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Objective To evaluate the efficacy and safety of the new left ventricular circulation assist device iVAC 2L in high-risk percutaneous coronaryintervention(HR-PCI)in Chinese patients.Methods We reported 6 PCIs in 5 patients supported by iVAC 2L,a new left ventricular circulation assist device,performed in Macao from September 2022 to March 2023.All patients were assessed by heart team and categorize to be high-risk for procedure.Clinical and intra-procedural data were analyzed.iVAC 2L-related complications and 30-day results were also documented.Results Insertion and removement of iVAC 2L successfully performed in all the 5 patients.Three of them underwent complete revascularization in the index procedure;one failed for the first time due to intolerance of the prolonged procedure,but succeeded for the reattempt of complete revascularization a month later,with the support of iVAC 2L.PCI was abandoned due to poor vessel condition.iVAC 2L,the new left ventricular circulation assist device,supported effectively during the 6 procedures.The patients were stable during the procedure.The success rate of hemodynamic support was 100%.No iVAC 2L-related complications and 30-day major adverse cardiac and cerebral events occurred,the 30-day survival was 100%.Conclusions Initial experience suggested that the new left ventricular circulation assist device iVAC 2L could provide effective and safe support in high-risk PCI.
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【Objective】 To analyze the changes of blood routine and platelet related parameters of the elderly apheresis platelet donors since the first donation, so as to ensure the health and platelet quality of the elderly apheresis donors. 【Methods】 From 2019 to 2021, a total of 69 apheresis platelet donors in our center, aged 55-60 years old, involving 3400 occasions of donation, were enrolled in this study. The change trends of blood routine and platelet related parameters before and after the age of 55 were retrospectively analyzed. One way ANOVA was used for group comparison, and Pearson correlation analysis of platelet parameters was performed. 【Results】 The values of blood routine and platelet related parameters were higher in men than in women (P0.05). As for the males in comparison of the parameters before 55 years old, WBC decreased significantly after 55 years of age (P0.05). The changes of PDW, MPV and P-LCR were consistent and showed a linear positive correlation. 【Conclusion】 The blood routine tests of the elderly apheresis platelet donors were all within the normal range and the proportion was relatively stable. Personalized blood donation schemes should be customized for the elderly blood donors and the health management of blood donors should be implemented.
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Posterior cortical atrophy (PCA) is a kind of neurodegenerative dementia. The core feature of the PCA includes progressive decline in visual processing and other posterior parietal-occipital cortex-related cognitive functions. Recently, neuroimaging features of PCA from magnetic resonance imaging/single photon emission computed tomography/ 18F-deoxyglucose positron emission tomography-computer tomography studies represent the typical characteristics of cortical atrophy, hypoperfusion, and hypometabolism in the posterior parietal-occipital cortex. The most common neuropathological changes of PCA are amyloid plaques deposition and neurofibrillary tangles in posterior cortex, while the molecular biomarkers are decreased amyloid β-protein 1-42 together with increased T-tau and/or P-tau in cerebral spinal fluid. From this point, PCA is also considered as an atypical form of Alzheimer′s disease (AD). However, individuals fulfilling the criteria for the core clinico-radiological PCA syndrome, can also fulfill the core clinical criteria for any other neurodegenerative syndrome, and represent negative AD-related pathophysiological biomarkers. Heterogeneity within the PCA syndrome and pathophysiological biomarkers prompt the PCA working group to establish a new consensus on PCA classification and diagnostic criteria, which is proposed for use in a number of different research contexts and the research of AD, atypical AD and related syndromes. This paper gives a brief introduction and interpretation of the newly proposed classification and diagnostic criteria of PCA.
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In recent years,magnetic resonance imaging (MRI) has been widely used in the early diagnosis as well as long-term follow-up study of Alzheimer's disease (AD).The studies were reviewed which applied the structural MRI and arterial spin labeling MRI (ASL-MRI) in AD over the past 20 years,and found more gray matter volume loss in multiple brain structures in individuals with AD spectrum.Among them,medial temporal lobe atrophy and posterior cortical atrophy are the most diagnostic.Meanwhile,cerebral blood flow changes in various brain regions with the progression of the AD.More investigations combining the changes of gray matter volume and cerebral blood flow to explore pathophysiological mechanisms underlying cognitive decline in AD spectrum are necessary in the future.
