Pancreatic cancer is known as one of the most fatal malignant diseases in digestive system.Approximately 15%-20%of patients are deemed resectable at the time of diagnosis.Neoadjuvant therapy to the borderline resectable pancreatic cancer ( BRPC) has been challenged to achieve down-staging of cancer, to avoid unnecessary major operation if the pancreatic cancer progres-ses and distant metastasis develops during preoperative treatment.However, there are some controversial issues influencing the clinical decision of surgeon in managing BRPC.This manuscript reviews the current controversial issues in managing BRPC in order to enhance proper understanding for the current status and potential role of neoadjuvant therapy in managing BRPC.

Objective To report the spectrum of electron transfer flavoprotein dehydrogenase (ETFDH)gene mutations in 20 Chinese RR-LsM families.Methods Twenty-four RR-LSM patients in the First Hospital of Peking University from January 2003 to May 2010 were collected and the clinical characteristics were analyzed.These patients came from 20 families in North Mainland China.Sixteen families had 1 patient each.and the other 4 families had 2 patients.ETFDH gene analysis was performed in all patients,11 family members and 100 healthy controls.Results The mean onset age was(27.9±9.9)years.The main symptoms were limb weakness(21,87.5%),dysmasesia(15,62.5%),neck weakness (14,58.3%)and myalgia(14,58.3%).Eighteen patients had high level of acyleamitine.Fifteen of 17patients had glutaric aciduria.Seventeen ETFDH mutations,including 13 missense mutations,2 splice mutations,and 2 nonsense mutations,were identified in 19 families:c.998A>G,c.1450T>C,c.1703T>C,c.1717C>T,c.821G>A,c.643G>A,c.251C>T,c.1763A>T,c.IVS7+2T>C and c.IVS6+1G>A were Hovel mutations which were not found in 100 healthy controls.Nine families had the mutation of c.770A>G(P.Y257C)and 5 families had the mutation of c.1227A>C(P.L409F).Conclusions The numerous novel mutations in ETFDH gene indicate that Chinese RR-LSM might have special mutation pattern.c.770A>G(P.Y257C)and c.1227A>C(p.L409F)may be hot spot mutations in North Mainland China.

ObjectiveTo report clinical, pathological and molecular genetic features in a Chinese family with hereditary motor and sensory neuropathy type 6. MethodsThe index case is a 15 years old boy.He developed progressive distal limb weakness at the age of 5.The disease deteriorated slowly,accompanied with contracture of achilles' tendon. At the age of 11 years old he suffered from decrease of visual acuity. At the age of 12, he found the muscular atrophy of both hands without sensory disturbances.Visual evoked potential revealed prolonged latency of bilateral P100. Ophthalmological examination showed bilateral optic atrophy. His mother had the similar symptoms at the age of 7 and reduced visual acuity at the age of 10. Nerve conduction velocity revealed in both pat1ents no compound motor and sensory nerve action potentials in most nerves or slightly reduced nerve conduction velocities with severely reduced amplitudes of the compound motor and sensory nerve action potentials. Sural nerve biopsy was performed on the proband.The sequence of MFN2 gene was analyzed in DNA from the index, his mother and 100 healthy controls.ResultsSural nerve biopsy revealed severe loss of myelinated fibers with few regenerating clusters.Ultrapathological examination showed a few of atypical bulbs of myelinated fibers, occasionally regenerating clusters, mitochondrial swelling and aggregation in a few of axons. A new mutation of W740R mutation in MFN2 gene has been identified in the index case, her mother, but not in 50 healthy controls. Conclusions A novel MFN2 gene mutation result in hereditary motor and sensory neuropathy type 6.Mild visual loss appeares after the lesion of spinal nerves. Demyelination of peripheral nerve appears in the disease.

ObjectiveTo investigate the characteristic of pathology in Chinese patients with Nonaka myopathy.MethodsThirteen patients (7 males and 6 females) diagnosed with Nonaka myopathy in our laboratory from January 2002 to March 2011 were included in this study.Their mean age was 39.5 years old and the mean duration of illness was 4.15 years.The most common symptoms were weakness of raising feet with sparing of quadriceps femoris muscles in the early stage of disease.One patient presented the initial symptoms of upper limb weakness. Muscles biopsies were obtained from all these 13 patients. Histology study including immunohistochemical (IHC) staining with antibody against amyloid 3,phosphorylated tau protein,ubiquitin,glucose-regulated protein of molecular weight 78 000(GRP78),calnexin,caspase-12and Bax were performed.Skeletal muscle samples from 3 chronic fatigue syndrome patients,2 myofibrillar myopathy patients were used for control in the IHC staining. All coding exons of uridinediphospho-N-acetylglucosamine 2-epimerase gene were directly sequenced in genomic DNA from these patients.Results The main pathological changes of tibialis anterior muscle in 12 cases were muscle dystrophy with rimmed vacuoles.The rimmed vacuoles were positive for anti-β-amyloid,tau protein and ubiquitin in IHC studies.In the atrophy fibers,IHC showed the increased expression of endoplasmic reticulum stress related proteins GRP78 and calnexin,and apoptosis proteins of caspase-12 and Bax.ConclusionsThere is accumulation of abnormal proteins in muscle fibers in Chinese patients with Nonaka myopahty.These proteins may stimulate endoplasmic reticulum stress and apoptosis,which may be a mechanism responsible for muscle damage.

