Computational identification of new potential transcriptional partners of ERRα in breast cancer cells: specific partners for specific targets.

Estrogen related receptors are orphan members of the nuclear receptor superfamily acting as transcription factors (TFs). In contrast to classical nuclear receptors, the activities of the ERRs are not controlled by a natural ligand. Regulation of their activities thus relies on availability of transcriptional co-regulators. In this paper, we focus on ERRα, whose involvement in cancer progression has been broadly demonstrated. We propose a new approach to identify potential co-activators, starting from previously identified ERRα-activated genes in a breast cancer (BC) cell line. Considering mRNA gene expression from two sets of human BC cells as major endpoint, we used sparse partial least squares modeling to uncover new transcriptional regulators associated with ERRα. Among them, DDX21, MYBBP1A, NFKB1, and SETD7 are functionally relevant in MDA-MB-231 cells, specifically activating the expression of subsets of ERRα-activated genes. We studied SET7 in more details and showed its co-localization with ERRα and its ERRα-dependent transcriptional and phenotypic effects. Our results thus demonstrate the ability of a modeling approach to identify new transcriptional partners from gene expression. Finally, experimental results show that ERRα cooperates with distinct co-regulators to control the expression of distinct sets of target genes, thus reinforcing the combinatorial specificity of transcription.

A survey of the frequency of medical exposure in Fangshan District of Beijing, 2019 / 中国辐射卫生

Objective To investigate the basic situation of radiodiagnosis and radiotherapy institutions and the frequency of medical exposure in Fangshan District, Beijing, China. Methods A general survey using the questionnaire was conducted online to obtain the basic situation of the radiodiagnosis and radiotherapy institutions, the number of people in each type of radiodiagnosis and radiotherapy project, and the number of the usually resident population in the whole district in 2019, thus obtaining the frequency of medical exposure in each type of radiodiagnosis and radiotherapy project. Results There were 60 radiodiagnosis and radiotherapy institutions, 565 radiology staff, and 199 sets of radiodiagnosis and radiotherapy equipment in the whole district in 2019. The frequency of medical exposure was 521.29 per 1000 people, among which conventional medical diagnostic X-ray workers accounted for 301.79 per 1000 people (57.89%) and computed tomography workers accounted for 207.56 per 1000 people (39.82%). The number of tertiary hospitals accounted for 6.67% of the radiodiagnosis and radiotherapy institutions, and the number of people exposed tomedical radiation in tertiary hospitals accounted for 52.25% of the total. The number of secondary hospitals accounted for 5.00% of the radiodiagnosis and radiotherapy institutions, and the number of people exposed to medical radiation in secondary hospitals accounted for 27.83% of the total. Conclusion The distribution of medical exposure in Fangshan District is uneven. The radiodiagnosis and radiotherapy technology used is relatively single. Relevant departments should strengthen macroscopic readjustment and control, and formulate reasonable policies, so as to rationally allocate and effectively utilize medical and health resources.

Knox homologs shoot meristemless (STM) and KNAT6 are epistatic to CLAVATA3 (CLV3) during shoot meristem development in Arabidopsis thaliana.

BACKGROUND: In Arabidopsis, the genes SHOOT MERISTEMLESS (STM) and CLAVATA3 (CLV3) antagonistically regulate shoot meristem development. STM is essential for both development and maintenance of the meristem, as stm mutants fail to develop a shoot meristem. CLV3, on the other hand, negatively regulates meristem proliferation, and clv3 mutants possess an enlarged shoot meristem. Genetic interaction studies revealed that stm and clv3 dominantly suppress each other's phenotypes. STM works in conjunction with its closely related homologue KNOTTED1-LIKE HOMEOBOX GENE 6 (KNAT6) to promote meristem development and organ separation, as stm knat6 double mutants fail to form shoot meristem and produce a fused cotyledon. RESULTS: In this study, we show that clv3 fails to promote shoot meristem formation in stm-1 background if we also remove KNAT6. stm-1 knat6 clv3 triple mutants result in shoot meristem termination and produce fused cotyledons similar to stm knat6 double mutant. Notably, the stm-1 knat6 and stm-1 knat6 clv3 alleles lack tissue in the presumed region of SAM that is a novel phenotype reported in Arabidopsis mutants. stm-1 knat6 clv3 also showed reduced inflorescence size as compared to clv3 single or stm clv3 double mutants. CONCLUSION: In contrast to previously published data, these data suggest that STM and KNAT6 are redundantly required for the vegetative SAM, but insufficient for the inflorescence meristem.

