Background:Gastroesophageal reflux disease(GERD)is a common disorder of digestive system,however,some of patients are not responding to conventional 4-8 weeks proton pump inhibitor therapy. Aims:To investigate the effect of digital music gastric electrical pacing on clinical symptoms,anxiety and depression and esophageal motility in patients with refractory GERD. Methods:Fifty-three patients with refractory GERD from Jan. 2014 to Oct. 2015 at the Third Affiliated Hospital,the Third Military Medical University were recruited. All of them fulfilled the Montreal definition of GERD. Digital music gastric electrical pacing was performed for 15 days and the efficacy was evaluated by clinical symptom scoring,Hamilton anxiety scale( HAMA),Hamilton depression scale( HAMD)and esophageal motility manometry. Results:After 15-day treatment,the main symptoms,including heartburn,daytime and nocturnal acid reflux,upper abdominal pain,nausea,and sleep disorder were significantly improved(P < 0. 001). A great proportion of patients were complicated with anxiety and/ or depression at recruitment,and after treatment the scores of HAMA and HAMD were decreased significantly(P < 0. 001). Meanwhile,the lower esophageal sphincter resting pressure(LESP),distal wave amplitude,peristaltic wave duration,speed of peristaltic wave and distal contraction integral after treatment were significantly increased as compared with the baseline values(P < 0. 05). Conclusions:Digital music gastric electrical pacing is effective for treatment of refractory GERD with increase of LESP and esophageal body motility. The clinical symptoms and anxiety and depression are improved simultaneously. Digital music gastric electrical pacing is expected to be a new choice of non-medicine treatment for esophageal motility disorders.

Objective To screen the active components of Bushen Huoxue Decoction ( BSHXD) involved in promoting the proliferation of bone marrow mesenchymal stem cells ( MSCs). Methods BSHXD and its subdivisions were extracted with petroleum ether, ethyl acetate, water-free ethanol and water respectively. MSCs were isolated and cultured by the bone marrow adherent method. At the third passage, MSCs were identified by the specific surface markers with immunofluorescence, and their osteogenic and adipogenic differentiation were tested by alizarin red staining and oil red “O” staining. After treated with the extracts of BSHXD and its subdivisions at gradient concentrations for 24 hours, cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay for the screening of active components and optimal concentration. MTT assay was used to describe the growth curve of MSCs treated with the most effective components, and cell cycle was analyzed by flow cytometry. Results Compared with the blank control group, the extracts of BSHXD and its subdivisions could protect MSCs from death to various degrees. Of all the extracts, the ethyl acetate extract of Bushen Division ( BSD) , ethyl acetate extract of BSHXD, ethyl acetate extract of Huoxue Division ( HXD) had the strongest effect, and the effect was dose-dependent, 100 μg/mL being the optimal active concentration while having no any cytotoxic reaction. The results of MTT assay revealed that BSD extracts promoted the proliferation of MSCs significantly and was the most effective component, and then came BSHXD. The results of flow cytometry indicated that BSD extract had the most strongest effect on increasing the amount of MSCs at proliferative phase, and then came BSHXD. Conclusion BSD ethyl acetate extract is the active component of BSHXD for promoting the proliferation of MSCs, showing an effect on increasing the proportion of MSCs at proliferative phase.

Objective:To investigate the risk factors of moderate to severe cancer-related fatigue (CRF) in patients undergoing chemotherapy of prostate cancer, and to construct a nomogram model to predict the occurrence of CRF.Methods:Using the case data questionnaire, Brief Fatigue Inventory, Social Support Rating Scale and International Prostate Symptom Scores, 724 patients of prostate cancer treated by chemotherapy in Shanghai Tenth People′s Hospital from August 2016 to June 2021 were selected and were treated with 1∶1 ratio, and the indexes of the moderate and severe CRF group (216 cases) and the non-moderate and severe CRF group (216 cases) were compared. According to the ratio of 7∶3, the envelope method was used to divide into training set and validation set. The independent risk factors of moderate and severe CRF were explored by univariate analysis and multivariate Logistic regression analysis, and the risk prediction model was established and the nomogram model was constructed. The C-index and area under ROC curve were used to verify the prediction effect of the model.Results:Multivariate Logistic regression analysis showed that BMI ranged from 24.0 to 27.9 kg/m 2 ( OR=1.733), BMI≥28.0 kg/m 2 ( OR=3.126), neutropenia occurred during chemotherapy ( OR=1.747), chemotherapy course >6 months ( OR=1.893), moderate social support level ( OR=1.244), low social support level ( OR=2.434), mild urinary tract symptoms ( OR=1.264), moderate urinary tract symptoms ( OR=3.371) and severe urinary tract symptoms ( OR=5.297) were independent risk factors for moderate and severe CRF. The nomogram model constructed according to the above risk factors was internally verified by the training set and the validation set, and its C-index was 0.854 and 0.741 respectively. The area under ROC curve training set was 0.823, and the validation set was 0.733. Conclusions:The nomogram model can effectively predict the occurrence of moderate to severe CRF in patients with prostate cancer undergoing chemotherapy.

