Quantitative study of cytotoxic T-lymphocyte immunotherapy for nasopharyngeal carcinoma.

BACKGROUND: In clinical practice, the common strategy for immunotherapy of nasopharyngeal carcinoma (NPC) is to infuse cytotoxic T-lymphocyte (CTL) lines several times by intravenous injection, but it is difficult by laboratory research to investigate the relationship between treatment time-point, the amount of CTL added and the therapeutic effect. The objective of this study is to establish a mathematical model to study the therapeutic effect of different treatment time-points and amounts of CTL, and to predict the change in therapeutic effect when the percentage of EBV LMP2-specific CTL is increased from 10% to 20%. RESULTS: The concentration of epidermal growth factor receptor (EGFR) in the tumor cell cytomembranes increases after CTL is added. Concurrently, there is a marked downward trend of the phosphorylated transforming growth factor-α (TGFα)-EGFR complex in the tumor cell cytomembranes, which indicates restriction of tumor growth after CTL immunotherapy. The relationships among the time of addition of CTL, the amount of CTL added, different CTL specificities for LMP2 and the increment rate k of the total number of tumor cells were evaluated. CONCLUSIONS: The simulation results quantify the relationships among treatment time-points, amount of CTL added, and the corresponding therapeutic effect of immunotherapy for NPC.

Changes and significance of IL-25 in chicken collagen II-induced experimental arthritis (CIA).

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease. It is a systemic inflammatory disease, characterized by chronic, symmetrical, multi-articular synovial arthritis. IL-25 (IL-17E) is a member of the recently emerged cytokine family (IL-17s), which is expressed in Th2 cells and bone marrow-derived mast cells. Unlike the other members of this family, IL-25 is capable of inducing Th2-associated cytokines (IL-4, IL-5, and IL-13) and also promotes the release of some pro-immune factors (IL-6 and IL-8). IL-25 is also a pleiotropic factor, which constitutes a tissue-specific pathological injury and chronic inflammation. In this study, we used chicken collagen II-induced experimental arthritis (CIA) model in DBA/1 mice to investigate the relationship between IL-25 and other inflammatory factors, revealing the possible mechanism in CIA. Our results showed that the expression level of IL-25 was enhanced in the late stage of CIA, and IL-17 was increased in the early stage of the disease. It is well known that IL-17 has a crucial role in the development of RA pathogenesis, and IL-25 plays a significant role in humoral immune. For reasons given above, we suggested that the IL-25 inhibited IL-17 expression to some extent, while enhancing the production of IL-4. It was confirmed that IL-25 not only regulated the cellular immune, but also involved the humoral immune in rheumatoid arthritis.

Complication following gastric pull-up reconstruction for advanced hypopharyngeal or cervical esophageal carcinoma: a 20-year review in a Chinese institute.

OBJECTIVES: Carcinoma of the hypopharynx and cervical esophagus is a very aggressive cancer with a high incidence of multifocal mucosal involvement and a high incidence of submucosal lymphatic spread. Total pharyngolaryngoesophagectomy and gastric pull-up reconstruction are often the procedures of choice. The aim of this study is to review the complication after gastric pull-up reconstruction in patients with advanced hypopharyngeal or cervical esophageal cancer. MATERIALS AND METHODS: A total of 208 patients undergoing gastric pull-up reconstruction for squamous cell carcinoma of the hypopharynx invading the cervical esophagus and cervical esophagus at the Affiliated Provincial Hospital of Anhui Medical University in China from 1988 to 2007 were reviewed. Of 208 patients, 124 patients had hypopharyngeal carcinoma invading cervical esophagus; and 84 patients had cervical esophageal carcinoma. The analysis focused on the most common complications and the survival following gastric pull-up reconstruction. This study and its methods have been approved by the institutional review board. RESULTS: Of the 208 patients, 87 (41.8%) developed some complications, including anastomotic leak (19, 9.1%), pneumonitis (23, 11.1%), pleural effusion (15, 7.2%), wound infection (8, 3.9%), heart failure (4, 1.9%), anastomosis stricture (7, 3.4%), chylous fistula (4, 1.9%), hemothorax (3, 1.4%), hemoperitoneum (2, 1.0%), and burst abdomen (2, 1.0%); there was no gastric necrosis. In our cases, there was no immediate operative mortality; but there were 4 hospital deaths. The average hospital stay was 15 days. CONCLUSIONS: Gastric pull-up reconstruction is a relatively safe and effective method and can be performed with low mortality and acceptable morbidity and result in good quality of lives.