The research progress of the variation of lumbosacral nerve root / 中华骨科杂志

Lumbosacral nerve root anomalies (LNRA) refers to the abnormality of lumbosacral nerve root in morphology, course and initial position, which may be related to the abnormal migration of nerve root in embryo. Imaging examination is a commonly used method for localization and qualitative diagnosis of LNRA. Clinically, many classification systems have been established based on imaging results, autopsy reports and Book observations. However, the lack of evaluation on the advantages and disadvantages of each classification is not conducive to the development of clinical work. In this paper, the classification and characteristics of LNRA at home and abroad were reviewed, and the advantages and limitations of each classification were evaluated. Through the literature retrieval and summary, it is not reliable to design the corresponding classification based on the imaging results. Not only is the detection rate of MRI as the preferred examination method far lower than that of autopsy, but also it is not an intuitive study of the lesions, and its authenticity is questionable. Based on the classification of autopsy results, the spinal cord is directly stripped in the study, excluding the surrounding soft tissue and bone marrow. The interference of spinal bone structure is more conducive to the comprehensive observation of variation, which has a certain guiding significance for clinical; based on the classification of intraoperative observation results, the number of research samples is large, easy to obtain, and there are matching imaging data to do the follow-up comparative study, among which the Neidre classification is themost widely used classification, which provides considerable convenience for clinical work. LNRA may not be treated as a common disease due to the limitation of technology and lack of understanding. The lack of specific symptoms and the characteristics of combined compression will affect the detection rate. In terms of treatment, traditional discectomy and spinal canal decompression cannot meet the clinical needs. More new surgical methods need to be proposed to improve the prognosis and quality of life of patients.

Alterations of cholinergic and monoamine neurotransmitters in cerebrospinal fluid in patients with postoperative delirium / 中华行为医学与脑科学杂志

Objective:To investigate the alterations of cholinergic and monoamine neurotransmitters in cerebrospinal fluid in patients with postoperative delirium.Methods:Sixty-eight patients with normal preoperative cognitive functions were enrolled.They were diagnosed with spinal extramedullary intradural space-occupying lesion and underwent surgical resection.Among these patients, 18 developed postoperative delirium (delirium group), 46 had no postoperative delirium (control group), and the diagnosis of delirium was unclear in four cases (excluded). Cerebrospinal fluid (CSF) was collected before the surgical resection of lesions and on the third day postoperatively.The concentrations of acetylcholine (Ach), norepinephrine (NE), adrenaline (E), dopamine (DA) and serotonin (5-HT) were measured using the high-performance liquid chromatography/electrochemical method.Results:Prior to the surgical resection, there were no significant differences in the Ach, NE, E, DA or 5-HT baseline levels in the CSF between the delirium group and the control group (all P>0.05). After surgery, the Ach level in the delirium group ((0.63±0.26) μmol/L) was significantly lower than that in the control group ((0.77±0.19) μmol/L) ( P=0.032), and there were no significant differences in other neurotransmitter levels (all P>0.05). In the delirium group, the level of Ach in the CSF after surgery ((0.63±0.26) μmol/L) was significantly lower than the baseline level ((0.75±0.19) μmol/L) ( P=0.021). The postoperative NE level ((1.58±0.28) μmol/L) was significantly higher than the baseline level ((1.49±0.21) μmol/L) ( P=0.036). There was no significant difference in the adrenaline level ( P=0.497). The postoperative DA level ((0.86±0.18) μmol/L) was significantly higher than the baseline level ((0.82±0.15) μmol/L) ( P=0.045), and the postoperative 5-HT level ((2.94±0.28) μmol/L) was also significantly higher than the baseline level ((2.75±0.35) μmol/L) ( P=0.022). In the control group, only the postoperative 5-HT level ((2.90±0.31) μmol/L) was significantly higher than the baseline level ((2.76±0.26) μmol/L) ( P=0.016), while the postoperative levels of other neurotransmitters were not significantly changed when compared to the baseline levels (all P>0.05). Conclusion:The cholinergic neurotransmitter levels were reduced while the monoamine neurotransmitter levels were increased in the cerebrospinal fluid in patients with postoperative delirium, which suggests that cholinergic hypoactivity and monoaminergic hyperexcitability may be important pathophysiological processes in the occurrence and development of postoperative delirium.

