[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

HGFK1 inhibits bone metastasis in breast cancer through the TAK1/p38 MAPK signaling pathway.

Breast cancer metastasis to bone represents a devastating complication of advanced breast cancer, frequently resulting in significant increases in morbidity and mortality. An understanding of the mechanisms that govern breast cancer metastasis at the molecular level should lead to more effective therapies. Recently, the kringle 1 domain of human hepatocyte growth factor (HGFK1) was identified as a candidate metastasis suppressor gene. Here, we investigated whether HGFK1 is a key regulator of breast cancer bone metastasis. Of the 193 human breast carcinoma tissue samples examined, HGFK1 expression was relative higher in 82 (42.4%) by western blot and in 84 (43.5%) by quantitative real-time PCR. The higher expression of HGFK1 was significantly associated with a better prognostic value (P<0.001) and inversely correlated with bone metastasis (P=0.003). The efficacy of adeno-associated virus carrying HGFK1 (AAV-HGFK1) in osteolytic bone metastasis was then evaluated using an in vivo bone metastasis model. AAV-HGFK1 significantly inhibited osteolytic bone metastasis and prolonged the survival of mice in this model (P<0.01). In vitro, HGFK1 expression resulted in significant anti-invasion effects, enhanced the phosphorylation of TAK1 (transforming growth factor-ß-activated kinase 1), p38 MAPK (mitogen-activated protein kinase) and MAPKAPK2 (MAPK-activated protein kinase 2) and decreased the expression of receptor activator of nuclear factor-κB (RANK), which was abrogated by the p38 MAPK inhibitor SB203580. This study shows for the first time that HGFK1 significantly inhibits the metastasis of breast cancer to bone by activating the TAK1/p38 MAPK signaling pathway and inhibiting RANK expression. Thus, AAV-HGFK1 treatment represents a potential therapy for bone metastasis in breast cancer.

Improving the system stability of a digital Shack-Hartmann wavefront sensor with a special lenslet array.

There has been very limited study on the stability of a Shack-Hartmann wavefront sensor (SHWS) since its emergence in the early 1970s. In this paper, through experimental study of the system stability of a digital SHWS, a special lenslet array with long focal range is designed and implemented with a spatial light modulator to improve the system performance. Diffractive lenses with long focal length range can provide pseudo-nondiffracting beams and a long range of focusing plane. The performance and effect of the modified SHWS with this lenslet array are investigated, and the experimental results show that the system stability and measurement repeatability are not sensitive to the sensing distance and stay at an acceptable level.

Selectivity and sensitivity of intramuscular and transcutaneous electromyography electrodes.

We evaluated the differences in selectivity and sensitivity of intramuscular fine-wire electrodes and transcutaneous electrodes in detecting dynamic electromyography (EMG) signals from extensor digitorum (EDC) and extensor carpi radialis (ECR) muscles during isolated EDC and ECR contractions in two able-bodied subjects. Intramuscular fine-wire electrodes differentiated EDC and ECR EMG activities better than transcutaneous electrodes, and intramuscular fine-wire electrodes recorded higher amplitude signals than transcutaneous electrodes. Data suggest that intramuscular fine-wire electrodes are more selective and sensitive than transcutaneous electrodes in detecting EMG signals from adjacent forearm muscles.

Percutaneous intramuscular neuromuscular electric stimulation for the treatment of shoulder subluxation and pain in patients with chronic hemiplegia: a pilot study.