Application of healthcare simulation in post-graduation education of pediatric emergency and critical care medicine / 中国小儿急救医学

This review discussesed the application of healthcare simulation in the post-graduation education of pediatric emergency and critical care medicine in China,puting forward the necessity of its application,introducing the application scenarios from four aspects:basic skills simulation training,specialized skills simulation training,situational simulation training and screen simulation training,and analyzing the existing problems from three aspects:teaching staff,curriculum research and training equipment.Some suggestions are put forward to strengthen the system guarantee,concentrate the development of multidisciplinary forces,and integrate the strength of domestic industry,university and research.

A case of autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant and literature review / 中华神经科杂志

Objective:To discuss the clinical characteristics of autosomal recessive spinocerebellar ataxia type 16 patients caused by STUB1 gene mutation, in order to improve the clinical doctors′ understanding of the disease. Methods:The clinical manifestations, auxiliary examinations and genetic testing of 1 autosomal recessive spinocerebellar ataxia type 16 patient caused by STUB1 gene variants diagnosed in Qilu Hospital of Shandong University in May 2022 were collected, and the relevant literature was reviewed to summarize the clinical and genetic characteristics of this type of disease. Results:The proband was a 35-year-old male presenting with unsteady walk and dysarthria. Magnetic resonance imaging showed cerebellar atrophy. Next generation sequencing revealed compound heterozygous c.322dupG (p.Glu108Glyfs *4) and c.433A>C (p.Lys145Gln) variants in the STUB1 gene (according to the transcript NM_005861.4), and the c.322dupG (p.Glu108Glyfs *4) variant was a novel variant. Pedigree verification revealed the 2 variants were respectively inherited from the proband′s healthy parents. A total of 12 foreign literatures reported 32 autosomal recessive spinocerebellar ataxia type 16 patients. The main clinical manifestations were ataxia, dysarthria and tendon hyperreflexia. Besides, nystagmus, spasticity, action tremors, and myoclonus can be present. Magnetic resonance imaging predominantly showed cerebellar atrophy. Conclusions:The patient with autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant is rare in China. The main clinical manifestation is cerebellar ataxia, and brain imaging reveals remarkable cerebellar atrophy. Genetic testing is helpful for definite diagnosis.

The clinical and radiological features of myelin oligodendrocyte glycoprotein antibody associated disease / 中华神经科杂志

Objective To explore the clinical and radiological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease.Methods The clinical data of 22 MOG antibody associated disease cases treated in the Department of Neurology,Qilu Hospital of Shandong University from January 2017 to June 2019 were retrospectively analyzed.The clinical data of MOG antibody associated disease were summarized,including clinical and imaging features.Results Of the 22 included patients with MOG antibody associated disease,the average age was 38.5 years,13 were male and nine were female.Among them,11 cases manifested as aquaporin-4 (AQP4)-negative neuromyelitis optica spectrum disorder (NMOSD),four cases optic neuritis,two cases transverse myelitis,one case acute disseminated encephalomyelitis (ADEM),two cases cortical encephalitis and two cases vestibular neuronitis.Magnetic resonance imaging (MRI) results showed that multiple anatomical areas were involved.Among the nine patients with optic nerve involvement,five patients had longitudinally extensive optic nerve lesions,which were longitudinally enhanced.In eight patients,MRI lesions in the spinal cord showed mostly long or short segments involvement,involving 2-5 spinal cord segments.Five cases involved the cervical spinal cord,six cases involved the thoracic spinal cord,and one case involved the lumbar spinal cord.Brain MRI abnormalities were found in 13 cases and the lesions were mostly patchy and point-shaped.MRI lesions demonstrated T2 hyperintensity and some of them could be strengthened,which may involve the basal ganglia,thalamus,radiographic crown,frontal temporal lobe,brain stem and other parts.Among them,16 patients were sensitive to high-dose intravenous/oral methylprednisolone in the acute phase.Seven patients had recurrence after two months to two years of follow-up.Conclusions MOG antibody associated disease include multiple manifestations.Among them,AQP4-negative NMOSD is the most common form.The clinical manifestations of patients showed diversity.Imaging is characterized by multiple parts involvement such as optic nerve,spinal cord,and brain.Most patients are sensitive to high-dose intravenous/oral methylprednisolone,and have a good prognosis in the acute phase,but some patients may relapse.