Nosocomial infection prevention and control of hospitals within a medical alliance: status and development strategies / 中华医院管理杂志

Objective:To investigate the current management of nosocomial infection at medical institutions of all levels in Changzhou, so as to provide basis for standardizing nosocomial infections control of hospitals within a medical alliance.Methods:An electronic questionnaire was customized for online survey of 91 hospitals affiliated to eight regional medical alliances in Changzhou city in March 2019. The survey covered such aspects as general conditions of the hospital, profile of nosocomial infection control administrators and other staffing, supervision of hospital nosocomial infection programs, and training needs, as well as outstanding problems and suggestions.Frequency number and percentage represent enumeration data, and χ2 test was used to analyze the in-group differences of medical institutions of three levels. Results:Tertiary public hospitals were superior to the secondary and primary hospitals in organizational structure, professional staffing and target monitoring, with the differences of statistical significance( P<0.05). The most urgent training needs of medical institutions at all levels were knowledge in determination and reporting of infectious diseases/nosocomial infection/infection outbreaks; top imperatives and recommendations were development of operation rules for primary medical institutions and standardization of workflows. Conclusions:Staff of primary medical institutions need capacity building in nosocomial infection control; primary hospitals are equipped with incomplete nosocomial infection control information platform; key departments in general lack homogenous management. Tertiary hospitals are encouraged to play leadership in medical alliances in achieving standardized, homogenous and informationized nosocomial infection control within the medical alliances.

Cathepsin L Causes Proteolytic Cleavage of Chinese-Hamster-Ovary Cell Expressed Proteins During Processing and Storage: Identification, Characterization, and Mitigation.

A stochastic approach of copurification of the protease Cathepsin L that results in product fragmentation during purification processing and storage is presented. Cathepsin L was identified using mass spectroscopy, characterization of proteolytic activity, and comparison with fragmentation patterns observed using recombinant Cathepsin L. Cathepsin L existed in Chinese hamster ovary cell culture fluids obtained from cell lines expressing different products and cleaved a variety of recombinant proteins including monoclonal antibodies, antibody fragments, bispecific antibodies, and fusion proteins. Therefore, characterization its chromatographic behavior is essential to ensure robust manufacturing and sufficient shelf life. The chromatographic behaviors of Cathepsin L using a variety of techniques including affinity, cation exchange, anion exchange, and mixed mode chromatography were systematically evaluated. Our data demonstrates that copurification of Cathepsin L on nonaffinity modalities is principally because of similar retention on the stationary phase and not through interactions with product. Lastly, Cathespin L exhibits a broad elution profile in cation exchange chromatography (CEX) likely because of its different forms. Affinity purification is free of fragmentation issue, making affinity capture the best mitigation of Cathepsin L. When affinity purification is not feasible, a high pH wash on CEX can effectively remove Cathepsin L but resulted in significant product loss, while anion exchange chromatography operated in flow-through mode does not efficiently remove Cathepsin L. Mixed mode chromatography, using Capto™ adhere in this example, provides robust clearance over wide process parameter range (pH 7.7 ± 0.3 and 100 ± 50 mM NaCl), making it an ideal technique to clear Cathepsin L. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2732, 2019.

Etiological characteristics and related factors of infectious endophthalmitis age-related cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To explore the etiology, related factors and prevention of infectious endophthalmitis after age-related cataract surgery.<p>METHODS: A retrospective analysis of 1 365 age-related cataract patients admitted to our hospital from 2016-01/2018-01, statistics of the incidence of infectious endophthalmitis, and analysis of the pathogenic characteristics of infectious endophthalmitis and related risk factors.<p>RESULTS: Infective endophthalmitis occurred in 28 patients, and 36 pathogens were detected, including 9 strains of staphylococcus epidermidis(25.00%), 9 strains of pseudomonas aeruginosa(25.00%), and 8 strains of bacillus(22.22%). Pseudomonas aeruginosa and Bacillus have strong resistance to cefazolin, cefotaxime and amoxicillin; high sensitivity to cefoperazone-sulbactam and meropenem; staphylococcus to epidermidis erythromycin and azithromycin have strong drug resistance, and have high sensitivity to vancomycin, nitrofurantoin and minocycline. Multivariate regression analysis of Logistic, age(≥70 years), diabetes, operative time(≥15min), intraoperative vitreous spillover were independent risk factors for infectious endophthalmitis after age-related cataract surgery(<i>P</i><0.05).<p>CONCLUSION: Infectious endophthalmitis pathogens after age-related cataract surgery are more common with Staphylococcus epidermidis, Pseudomonas aeruginosa, and Bacillus. Age(≥70 years), diabetes, operative time(≥15min), intraoperative vitreous spillover were independent risk factors for infectious endophthalmitis after age-related cataract surgery.