ObjectiveTo optimize the condition of multiple fluorescence quantitative PCR and establish a new assay of four human herpes virus (HHV) detected by AllGlo quadruple fluorescence quantitative PCR.MethodsFour HHV including HSV-1,HSV-2,EBV and CMV were identified by sequence analysing the qualitative PCR production.Furthermore,they were quantitatively detected by AllGlo and TaqMan multiple fluorescence quantitative PCR respectively.ResultsBoth the positive rate and specificity of AllGlo and TaqMan in detecting single HHV achieved 100％.And AllGlo single fluorescence quantitative PCR prevailed over TaqMan's by Ct of 1-3.Four HHV can be simultaneously detected by AllGlo quadruple fluorescence quantitative PCR,comparing to the only two by TaqMan.ConclusionAllGlo fluorescence quantitative PCR assay allows a higher throughput,sensitivity and specificity than TaqMan in detection and thus provides a board prospect.

Objective To construct the mice pneumonia model with imipenem-resistant Acinetobacter baumannii and provide experimental model in anti-pan-resistant Acinetobacter baumannii therapy study. Methods A total number of 120 4-week-old BALB/C male mice were randomly selected and divided into three groups including micro-intratracheal injection, ultrasonic atomizing and nasal dripping. The mice were treated with methotrexate to induce hypo-immunity in every group. These BALB/C mice of normal immunity and hypo-immunity were infected through Imipenem-resistant Acinetobacter baumannii by microintratracheal injection, ultrasonic atomizing and nasal dripping, respectively. The morbidity, mortality,bacterial clearance rate and histopathology in lung were determined. Results The morbidities of BALB/C mice with hypo-immunity infected by micro-intratracheal injection and ultrasonic atomizing achieved 100%(30/30), while the mortalities were 100% (10/10) and 33.3% (3/10), respectively. Mice in two groups above displayed the influx of neutrophils, lymphocytes and macrophages in the peri-bronchial and alveolar interstitial space 12-24 h after pulmonary infection. In addtion, the mice in micro-intratracheal injection group displayed coUapse of partial alveolar walls, formation of abscesses and bacterial colonies in alveoli. While the lung pathology in mice of ultrasonic atomizing group was characterized by cell degeneration in some regions in the lungs, slight relaxation, congestion in alveolar wall vessels and normal of bronchial and alveolar tissue 24 h after inoculation. Degeneration in peri-tracheal and peri-bronchial areas was observed 24-48 h after inoculation, along with highly expanded pulmonary blood vessels and edems. The inflammation was reduced at 48 hours. There was no obvious pulmonary infection in BALB/C mice with hypo-immunity by nasal dripping with mortality of 0% (0/10) and no significant histopathologic change in lungs. Conclusions BALB/C mice with hypo-immunity pneumonia model with Imipenem-resistant Acinetobacter baumannii can be conducted by micro-intratracheal injection or ultrasonic atomizing, but the latter has the advantages of high-productivity, easy-operation, low-cost, time-saving and usefulness. Mice with normal immunity are not susceptible to imipenem-resistant Acinetobacter baumannii.

Objective To evaluate the application of fluorescence PCR in detecting ureA gene of Helicobacter pylori(HP)in feces.Methods Fluorescence PCR was used to detect ureA gene of HP in feces from 50 patients,including 23 confirmed by gastric biopsy urease test and histological staining.Bacterium culture and serum antibody detection were also performed, and chi-square test was used to compare the sensitivity,specificity,positive predictive value and negative predictive value among three methods.Results The sensitivity,specificity,positive predictive value and negative predictive value of fluorescence PCR were 1.00,0.96,96.O%and 100.0%,while those for HP culture were 0.78,1.00,100.0%and 84.0%,and thee for serum antibody detection Was 0.96,0.74,76.O%and 95.0%.There were significant differences in sensitivity and negative predictive value between PCR and bacterium culture (X2=5.60 and 4.44,P<0.05),and significant differences in specificity and positive predictive value between PCR and serum antibody detection(X2=5.28 and 4.08,P<0.05).Conclusion ureA gene detection in feces by fluorescence PCR is of value for the diagnosis of HP infection.