The clinical and radiological features of myelin oligodendrocyte glycoprotein antibody associated disease / 中华神经科杂志

Objective@#To explore the clinical and radiological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease.@*Methods@#The clinical data of 22 MOG antibody associated disease cases treated in the Department of Neurology, Qilu Hospital of Shandong University from January 2017 to June 2019 were retrospectively analyzed. The clinical data of MOG antibody associated disease were summarized, including clinical and imaging features.@*Results@#Of the 22 included patients with MOG antibody associated disease, the average age was 38.5 years, 13 were male and nine were female. Among them, 11 cases manifested as aquaporin-4 (AQP4)-negative neuromyelitis optica spectrum disorder (NMOSD), four cases optic neuritis, two cases transverse myelitis, one case acute disseminated encephalomyelitis (ADEM), two cases cortical encephalitis and two cases vestibular neuronitis. Magnetic resonance imaging (MRI) results showed that multiple anatomical areas were involved. Among the nine patients with optic nerve involvement, five patients had longitudinally extensive optic nerve lesions, which were longitudinally enhanced. In eight patients, MRI lesions in the spinal cord showed mostly long or short segments involvement, involving 2-5 spinal cord segments. Five cases involved the cervical spinal cord, six cases involved the thoracic spinal cord, and one case involved the lumbar spinal cord. Brain MRI abnormalities were found in 13 cases and the lesions were mostly patchy and point-shaped. MRI lesions demonstrated T2 hyperintensity and some of them could be strengthened, which may involve the basal ganglia, thalamus, radiographic crown, frontal temporal lobe, brain stem and other parts. Among them, 16 patients were sensitive to high-dose intravenous/oral methylprednisolone in the acute phase. Seven patients had recurrence after two months to two years of follow-up.@*Conclusions@#MOG antibody associated disease include multiple manifestations. Among them, AQP4-negative NMOSD is the most common form. The clinical manifestations of patients showed diversity. Imaging is characterized by multiple parts involvement such as optic nerve, spinal cord, and brain. Most patients are sensitive to high-dose intravenous/oral methylprednisolone, and have a good prognosis in the acute phase, but some patients may relapse.

Analysis of the implementation and effect of PEARS course in a hospital / 中华医学教育探索杂志

The pediatric emergency assessment,recognition and stability (PEARS) courses were launched by American Heart Association in December 2007.The Shanghai Children's Medical Center (SCMC) affiliated to the Medicine School of Shanghai Jiao Tong University implemented the PEARS course training for all pediatric health care staff in batches in 2015 with the purpose of enhancing the capacity of initial judgment and stability and practicing the high-quality cardiopulmonary resuscitation,which achieved good results and better training satisfaction.The PEARS courses are helpful for paramedics to master the pediatric first-aid system evaluation method,and identification;assessment and processing of severe children properly,and meanwhile also emphasize the teamwork.The PEARS courses meet the requirements of the clinical practice of paramedics,and bear strong clinical practicability and maneuverability,furthermore,the training of them is effective in reducing medical errors.Consequently,it is recommended that the training is added into the continuing education and vocational education.

Epidemiology of stroke and its risk factors in Shandong province, China / 中华神经科杂志

