Glycosides of Cistanche（GC）is a preparation used extensively for its neuroprotective effect against neurological diseases,but its mechanisms of action remains incompletely understood.Here,we established a bilateral ...Glycosides of Cistanche（GC）is a preparation used extensively for its neuroprotective effect against neurological diseases,but its mechanisms of action remains incompletely understood.Here,we established a bilateral common carotid artery occlusion model of vascular dementia in rats and injected the model rats with a suspension of GC（10 mg/kg/day,intraperitoneally）for 14 consecutive days.Immunohistochemistry showed that GC significantly reduced p-tau and amyloid beta（Aβ）immunoreactivity in the hippocampus of the model rats.Proteomic analysis demonstrated upregulation of mitochondrial precursor protein and downregulation of keratin type II cytoskeletal6A after GC treatment compared with model rats that had received saline.Western blot assay confirmed these findings.Our results suggest that the neuroprotective effect of GC in vascular dementia occurs via the promotion of neuronal cytoskeleton regeneration.展开更多
Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of I...Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.展开更多
To establish a better method of primary culture for alveolar epithelial type Ⅱ cells （AEC Ⅱ ） and to study its bionomics, alveolar epithelial type Ⅱ cells were isolated by digestion with trypsin and collagenase, ...To establish a better method of primary culture for alveolar epithelial type Ⅱ cells （AEC Ⅱ ） and to study its bionomics, alveolar epithelial type Ⅱ cells were isolated by digestion with trypsin and collagenase, which were then purified by plated into culture flask coated with rat immunoglobulin （i The purified AEC Ⅱ were identified by alkaline phosphatase staining, electron mi- croscopy, immunocytochemical staining of pulmonary surfactant protein A （SPA）. The SPA expression and transfection characteristics were compared with those of A549 cell line. The results showed that AEC Ⅱ could be isolated by digestion with trysin and collagenase and purified by adhesive purification by using IgG, with a yield of about 2-3 × 10^7, and a purity of about 75%-84 %. Cells could be quickly identified with AKP staining. AEC Ⅱ were different from A549 cell line in terms of SPA expression and transfection characteristics. It is concluded that adhesive purification with IgG can improve the purity of AEC Ⅱ, and AKP staining is simple in cell identification. AEC Ⅱ can not be completely replaced by A549 cells in some studies because the differences between them, such as SPA expression.展开更多
BACKGROUND： The pharmacological action of opioid drugs is related to signal transduction of inhibitory guanine nucleotide binding protein. OBJECTIVE： To quantitatively and qualitatively analyze the influence of morp...BACKGROUND： The pharmacological action of opioid drugs is related to signal transduction of inhibitory guanine nucleotide binding protein. OBJECTIVE： To quantitatively and qualitatively analyze the influence of morphine on levels of type Ⅱ inhibitory guanine nucleotide binding protein （Gi2 protein） in primary cultured hippocampal neurons at different time points. DESIGN, TIME AND SETTING： A randomized controlled study, which was performed at the Department of Neurobiology, Changzheng Hospital, Second Military Medical University of Chinese PLA between September 2002 and March 2004. MATERIALS： Cerebral hippocampal neurons were obtained from newborn SD rats at 1 2 days of age. Biotin-antibody Ⅱ-avidin fluorescein isothiocyanate （Avidin-FITC） was purchased from Sigma Company （USA） and the Gi2 protein polyclonal antibody from Santa Cruz Biochemistry Company （USA）. METHODS： Seven days after culture, mature hippocampal neurons were randomly divided into six groups： 4-, 8-, 16-, 24-, and 48-hour morphine groups, and a blank control group. Neurons in the morphine groups received morphine （10 μ mol/L）, which could cause alterations of G-protein mRNA and cAMP expression in the prefrontal cortex. Neurons in the blank control group were given the same volume of saline. MAIN OUTCOME MEASURES： Gi2 protein levels were detected by an immunofluorescence technique, and were analyzed by the image analytic system with the use of green fluorescence intensity. RESULTS： Gi2 protein levels in hippocampal neurons gradually decreased in the 4-, 8-, 16-, 24-, and 48-hour morphine groups. In particular, Gi2 protein levels in the 16-, 24-, and 48-hour morphine groups were significantly lower than that in the blank control group （P 〈 0.05 0.01）. CONCLUSION： Morphine may decrease Gi2 protein level in primary hippocampal neurons, and the decreasing trend is positively related to morphine-induced time.展开更多