Effect of continuous negative pressure drainage with intermittent irrigation on surgical site infection after laparoscopic extralevator abdominoperineal excison / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the effect of continuous negative pressure drainage with intermittent irrigation on surgical site infection (SSI) after laparoscopic extralevator abdominoperineal excison (ELAPE).</p><p><b>METHODS</b>Clinical data of 28 rectal cancer patients who underwent continuous negative pressure drainage with intermittent irrigation following laparoscopic ELAPE (negative irrigation group) at our department from March 2016 to August 2017 were analyzed retrospectively. At the same time, 32 rectal cancer patients who underwent laparoscopic ELAPE and simple presacral drainage from January 2014 to February 2016 were included as controls (simple drainage group). Self-made double cannula: one silicon rubber drainage tube was used; 3 side holes were cut at the front end with 1-2 cm interval; tube was ranked intermittently and oppositely; a small hole was cut in the middle of rear; the infusion tube was placed through the small hole to the front side of the drainage tube (to rinse when the drainage was turbid). The placement and use of self-made double cannula: it was placed in the presacral space and was drawn from the medial to the sciatic tubercle, then was connected to drainage bag for 24 hours; when no blood was observed, the drainage tube was connected to negative pressure drainage ball, keeping negative pressure status. The development of SSI within 30 days postoperatively and other perioperative parameters were compared between the two groups.</p><p><b>RESULTS</b>There were no statistically significant differences in baseline data between two groups (all P>0.05). Incidence of SSI in negative irrigation group was significantly lower than that in simple drainage group [14.3% (4/28) vs. 43.8% (14/32), χ=6.173, P=0.013]. Additionally, a shorter postoperative hospital stay was observed in negative irrigation group [(9.8±1.5) days vs. (11.4±2.6) days, t=2.918, P=0.005]. Besides, other perioperative parameters, including operative time, intraoperative blood loss, time to removal of drainage tube, etc were not significantly different between two groups (all P>0.05). After adjusting to confounders, multivariate analysis showed that negative pressure drainage was an independent protective factor for SSI following laparoscopic ELAPE (OR=0.214, 95%CI:0.060-0.762, P=0.002).</p><p><b>CONCLUSION</b>Continuous negative pressure drainage with intermittent irrigation can effectively decrease the incidence of SSI following laparoscopic ELAPE, and is safe and simple.</p>

Advances in prevention and treatment of bone cement pulmonary embolism in patients with vertebral augmentation / 中国医师进修杂志

The efficacy of vertebroplasty and percutaneous kyphoplasty in treatment of osteoporotic compression fracture was widely recognized recently.But the complication of bone cement pulmonary embolism was severe and it can threaten life.In this article,the incidence,pathogenesy,risk factors,symptom,auxiliary examination,treatment and prevention of bone cement pulmonary embolism were reviewed.

Safety evaluation of unilateral percutaneous kyphoplasty in treating osteoporotic vertebral burst fracture / 中国医师进修杂志

Objective To explore the safety of unilateral percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral burst fracture.Methods All 25 osteoporotic vertebral burst fracture cases (25 fracture segments) treated from April 2014 to July 2015 were analyzed retrospectively.In 25 cases,there were 17 males and 16 females,aged from 58.0 to 88.0 years with a mean age of 76.6 years.All patients included in the study had preoperative thoracic or lumbar X-rays,CT reconstruction and MR fatsuppression sequence scan in order to definite fracture sites and the integrality of the posterior wall of fracture vertebral.The unilateral PKP were performed by the same operator.All patients included in the study had postoperative thoracic or lumbar X-rays,and CT reconstruction to observe the bone cement leakage.After patients were out of hospital,X-rays were done regularly.The types of bone leakage were recorded.The pre-and post-operational anterior and posterior wall and the kyphotic angle were measured by one doctor.Results The scores of VAS at the first day after operation and the end of follow up decreased compared with the pre-operative scores:(2.8 ± 1.2),(2.4 ± 1.6) scores vs.(6.4 ± 2.6) scores,and there were significant differences (P ＜ 0.05).The kyphotic angle at the first day after operation and the end of follow up decreased compared with the pre-operative,but there were no significant differences (P ＞ 0.05).The post-operative height of vertebral anterior wall increased at the first day after operation and the end of follow up compared with the pre-operative:(21.7 ± 5.0),(21.4 ± 4.1) mm vs.(20.3 ± 3.8)mm,and there were significant differences (P ＜ 0.05).The post-operative height of vertebral posterior wall increased at the first day after operation and the end of follow up compared with the pre-operative,but there were no significant differences (P ＞ 0.05).The above index at the first day after operation and the end of follow up had no significant differences (P ＞ 0.05).Conclusions The unilateral PKP in treating osteoporotic vertebral burst fracture is safe and reliable.Clear image display,skillful puncture techniques and suitable injection timing are necessary factors for a successful operation.