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Ulcerative colitis (UC) is a chronic nonspecific inflammation mainly involving rectum and colon mucosa, which seriously affects the health and quality of life of patients, and is listed as one of modern refractory diseases by WHO. Professor XU Jing-fan, a great master of traditional Chinese medicine, has accumulated rich experiences in the treatment of UC. The study collected Professor XU's 77 prescriptions of treating UC, analyzed the frequency of traditional Chinese medicines and there categories, and investigated the medication regularity by the system clustering method. The findings showed that the most frequently used drugs were clearing-heat herbs, which were followed by hemostatic herbs, excreting-dampness herbs, improving-digestion herbs and tonifying-Qi herbs. At the same time, the commonly combined drugs were excavated. Finally, in order to analyze potential molecular targets of the frequently used herbs, GO enrichment analysis and KEGG signal pathway enrichment analysis were performed with bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM). The results indicated that Chinese herbal compounds may treat UC by activating PPAR-γ pathway and regulating intestinal inflammation. The exact mechanisms shall be verified through subsequent molecular biological experiments.
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<p><b>INTRODUCTION</b>Obesity is a key risk factor in the development of Type 2 diabetes mellitus (T2DM). Bariatric surgery causes a large amount of durable weight loss in those with clinically severe obesity. We reported the effect of weight loss via bariatric surgery on DM prevention in those at high risk of developing DM.</p><p><b>METHODS</b>This was a retrospective cohort study of 44 patients with obesity (mean body mass index 43.8 kg/m) and pre-DM who underwent bariatric surgery and were followed up for up to three years. We also reviewed a non-surgical cohort of patients with obesity and pre-DM seen at the weight management clinic.</p><p><b>RESULTS</b>91% of patients attained normal glycaemic status at one year after bariatric surgery. At the three-year follow-up, 87.5% of the patients maintained normoglycaemia. None of the patients developed T2DM after surgery. 26.9% of patients achieved absolute weight loss at one year after bariatric surgery and maintained this at two and three years post surgery (p < 0.001 vs. baseline). The homeostatic model assessment-insulin resistance index in patients also decreased from 5.50 at baseline to 1.20, 1.14 and 1.44 at one, two and three years, respectively (p < 0.001).</p><p><b>CONCLUSION</b>Bariatric surgery produces significant weight loss, and leads to reversion from the pre-diabetic state to normal glycaemic status and reduction of the incident DM rate in those with pre-DM and morbid obesity.</p>
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<p><b>INTRODUCTION</b>We aimed to compare the malignancy risk stratification of histologically proven thyroid nodules using the 2015 American Thyroid Association (ATA) Management Guidelines, 2014 British Thyroid Association (BTA) Guidelines for the Management of Thyroid Cancer and the Thyroid Imaging Reporting and Data System (TIRADS).</p><p><b>METHODS</b>Thyroid nodules measuring > 1 cm resected over 5.5 years were retrospectively studied. Demographic information as well as cytology and histopathology results were collected. Static ultrasonography (US) images and radiologists' reports of each resected nodules were reviewed and classified based on the above risk classification systems.</p><p><b>RESULTS</b>A total of 167 thyroid nodules from 150 patients were examined. More malignant nodules were solid (78.4% vs. 62.5%; p = 0.049) or hypoechoic (70.6% vs. 28.6%; p < 0.001), and had irregular margins (35.3% vs. 8.0%; p < 0.001), taller-than-wide morphology (9.8% vs. 2.7%; p = 0.031), microcalcifications (33.3% vs. 8.0%; p < 0.001), disrupted rim calcifications (9.8% vs. 0.9%; p = 0.012) or associated abnormal cervical lymphadenopathy (13.7% vs. 0.9%; p = 0.001) compared with benign nodules. The guidelines' diagnostic performance was: ATA - sensitivity 98.0%, specificity 17.3%, positive predictive value (PPV) 35.0%, negative predictive value (NPV) 95.0%; BTA - sensitivity 90%, specificity 50.9%, PPV 45.5%, NPV 91.8%; and TIRADS - sensitivity 94.0%, specificity 28.2%, PPV 37.3%%, NPV 91.2%.</p><p><b>CONCLUSION</b>Sonographic patterns outlined by the three guidelines displayed high sensitivity and NPV. Although isolated suspicious US features cannot predict malignancy risk, they should be considered when risk stratifying nodules that do not fit into particular sonographic patterns based on current guidelines.</p>