The two-parameter exponential distribution is proposed to be an underlying model,and prediction bounds for future observations are obtained by using Bayesian approach.Prediction intervals are derived for unobserved li...The two-parameter exponential distribution is proposed to be an underlying model,and prediction bounds for future observations are obtained by using Bayesian approach.Prediction intervals are derived for unobserved lifetimes in one-sample prediction and two-sample prediction based on type Ⅱ doubly censored samples.A numerical example is given to illustrate the procedures,prediction intervals are investigated via Monte Carlo method,and the accuracy of prediction intervals is presented.展开更多
BACKGROUND For Siewert type Ⅱ/Ⅲ adenocarcinoma of gastroesophageal junction(AGE), the efficacy of adjuvant chemoradiotherapy(CRT) after D2/R0 resection remains uncertain.AIM To determine whether CRT was superior to ...BACKGROUND For Siewert type Ⅱ/Ⅲ adenocarcinoma of gastroesophageal junction(AGE), the efficacy of adjuvant chemoradiotherapy(CRT) after D2/R0 resection remains uncertain.AIM To determine whether CRT was superior to chemotherapy(CT) alone after D2/R0 resection for locally advanced Siewert type Ⅱ/Ⅲ AGE.METHODS We identified 316 locally advanced Siewert type Ⅱ/Ⅲ AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018.57 patients received adjuvant CRT and 259 patients received adjuvant CT.We followed patients for overall survival(OS), relapse-free survival, and recurrence pattern.RESULTS Five-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9%(P = 0.010).Five-year OS rates of the CRT group and the CT group for Siewert type Ⅲ AGE patients were 65.7% and 43.9%(P = 0.006).Among the 195 patients whose recurrence information could be obtained, 18 cases(34.6%) and 61 cases(42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively.The local and regional recurrence rates in the CRT group were lower than that in the CT group(22.2% vs 24.6%, 27.8% vs 39.3%).Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type Ⅲ AGE.CONCLUSION For locally advanced Siewert type Ⅲ AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.展开更多
Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous i...Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and safety.Herein,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal epithelium.After oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅡdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells activity.Surprisingly,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira.Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal epithelium.This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of liraglutide.In general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.展开更多
As energy crisis and environment pollution all around the world threaten the widespread use of fossil fuels,compressed natural gas(CNG)vehicles are explored as an alternative to the conventional gasoline powered vehic...As energy crisis and environment pollution all around the world threaten the widespread use of fossil fuels,compressed natural gas(CNG)vehicles are explored as an alternative to the conventional gasoline powered vehicles.Because of the limited space available for the car,the composite pressure vessel(TypeⅡ)has been applied to the CNG vehicles to reach large capacity and weight lightening vehicles.High pressure vessel(TypeⅡ)is composed of a composite layer and a metal liner.The metal liner is formed by the deep drawing and ironing(D.D.I.)process,which is a complex process of deep drawing and ironing.The cylinder part is reinforced by composite layer wrapped through the filament winding process and is bonded to the liner by the curing process.In this study,an integrated design method was presented by establishing the techniques for FE analysis of entire processes(D.D.I.,filament winding and curing processes)to manufacture the CNG composite pressure vessel(TypeⅡ).Dimensions of the dies and the punches of the 1 st(cup drawing),2 nd(redrawing-ironing 1-ironing 2)and 3 rd(redrawing-ironing)stages were calculated theoretically,and shape of tractrix die to be satisfied with the minimum forming load was suggested for life improvement and manufacturing costs in the D.D.I.process.Thickness of the composite material was determined in the filament winding process,finally,conditions of the curing process(number of heating stage,curing temperature,heating rate and time)were proposed to reinforce adhesive strength between the composite layers.展开更多
Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid im...Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type Ⅱ odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid nonunion successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.展开更多
Glutaric acidemia type Ⅱ(GAⅡ), also known as multiple acyl-CoA dehydrogenase deficiency, is an autosomal recessive inborn error of amino acid and fatty acid metabolism. We report a case of GAⅡ with novel electron t...Glutaric acidemia type Ⅱ(GAⅡ), also known as multiple acyl-CoA dehydrogenase deficiency, is an autosomal recessive inborn error of amino acid and fatty acid metabolism. We report a case of GAⅡ with novel electron transfer flavoprotein(ETF)-A mutations in a 2-year-old female with thalassemia minor. The patient developed an episode of hypoglycemia and hypotonicityon the postnatal first day. Laboratory investigations revealed elevations of multiple acyl carnitines indicating glutaric acidemia type Ⅱ in newborn screening analysis. Urinary organic acids were evaluated for the confirmation and revealed a high glutaric acid excretion.Genetic analysis revealed two novel mutations in the ETF-A gene, which are considered to be compound heterozygote. At the 8 mo of life ketone therapy was added, which significantly increased the neuromotor development. The patient had been closely followed for two years with carnitine, riboflavin, coenzyme Q10,and ketone supplementation in addition to a high carbohydrate diet. Although the patient had comorbidity like thalassemia minor, her neuromotor development was normal for her age and had no major health problems. This specific case expands the previously reported spectrum of this disease.展开更多
The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T...The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T cells can be reduced through exposure to modified CⅡ(263-272)glycopeptide fragment via competitive inhibition with self-antigen.In this work,30 peptides based on the sequence of CⅡ(263-272)were prepared and evaluated for their binding to DR4 protein by surface plasmon resonance(SPR)assay.The effect on the secretion of pro-inflammatory factors by the spleen cells in collagen induced rheumatoid arthritis(CIA)mouse was also investigated.Two N-glycosylated CⅡ peptides were identified to have strong binding to the human recombinant DR4 protein and weak proinflammatory effect.These glycopeptides could be developed as therapeutic saccharide vaccines for the treatment of rheumatoid arthritis(RA).展开更多
Based on the observation data of meteorological stations,Doppler radar observation data of Ulanqab City,and ERA-5 reanalysis data,a snowstorm process in Ulanqab City from March 17 to 18,2022 was analyzed.The results s...Based on the observation data of meteorological stations,Doppler radar observation data of Ulanqab City,and ERA-5 reanalysis data,a snowstorm process in Ulanqab City from March 17 to 18,2022 was analyzed.The results show that this was a type Ⅱ snowstorm process generated under the joint influence of upper trough and ground low inverted trough and frontal cyclone.The main period of snowfall can be divided into two time stages,and the total snowfall was more in the south and less in the north,which was consistent with that of average specific humidity field.Water vapor conditions provided by strong water vapor transport and convergence,strong upward movement shown by large vertical velocity field,and the suction action of high-and low-layer divergence and convergence were the reasons for the hourly heavy snowfall on the 18^(th).During the process,radar echoes were mainly sheet-shaped,and composite reflectivity was 15-25 dBZ in most areas.The zero speed line in the first period was positively"S"-shaped,and there was warm advection and southwest wind.On the morning of the 18^(th),after the cold front transited the city,Ulanqab City was gradually controlled by northwest wind,and the snow tended to end.展开更多
BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients ...BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7(ClCN7)gene and present early-onset osteoarthritis or recurrent fractures.In this study,we report a case of persistent joint pain without bone injury or underlying history.CASE SUMMARY We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II.The clinical diagnosis was based on increased bone density and typical radiographic features.Two heterozygous mutations in the ClCN7 and Tcell immune regulator 1(TCIRG1)genes by whole exome sequencing were identified in the patient and her daughter.The missense mutation(c.857G>A)occurred in the CLCN7 gene p.R286Q,which is highly conserved across species.The TCIRG1 gene point mutation(c.714-20G>A)in intron 7(near the splicing site of exon 7)had no effect on subsequent transcription.CONCLUSION This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms.For the diagnosis and assessment of the prognosis for osteopetrosis,genetic analysis is advised.展开更多