Objective@#To investigate the stroke burden (prevalence, incidence, and mortality) and its risk factors for men and women, urban and rural residents at the provincial level in Shandong province.@*Methods@#This study formed part of the National Epidemiological Survey of Stroke in China (NESS-China). This population-based study included 25 190 adults living in Shandong province and was conducted in 2013. The data were derived from eight disease surveillance points (DSPs). They were located in Qingdao Shibei district, Zaozhuang Xuecheng district, Yantai Zhifu district, Laiwu Laicheng district, Yantai Penglai, Weifang Gaomi, Zaozhuang Yiyuan, Linyi Junan. All living subjects who had suffered a stroke by August 31, 2013 were considered as having a prevalent stroke. Incident stroke was defined as a first-ever stroke (both fatal and non-fatal) between September 1, 2012 and August 31, 2013. Fatal cases of incident strokes were used to estimate stroke mortality rate. Stroke cases were subcategorized as follows: ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Stroke cases with no brain imaging within the first week of stroke onset or cases where the results of imaging were not available were classified as stroke of undetermined pathological type (UND).@*Results@#Of the 25 190 participants, 449 had experienced a prevalent stroke, 118 participants were diagnosed as having an incident stroke, 33 fatal cases were identified over the 12-month period. The crude rate of prevalence, incidence and mortality were 1 782.5 per 100 000 people, 468.4 per 100 000 person-years and 131.0 per 100 000 person-years. The age-standard rate of prevalence, incidence and mortality were 1 059.0 per 100 000 people, 279.7 per 100 000 person-years, and 76.0 per 100 000 person-years. Compared to women, the prevalence of stroke was markedly higher among men (1 463.3 per 100 000 people vs 2 265.0 per 100 000 people). Compared to urban residents, the prevalence of stroke was markedly higher among rural residents (563.7 per 100 000 people vs 2 203.6 per 100 000 people). Among all prevalent cases, there were 348 people suffering from IS, 75 cases suffering from ICH, 6 cases suffering from SAH, and 20 cases of UND. The prevalece rates of IS, ICH, SAH and UND were 1 385.5 per 100 000 people, 301.7 per 100 000 people, 23.8 per 100 000 people and 79.4 per 100 000 people, respectively. The three most prevalent risk factors in stroke cases were hypertension (66.4%), current smoking (26.1%), and alcohol drinking (24.9%).@*Conclusions@#Stroke was highly prevalent in Shandong province, China. The prevalence and incidence rates of stroke were significantly greater for men than women. Large geographical variations in the stroke burden were also observed in Shandong province, with a greater stroke burden observed in rural areas.

Epidemiology of stroke and its risk factors in Shandong province, China / 中华神经科杂志

Objective To investigate the stroke burden (prevalence, incidence, and mortality) and its risk factors for men and women, urban and rural residents at the provincial level in Shandong province. Methods This study formed part of the National Epidemiological Survey of Stroke in China (NESS?China). This population?based study included 25 190 adults living in Shandong province and was conducted in 2013. The data were derived from eight disease surveillance points (DSPs). They were located in Qingdao Shibei district, Zaozhuang Xuecheng district, Yantai Zhifu district, Laiwu Laicheng district, Yantai Penglai, Weifang Gaomi, Zaozhuang Yiyuan, Linyi Junan. All living subjects who had suffered a stroke by August 31, 2013 were considered as having a prevalent stroke. Incident stroke was defined as a first?ever stroke (both fatal and non?fatal) between September 1, 2012 and August 31, 2013. Fatal cases of incident strokes were used to estimate stroke mortality rate. Stroke cases were subcategorized as follows:ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Stroke cases with no brain imaging within the first week of stroke onset or cases where the results of imaging were not available were classified as stroke of undetermined pathological type (UND). Results Of the 25 190 participants, 449 had experienced a prevalent stroke, 118 participants were diagnosed as having an incident stroke, 33 fatal cases were identified over the 12?month period. The crude rate of prevalence, incidence and mortality were 1 782.5 per 100 000 people, 468.4 per 100 000 person?years and 131.0 per 100 000 person?years. The age?standard rate of prevalence, incidence and mortality were 1 059.0 per 100 000 people, 279.7 per 100 000 person?years, and 76.0 per 100 000 person?years. Compared to women, the prevalence of stroke was markedly higher among men (1 463.3 per 100 000 people vs 2 265.0 per 100 000 people). Compared to urban residents, the prevalence of stroke was markedly higher among rural residents (563.7 per 100 000 people vs 2 203.6 per 100 000 people). Among all prevalent cases, there were 348 people suffering from IS, 75 cases suffering from ICH, 6 cases suffering from SAH, and 20 cases of UND. The prevalece rates of IS, ICH, SAH and UND were 1 385.5 per 100 000 people, 301.7 per 100 000 people, 23.8 per 100 000 people and 79.4 per 100 000 people, respectively. The three most prevalent risk factors in stroke cases were hypertension (66.4%), current smoking (26.1%), and alcohol drinking (24.9%). Conclusions Stroke was highly prevalent in Shandong province, China. The prevalence and incidence rates of stroke were significantly greater for men than women. Large geographical variations in the stroke burden were also observed in Shandong province, with a greater stroke burden observed in rural areas.