Objective To explore the significance of GBA gene mutation and gene detection in diagnosis of Gaucher disease. Method The clinical data and genetic testing results of 3 probands from 3 unrelated Gaucher families and their family members were analyzed. Results A compound heterozygous mutation of c.907C>A and c.1448T>C was found in the proband of the first family, which was inherited from parents respectively. Another complex heterozygous mutation of c.1174delC and c.1226A>G was found in the proband of second family, which was inherited from parents respectively, and the variant c.1174delC was a new mutation, which has not been reported in the literature according to the search by HGMD. The homozygous nucleotide variation of c.1342G>C and heterozygous nucleotide variation of c.1263_1317del was found in the proband of the third family and the c.1263_1317del heterozygous mutation was inherited from father. Conclusion The mutation of GBA gene was the cause of Gaucher disease in these 3 families and Gaucher disease can be diagnosed by molecular genetics in clinic.

Objective:To investigate the effect of slow intravenous infusion of low-dose mannitol on the hemodynamics of patients after cardiopulmonary bypass.Methods:Prospective, continuous inclusion of 62 patients after cardiac surgery under cardiopulmonary bypass. By random number method, they were divided into normal treatment group(group C) with 29 cases and mannitol treatment group(group M) with 33 cases. Group C was treated according to the postoperative routine treatment measures. On the basis of conventional treatment, group M received intravenous infusion of 20% mannitol injection 0.25 g/kg at 1、8、24 hours after operation, and the intravenous infusion time was 60 minutes each time. According to the hemodynamic changes during the two groups of treatment, the effect of slow intravenous infusion of low-dose mannitol on patients after cardiopulmonary bypass under cardiopulmonary bypass was analyzed.Results:In group M, CI and SVI were significantly increased after use of mannitol than before, with statistical significance( P<0.01). SVRI showed a downward trend, and the changes were statistically significant after use of mannitol( P<0.01). PAWP increased first and then decreased after operation, and the changes were statistically significant after mannitol use than before( P<0.05). RAP and MPAP had no significant changes after the first use of mannitol, but the changes after the latter two use mannitol were statistically significant than before( P<0.05). Repeated-measurement data analysis of variance was performed on the hemodynamic parameters of each group, and the results were all P<0.01. Conclusion:Postoperative slow intravenous infusion of low-dose mannitol optimizes hemodynamic status, increases stroke volume, reduces cardiac preload, improves systemic and pulmonary circulation resistance, and promotes recovery of postoperative cardiopulmonary function.

Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.
Animals ; Cyproheptadine ; pharmacology ; Female ; Histamine H1 Antagonists ; pharmacology ; Membrane Potentials ; drug effects ; physiology ; Mice, Inbred C57BL ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Prefrontal Cortex ; drug effects ; physiology ; Pyramidal Cells ; drug effects ; physiology ; Receptors, sigma ; agonists ; metabolism ; Tetraethylammonium ; pharmacology ; Tissue Culture Techniques