基金supported by the National Natural Science Foundation of China,No.30960520the Natural Science Foundation of Inner Mongolia Autonomous Region of China,No.2016MS0837
文摘Glycosides of Cistanche（GC）is a preparation used extensively for its neuroprotective effect against neurological diseases,but its mechanisms of action remains incompletely understood.Here,we established a bilateral common carotid artery occlusion model of vascular dementia in rats and injected the model rats with a suspension of GC（10 mg/kg/day,intraperitoneally）for 14 consecutive days.Immunohistochemistry showed that GC significantly reduced p-tau and amyloid beta（Aβ）immunoreactivity in the hippocampus of the model rats.Proteomic analysis demonstrated upregulation of mitochondrial precursor protein and downregulation of keratin type II cytoskeletal6A after GC treatment compared with model rats that had received saline.Western blot assay confirmed these findings.Our results suggest that the neuroprotective effect of GC in vascular dementia occurs via the promotion of neuronal cytoskeleton regeneration.
基金supported by funding from Innovative Research Team in Nanjing Medical University(IRT0631)the collaborating Grants(30611120524)
文摘Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.
基金the National Natural Sciences Foundation of China (No. 30500224 and No. 30400193).
文摘To establish a better method of primary culture for alveolar epithelial type Ⅱ cells （AEC Ⅱ ） and to study its bionomics, alveolar epithelial type Ⅱ cells were isolated by digestion with trypsin and collagenase, which were then purified by plated into culture flask coated with rat immunoglobulin （i The purified AEC Ⅱ were identified by alkaline phosphatase staining, electron mi- croscopy, immunocytochemical staining of pulmonary surfactant protein A （SPA）. The SPA expression and transfection characteristics were compared with those of A549 cell line. The results showed that AEC Ⅱ could be isolated by digestion with trysin and collagenase and purified by adhesive purification by using IgG, with a yield of about 2-3 × 10^7, and a purity of about 75%-84 %. Cells could be quickly identified with AKP staining. AEC Ⅱ were different from A549 cell line in terms of SPA expression and transfection characteristics. It is concluded that adhesive purification with IgG can improve the purity of AEC Ⅱ, and AKP staining is simple in cell identification. AEC Ⅱ can not be completely replaced by A549 cells in some studies because the differences between them, such as SPA expression.
文摘BACKGROUND： The pharmacological action of opioid drugs is related to signal transduction of inhibitory guanine nucleotide binding protein. OBJECTIVE： To quantitatively and qualitatively analyze the influence of morphine on levels of type Ⅱ inhibitory guanine nucleotide binding protein （Gi2 protein） in primary cultured hippocampal neurons at different time points. DESIGN, TIME AND SETTING： A randomized controlled study, which was performed at the Department of Neurobiology, Changzheng Hospital, Second Military Medical University of Chinese PLA between September 2002 and March 2004. MATERIALS： Cerebral hippocampal neurons were obtained from newborn SD rats at 1 2 days of age. Biotin-antibody Ⅱ-avidin fluorescein isothiocyanate （Avidin-FITC） was purchased from Sigma Company （USA） and the Gi2 protein polyclonal antibody from Santa Cruz Biochemistry Company （USA）. METHODS： Seven days after culture, mature hippocampal neurons were randomly divided into six groups： 4-, 8-, 16-, 24-, and 48-hour morphine groups, and a blank control group. Neurons in the morphine groups received morphine （10 μ mol/L）, which could cause alterations of G-protein mRNA and cAMP expression in the prefrontal cortex. Neurons in the blank control group were given the same volume of saline. MAIN OUTCOME MEASURES： Gi2 protein levels were detected by an immunofluorescence technique, and were analyzed by the image analytic system with the use of green fluorescence intensity. RESULTS： Gi2 protein levels in hippocampal neurons gradually decreased in the 4-, 8-, 16-, 24-, and 48-hour morphine groups. In particular, Gi2 protein levels in the 16-, 24-, and 48-hour morphine groups were significantly lower than that in the blank control group （P 〈 0.05 0.01）. CONCLUSION： Morphine may decrease Gi2 protein level in primary hippocampal neurons, and the decreasing trend is positively related to morphine-induced time.