Value of 68 Ga-DOTANOC PET/CT imaging in primary diagnosis and staging of pancreatic neuroen-docrine neoplasms / 中华核医学与分子影像杂志

Objective To evaluate the value of 68 Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-1-Nal3-octreotide ( DOTANOC) PET/CT imaging in the diagnosis and staging of pancreatic neuroendocrine neoplasms ( pNENs) . Methods Data of 48 patients ( 18 males, 30 females, age: 23-86 (50.0±14.7) years) who underwent 68Ga-DOTANOC PET/CT imaging from June 2016 to June 2018 were retrospectively analyzed. The histopathological results were considered as the gold standard. The diagnostic efficacies of 68 Ga-DOTANOC PET/CT imaging and conventional imaging ( CI) for pNENs were analyzed and compared ( McNemar test) . Imaging characteristics of true positive lesions in 68 Ga-DOTANOC PET/CT ima-ging were analyzed. The maximum standardized uptake value ( SUVmax ) in different pathological grades of pNENs lesions were compared (Kruskal-Wallis rank sum test). Accuracy for TNM staging by 68Ga-DOTANOC PET/CT imaging and the correlations between the staging results and clinical TNM stages were analyzed (R× C contingency table). Results (1) The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 68Ga-DOTANOC PET/CT imaging were 93.8％(30/32), 14/16, 93.8％(30/32), 14/16 and 91.7％(44/48). All true positive lesions detected by PET/CT showed focal up-take of 68 Ga-DOTANOC with SUVmax of 30. 52 ± 23. 57. There were 26 patients with confirmed pathological grades of G1 (n=10;SUVmax:28.20 (17.60, 49.22)), G2 (n=13; SUVmax: 27.60 (13.05, 56.08)) and G3 (n=3;SUVmax:13.68(10.02, 27.80)), with no significant difference in SUVmax among 3 groups (H=0.495, P>0.05). (2)Of the 48 patients, 95.8％(46/48) also underwent CI concurrent with PET/CT. The sensitivity, specificity, PPV, NPV and accuracy of CI were 60.0％(18/30), 9/16, 72.0％(18/25), 9/21 and 58.7％(27/46). The diagnostic efficacy of 68Ga-DOTANOC PET/CT imaging was significantly higher than that of CI ( P=0.041) . ( 3) The accuracies of 68 Ga-DOTANOC PET/CT imaging for T, N, M staging were 93.3％(28/30), 6/6, 9/10, respectively, and the staging results were significantly correlated with clinical TNM stages (r=0.880, P<0.05). Conclusion 68Ga-DOTANOC PET/CT imaging has great values in the diagnosis and staging of pNENs.

Comparative study in diagnostic value of 68Ga-PSMA-617 PET/CT and multi-parameter MRI for primary prostate cancer / 中华核医学与分子影像杂志

Objective To compare the diagnostic efficacy of 68Ga-prostate specific membrane antigen (PSMA)-617 PET/CT and multi-parameter MRI for primary prostate cancer.Methods From June 2017 to November 2017,24 patients (age (67.6±7.0) years) with suspected prostate cancer were prospectively enrolled.All patients underwent 68Ga-PSMA-617 PET/CT and multi-parameter MRI.Pathological diagnosis was considered as the gold standard.The diagnostic efficacy of the two methods was analyzed and the difference was evaluated by receiver operating characteristic (ROC) curve analysis(Z test).Results Based on the puncture biopsy and/or excision biopsy,18 patients were diagnosed as prostate cancer and 6 patients were diagnosed as benign diseases.According to the five-zone analysis for the prostate (24 patients with 120 zones),48 and 56 zones were detected accurately in prostate cancer patients by PET/CT and multi-parameter MRI respectively,which was 54 and 41 for benign patients.The cut-off value of maximum standardized uptake value (SUVmax) in 68Ga-PSMA-617 PET/CT for diagnosing prostate cancer was 4.85,the area under curve (AUC),sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index were 0.890,75.00％ (48/64),96.43％ (54/56),96.00％ (48/50),77.14％ (54/70),85.00％(102/120),71.43％ respectively for prostate cancer by PET/CT,and 0.837,87.50％(56/64),73.21％ (41/56),78.87％ (56/71),83.67％ (41/49),80.83％ (97/120) and 60.71％ respectively by multi-parameter MRI.The difference of AUC was statistically significant (Z=2.82,P＜0.01).Conclusions The diagnostic accuracy of 68Ga-PSMA-617 PET/CT imaging for prostate cancer is higher than that of multi-parameter MRI.Both modalities have high diagnostic efficiency and can be used scientifically as complementary.