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Objective To study the apllication value of cerebraspinal fluid minimal residual leukemia cells(MRLCs) combined with lactate dehydrogenase(LDH) detection in early diagnosis of central nervous system leukemia(CNSL) to provide a laboratory basis for clinical diagnosis and evaluation of disease progression and therapeutic effect.Methods Thirty inpatiernts without blood disease and central nervous system(CNS) organic diseases,and normal CSF routine and detected biochemical indexes were selected as the control group and 96 cases of acute leukemia (AL) diagnosed by bone marrow puncture FAB morphology and flow cytometry typing served as the disease group.Flow cytometry was used to detect the MRLCs in CSF,the activity of LDH in CSF was detected by the rate method,and the detection results were performed the comparative analysis.Results Among 96 cases of AL,30 patients with CNSL had 13 cases of positive MRLCs in CSF,the positive rate was 43.33%,among 66 cases of non-MRLCs,MRLCs was not detected detected.Among 96 cases of AL,CSF LDH level in 30 cases of CNSL was (30.54±10.29)U/L,which was significantly higher (16.16±7.12)U/L in the patients without CNSL,the difference between the two groups was statistically significant (P<0.05).Conclusion The detection of MRLCs and LDH in CSF of AL can be used as a laboratory diagnostic index for early diagnosis of CNSL,and MRLCs combined with LDH detection can improve the positive diagnosis rate of CNSL.
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<p><b>OBJECTIVE</b>To assess the association of single nucleotide polymorphisms (SNPs) of PLEKHA7, COL11A1 and PCMTD1-ST18 genes and primary angle closure glaucoma (PACG) among ethnic Han Chinese from Sichuan Province.</p><p><b>METHODS</b>In this study, 362 subjects with PACG and 1056 age- and sex-matched healthy controls were recruited. Genotypes of 3 reported SNPs, including PLEKHA7 rs11024102, COL11A1 rs3753841 and PCMTD1-ST18 rs1015213 were determined with a SNaPshot method.</p><p><b>RESULTS</b>The P values for the genotype frequencies of rs11024102, rs3753841 and rs1015213 between the patient and control groups were 0.62 (OR=1.09, 95%CI: 0.91-1.30), 0.42 (OR=1.04, 95%CI: 0.87-1.41) and 0.34 (OR=1.35, 95%CI: 0.73-2.49), respectively. And the P values for the allele frequency distributions of PLEKHA7 rs11024102, COL11A1 rs3753841 and PCMTD1-ST18 rs1015213 between the two groups were 0.347, 0.698 and 0.344, respectively.</p><p><b>CONCLUSION</b>No significant association of PLEKHA7 rs11024102, COL11A1 rs3753841 and PCMTD1-ST18 rs1015213 with PACG was found among ethnic Han Chinese from Sichuan.</p>
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Feminino , Humanos , Masculino , Proteínas de Transporte , Genética , China , Etnologia , Colágeno Tipo XI , Genética , Glaucoma de Ângulo Fechado , Genética , Polimorfismo de Nucleotídeo Único , Proteína D-Aspartato-L-Isoaspartato Metiltransferase , GenéticaRESUMO
PURPOSE: This study evaluated the effect of fluid-filled intragastric balloon treatment on the scintigraphic gastric emptying times in humans for weight control. PATIENTS AND METHODS: Ten obese patients were prospectively recruited in our study. Three participants followed a solid food diet, and 7 participants followed a liquid meal diet to evaluate their scintigraphic gastric emptying times before and 3 months after fluid-filled intragastric balloon treatment. RESULTS: The participants included 3 males and 7 females. The mean age, body mass index, and body weight before intragastric balloon treatment were 36.8 ± 9.16 years, 35.91 ± 8.86 kg/m(2), and 93.9 ± 24.09 kg, respectively. The mean body weight, body mass index, and body weight loss 3 months after the treatment were 80.2 ± 21.32 kg, 31.50 ± 8.90 kg/m(2), and 13.7 ± 6.60 kg, respectively. The solid gastric emptying times before and 3 months after intragastric balloon treatment were 114 ± 18.52 minutes and 375.33 ± 207.04 minutes, respectively. The liquid gastric emptying times before and after intragastric balloon