Objectives To report the clinical and myopathological features in a case with Danon disease caused by a novel mutation in the lysosome-associated membrane protein-2 ( LAMP2 ) B gene.Methods A 16-year-old boy presenting progressive muscle weakness and atrophy, accompanied with spinal ankylosis was clinically evaluated including electrocardiogram, echocardiogram and electromyogram.Muscle biopsy was carried out in the patient.The histological staining, ultrastructural examination, and immunohistochemical staining with antibodies against dystrophin, merosin and C5b9 were performed in frozen sections.LAMP2B sequence was analyzed in the patient and his parents.Results Electrocardiogram in the patient showed Ⅰ atrioventricular block; echocardiogram revealed focal hypertrophy in mitral valve with mild cardiac diastolic dysfunction; electromyogram indicated myogenic and neurogenic patterns.Muscle pathology study revealed numerous vacuoles located at the fibers.Dystrophin, merosin and C5b9 was immuno-positive around the vacuoles.Electron microscopy revealed vacuoles surrounded by sarcolemma and abnormal lysosome aggregating at the fibers.A novel nonsense mutation ( K402X ) in the LAMP2B gene has been identified in the patient but not in his mother and 50 normal controls.Conclusions Danon disease caused by K402X mutation in C-terminus of LAMP2B presented benign course of the disease characterized by prominent vacuolar skeletal myopathy, mild cardiac abnormalities and peripheral neuropathy.

Objective:To explore the clinical efficacy of alanyl glutamine (Ala-Gln) combined with octreotide in the treatment of severe acute pancreatitis (SAP) and its effects on the serum interleukin-6 (IL-6),C reactive protein (CRP) levels and related biochemical parameters.Methods:100 cases of patients with SAP in our hospital from January 2013 to December 2016 were selected and randomly divided into two groups.The control group was treated by octreotide,while the observation group was treated by Ala-Gln combined with octreotide.The clinical effect,changes of serum IL-6,CRP,amylase (AMY),lactate dehydrogenase (LDH),prealbumin (PA) and albumin (ALB) levels before and after therapy were compared between two groups.Results:On the 10th day after treatment,the overall effective rate of observation group was 88.0％ which was significantly higher than that of the control group (64.0％,P＜0.05).The serum IL-6,CRP,AMY and LDH levels of both groups on the 10th day after treatment were significantly lower than those before treatment (P＜0.01).Compared with the control group,the improvement of serum IL-6,CRP,AMY,LDH levels of observation group were more significant(P＜0.01).Compared with those before treatment,the serum PA and ALB levels of both groups were significantly increased on the 10th day after treatment(P＜0.05),and the improvement of serum PA and ALB levels of observation group on the 10th day after treatment were significantly better than those of the control group(P＜0.01).Conclusion:Alanyl glutamine combined with octreotide could effectively eliminate or alleviate the symptoms and signs of patients with severe acute pancreatitis,control the inflammatory reaction,improve the level of metabolism,improve the prognosis.

Objective To report 2 cases of Fabry disease with early-onset ischemic stroke and investigate the clinical and image features. Methods The 2 patients developed dizziness, diplopia and progressive memory decline at 32 and 25 years of age respectively. The α-galactosidase A (GLA)activity was 4. 3 U in case 1 and 1. 0 U in case 2 ( normal range 100-500 U). Skin biopsy showed numerous membrane bounded osmiophilic laminar material in vascular smooth muscle cells and endothelial cells. GLA gene analysis revealed GLA exon 7 1033-1034 TC del in case 1 and GLA exon 3 466G ＞ A in case 2. The 2 patients were evaluated by Mainz severity score index (MSSI) and cranial MRI. Results The general MSSI was 32 in case 1 and 16 in case 2, with the highest score of neurological score ( 11 and 14). Both cases showed multifocal infarcts in bilateral cerebellum, occipital lobe, basal ganglia, which were hypointensity on T1 WI and hyperintensity on T2WI. There were hyperintensity changes in the pulvinar and basal ganglia on T1 WI in case 2. Conclusions Cerebral ischemic stroke could appear as initial symptoms in Fabry disease,which predominantly involved the posterior circulation. There might be no dilation of basal-vertebral artery.