OBJECTIVE: To investigate the feasibility of percutaneous intramuscular neuromuscular electric stimulation (perc-NMES) for treating shoulder subluxation and pain in patients with chronic hemiplegia. DESIGN: Before-after trial. SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: A convenience sample of 8 neurologically stable subjects with chronic hemiplegia and shoulder subluxation. INTERVENTION: Six weeks of perc-NMES to the subluxated shoulder. MAIN OUTCOME MEASURES: Shoulder subluxation (radiograph), shoulder pain (Brief Pain Inventory), motor impairment (Fugl-Meyer score), shoulder pain-free external rotation (handheld goniometer), and disability (FIM instrument) were assessed before treatment (T1), after 6 weeks of neuromuscular stimulation (T2), and at 3-month follow-up (T3). A 1-way, repeated-measures analysis of variance using the generalized estimating equation approach was used to evaluate differences from T1 to T2 and from T1 to T3 for all outcome measures. RESULTS: Subluxation (p =.0117), pain (p =.0115), shoulder pain-free external rotation (p <.0001), and disability (p =.0044) improved significantly from T1 to T2. Subluxation (p =.0066), pain (p =.0136), motor impairment (p <.0001), shoulder pain-free external rotation (p =.0234), and disability (p =.0152) improved significantly from T1 to T3. CONCLUSIONS: Perc-NMES is feasible for treating shoulder dysfunction in hemiplegia and may reduce shoulder subluxation, reduce pain, improve range of motion, enhance motor recovery, and reduce disability in patients with chronic hemiplegia and shoulder subluxation. Further investigation is warranted.

Intramuscular electromyographically controlled neuromuscular electrical stimulation for ankle dorsiflexion recovery in chronic hemiplegia.

We report three cases of survivors of chronic stroke treated with active repetitive movement training of the paretic ankle dorsiflexors mediated by intramuscular electromyographically controlled neuromuscular electrical stimulation (NMES). These case reports demonstrate the feasibility of using intramuscular electromyographically controlled NMES for facilitating ankle dorsiflexion recovery among survivors chronic stroke with moderate hemiplegia. Relevant issues for clinical implementation and future investigations are reviewed.

Intramuscular electromyographically controlled neuromuscular electrical stimulation for upper limb recovery in chronic hemiplegia.

We report three cases of survivors of chronic stroke who were treated with active repetitive movement training of the paretic finger extensors mediated by intramuscular electromyographically controlled neuromuscular electrical stimulation for the purpose of motor relearning. These case reports demonstrate the feasibility of using intramuscular electromyographically controlled neuromuscular electrical stimulation for facilitating the upper limb motor recovery of chronic stroke survivors with mild to moderate hemiplegia.

[Structure of gypentonoside A from Gynostemma pentaphylum Makino].

A new saponin named gypentonoside has been isolated from Gynostemma pentaphylum (Thunb) Makino, C54H88O21, mp 272-274 degrees C. Its structure was established on the basis of chemical and spectroscopic (IR, FAB-MS, UV, 1H-NMR, 13C-NMR, 2D-NMR) analyses.

[Chemical constituents of Aralia decaisneana Hance].

Six compounds were isolated from the root bark of Aralia decaisneana and elucidated by spectral and chemical analyses as 3-O-[beta-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl- (1-->3)-beta-D-glucuronopyranosyl]-oleanolic acid (Ad-V), chikusetsusaponin IVa (Ad-IX), deglucose chikusetsusaponin IVa (Ad-X), palmitic acid (Ad-VI), beta-sitosterol (Ad-VII) and oleanolic acid (Ad-VIII). Ad-V was obtained from nature for the first time, and the rest were all obtained from this plant for the first time.

[Chemical constituents of Luffa cylindrica (L.) Roem].

Six compounds were isolated from the fruits of Luffa cylindrica. They were identified as lucyosides C, E, F, H, a mixture of alpha-spinasterol and stigmasta-7,22,25-trien-3 beta-OH and a mixture of alpha-spinasteryl glucoside and delta 7,22,25-stigmasteryl-beta-D-glucoside by means of chemical evidence and spectral analysis.

An immunocytochemical study of endocrine cells in the gut of a stomachless teleost fish, grass carp, Cyprinidae.