treatment were 38.71 ± 15.91 minutes and 318.71 ± 168.07 minutes, respectively. Statistically significant differences were observed in the solid and liquid gastric emptying times before and 3 months after intragastric balloon treatment using the Wilcoxon t test (P = 0.027, P = 0.001). Significantly positive correlations were observed between body weight loss and solid and liquid gastric emptying times after intragastric balloon placement using the Spearman correlation (ß = 1.0, P < 0.001; ß = 0.95, P = 0.001). CONCLUSIONS: The solid and liquid scintigraphic gastric emptying half time is significantly longer after intragastric balloon treatment in humans. A significantly positive correlation between body weight loss and scintigraphic gastric emptying time was observed after intragastric balloon treatment. We can predict the effect of intragastric balloons on weight control through scintigraphic gastric emptying times after the treatment. The effect of intragastric balloons on weight loss may be reinforced by combining intragastric balloon treatment with medication that can reduce gastric motility.
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Balão Gástrico , Esvaziamento Gástrico , Redução de Peso/fisiologia , Adulto , Demografia , Feminino , Humanos , Masculino , Fatores de TempoRESUMO
<p><b>OBJECTIVE</b>To explore curative effects of advanced elastic intramedullary nail technology in treating children with femoral subtrochanteric fracture.</p><p><b>METHODS</b>Form March 2009 to December 2010, 16 children with femoral subtrochanteric fracture were treated with advanced elastic intramedullary nail technology. There were 12 males and 4 females ranging in age from 7 to 15 years old with a mean of 9.8 years old. According to fracture classification, 9 cases were stable fractures (traverse or short oblique type) and 7 cases were unstable fractures (comminuted or long oblique type). Radiographs and complications were retrospectively reviewed. Fracture healing were evaluated according to Flynn criteria.</p><p><b>RESULTS</b>All children were followed up from 11 to 32 months with an average of 21 months. No incision infecton,bone nonunion and breakage of screw occurred. The fracture healing time was from 8 to 16 weeks with an average of 10.1 weeks. According to Flynn criteria, 14 cases got excellent results, 1 moderate and 1 poor.</p><p><b>CONCLUSION</b>Advanced elastic intramedullary nail technology for the treatment of children with femoral subtrochanteric fracture is a safe and effective fixation, which is good for early mobilization, shorter the duration of hospital stays and reduce complications.</p>
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Adolescente , Criança , Feminino , Humanos , Masculino , Seguimentos , Fixação Intramedular de Fraturas , Métodos , Fraturas do Quadril , Cirurgia GeralRESUMO
<p><b>INTRODUCTION</b>Obesity is a risk factor for type 2 diabetes mellitus (T2DM). Metabolic-bariatric surgery (MBS) results in significant weight loss with dramatic improvement in T2DM. This study analysed the effects of MBS on patients with T2DM in a tertiary centre in Singapore.</p><p><b>METHODS</b>Individuals with T2DM who underwent MBS in a single centre from September 2008 to May 2012, with at least 12 months of regular follow-up, were included in our study. The primary outcome measure was good glycaemic control (glycated haemoglobin [HbA1c] < 6.5%, with or without medications) 12 months after surgery. Secondary outcome measures were partial DM remission (fasting blood glucose [FBG] < 7.0 mmol/L and HbA1c < 6.5% without DM medications), complete DM remission (FBG < 5.6 mmol/L and HbA1c < 6.0% without DM medications), weight, body mass index, blood pressure, and fasting serum lipid, serum glucose and serum insulin levels.</p><p><b>RESULTS</b>Of the 19 patients who met the inclusion criteria, 14 underwent gastric bypass and 5 underwent sleeve gastrectomy. At 12 months postoperatively, 17 (89.5%) patients achieved good glycaemic control. DM remission was achieved in 14 (73.7%) patients, with 10 (52.6%) attaining complete remission.</p><p><b>CONCLUSION</b>In Singapore, MBS is an effective treatment modality for obese patients with T2DM. Despite the small sample size and lack of matched controls, the present study suggests that MBS is effective in achieving significant weight loss and eliciting a significant and sustainable improvement in the glycaemic control of patients with T2DM, for up to 12 months.</p>
