Gait analysis in the elderly patients with lumbar spinal stenosis.

PURPOSE: This study aims to analyze the gait characteristics of the elderly patients with lumbar spinal stenosis by an intelligent device for energy expenditure and activity (IDEEA) to assist clinical work. METHODS: A total of 98 subjects were included in this study from January 2017 to December 2018. A total of 49 elderly outpatients with symptomatic lumbar spinal stenosis in unilateral lower extremity were included as the experimental group, and another 49 healthy subjects matched with gender, age, and body mass index (BMI) were analyzed as the control group. The gait data of the subjects (including single support, double support, SLS/DLS, swing duration, step duration, cycle duration, pulling accel, swing power, ground impact, foot fall, foot off, push off, speed, cadence, step length, and stride length) were collected to compare between the experience group and control group, the affected leg and the healthy leg in experimental group. RESULTS: The results of this study presented that small intermittent claudication occurred in all patients. The time of single support was significantly increased (p < 0.05). Double support, step duration, and pulling accel were increased (p < 0.05), and the Push off, speed, step length, and Stride length were decreased (p < 0.05) in the experimental group compared with the control group. CONCLUSION: Small intermittent claudication was the basic gait composition of the elderly patients with lumbar spinal stenosis that can reflect the abnormal gait characteristics by IDEEA.

Methylation-driven model for analysis of dinucleotide evolution in genomes.

BACKGROUND: CpGs, the major methylation sites in vertebrate genomes, exhibit a high mutation rate from the methylated form of CpG to TpG/CpA and, therefore, influence the evolution of genome composition. However, the quantitative effects of CpG to TpG/CpA mutations on the evolution of genome composition in terms of the dinucleotide frequencies/proportions remain poorly understood. RESULTS: Based on the neutral theory of molecular evolution, we propose a methylation-driven model (MDM) that allows predicting the changes in frequencies/proportions of the 16 dinucleotides and in the GC content of a genome given the known number of CpG to TpG/CpA mutations. The application of MDM to the 10 published vertebrate genomes shows that, for most of the 16 dinucleotides and the GC content, a good consistency is achieved between the predicted and observed trends of changes in the frequencies and content relative to the assumed initial values, and that the model performs better on the mammalian genomes than it does on the lower-vertebrate genomes. The model's performance depends on the genome composition characteristics, the assumed initial state of the genome, and the estimated parameters, one or more of which are responsible for the different application effects on the mammalian and lower-vertebrate genomes and for the large deviations of the predicted frequencies of a few dinucleotides from their observed frequencies. CONCLUSIONS: Despite certain limitations of the current model, the successful application to the higher-vertebrate (mammalian) genomes witnesses its potential for facilitating studies aimed at understanding the role of methylation in driving the evolution of genome dinucleotide composition.

Data mining and systematic pharmacology to reveal the mechanisms of traditional Chinese medicine in Mycoplasma pneumoniae pneumonia treatment.

Traditional Chinese Medicine (TCM) is widely used in the treatment of Mycoplasma pneumoniae Pneumonia (MPP) in East Asia. However, our current understanding of the underlying molecular mechanism remains dispersive and promiscuous. In this study, a systematic pharmacological approach combined with literature data mining was applied for drug similarity evaluation, drug half-life evaluation, oral bioavailability prediction, drug target exploration, Gene Ontology (GO) analysis, KEGG pathway enrichment and network construction, thus providing the rationale for its clinical performance. Five mostly studied herbs, including Ephedra Herba, Amygdalus communis Vas, Platycodon grandiforus, Licorice and Scutellariae Radix, were selected from the literature. Total ninety-three active ingredients, which are expected to be the effective components for MPP treatment, were screened out. Interrelationship between active compounds, drug targets and signaling pathways were analyzed to reveal the therapeutic effect of TCM in detail. Of importance, we found that TNF, ß2AR and PTGS2 play pivotal role in TCM mediated MPP inhibition. And mechanistically, epithelial apoptosis (defensive barrier function), GPCR signaling (symptom amelioration) and immune pathways (innate signaling and adaptive Th17 response) are critically involved. Our work, achieved through systematic pharmacology and data mining, enlarges the knowledge of TCM in MPP therapy, and could provide valuable insights for further drug discovery studies.

Efficacy of intravenous lidocaine in improving post-operative nausea, vomiting and early recovery after laparoscopic gynaecological surgery.

