of TRPM7 expression by siRNA also significantly inhibited the growth and proliferation of these cells (t = 4.3446, P = 0.0002, n = 32, compared with nontransfected cells),whereas cells transfected with negative control siRNA showed no difference in cell proliferation compared with nontransfected cells.</p><p><b>CONCLUSIONS</b>All of those results strongly suggest the existence of TRPM7 channel in human head and neck squamous carcinoma cells. Ion channel blockers serve as a potent inhibitor of SCC-25 cell proliferation. The striking inhibitory effect of 2-APB on cell growth and proliferation may promise clinical workers an inspiring remedy for fighting against carcinoma.</p>
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Humanos , Carcinoma de Células Escamosas , Metabolismo , Patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias de Cabeça e Pescoço , Metabolismo , Patologia , Proteínas Serina-Treonina Quinases , Canais de Cátion TRPM , MetabolismoRESUMO
Objective To investigate the inhibitory effect of recombinant LIGHT-Fe gene on the proliferation of human esophageal carcinoma cell line Eea109. Methods LIGHT-Fc expression vector was transfected into human esophageal squamous carcinoma cell line Eca109 by using DOTAP liposomal transfection reagents. The effects of LIGHT-Fc gene on the proliferation of esophageal carcinoma cell line Eca109 in vitro were detected by cell growth curve and MTr assay. Forty-five nude mice were equally divided into Eea109/Wt group, Eca109/neo group and Eca109/LIGHT group. Carcinogenesis and pathological expression of the esophageal carcinoma tissues were observed. Results The expressions of LIGHT receptors were detected in Eca109 cells. The proliferation of Eca109 cells was inhibited after trasfecting LIGHT-Fc gene into Eca109 cells. The numbers of tumors generated in Eea109/Wt group, Eca109/neo group and Eca109/LIGHT group were 12, 11 and 5, with statistical significance between Eca109/LIGHT group and the other two groups (X2 =6.652, 4.821, P <0.05). The result of histopatholagical examination indicated that the tissue necrosis appeared significantly in tumors derived from Eea109/LIGHT cells. Conclusions The growth of esophageal squamous carcinoma cell line Eca109 can be suppressed by LIGHT-Fc gene whether in vitro or in vivo.
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0.05).CONCLUSION:Nedaplatin combined with docetaxel is effective and safe for advanced NSCLC with high short-term efficacy and mild toxic side reaction in digestive tract and kidney.but the long-term efficacy of it require further study.
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<p><b>OBJECTIVE</b>To establish two-dimensional electrophoresis profiles from human esophageal cancer tissue and paired normal esophageal tissue and identify differentially expressed proteins to identify the molecular markers for early-stage diagnosis.</p><p><b>METHODS</b>The total proteins of human esophageal cancer tissue and paired normal esophageal tissue were separated by immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE). The 6 differentially expressed proteins were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The peptide mass fingerprintings (PMF) were identified by database searching. Six differentially expressed proteins were validated by RT-PCR.</p><p><b>RESULTS</b>The well-resolved, reproducible 2-DE patterns of esophageal cancer tissue and esophageal normal tissue were established. Using MALDI-TOF-MS technology, 6 differential protein spots were identified. Among them, the expressions of squamous cell carcinoma antigen 1 (SCCA1b), KRT4 and annexin A1 were downregulated and triosephosphate isomerase (TPI1), heat shock protein 27 (HSP27) and manganese superoxide dismutase (MnSOD) were upregulated in esophageal cancer tissues.</p><p><b>CONCLUSION</b>The identification of differential expressed proteins in human esophageal cancer and normal tissue will be helpful for screening the biomarker for early-stage diagnosis.</p>
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Humanos , Biomarcadores Tumorais , Genética , Metabolismo , Diagnóstico Precoce , Eletroforese em Gel Bidimensional , Neoplasias Esofágicas , Diagnóstico , Genética , Patologia , Esôfago , Biologia Celular , Metabolismo , Patologia , Regulação Neoplásica da Expressão Gênica , Espectrometria de Massas , Estadiamento de Neoplasias , Proteínas , Genética , MetabolismoRESUMO
Objective To evaluate the clinical application and significance of lengthen-stem bipolar-femur prosthetic replacement for the treatment of old-age patients with intertrochanteric fracture osteoporosis.Methods 28 cases of patients aging from 75 to 99 years old of intertrochanteric fracture osteoporosis treated with lengthen- stem cemented bipolar prosthesis were studicd from March 2000 to December 2006.After taking the blank margin, the bones of different sizes were replaced and the steel wire was fixed.After determining the depth of the front an- gle,the artificial bone was placed.Results After 28 examples attaining the following-up examination for 7 months to 3 years,with an average of 1.5 years,its function according to Harris standard was evaluated 3 months after the operation,8 examples were excellent,13 examples good,5 examples pass,2 examples inferior.The excellent or good rate reached 75% ,with no abnormal cases,no joint dislocation during the followed-up period.1 example had the phantom phenomenon 1 year after the operation.2 examples among the inferior had got more serious internal medicine disease which affected the restoring function.1 example died of the internal medicine disease 1 year after the operation.Conclusion By using the lengthen-stem bipolar-femur prosthetic replacement for the treatment of old patients with inrertrochanteric fracture osteoporosis,the patients will restore quickly after the operation and can carry a heavy load at an early time.The illness complication and the mortality rate will be redaced.But its related disease must be strictly dealt with and the surgery operating skill must be grasped.