文摘The two-parameter exponential distribution is proposed to be an underlying model,and prediction bounds for future observations are obtained by using Bayesian approach.Prediction intervals are derived for unobserved lifetimes in one-sample prediction and two-sample prediction based on type Ⅱ doubly censored samples.A numerical example is given to illustrate the procedures,prediction intervals are investigated via Monte Carlo method,and the accuracy of prediction intervals is presented.
基金Supported by National Natural Science Foundation of China,No.82072734.
文摘BACKGROUND For Siewert type Ⅱ/Ⅲ adenocarcinoma of gastroesophageal junction(AGE), the efficacy of adjuvant chemoradiotherapy(CRT) after D2/R0 resection remains uncertain.AIM To determine whether CRT was superior to chemotherapy(CT) alone after D2/R0 resection for locally advanced Siewert type Ⅱ/Ⅲ AGE.METHODS We identified 316 locally advanced Siewert type Ⅱ/Ⅲ AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018.57 patients received adjuvant CRT and 259 patients received adjuvant CT.We followed patients for overall survival(OS), relapse-free survival, and recurrence pattern.RESULTS Five-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9%(P = 0.010).Five-year OS rates of the CRT group and the CT group for Siewert type Ⅲ AGE patients were 65.7% and 43.9%(P = 0.006).Among the 195 patients whose recurrence information could be obtained, 18 cases(34.6%) and 61 cases(42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively.The local and regional recurrence rates in the CRT group were lower than that in the CT group(22.2% vs 24.6%, 27.8% vs 39.3%).Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type Ⅲ AGE.CONCLUSION For locally advanced Siewert type Ⅲ AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.
基金financial support from National Natural Science Foundation of China (81872818)National Key R&D Program of China (2021YFE0115200)
文摘Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and safety.Herein,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal epithelium.After oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅡdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells activity.Surprisingly,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira.Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal epithelium.This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of liraglutide.In general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.
基金Supported by National Research Foundation of Korea(NRF)Korea Government(MSIT)(Grant No.2019R1F1A1058521)
文摘As energy crisis and environment pollution all around the world threaten the widespread use of fossil fuels,compressed natural gas(CNG)vehicles are explored as an alternative to the conventional gasoline powered vehicles.Because of the limited space available for the car,the composite pressure vessel(TypeⅡ)has been applied to the CNG vehicles to reach large capacity and weight lightening vehicles.High pressure vessel(TypeⅡ)is composed of a composite layer and a metal liner.The metal liner is formed by the deep drawing and ironing(D.D.I.)process,which is a complex process of deep drawing and ironing.The cylinder part is reinforced by composite layer wrapped through the filament winding process and is bonded to the liner by the curing process.In this study,an integrated design method was presented by establishing the techniques for FE analysis of entire processes(D.D.I.,filament winding and curing processes)to manufacture the CNG composite pressure vessel(TypeⅡ).Dimensions of the dies and the punches of the 1 st(cup drawing),2 nd(redrawing-ironing 1-ironing 2)and 3 rd(redrawing-ironing)stages were calculated theoretically,and shape of tractrix die to be satisfied with the minimum forming load was suggested for life improvement and manufacturing costs in the D.D.I.process.Thickness of the composite material was determined in the filament winding process,finally,conditions of the curing process(number of heating stage,curing temperature,heating rate and time)were proposed to reinforce adhesive strength between the composite layers.
