ObjectiveTo investigate the correlation between ineffective esophageal motility (IEM)and gastroesophageal reflux disease (GERD).MethodsA total of 90 GERD patients were enrolled in our study,including 62 patients with reflux esophagitis (RE) and 28 with non-erosive reflux disease (NERD).All the patients underwent gastroscopy,24-hour esophageal pH monitoring and esophageal manometry.ResultsIn the RE group 30 (48.4％) patients were diagnosed as having IEM,which was significantly higher than the NERD group (6 patients,21.4％ ) (P＜0.05).Positive esophageal acid exposure was more often seen in patients with IEM than in those with normal esophageal motility (91.7％ v.s.57.2％,P ＜0.01 ).The values of total percentage of time with pH ＜4,percentage of reflux time in supine position,long-duration episodes ( ＞5 min) and the longest reflux time and DeMeester score were significantly higher in the IEM cases than those in the normal esophageal motility cases ( P ＜ 0.01 ),so was the values of number of reflux episodes (P ＜ 0.05).ConclusionIEM is the most common esophageal dysmotility in patients with GERD and closely related to distal esophageal acid exposure and RE.

We studied the aggregation of a recombinant engineering antibody (chA21). Anti-ErbB2 antibody chA21 was produced by fusing single-chain Fv (scFv) with human IgG1 Fc fragment, and it was proved to be a drug candidate for cancer therapy. We characterized the aggregation of chA21 by high performance sized-exclusive chromatography (HPSEC), dynamic light scattering (DLS), SDS-PAGE, indirect ELISA assay, and compared the influence of temperature and additive on the level of aggregation and binding activity. Conformation changes of different levels of aggregation were also analyzed via circular dichroism (CD). Finally, we analyzed which part of chA21 was involved in aggregation by cleaving it into scFv and Fc fragments. The results showed that chA21 could form aggregates in the storage solution. The aggregates interacted through non-covalent bonds and remained binding activity. Temperature and additive could slightly affect the level of aggregation and binding activity, while the conformations of chA21 were stable. Aggregation propensity of scFv fragment was almost same as chA21, indicating that scFv may be the major part to form the aggregates. The research on aggregation may be helpful to develop a suitable formulation for chA21 clinical application as well as provide direction for future antibody design and reconstruction.
Antibodies ; chemistry ; metabolism ; Humans ; Immunoglobulin Fc Fragments ; chemistry ; metabolism ; Immunoglobulin Variable Region ; chemistry ; metabolism ; Protein Conformation ; Protein Engineering ; methods ; Receptor Aggregation ; immunology ; Receptor, ErbB-2 ; chemistry ; immunology ; Recombinant Proteins ; biosynthesis ; chemistry ; genetics ; immunology

Objective To explore relevant factors of drinking relapse after alcohol withdrawal for patients with alcohol dependence. Methods 130 patients with pure alcohol dependence who were admitted from January 2012 to February 2013 were selected. They received withdrawal treatment and were followed-up after discharge. They were assigned to relapse group and non-relapse group. The relations between drinking relapse and clinical characteristics, socio-demographic data, family environment and cognitive functions during withdrawal period in the two groups were analyzed. Results Excepted for 21 patients who were out of touch, there were 67 patients in the relapse group and 42 patients in the non-relapse group. Amount of drinking, frequency of drinking, personality changes, emotional symptoms, being single/divorced, finan-cial situation, education years, and family history of alcoholism before the treatment between the two groups were signifi-cantly different (P<0.05). Intimacy, emotional expression, independence, entertainment, organization, controlling and con-tradictoriness in the family environment between the two groups were significantly different (P<0.05). During withdrawal pe-riod, total response number, number of completed classification and correct response rate of attention (DST and CPT-IP), memory (S/VM, SS and DS) and execution (WCST) between the two groups were significantly different (P<0.05). Amount of drinking, emotional symptoms, family intimacy, family organization, family independence, attention and execu-tion were independent influencing factors of drinking relapse for patients with alcohol dependence after withdrawal (P<0.05). Conclusion Patients with alcohol dependence have a large capacity for alcohol previously, and patients with emo-tional symptoms, in lack of intimacy, organization and independence in family environment, or in lack of attention and ex-ecution during withdrawal period are highly likely to relapse. Management of family environment and psychological thera-py should be attached great importance so as to improve patients' cognitive function during withdrawal period.

Objective The research aims to optimize the hospital research performance appraisal ,clarify the scientific characteristics and possible shortages of different clinic departments in various types ,to enhance the effectiveness of research performance appraisal .Methods Descriptive statistics were used to generalize hospital research performance appraisal in 2017 . Hierarchical clustering was used to cluster and analyze performance appraisal characteristics of 75 clinic departments .Results SCI papers (405) ,National projects (181) and National core journal papers (106) took 75 .2％ of total average score .The op-timal solution of the cluster was 6 types for 75 departments and the dendrogram illustrated significant varieties among the 6 types .Six departments' types were academic-conference-oriented ,national-paper-oriented ,SCI-paper-oriented ,advanced-pro-ject-oriented ,provincial/horizontal-project-oriented and attending-conference-oriented .The percentages of the oriented indica-tors that took their total average scores were 59 .4％ ,42 .0％ ,66 .7％ ,57 .0％ ,61 .8％ ,52 .3％ .Conclusions Compared with K-means method ,the results of hierarchical clustering equipped with better characteristics and interpretative power .Research performance appraisal has been further optimized .Departments in different types showed significant characteristics and weak-nesses ,which provides managers with effective guidance on countermeasures .