An imaging study on effect of total artificial disc replacement on lumbar sagittal alignment / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate effect of Activ L total lumbar disc replacement on lumbar sagittal alignment.</p><p><b>METHODS</b>The imaging data of patients with degenerative disc disease received Activ L total lumbar disc replacement at Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University from March 2009 to March 2013 were retrospectively analyzed. The average age was 45.6 years(range, 35-60 years)and the surgery levels were as follows: L3-4 2 cases, L4-5 15 cases, L5/S1 5 cases, L3-4+ L4-5 3 cases, L4-5+ L5/S1 7 cases. All patients were followed up for 15 to 63 months(average, 32 months). Radiographic parameters such as lumbar lordosis angle(LL), segment lordosis angle(SL) and sacral slope angle(SS) were recorded. All the radiographic parameters were compared using one-way ANOVA at different stage. Lumbar lordosis angle of the two-level was compared with the one of one-level by using independent sample t-test before and after the operation. A partial correction test was carried out to determine the corrections between the parameters preoperatively, one month after the operation and at final follow-up.</p><p><b>RESULTS</b>One month after the operation, the lumbar lordosis angle decreased by an average of 1.8°, but there was no statistically significant(P>0.05). Compared with one month postoperation, the lumbar lordosis angle increased by an average of 6.8°(P<0.05), which also increased a lot compared with preoperation(P<0.05). The value of segment lordosis angle was rising up from preoperation to the final follow-up(P<0.05), so was the value of sacral slope angle, but there was no statistically significant between different stage(P>0.05). The lumbar lordosis angle showed no significant difference between double-level ones and single-level ones at different stage(P<0.05). The lumbar lordosis angle showed positive correlation with the sacral slope(P<0.001), however, the lumbar lordosis angle showed no corrected with the segment angle all the time(P>0.05).</p><p><b>CONCLUSIONS</b>The total lumbar disc replacement with Activ L prosthesis had contributed to maintain and improve the lumbar alignment in the short and medium term. Double- or single-level total lumbar disc replacement had no significant effect on the value of lumbar lordosis angle. The lumbar lordosis angle showed positive correlation with the sacral slope all the time with no correlation between lumbar lordosis angle and sacral slope.</p>

Trace levels of the CHO host cell protease cathepsin D caused particle formation in a monoclonal antibody product.

Chinese hamster ovary (CHO) cells are often used to produce therapeutic monoclonal antibodies (mAbs). CHO cells express many host cell proteins (HCPs) required for their growth. Interactions of HCPs with mAbs can sometimes result in co-purification of trace levels of 'hitchhiker' HCPs during the manufacturing process. Purified mAb-1 product produced in early stages of process optimization had high HCP levels. In addition, these lots formed delayed-onset particles containing mAb-1 and its heavy chain C-terminal fragments. Studies were performed to determine the cause of the observed particle formation and to optimize the purification for improved HCP clearance. Protease activity and inhibitor stability studies confirmed that an aspartyl protease was responsible for fragmentation of mAb-1 resulting in particle formation. An affinity resin was used to selectively capture aspartyl proteases from the mAb-1 product. Mass spectrometry identified the captured aspartyl protease as CHO cathepsin D. A wash step at high pH with salt and caprylate was implemented during the protein A affinity step to disrupt the HCP-mAb interactions and improve HCP clearance. The product at the end of purification using the optimized process had very low HCP levels, did not contain detectable protease activity, and did not form particles. Spiking of CHO cathepsin D back into mAb-1 product from the optimized process confirmed that it was the cause of the particle formation. This work demonstrated that process optimization focused on removal of HCPs was successful in eliminating particle formation in the final mAb-1 product.