68Ga-NOTA-NFB PET/CT imaging in breast cancer: clinical study of a new targeted agent for chemokine receptor 4 / 中华核医学与分子影像杂志

Objective To investigate the clinical application of chemokine receptor 4 (CXCR4)-targeted PET/CT imaging in breast cancer using 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid-TN14003 (NOTA-NFB) and the correlation between 68Ga-NOTA-NFB uptake and pathology.Methods From June 2014 to December 2014,11 female patients (age range:38-68 years) with non-specific invasive breast cancer were recruited in this study.All patients underwent neoadjuvant chemotherapy before surgery.68GaNOTA-NFB and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed before the chemotherapy.Three patients also underwent 68Ga-NOTA-NFB PET/CT imaging after the fourth cycle of chemotherapy.The region of interest (ROI) method was used to measure the maximum standardized value (SUVmax) and tumor/non-tumor (T/NT) ratio was calculated.Paired t test and Spearman correlation analysis were used for statistical analysis.Results The SUVmax values of primary lesions were 3.78±2.03 and 8.11±5.14 (t=-3.01,P＜0.05) respectively in 68Ga-NOTA-NFB imaging and 18F-FDG imaging.The T/NT ratios for primary lesions were not significantly different between the two imaging methods (9.36±7.81 vs 15.62±14.51;t=-1.63,P＞0.05).In the metastatic lymph nodes,SUVmax values were not significantly different between 68Ga-NOTA-NFB imaging and 18F-FDG imaging (t=-2.02,P＞0.05),but T/NT ratios were significantly different (t=-2.43,P＜0.05).After neoadjuvant chemotherapy,T/NT ratios were decreased in the 3 patients.Correlation was not found between T/NT in 68Ga-NOTA-NFB imaging and Ki-67,but the P value was close to 0.05 (rs =0.600,P=0.051).Conclusion 68Ga-NOTA-NFB PET/CT can be used as a new CXCR4-targered imaging in diagnosis of breast cancer,and it may be beneficial to evaluate the effect of neoadjuvant chemotherapy.

Characteristics of clinical manifestations and molecular genetics of late-onset cobalamin C deficiency / 中华神经科杂志

Objective To investigate the characteristics of clinical manifestations and genetics of late-onset cobalamin (cbl) C deficiency,also named as combined methylmalonic acidemia and homocystinemia, cblC type. Methods We reviewed 26 late-onset cblC deficiency patients diagnosed in Qilu Hospital, Shandong University from 2012 to 2017 and analysed the clinical, biochemistry, neuroimaging, follow-up and MMACHC gene data. Results Among the 26 patients, male:female ratio is 11:15, with the age of diagnosis from 4 to 39 years and sibling comorbidity in 4 families. The clinical manifestaions of nervous system included spastic paraplegia,mental and behavior disorder,intelectual decline,epilepsy,ataxia,dystonia and peripheral neuropathy. There were four cases with proteinuria at onset. At first visit, the levels of serum total homocystinuria of all patients were elevated, from 61.4 to 193.4μmol/Lwith methylmalonic acidemia. The neuroimaging data of the 26 cases showed 11 with cerebral atrophy, 10 with thoracic spinal cord atrophy, five with brain parenchymal lesions, three with longitudinal myelopathy which were reversible in follow-up, one with syringomyelia, one with multiple cerebral artery stenosis. In all the cases, cobalamins were supplied parenterally and folate, betaine, L-carnitine, vitamin B6 were supplied orally during acute metabolic crisis, and the symptoms of acute encephalopathy disappeared but symptoms of spastic paraplegia had little improvement. In chronic stage, frequency of intramuscular injection of hydroxocobalamine could be decreased while the index can still be improved. All the 26 cases had definite mutations in MMACHC gene, the most common mutations of which were found to be c.482G>A(15/52) and c. 609G>A(13/52). Conclusions Homocystine is the important biomarker for cblC deficiency. Once diagnosed, parenteral hydroxocobalamin and oral betaine should be supplied for a lifetime with good prognosis. The most common mutations of MMACHC gene in our cases are c. 482G>A and c. 609G>A missense mutations.