BACKGROUND:Heterotopic ossification is a dynamic growth process.Diverse heterotopic ossification subtypes have diverse etiologies or induction factors,but they exhibit a similar clinical process in the intermediate and later phases of the disease.Acquired heterotopic ossification produced by trauma and other circumstances has a high incidence. OBJECTIVE:To summarize the molecular biological mechanisms linked to the occurrence and progression of acquired heterotopic ossification in recent years. METHODS:The keywords"molecular biology,heterotopic ossification,mechanisms"were searched in CNKI,Wanfang,PubMed,Embase,Web of Science,and Google Scholar databases for articles published from January 2016 to August 2022.Supplementary searches were conducted based on the obtained articles.After the collected literature was screened,131 articles were finally included and summarized. RESULTS AND CONCLUSION:(1)The occurrence and development of acquired heterotopic ossification is a dynamic process with certain concealment,making diagnosis and treatment of the disease difficult.(2)By reviewing relevant literature,it was found that acquired heterotopic ossification involves signaling pathways such as bone morphogenetic protein,transforming growth factor-β,Hedgehog,Wnt,and mTOR,as well as core factors such as Runx-2,vascular endothelial growth factor,hypoxia-inducing factor,fibroblast growth factor,and Sox9.The core mechanism may be the interaction between different signaling pathways,affecting the body's osteoblast precursor cells,osteoblast microenvironment,and related cytokines,thereby affecting the body's bone metabolism and leading to the occurrence of acquired heterotopic ossification.(3)In the future,it is possible to take the heterotopic ossification-related single-cell osteogenic homeostasis as the research direction,take the osteoblast precursor cells-osteogenic microenvironment-signaling pathways and cytokines as the research elements,explore the characteristics of each element under different temporal and spatial conditions,compare the similarities and differences of the osteogenic homeostasis of different types and individuals,observe the regulatory mechanism of the molecular signaling network of heterotopic ossification from a holistic perspective.It is beneficial to the exploration of new methods for the future clinical prevention and treatment of heterotopic ossification.(4)Meanwhile,the treatment methods represented by traditional Chinese medicine and targeted therapy have become research hotspots in recent years.How to link traditional Chinese medicine with the osteogenic homeostasis in the body and combine it with targeted therapy is also one of the future research directions.(5)At present,the research on acquired heterotopic ossification is still limited to basic experimental research and the clinical prevention and treatment methods still have defects such as uncertain efficacy and obvious side effects.The safety and effectiveness of relevant targeted prevention and treatment drugs in clinical application still need to be verified.Future research should focus on clinical prevention and treatment based on basic experimental research combined with the mechanism of occurrence and development.

ObjectiveTo compare the differences in resistance and structure of skin between acupoints and non-acupoints， and to study the difference in skin permeability characteristics of Corydalis Rhizoma total alkaloid patches （CTTP） after administration at Shenque acupoint and non-acupoint， so as to provide experimental support for its clinical acupoint application to prevent and treat chronic pain. MethodTaking corydaline （CD）， tetrahydropalmatine （THP） and corydalis L （CDL） as evaluation indexes， and the quantitative analysis was carried out by high performance liquid chromatography （HPLC）. The mobile phase was methanol-0.04 mol·L^-1 phosphoric acid aqueous solution （70∶30， pH 6.0 adjusted with triethylamine）， the detection wavelength was 281 nm. In vitro transdermal test in Franz diffusion cell and in vivo transdermal test were used to study the skin permeability characteristics of CTTP through Shenque acupoint and non-acupoint administration. At the same time， the skin resistance between Shenque acupoint and non-acupoint was measured before and after the administration， and the distribution of the drug in each layer of the skin was compared by freezing sectioning， and visual verification was performed with fluorescence inverted microscope. ResultAfter 24 h of administration， the results of in vivo and in vitro experiments showed that the cumulative permeation and retention of CD， THP and CDL at Shenque acupoint skin were higher than those at non-acupoint skin （P<0.05， P<0.01）， the skin resistance of Shenque acupoint was lower than that of non-acupoint at all time points. The fluorescence microscopic observation results showed that the drug content of each layer of the skin was all Shenque acupoint>non-acupoint， indicating that the skin of Shenque acupoint had better effect on drug penetration and storage than non-acupoint. ConclusionThe 24 h cumulative permeation and retention of CTTP in Shenque acupoint skin are higher than those in non-acupoint skin， and the mechanism may be related to the thin skin， low electrical resistance and large number of hair follicle bodies at Shenque acupoint.