The accuracy of CT and MR estimating whole liver volume: a meta-analysis / 中华器官移植杂志

Objective To systemically evaluate the accuracy of CT and MR estimating whole liver volume with evidence based medicine methods.Method Published papers about whole liver volume estimation with CT or MR modality were searched in Cochrane library,MEDLINE,EMBASE,CMBdisc(China biology medicine disc) for English and Chinese abstracts.Inclusion criteria were formulated according to validity criteria for diagnostic research published by the Cochrane collaboration.Heterogeneity test of extracted data of Eligible papers was performed first to determine the appropriate statistical model used to pool the result.Finally,sensitivity and publish bias analysis was performed.Result Seventeen articles with 37 studies including 351 patients met the inclusion criteria.There was no heterogeneity between included studies (I2 =0％,Q =5.85,P =1).Fixed effect model was selected for the meta analysis and there was no statistically significant difference between true and radiological estimated whole liver volume (WMD =21.61 mL,95％ confidence interval:-6.33-49.57 mL,z =1.51,P =0.13).Sensitivity analysis revealed the result was robust which was not affected by excluding any of the included studies.Funnel plot and publish bias analysis showed no publish bias (t =-1.55,P=0.13).Conclusion CT and MR volume estimation is accurate for liver volume measurement,which provides important information for preoperative evaluation,postoperative monitoring and follow-up studies of other hepatic pathologies.aximum benefit to patients.

Comparison of effects of hand-assisted laparoscopic and traditional laparoscopic right hemicolectomy on immune function / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the effects of hand-assisted laparoscopic and traditional laparoscopic right hemicolectomy on immune function.</p><p><b>METHODS</b>From May 2010 to November 2013, 60 patients with right colon carcinoma were prospectively enrolled and randomly divided into hand-assisted laparoscopic surgery(HALS) group and traditional laparoscopic surgery(TLS) group with 30 cases in each group. CRP, IL-6, CD3+, CD4+, CD8+ in the peripheral blood were measured and compared on the first day before operation, the first, third and fifth day after operation.</p><p><b>RESULTS</b>CRP and IL-6 levels in two groups were significantly increased on the first, third and fifth days(P<0.01), and peaked on the third day after operation. Postoperative CRP and IL-6 levels were slightly higher in HALS group, but the difference was not statistically significant (P>0.05). CD3+ and CD4+ levels were significantly decreased on the first, third day after operation(P<0.05), and returned to preoperative levels on the fifth day after operation in both two groups, and the difference was not statistically significant(P>0.05). There was no significant difference in CD8+ between two groups either before surgery or after operation(P>0.05).</p><p><b>CONCLUSION</b>Hand-assisted laparoscopic right hemicolectomy has the same effects of traditional laparoscopic right hemicolectomy in the relief of postoperative stress and the protection of immune function.</p>

Improved detection of host cell proteins (HCPs) in a mammalian cell-derived antibody drug using liquid chromatography/mass spectrometry in conjunction with an HCP-enrichment strategy.

RATIONALE: Host cell proteins (HCPs), which are process-related impurities typically present at low levels in recombinant biopharmaceutical products, are often measured using an immunological technique, such as an enzyme-linked immunosorbent assay (ELISA). In contrast to ELISA which only provides the total amount of HCP, liquid chromatography/mass spectrometry (LC/MS) can provide both qualitative and quantitative information about the major HCP species. In this study, an HCP-enrichment step was optimized and combined with LC/MS to identify and determine the relative abundance of HCPs present in a monoclonal antibody (mAb) drug product. METHODS: An NS0 (mouse myeloma) cell-derived mAb drug product, whose total HCP level was less than 100 ng/mg of protein, was subjected to analysis by LC/MS. One-dimensional and two-dimensional chromatography options, together with the off-line HCP enrichment strategy based on Protein A chromatography, were evaluated for optimal HCP detection. RESULTS: With this approach, nineteen HCPs were detected from a therapeutic mAb, an improvement over the detection of only one HCP without depletion. CONCLUSIONS: Compared with other published HCP studies with LC/MS, the HCP-enrichment step in our method enables a more practical and relevant application to approved protein therapeutics, which are mostly mammalian cell-derived products with HCPs present at very low levels.