Post-operative nausea and vomiting (PONV) is a major peri-operative complication. It has numerous adverse consequences that seriously affect the post-operative recovery of patients. The aim of the present study was to investigate the efficacy of intravenous lidocaine in improving PONV and recovery after laparoscopic gynaecological surgery. A total of 40 patients were randomly assigned to 2 groups: Group L (lidocaine group) and Group C (control group). The patients in Group L received intravenous lidocaine throughout the operation, while patients in Group C were given a saline infusion. Vital signs, recovery time, extubation time, dosage of remifentanil, first flatus time and defecation time of each patient were recorded. The incidence of PONV after surgery was also recorded. The recovery of the patients was evaluated by using the quality of recovery score (QoR-40). The total dose of remifentanil was significantly lower in Group L (P<0.05). However, the recovery time and extubation time were shorter in Group C (P<0.05). The first flatus time and defecation time were longer in Group C (P<0.05). The mean arterial pressure and heart rate in Group L were lower and more stable (P<0.05). At 6 h after surgery, the incidence of PONV was significantly lower in Group L vs. that in Group C (P<0.05). The QoR-40 score in Group C was significantly lower at 1 and 3 days after the operation compared with that in Group C (P<0.05). In conclusion, intravenous lidocaine administered to patients undergoing laparoscopic gynaecological surgery may reduce PONV and supports their early recovery [trial registration number in Chinese Clinical Trial Registry: ChiCTR-IOR-17010782 (March 5, 2017)].

Insights into the role of electrostatics in temperature adaptation: a comparative study of psychrophilic, mesophilic, and thermophilic subtilisin-like serine proteases.

To investigate the role of electrostatics in different temperature adaptations, we performed a comparative study on subtilisin-like serine proteases from psychrophilic Vibrio sp. PA-44 (VPR), mesophilic Engyodontium album (Tritirachium album) (PRK), and thermophilic Thermus aquaticus (AQN) using multiple-replica molecular dynamics (MD) simulations combined with continuum electrostatics calculations. The results reveal that although salt bridges are not a crucial factor in determining the overall thermostability of these three proteases, they on average provide the greatest, moderate, and least electrostatic stabilization to AQN, PRK, and VPR, respectively, at the respective organism growth temperatures. Most salt bridges in AQN are effectively stabilizing and thus contribute to maintaining the overall structural stability at 343 K, while nearly half of the salt bridges in VPR interconvert between being stabilizing and being destabilizing, likely aiding in enhancing the local conformational flexibility at 283 K. The individual salt bridges, salt-bridge networks, and calcium ions contribute differentially to local stability and flexibility of these three enzyme structures, depending on their spatial distributions and electrostatic strengths. The shared negatively charged surface potential at the active center of the three enzymes may provide the active-center flexibility necessary for nucleophilic attack and proton transfer. The differences in distributions of the electro-negative, electro-positive, and electro-neutral potentials, particularly over the back surfaces of the three proteases, may modulate/affect not only protein solubility and thermostability but also structural stability and flexibility/rigidity. These results demonstrate that electrostatics contributes to both heat and cold adaptation of subtilisin-like serine proteases through fine-tuning, either globally or locally, the structural stability and conformational flexibility/rigidity, thus providing a foundation for further engineering and mutagenesis studies.

Effects of pretreatment with different doses of cisatracurium on succinylcholine-induced fasciculations.

OBJECTIVE: To compare the effects of different doses of cisatracurium pretreatment on succinylcholine-induced fasciculations. METHODS: 90 patients scheduled for laparoscopic cholecystectomies were equally randomized into three groups to receive pretreatment of 0.005, 0.01, and 0.02 mg/kg cisatracurium, respectively. After the pretreatments, general anesthesia was induced 3.5 minutes later, train-of-four stimulation was monitored 4.5 minutes later, succinylcholine 1.5 mg/kg was injected 5 minutes later, and endotracheal intubation was implemented 6.5 minutes later. Side effects of cisatracurium, intensity of fasciculations, intubating conditions, time and extent to maximal depression of twitch and time for its recovery to 20% of control value, and severity of myalgia at 24 hours postoperatively were recorded. RESULTS: Fasciculations were alleviated significantly after the cisatracurium pretreatment of 0.02 mg/kg, more than with the other two doses (p < 0.01). Intubating conditions, time and extent to maximal depression of twitch, time for its recovery to 20% of the controls, and incidence of myalgia had no significant changes among the three groups (p > 0.05). Transient and tolerable diplopia and difficulty opening eyes emerged after pretreatment of 0.02 mg/kg cisatracurium. CONCLUSION: The pretreatment of 0.02 mg/kg cisatracurium given 5 minutes before succinylcholine injection could alleviate succinylcholine-induced fasciculations without influence on muscle relaxation effects or endotracheal intubating conditions, but did not affect the occurrence of myalgia, and might produce transient diplopia and difficulty opening eyes.

Active immunisation targeting soluble murine tumour necrosis factor alpha is safe and effective in collagen-induced arthritis model treatment.