文摘Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type Ⅱ odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid nonunion successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.
文摘Glutaric acidemia type Ⅱ(GAⅡ), also known as multiple acyl-CoA dehydrogenase deficiency, is an autosomal recessive inborn error of amino acid and fatty acid metabolism. We report a case of GAⅡ with novel electron transfer flavoprotein(ETF)-A mutations in a 2-year-old female with thalassemia minor. The patient developed an episode of hypoglycemia and hypotonicityon the postnatal first day. Laboratory investigations revealed elevations of multiple acyl carnitines indicating glutaric acidemia type Ⅱ in newborn screening analysis. Urinary organic acids were evaluated for the confirmation and revealed a high glutaric acid excretion.Genetic analysis revealed two novel mutations in the ETF-A gene, which are considered to be compound heterozygote. At the 8 mo of life ketone therapy was added, which significantly increased the neuromotor development. The patient had been closely followed for two years with carnitine, riboflavin, coenzyme Q10,and ketone supplementation in addition to a high carbohydrate diet. Although the patient had comorbidity like thalassemia minor, her neuromotor development was normal for her age and had no major health problems. This specific case expands the previously reported spectrum of this disease.
基金supported by the National Natural Science Foundation of China(Nos.81930097,21977005,82151223)supported by the National Key R&D Program of China(No.2022YFF1203005).
文摘The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T cells can be reduced through exposure to modified CⅡ(263-272)glycopeptide fragment via competitive inhibition with self-antigen.In this work,30 peptides based on the sequence of CⅡ(263-272)were prepared and evaluated for their binding to DR4 protein by surface plasmon resonance(SPR)assay.The effect on the secretion of pro-inflammatory factors by the spleen cells in collagen induced rheumatoid arthritis(CIA)mouse was also investigated.Two N-glycosylated CⅡ peptides were identified to have strong binding to the human recombinant DR4 protein and weak proinflammatory effect.These glycopeptides could be developed as therapeutic saccharide vaccines for the treatment of rheumatoid arthritis(RA).
文摘Based on the observation data of meteorological stations,Doppler radar observation data of Ulanqab City,and ERA-5 reanalysis data,a snowstorm process in Ulanqab City from March 17 to 18,2022 was analyzed.The results show that this was a type Ⅱ snowstorm process generated under the joint influence of upper trough and ground low inverted trough and frontal cyclone.The main period of snowfall can be divided into two time stages,and the total snowfall was more in the south and less in the north,which was consistent with that of average specific humidity field.Water vapor conditions provided by strong water vapor transport and convergence,strong upward movement shown by large vertical velocity field,and the suction action of high-and low-layer divergence and convergence were the reasons for the hourly heavy snowfall on the 18^(th).During the process,radar echoes were mainly sheet-shaped,and composite reflectivity was 15-25 dBZ in most areas.The zero speed line in the first period was positively"S"-shaped,and there was warm advection and southwest wind.On the morning of the 18^(th),after the cold front transited the city,Ulanqab City was gradually controlled by northwest wind,and the snow tended to end.
基金Supported by the Science and Technology Plan Program of Sichuan of China,No.2018JY0608。
文摘BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7(ClCN7)gene and present early-onset osteoarthritis or recurrent fractures.In this study,we report a case of persistent joint pain without bone injury or underlying history.CASE SUMMARY We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II.The clinical diagnosis was based on increased bone density and typical radiographic features.Two heterozygous mutations in the ClCN7 and Tcell immune regulator 1(TCIRG1)genes by whole exome sequencing were identified in the patient and her daughter.The missense mutation(c.857G>A)occurred in the CLCN7 gene p.R286Q,which is highly conserved across species.The TCIRG1 gene point mutation(c.714-20G>A)in intron 7(near the splicing site of exon 7)had no effect on subsequent transcription.CONCLUSION This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms.For the diagnosis and assessment of the prognosis for osteopetrosis,genetic analysis is advised.