Gastric ''inflammation-cancer'' transformation stars from inflammation and ends as gastric cancer （GC）， and the pathogenesis is still unclear. In China， GC features high morbidity and mortality and poor prognosis， influencing the quality of life and physical and mental health of patients. Therefore， it is of great significance to construct the prevention and treatment system for GC. Chronic atrophic gastritis （CAG） plays a key role in the occurrence， development， and outcome of gastric ''inflammation-cancer'' transformation. Modern therapies for CAG generally aim at eliminating causes and alleviating clinical symptoms， which show satisfactory short-term efficacy， but the reverse and recurrence are common. Based on the holistic view， syndrome differentiation-based treatment， and the ''inflammation-cancer'' transformation in modern medicine， traditional Chinese medicine emphasizes both prevention and treatment， with individualized therapies for CAG and GC to control the transformation. According to the pathogenesis of CAG-asthenia in origin and sthenia in superficiality and deficiency-excess in complexity， this study proposed the theory of spleen deficiency and pathogen stagnation in CAG， and believed spleen deficiency， pathogen， and stagnation are respectively the root cause of， the main factor of， and the key to ''inflammation-cancer'' transformation， respectively. Spleen deficiency and pathogen stagnation are closely related to the process of the transformation. For the treatment， the spleen-invigorating and pathogen-eliminating method should be used for invigorating the spleen to consolidate original Qi， improve the blood supply in stomach， and regulate immunity， and eliminating the pathogen to relieve stagnation， reduce the occurrence of non-controllable inflammation， and improve inflammatory micro-environment. As a result， the gastric inflammation is controlled at the early stage and the gastric ''inflammation-cancer'' transformation is blocked. The gastric mucosal lesions are blocked， delayed， or even reversed. This study provides a new idea in clinical diagnosis and treatment of CAG and in the prevention of GC.

Objective To explore the differential gene expression profile and small molecule drugs for chronic atrophic gastritis(CAG)by bioinformatics technology.Methods Two gene expression samples of CAG chips(GSE27411,GSE116312)were obtained through the Gene Expression Synthesis(GEO)database,screen the differentially expressed genes(DEGs)of CAG by R language,and CAG immune-related genes were obtained for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Protein-protein interaction(PPI)network was constructed using STRING database to screen out core genes,further study on immune invasion of core genes based on GSE27411 dataset,small molecular compounds interacting with core genes were predicted,molecular docking was carried out by MOE2022,and survival analysis was carried out by GEPIA2 website.Results A total of 517 DEGs were screened out based on GEO database.GO function enrichment analysis found that it mainly involved in granulocyte chemotaxis、leukocyte chemotaxis and neutrophil chemotaxis biological processes.KEGG pathway enrichment analysis showed that it mainly involved in cytokine-cytokine receptor interaction、nuclear factor kappa B signaling pathway、interleukin-17 signaling pathway.Six key genes of NR1H4、CCK、CCL20、CXCL1、LCN2、SAA1 were obtained by PPI network,through relevant verification,NR1H4 was regarded as the core gene.Immune cell infiltration analysis showed that central memory CD8 T cell、effector memeory CD4 T cell、gamma delta T cell、natural killer T cell、neutrophil and other immune cells may be involved in the development of CAG,and the neutrophil was positively correlated with NR1H4.It was predicted that six small molecular drugs,corilagin,stigmasterol,geniposide,tangeretin,chenodeoxycholic acid and epigallocatechin 3-gallate,have good binding force with NR1H4.Conclusion The potential mechanism of CAG is preliminarily explored in this study,the key gene of NR1H4 and neutrophil may play an important role in the"inflammatory cancer transformation"process of CAG,which can provide a certain reference for the study of the"inflammatory cancer transformation"mechanism of CAG.

As a newly-identified protein post-translational modification, malonylation is involved in a variety of biological functions. Recognizing malonylation sites in substrates represents an initial but crucial step in elucidating the molecular mechanisms underlying protein malonylation. In this study, we constructed a deep learning (DL) network classifier based on long short-term memory (LSTM) with word embedding (LSTM) for the prediction of mammalian malonylation sites. LSTM performs better than traditional classifiers developed with common pre-defined feature encodings or a DL classifier based on LSTM with a one-hot vector. The performance of LSTM is sensitive to the size of the training set, but this limitation can be overcome by integration with a traditional machine learning (ML) classifier. Accordingly, an integrated approach called LEMP was developed, which includes LSTM and the random forest classifier with a novel encoding of enhanced amino acid content. LEMP performs not only better than the individual classifiers but also superior to the currently-available malonylation predictors. Additionally, it demonstrates a promising performance with a low false positive rate, which is highly useful in the prediction application. Overall, LEMP is a useful tool for easily identifying malonylation sites with high confidence. LEMP is available at http://www.bioinfogo.org/lemp.
Amino Acid Sequence ; genetics ; Amino Acids ; Animals ; Deep Learning ; Forecasting ; methods ; Lysine ; chemistry ; Machine Learning ; Malonates ; chemistry ; Protein Processing, Post-Translational ; genetics