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OBJECTIVE:To investigate the effect of shen-fu injection on toxic reaction relief in the chemotherapy for moderate to advanced non-small cell lung cancer(NSCLC).METHODS:130 patients of NSCLC were randomly divided into treatment group and control group,2 groups both received the second-generation regimen for chemotherapy,the major chemotherapeutic agents included vinorelbine,gemcitabine and paclitaxel,the treatment group was given intravenous shen-fu injection 60ml/d for continuous2weeks plus chemotherapy.RESULTS:The toxic reactions in treatment group significantly decreased compared to that in the control group(P
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OBJECTIVE:To compare amiodarone and cedilanid in the treatment of paroxysmal atrial fibrillation(AF) with intravenous administration and control of heart rate.METHODS:47 AF patients were randomly given 150~600 mg amiodarone(amiodarone group,n=24) and 0.2~0.6 mg cedilanid(cedilanid group,n=23) intravenously.The outcome,change of heart rate and adverse drug reaction of 2 groups were observed.RESULTS:Effective rate of amiodarone group was significantly higher than that of cedilanid groups(P
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Objective To investigate the in vitro inhibitory effect of LIGHT on human esophageal carcinoma cells. Methods LIGHT Fc expression vector was transfected into human esophageal squamous carcinoma cell line, Eca109. The inhibitory effect of LIGHT gene on cell growth was detected by MTT and cell growth curve. The expressions of LT?R and HVEM were detected by RT PCR. Results Expression of LIGHT Fc gene could inhibit Eca109 cell proliferation. The growth curve of Eca109/LIGHT was significantly lower than that of the control group in the culture medium containing 1% FCS. MTT test showed that there was significant difference in cell viability between Eca109/LIGHT and the control group ( P
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Objective To summarize the experience of surgical treatment of ascending aortic aneurysms and aortic dissections. Methods From February 2001 to October 2005, 31 patients including 26 male, 5 female, aged 41.3 years old (range 14-72) received surgical management. Twenty cases were diagnosed as ascending aortic aneurysm and aortic root aneurysm, 8 as Standford A dissection, 3 as Stanford B dissection. Twenty-one patients underwent classic Bentall procedure in which VSD repair was carried out in 1 case, mitral valvoplasty in 2 and mitral valve replacement in 2; Four patients underwent modified Bentall procedure (coronary button technique); Three patients underwent Wheat procedure; The remaining 3 patients with Stanford B dissection underwent graft replacement of descending aorta. Results There was no death during hospital stay that lasted 13-46 d with an average of 16.4 d after operation. The mean clinical follow-up was (21?18.5) months (range 1-63 months). One patient died without describable cause two years later. One patient had ascending aorta-pulmonary artery fistula at color Doppler examination half a year later. One patient was detected rupture of distal anastomoses half a year after operation and underwent stent-graft, SG. Conclusion The surgical treatment of aortic aneurysms and aortic dissections could be carried out safely based on the accurate diagnosis, specific surgical strategy and fine technique.
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AIM: To study the change of cellular immunological function in patients with locally advanced lung cancer before and after operations. METHODS: A lung cancer group of 20 cases with locally advanced lung cancer (group A), a benign disease group of 20 cases with lung benign disease (group B) and a normal group of 20 cases from healthy volunteers (group C) were set up. The levels of the peripheral blood T lymphocyte subsets (CD~+_3, CD~+_4, CD~+_8, CD~+_4/ CD~+_8 ratio) were detected in the group A before operation and on the 10th day and 17th day after operation by indirect immuno-fluorescence assay and contrasted with the group B and group C. RESULTS: The levels of T lymphocyte subsets in group A were abnormal before operation, CD~+_3, CD~+_4/ CD~+_8 ratio were significantly lower than those in group B and group C (P