The optimal insertion position of the lumbar interspinous dynamic stabilization device (Coflex): a biomechanical evaluation / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the optimal insertion position of the Coflex lumbar interspinous dynamic stabilization device.</p><p><b>METHODS</b>Six fresh adult human cadaveric lumbar spine specimens (L1-L5) were mounted in a materials testing machine by embedding to clamps with L1 and L5 vertebrae. L3-4 motion segment of each specimen was operated by selective decompression and Coflex interspinous device insertion. The L3 and L4 vertebrae was inserted one needle attached with four marker points respectively, which were used to record the range of motion (ROM). Each lumbar spine specimen was tested according to the loading sequence at 5 groups: intact (keeping lumbar ligamenta and facet joints intact) group, partial destabilized (resection of L3-4 interspinous ligamenta, ligamentum flavum, facet capsule, and bilateral resection 50% of L3 inferior facets) group, 10 mm insertion (distance between apex of U-shaped Coflex and dural sac was 10 mm)group, 5 mm insertion (distance was 5 mm)group, and 0 mm insertion (distance was 0 mm)group. Each lumbar spine specimen was tested repeatedly 3 times according to a loading sequence consisting of flexion, extension, left/right lateral bending, left/right axial rotation, loaded with pure moments of 8 N·m, and was recorded the ROM of operative segment at the third time. ROM of 5 groups in 6 directions respectively were analyzed with one-way ANOVA test and multiple comparisons were based on LSD method.</p><p><b>RESULTS</b>The means ROM of 5 groups were not all equal in flexion, extension, left/right lateral bending, left/right axial rotation (F = 8.472, 18.301, 7.700, 12.473, 16.809, 6.624; all P < 0.01). The 10 mm insertion group had significant high ROM in 6 directions than the intact group (t = 3.80, 3.82, 4.49, 5.60, 4.96, 2.98, all P < 0.01), but it was no difference comparing with the partial destabilized group (P > 0.05). The ROM of the 5 mm and 0 mm insertion group were no significant differences comparing with the intact group in flexion, extension, left/right axial rotation (P > 0.05), but it were significant differences comparing with the partial destabilized group in the same directions (5 mm insertion group: t = 3.19, 6.34, 5.26, 3.43, all P < 0.01; 0 mm insertion group: t = 4.21, 6.68, 5.81, 3.72, all P < 0.01). There were significant differences in the ROM of left/right lateral bending between the 5mm/0mm insertion groups and the intact group (5 mm insertion group: t = 3.71 and 5.22, all P < 0.01; 0 mm insertion group: t = 3.44 and 4.95, all P < 0.01), but there were no differences comparing with the partial destabilized group in the same directions (P > 0.05).</p><p><b>CONCLUSIONS</b>The insertion of Coflex interspinous dynamic stabilization device can maintain the stability of a partially destabilized specimen back to an intact one in flexion, extension and axial rotation when distance between apex of U-shaped Coflex and dural sac was ≤ 5 mm, but can't return the stability in lateral bending. The Coflex can't return the stability of a partially destabilized specimen back to an intact one in 6 directions when distance between apex of U-shaped Coflex and dural sac was ≥ 10 mm.</p>

MRI study on predicting the collapse of avascular necrosis of the femoral head / 中华放射学杂志

Objective To study the risk factors of MRI for the prediction of collapse in patients with avascular necrosis of the femoral head.Methods Twenty-two patients (39 hips) diagnosed avascular necrosis of femoral head by MR were enrolled in our study.The following MR appearances were evaluated:bone marrow edema,joint fluids,signal intensity and location of the lesion.The volume and surface area of the necrosis zone were calculated.The time of follow-up was 18-84 months (median,25 months).Logistic regression analysis was used to predict the risk factors by SPSS 13.0.The maximum value of Youden index was selected as the critical point to predict the collapse of femoral head and to define the sensitivity,specificity and accuracy.Results In the 39 hips with femoral head necrosis,21 hips had collapse.Bilateral collapse occurred in 5 cases.In 25 hips with the necrosis surface larger than 25％,collapse occurred in 21 (84％); In 8 hips with the volume of femoral head necrosis larger than 30％,collapse occurred in all cases; 1n 33 hips with the necrosis locating at the superolateral quadrant,collapse occurred in 21 (63.6％); In 22 hips with necrotic areas showing heterogeneous signal intensity,collapse occurred in 18(81.8％) ;In 25 hips with large amount of joint effusion,collapse occurred in 16 (64％) ;in 18 hips with bone marrow edema,collapse occurred in 13 (65％).Joint fluid,heterogeneous signal intensity and lesions in the superolateral quadrant,volume ratio,and area ratio were the high risk factors,while bone marrow edema was a relatively low risk factor.The area under ROC curves for area ratio of NASA was greater than that for volume ratio (0.987 vs 0.902).When the critical value for area ratio was 26.7％,the true positive rate was 95.2％,true negative rate was 94.4％,and Youden's index was 0.896.Conclusions The collapse of necrosis of femoral head may result from many factors.The femoral head was easy to collapse when it had large enough area of necrosis and mixed signal intensity,a large amount of joint effusion,bone marrow edema,and superolateral quadrant location.The critical value for area ratio to predict the collapse of femoral head was about 26.7％.The area ratio is more accurate than volume ratio in predicting the collapse of necrosis of femoral head.