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Bariátrica , Glicemia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Insulina , Sangue , Lipídeos , Sangue , Obesidade Mórbida , Cirurgia Geral , Estudos Prospectivos , Fatores de Risco , Singapura , Resultado do TratamentoRESUMO
<p><b>INTRODUCTION</b>New-onset diabetes after transplantation (NODAT) is an increasingly recognised metabolic complication of kidney transplantation that is associated with increased morbidity and mortality. This study aimed to determine the incidence of NODAT and identify risk factors for development of NODAT among kidney allograft recipients in a single centre.</p><p><b>MATERIALS AND METHODS</b>We retrospectively reviewed all kidney allograft recipients in our centre between 1998 and 2007. NODAT were determined using criteria as per American Diabetes Association guidelines. Logistic regression analyses were performed to identify predictors of NODAT.</p><p><b>RESULTS</b>Among 388 patients included in the analysis, NODAT was reported in 94 patients (24.2%) after a median follow-up time of 52.1 months. The cumulative incidence of NODAT was 15.8%, 22.8% and 24.5% at 1, 3, and 5 years following transplantation. Seven clinical factors were independent predictors of NODAT: older age, HLA B13 and B15 phenotypes, use of sirolimus, acute rejections, higher pre-transplant and post-transplant (day 1) plasma glucose levels. Patients with NODAT had poorer outcomes in both graft and patient survival.</p><p><b>CONCLUSION</b>Our study demonstrates a significant risk and burden of NODAT in an Asian transplant population. Risk stratification and aggressive monitoring of blood glucose early post-transplantation is necessary to identify high-risk patients so that appropriate tailoring of immunosuppression and early institution of lifestyle modifications can be implemented.</p>
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia , Diabetes Mellitus , Genética , Rejeição de Enxerto , Antígenos HLA-B , Imunossupressores , Transplante de Rim , Fatores de RiscoRESUMO
<p><b>OBJECTIVE</b>To explore the effect of minimally invasive Ivor-Lewis esophagectomy on acute phase responses in patients with esophageal carcinoma.</p><p><b>METHODS</b>Forty-eight patients with middle or low thoracic esophageal carcinoma underwent Ivor-Lewis esophagectomy. The patients were divided into small incision group (n = 25) and conventional group (n = 23) according to the patients' will. Serum levels of acute phase proteins C reactive protein (CRP), haptoglobin (HPT), α₁-acid glycoprotein (α₁-AG), ceruloplasmin (CER), transferrin (TRF), β₂-microglobulin (β₂-MG), album protein (ALB), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were measured and compared on 1st day before operation, at 18 hours as well as 3rd and 7th day after operation.</p><p><b>RESULTS</b>There was no significant difference in all the acute phase proteins indicators and IL-6 between the small incision and conventional groups at each time points after operation (P > 0.05). In both groups the levels of CRP, α₁-AG and HPT were significantly higher after operation than before operation (P < 0.05). The levels of ALB and TRF were significantly lower after operation than before operation (P < 0.05). The levels of CER and β₂-MG were not significantly different during perioperative period (P > 0.05). The level of TNF-α was significantly higher in the small incision group than that in the conventional group at the 18 hours postoperationally (P < 0.05), and were not significantly different on the other time points between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>Compared with conventional operation, the small incision Ivor-Lewis esophagectomy do not significantly alleviate the stress of the surgical trauma in patients. Unchanging the essence of operation, if one is trying to minimize the stress caused by surgery on patients, the key factor is not the size of incision. An effective approach should be found in other operation-related factors.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Fase Aguda , Metabolismo , Proteína C-Reativa , Metabolismo , Carcinoma de Células Escamosas , Sangue , Cirurgia Geral , Ceruloplasmina , Metabolismo , Neoplasias Esofágicas , Sangue , Cirurgia Geral , Esofagectomia , Métodos , Haptoglobinas , Metabolismo , Interleucina-6 , Sangue , Procedimentos Cirúrgicos Minimamente Invasivos , Métodos , Orosomucoide , Metabolismo , Período Perioperatório , Albumina Sérica , Metabolismo , Albumina Sérica Humana , Transferrina , Metabolismo , Fator de Necrose Tumoral alfa , Sangue , Microglobulina beta-2 , SangueRESUMO