Clinical application of auricular cartilage in intact bridge tympanomastoidectomy / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate and evaluate the effects of intact-bridge tympanoplasty using auricular cartilage in treating chronic otitis media. METHODS A retrospective review of 86 cases undergoing an intact-bridge tympanomastoidectomywas performed from July,2013 to May,2016.The auricular cartilage was placed on the attic and tympanic antrum entrance to reconstruct the attic. RESULTS The outcome of dry ear and well-epithelialized mastoid cavities was achieved after 4-6 weeks. After 6-month follow-up no recurrence occurred. The pure-tone average threshold improved by (25.4±6.3) dB HL after operation,and the mean air bone gap was elevated. CONCLUSION On the basis of combination of closed and open techniques,the IBM technique is a optimal cure strategy for chronic otitis media,which can not only remove the pathological changes thoroughly to prevent disease recurrence but also maximally improve the hearing of the diseased ear.The closure of attic with auricular cartilage can ensure the space of the ossicular chain.

Exosomal microRNAs and their roles in tumors / 国际肿瘤学杂志

Exosomes contain many components including variety kinds of lipids,proteins,microRNAs (miRNAs) and so on.They can transport their loaded substances to the recipient cells and play a role of biology.Exosomal miRNAs play important roles in the occurrence and development of tumors,and they are closely related to the tumor growth,metastasis,drug resistance and immune regulation.Exosomes and exosomal miRNAs can be served as reference indexes for tumor metastasis and prognosis,which provide new targets for tumor therapy.

Direct Analysis of Triglycerides in Edible Oils by Atmospheric Pressure Chemical Ionization Mass Spectrometry / 分析化学

An atmospheric pressure chemical ionization mass spectrometry (APCI-MS) method was developed for the direct analysis of triglycerides in edible oils.The edible oil sample was dissolved in acetonitrile.Under the optimal conditions such as positive ion detection,800 μL/h of sample flow rate,250℃ of vaporizer temperature and 5000 nA of corona needle current,the repeatability (RSD) of peak intensity rate of m/z 857.76 to m/z 881.76 was less than 5％.Then,different kinds of oil from different manufacturers were analyzed by the proposed method.After a principal component analysis for the analytical results,the peak intensity rate of m/z 857.76 and m/z 881.76 was selected for oil identification.The adulteration of 5％ lard in corn oil could be recognized directly using the peak intensity rate.Three characteristic triglycerides in edible oil were preliminarily identified by collision induced dissociation (CID) experiments.The method was applied to analyze the swill oil and fried oil samples,and the results showed that the swill oil contained both vegetable oil and animal fat,and the fried oil was also different with commercial vegetable oil.

Quantitative comparison of 68Ga-NGR and 18F-FDG uptake in well-differentiated hepatocellular carcinoma bearing mice / 中华核医学与分子影像杂志

Objective To quantitatively compare the diagnostic capability of 68Ga-NGR and 18F-FDG in well-differentiated hepatocellular carcinoma (HCC) bearing mice by microPET/CT imaging.Methods The in vitro cellular uptake, in vivo microPET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC.The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) cells/xenografts were respectively used as positive and negative reference groups for CD13.The expression of CD13 was qualitatively verified by immunohistostaining.The levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by Western blot test for all 3 types of tumors.Two-sample t test was used for data analysis.Results The in vitro cellular uptake showed that the 68Ga-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells, and the 68Ga-NGR uptake was higher than 18F-FDG uptake in SMMC-7721 cells.The in vivo microPET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721 tumor was (2.17±0.21) %ID/g, remarkably higher compared to (0.73±0.26) %ID/g of 18F-FDG uptake (t=8.826, P<0.01).The tumor/liver ratio of 68Ga-NGR was 2.05±0.16, which was 2.03-fold higher than that of 18F-FDG.In the HT-1080 tumors, the uptakes of 68Ga-NGR and 18F-FDG were both high, and the values were (2.46±0.23) %ID/g, (3.47±0.31) %ID/g.The uptake of 68Ga-NGR was significantly lower than that of 18F-FDG in HT-29 tumors: (0.67±0.20) %ID/g vs (3.17±0.29) %ID/g;t=4.221, P<0.01.Western blot and immunohistostaining results were as follows: HT-1080(CD13+, G6Pase-), SMMC-7721(CD13+, G6Pase+), HT-29(CD13-, G6Pase-).Conclusions The uptake of 68Ga-NGR is higher than 18F-FDG uptake in SMMC-7721 tumor bearing mice, therefore it is worthwhile to consider the feasibility of clinical translation for PET/CT in diagnosis of HCC.Furthermore, because of the difference in 68Ga-NGR and 18F-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase, there is an underlying potential for molecular imaging in the determination of molecular phenotypes.