OBJECTIVES: TNF-α has been proved to be an effective target in rheumatoid arthritis treatment. So far, all the commercialised TNF-α antagonists function as passive immunotherapy. The aim of this study was to design a complex which can trigger active immunisation and overcome self-tolerance to elicit antibodies against murine TNF-α. METHODS: The complex (KLH-TNF) was chemically synthesised by linking a selected peptide TNFα(4-23) from murine soluble TNF-α to a carrier protein, keyhole limpet haemocyanin (KLH). We evaluated its safety and antibody eliciting performance. We also evaluated its disease-regulating ability on collagen-induced arthritis models. Furthermore, the immune cells responses were analysed by T cell proliferation assay and B cell memory experiments. RESULTS: The complex was safe without cytotoxity. The anti-mTNF-α antibody titers of the KLH-TNF group were 400 times greater than the control groups (p<0.0001). The elicited antibodies could combine with soluble TNF-α. The antibody response was independent of autologous TNF-α and could be reinforced by booster immunisation. Moreover, the complex did not trigger T cell activation and B cell memory response against native TNF-α. In animal experiments, KLH-TNF immunized mice showed a lower arthritis score (p<0.001) and better weight gain (p<0.01). Histological evaluations showed milder inflammation and cartilage depletion. CONCLUSIONS: Active immunotherapy against cytokine TNF-α is feasible by conjugating cytokine peptide with carrier protein. The elicited antibodies could combine with the native TNF-α and inhibit its activity. Importantly, the antibody response is reversible and independent of autologous TNF-α.

Use of hypophysin in hypotensive patients with low systemic vascular resistance following cardiopulmonary bypass.

OBJECTIVE: This study aimed to test the effects of hypophysin on hemodynamics and coronary artery caliber of patients with hypotension and decreased systemic vascular resistance (SVR) following cardiopulmonary bypass (CPB). METHODS: Twenty-four patients with mean arterial pressure (MAP) < 60 mmHg, mean aorta pressure < 70 mmHg, SVR < 800 dynes.sec.cm-5, cardiac index (CI) > 2.5 l.min-1.m-2, central venous pressure > 8 mmHg and refractory to dopamine, norepinephrine, and fluid resuscitation were treated with hypophysin at an initial dose of 0.6 IU and a continuous infusion rate of 1 - 4 IU/h till the end of operation. The hemodynamics and the diameter of proximal left main coronary artery were evaluated before incision, before hypophysin administration, 5 min after hypophysin administration, and at the end of operation. RESULTS: MAP, SVR, and the diameter of proximal left main coronary artery increased whereas heart rate, CI, stroke volume index, and mean pulmonary artery pressure had no significant changes after hypophysin administration compared with before hypophysin administration. All hypophysin-treated patients successfully recovered. CONCLUSION: Hypophysin may improve the hemodynamics and dilate the proximal left main coronary artery in hypotensive patients with low SVR following CPB.

Differential expression of Axin1, Cdc25c and Cdkn2d mRNA in 2-cell stage mouse blastomeres.

There is increasing evidence to show that 2-cell stage mouse blastomeres have differing developmental properties. Additionally, it has been suggested that such a difference might be due to their distribution of mRNA and/or protein asymmetry. However, to date, the exact genes that are involved in the orientation and order of blastomere division are not known. In this study, some differentially expressed transcripts were identified. Axin1, cell division cycle 25 homolog C (Cdc25c) and cyclin-dependent inhibitor 2D (Cdkn2d) were selected for validation by real-time polymerase chain reaction (PCR) based on published data. Our real-time PCR results demonstrated that Axin1, Cdc25c and Cdkn2d genes had different levels of expression among blastomeres of the mouse 2-cell embryo i.e. the level of Axin1 mRNA was significantly higher in one blastomere when compared with the other blastomeres of the 2-cell embryo (p < 0.05). The variation in Cdc25c (p < 0.05) and Cdkn2d (p < 0.01) mRNA expression followed a similar trend to that of Axin1. In addition, the highest levels of expression of these three genes were detected in the same blastomere in the 2-cell embryo. We confirmed that there was an asymmetrical distribution pattern for Axin1, Cdc25c and Cdkn2d transcripts in 2-cell embryos. In conclusion, this study demonstrated clearly that there is embryonic asymmetry at the 2-cell stage and that these differentially expressed genes may result in differentiation in expression in embryo development.

Prostaglandin E2 inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors.