Device related complications of the Coflex interspinous process implant for the lumbar spine / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coflex, a type of interspinous process implant, can provide intervertebral dynamic stability for surgical segments and effectively relieve lumbocrural pain. However, few studies have described therapeutic strategies and the avoidance of Coflex implant complications.</p><p><b>METHODS</b>Coflex implant complications in this study included intraoperative or postoperative spinous process fracture, aggravated postoperative lumbocrural pain, dislodgment and malposition. The complications were analyzed, and therapeutic strategies were applied according to the specific complication. The Visual Analogue Scale and Oswestry Disability Index scores were evaluated by using the paired-samples test from SPSS 12.0.</p><p><b>RESULTS</b>Conservative treatment was provided to seven patients who experienced aggravated lumbocrural pain even though their devices remained in the correct position, and pedicle screw treatment was used as an alternative in four cases. The Visual Analogue Scale and Oswestry Disability Index scores showed evident improvement in these patients. The Visual Analogue Scale and Oswestry Disability Index scores of two patients who underwent revision were also improved.</p><p><b>CONCLUSIONS</b>Coflex implants should be avoided in patients with osteoporosis, a narrow interspinous space and intervertebral coronal spondylolysis, or sagittal instability. Furthermore the device choice, depth of implantation, and clamping intensity should be appropriate. Conservative treatment can be provided to patients with symptoms if the device remains in the correct position; however, revisions and salvages should be undertaken with internal fixation of pedicle screws for patients with device malposition, intraoperative implantation failure, or device intolerance.</p>

Resting-state functional MR changes in Alzheimer's disease patients visualized by amplitude of low-frequency fluctuation and fraction of amplitude of low-frequency fluctuation / 中华放射学杂志

Objective To investigate the difference of amplitude of low-frequency fluctuation (ALFF) and fraction of amplitude of low-frequency fluctuation(fALFF) between Alzheimer's disease (AD)patients and normal aging (NA) controls by voxel-based analysis.Methods Thirty-one AD patients and 44 NA controls were enrolled in the study.Blood oxygen level dependent functional (BOLD) EPI data were obtained during resting-state by using 32-channel head coil.Data were realigned,normalized and then smoothed with 8 mm FWHM kernel.Resting-state fMRI toolkit(version 1.6) was used to generate ALFF and fALFF images.Independent two sample t-test was performed with SPM5 to compare ALFF and fALFF of AD and NA controls.Pearson correlation analysis was performed to examine the relationship between MMSE score and ALFF,fALFF parameters.The significance level was set to be uncorrected O.001 on the voxel level and 0.05 on the cluster level.Results AD patients showed increased ALFF in left temporal lobe (0.492 ±0.119) and right cingulated cortex (0.434 ± 0.093) of AD patients,which were 0.443 ± 0.068 and 0.380 ±0.081 in NA controls (t =2.658,2.227,P ＜ 0.05).Decreased fALFF was found in bilateral posterior cingulate cortices (1.167 ± 0.203) and increased fALFF was found in bilateral temporal lobes (left 1.226 ±0.127,right 1.146 ±0.214) with left side dominance,which were 1.453 ±0.269,1.134 ±0.088,1.014 ± O.132 in NA controls (t =5.001,3.695,3.285,P ＜ 0.05).Bilateral temporal ALFF and fALFF correlated with MMSE positively (r =0.768—0.909,P ＜ 0.05) with left dominance.Conclusion AD patients showed increased resting-state functional MRI changes correlated with MMSE score in the temporal lobes with left dominance,which indicated left temporal lobe may be the best location for the observation of disease progression in AD patients.