Quantitative comparison of 68Ga-NGR and 18F-FDG uptake in well-differentiated hepatocellular carcinoma bearing mice / 中华核医学与分子影像杂志

Objective To quantitatively compare the diagnostic capability of 68Ga-NGR and 18F-FDG in well-differentiated hepatocellular carcinoma (HCC) bearing mice by microPET/CT imaging.Methods The in vitro cellular uptake,in vivo microPET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC.The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) cells/xenografts were respectively used as positive and negative reference groups for CD13.The expression of CD13 was qualitatively verified by immunohistostaining.The levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by Western blot test for all 3 types of tumors.Two-sample t test was used for data analysis.Results The in vitro cellular uptake showed that the 68Ga-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells,and the 68Ga-NGR uptake was higher than 18F-FDG uptake in SMMC-7721 cells.The in vivo micro-PET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721 tumor was (2.17±0.21) ％ID/g,remarkably higher compared to (0.73±0.26) ％ID/g of 18F-FDG uptake (t =8.826,P＜0.01).The tumor/liver ratio of 68Ga-NGR was 2.05±0.16,which was 2.03-fold higher than that of 18F-FDG.In the HT-1080 tumors,the uptakes of 68 Ga-NGR and 18F-FDG were both high,and the values were (2.46±0.23) ％ID/g,(3.47±0.31) ％ID/g.The uptake of 68Ga-NGR was significantly lower than that of 18F-FDG in HT-29 tumors:(0.67±0.20) ％ID/g vs (3.17±0.29) ％ID/g;t=4.221,P＜0.01.Western blot and immunohistostaining results were as follows:HT-1080(CD13+,G6Pase-),SMMC-7721(CD13+,G6Pase+),HT-29 (CD13-,G6Pase-).Conclusions The uptake of 68Ga-NGR is higher than 18F-FDG uptake in SMMC-7721 tumor bearing mice,therefore it is worthwhile to consider the feasibility of clinical translation for PET/CT in diagnosis of HCC.Furthermore,because of the difference in 68Ga-NGR and 18F-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase,there is an underlying potential for molecular imaging in the determination of molecular phenotypes.

Corynebacterium pyruviciproducens promotes the production of ovalbumin specific antibody via stimulating dendritic cell differentiation and up-regulating Th2 biased immune response.

Corynebacterium pyruviciproducens (C. pyruviciproducens), a newly discovered Corynebacterium, is gram-positive, non-flagellate, non-spore-forming lipophilic rod. No known pathogenic components of Corynebacteria have been found in this new bacterium, such as diphtheria toxin and tuberculostearic acid. In the present study, referring to Propionibacterium acnes (P. acnes), a well-known bacterial adjuvant, the stimulation of dendritic cells by C. pyruviciproducens was analyzed through detecting the levels of cytokine-secretion, ability of cell-proliferation and expression of membrane molecules. In addition, the effect of C. pyruviciproducens in promoting antibody production in vivo was detected. Compared with P. acnes, C. pyruviciproducens more strongly enhanced cytokine secretion including inflammatory factor IL-6 and Th1-associated molecule IL-12, and more effectively induced proliferation, activation or maturation of D2SC/1 (a murine dendritic cell line) and bone marrow-derived dendritic cells (BMDC). Vaccination studies in mice using ovalbumin (OVA) as a model antigen showed that C. pyruviciproducens effectively promoted antigen-specific humoral immune response by increasing OVA-specific antibody, Th2-biased response in spleen and high IL-4/IFN-γ ratio in serum.