The migration of fibroblasts is believed to play a key role in both normal wound repair and abnormal tissue remodeling. Prostaglandin E (PGE)(2), a mediator that can inhibit many fibroblast functions including chemotaxis, was reported to be mediated by the E-prostanoid (EP) receptor EP2. PGE(2), however, can act on four receptors. This study was designed to determine if EP receptors, in addition to EP2, can modulate fibroblast chemotaxis. Using human fetal lung fibroblasts, the expression of all four EP receptors was demonstrated by Western blotting. EP2-selective and EP4-selective agonists inhibited both chemotaxis toward fibronectin in the blindwell assay and migration in a wound-closure assay. In contrast, EP1-selective and EP3-selective agonists stimulated cell migration in both assay systems. These results were confirmed using EP-selective antagonists. The role of both EP2 and EP4 receptors in mediating the PGE(2) inhibition of chemotaxis was also confirmed by small interfering RNA suppression. Furthermore, the role of EP receptors was confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE(2) can act on multiple EP receptors in human lung fibroblasts, to exert disparate effects. Alterations in EP receptor expression may have the potential to alter PGE(2) action. Targeting specific EP receptors may offer therapeutic opportunities in conditions characterized by abnormal tissue repair and remodeling.

[Comparison of proximal femoral nail and dynamic hip screw for treating intertrochanteric fractures].

OBJECTIVE: To discuss characters of proximal femoral nail and dynamic hip screw for treating type A1, A2, A3 of intertrochanteric fractures. METHODS: We review 104 patients with intertrochanteic fractures, 33 patients were treated with proximal femoral nail (PFN), including 13 males and 20 females with an average age of 76 years (ranging from 63 to 87 years). 12 cases of type A1; 18 cases of type A2 and 3 cases of type A3; and 71 patients were treated with dynamic hip screw (DHS), including 29 males and 42 females with an average age of 74.5 years (ranging from 61 to 92 years), 32 cases of type A1, 34 cases of type A2 and 5 cases of type A3. Comparision in an average time of operations, the length of incision, blood loss, weight loading time and complications between two groups. RESULTS: An average time of operation was (51.5 +/- 4.4) min in PFN; (68.8 +/- 5.9) min in DHS. The length of incision was (9.6 +/- 0.9) cm in PFN; (15.5 +/- 1.5) cm in DHS. The blood loss was (179.0 +/- 12.9) ml in PFN; (269.3 +/- 40.0) ml in DHS. Varus collapse was none in PFN, 1 case in DHS. The collodiaphyseal angle of 7 cases decreased in DHS. Lateral hip pain caused by proximal screw removal was 6 cases in PEN. CONCLUSION: The therapeutic effect of DHS and PEN was primitively same in treating type A1 of intertrochanteric fracture. Operative injuries of PFN were less than that of DHS and anti-tonia was more stronger which is more suitable for type A2 and A3 of intertrochateric fractures.

Isolation and culture of bovine mammary epithelial stem cells.

Bovine mammary epithelial stem cells (MESCs) are very important in agricultural production and bioengineering. In the present study, we compared different isolation and culture methods for MESCs and observed their growth and differentiation characteristics. MESCs have an extremely weak proliferation capacity, and it is very difficult to obtain and prolong subculture of a bovine mammary epithelial stem cell line. We obtained some multipotent MESC aggregates that looked like spherical colonies. These colonies were only derived from suspension culture and were induced to differentiate into epithelial-like cells, myoepithelial-like cells and secretory cells and to establish a ductal-like structure. In contrast, MESCs cultured in adherent culture displayed low morphogenetic competence and only differentiated into epithelial-like cells. MESCs are often identified by testing their differentiation in vivo; however, herein, we have demonstrated the in vitro differentiation potential of bovine MESCs. In our study, beta 1-integrin and alpha 6-integrin which are expressed by human epidermal stem cells, were found in bovine, which shows that bovine MESCs share the same molecular signature as human MESCs.

Connexin37 mRNA expression in in vivo and in vitro mouse oocyte.

To evaluate gene expression of Connexin37 (Cx37) in oocytes from in vitro follicles at different stages, mouse preantral follicles were isolated and cultured for 12 days in vitro. Compared with in vitro follicles, follicles grown in vivo were collected at day 14 (d14), d16, d18, d20, d22 and d24 with the same stages for gene expression of Cx37 in oocytes. Our results showed that Cx37 mRNA increased along with follicular development, reached the highest level at the onset of antrum cavity formation and decreased after antrum formation in both in vivo and in vitro mouse oocytes. However, Cx37 mRNA was significant higher (p < 0.01) in in vitro cultured oocytes than in vivo oocytes. Moreover, significantly higher levels of Cx37 mRNA were found in oocytes from in vitro disrupted follicles (p < 0.01) and non-grown follicles (p < 0.05) than those from normal follicles with a similar size. These data determine temporal gene expression of Cx37 in oocytes from follicules at different stages and indicate that the gene expression level of Cx37 in oocytes could be evaluated as a criterion to the regulatory mechanism of Cx37 in an in vitro model.