OBJECTIVE@#To evaluate the clinical significance of serum hepatitis C virus (HCV) core antigen detected by enzyme linked immunosorbent assay (ELISA).@*METHODS@#The serum HCV core antigen, which was taken from 149 patients with chronic hepatitis C, 20 patients of chronic hepatitis B and 20 health volunteers, was detected by ELISA. Meanwhile, the serum HCV RNA was detected by RT-PCR, and anti-HCV was detected by ELISA.@*RESULTS@#The qualitative HCV core antigen in the serum, which was take from 20 patients of chronic hepatitis B and 20 health volunteers, was negative.The positive percentage of HCV core antigen was 49.66% in the 149 sera of patients with chronic hepatitis C. The coincidence of detective results of HCV RNA and HCV core antigen was 54.36%, without significant difference (P>0.05). The positive percentage of HCV RNA and HCV core antigen in the 149 anti-HCV antibody positive sera samples were 55.03% (82/149) and 49.66% (74/149), respectively, and there was no significant difference (P>0.05).@*CONCLUSION@#The qualitative HCV core antigen detected by ELISA has a high specificity. The positive percentage of HCV core antigen in the serum of patients with chronic hepatitis C is 49.66%. HCV core antigen is related to HCV RNA. HCV core antigen may be a useful serum marker which could show HCV viraemia like HCV RNA.
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Humanos , Antígenos da Hepatite C , Sangue , Hepatite C Crônica , Sangue , RNA Viral , Sangue , Proteínas do Core Viral , SangueRESUMO
To establish a cell model in vitro that stable expressing HBV by integrating HBA1.3 DNA into cell chromosome. The HBV1.3 full-length DNA was obtained by digested pGEM-HBV1.3 plasmid with HindIII and then was linked with PU-21 vector digested by HindIII. This was resulted in generation of a recombined plasmid named PU21-HBV plasmid. The recombined plasmid was introduced into HepG2 cells by electroporation. The transfected cells were screened with G418. The insertion and expression of HBV were identified by X-gal staining, RT-PCR and Southern blot. The result of PU21-HBV plasmid sequence demonstrated that HBV1.3 DNA was linked correctly with PU-21 vector. A series of positive cell colonies were obtained with G418 screening followed transfecting PU21-HBV plasmid into HepG2 cells. The results of Southern blot and RT-PCR exhibit that HBV1.3 DNA had successfully integrated into the chromosomes of HepG2 cells and had functional HBV gene transcription. HBV1.3 DNA was inserted into HepG2 genome and could stable transcript HBV RNA. The stable HBV expression cell line was constructed successfully. There are LoxP sites in the trapping vector PU21. With the Cre enzyme, interesting genes could be excganged into the LoxP sites. Therefore, double stable expression of interesting gene and HBV cell lines could be generated. The cell lines will be useful for further research some target gene function on replication of HBV.
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The optical spectra, the zero-field splitting parameter D and the g-factor of transition-metal ions in crystal are related to the crystal structure. A method, which can be used to calculate accurately the optical spectra, the zero-field splitting parameter D and the g-factor, was founded by using the parametrization d orbital for Ni2+, the energy matrix elements of strong-field coupling scheme for d2 (d8) electron configuration in trigonal crystal field and by adopting the method of complete diagonalization. In the calculation, all spin singlet states and spin triplet states have been considered, and then the result is exact. The present theory shows that g(parallel) > g(perpendicular), D < 0 or g(parallel) < g(perpendicular), and D > 0 are due to the different distortion of ligands along C3 axis. The electron paramagnetic resonance spectrum in Ni2+:RbMgF3 with C3v and D3d symmetry was calculated by using the theory. The relationship between the EPR spectrum in Ni2+:RbMgF3 and the crystal structure were investigated. The agreement of the theory with the experiment shows that the present theory is reasonable.