Nineteen different antisera raised against mammalian hormones were used to identify the occurrence and distribution of endocrine cells in the gut of grass carp (Ctenopharyngodon idellus). Positive reactions were obtained in gut epithelium with antisera gastrin, glucagon, gastric inhibitory peptide, leucine enkephalin, substance P, and bovine pancreatic polypeptide. No immunoreactive product was formed using antisera against somatostatin, 5-hydroxytryptamine, insulin, avian pancreatic polypeptide, motilin, cholecystokinin, secretin, neurotensin, vasoactive intestinal polypeptide, bombesin, neuron-specific enolase, prochymosin, and pepsinogen. The exact distribution mapping of six kinds of immunoreactive endocrine cells throughout the gut of grass carp (C. idellus) is presented. The morphological characteristics of immunoreactive endocrine cells is described. Their distribution characteristics and possible modes of secretion and function are discussed. Finally, the possible relationship between the transplantation of these cells in the gastro-entero-pancreatic endocrine system is discussed.

Alternate excitation of large and small axons with different stimulation waveforms: an application to muscle activation.

A method has been developed to activate separately and alternately two axon groups in an intact nerve trunk through a single-channel stimulation electrode. Two types of stimuli, quasitrapezoidal-shaped and narrow rectangular-shaped current pulses, were employed to activate smaller and larger axons, respectively. The technique was demonstrated on an alpha motor fibre population in cat peripheral nerve and was utilised to reduce muscle fatigue during repetitive stimulation. This method may have applications in physiological research and the design of neural prostheses.

Plasticity of presynaptic and postsynaptic elements of neuromuscular junctions repeatedly observed in living adult mice.

In order to assay the extent of ongoing synaptic remodelling in adult mouse neuromuscular junctions, dynamic structural changes of identified neuromuscular junctions were monitored in vivo over periods up to three months. Nerve terminal outgrowths as small as 1 micron were detectable with a new fluorescent tetanus toxin C-fragment stain combined with fluoresceinated alpha-bungarotoxin to stain postsynaptic acetylcholine receptors. With limited illumination, the new stain did not affect miniature endplate potential frequency, nor morphometric parameters of repeatedly observed neuromuscular junctions. At each observation, areas of presynaptic nerve terminal extending beyond underlying acetylcholine receptor ('preprojections'), and areas of acetylcholine receptor without overlying nerve terminal ('postprojections') were measured. Regions of the neuromuscular junction in which nerve terminal-postsynaptic acetylcholine receptor complexes either 'lengthened' or 'shortened' between observations were also measured. The total area of pre- and postprojections (relative to total junctional area) remained the same over three months but most had been replaced; only 20% of preprojections gave rise to lengthenings, the rest retracted or were unchanged. Lengthening and shortening of branches were about 1-2% of junctional area per month. These more permanent changes occurred against a background of ongoing transient nerve terminal outgrowth and retraction (which constituted 80% of all neuromuscular junction shape changes from one observation to the next, compared with 20% for the postsynaptic component). Breaks in the continuity of the underlying acetylcholine receptor were also observed between observations as were instances where acetylcholine receptor continuity was re-established. A newly observed form of plasticity was a shift in position and angle of pre-existing branches. Establishment of new acetylcholine receptor-positive synaptic regions was mostly preceded by nerve terminal outgrowth on the previous observation. In animals in which spontaneous wheel-running increased locomotor activity approximately tenfold over a period of 35 days, the findings were identical to those in unexercised mice. In summary, in the adult neuromuscular junction, the nerve terminal, not the postsynaptic component, is the dynamic entity, continually changing shape on the scale of micrometers, with relatively small permanent changes. These ongoing exploratory excursions may supply the substrate for synaptic plasticity, which would involve regulation of the dynamics or stability of nerve outgrowth.

Selective activation of small motor axons by quasi-trapezoidal current pulses.

We have found a method to activate electrically smaller nerve fibers without activating larger fibers in the same nerve trunk. The method takes advantage of the fact that action potentials are blocked with less membrane hyperpolarization in larger fibers than in smaller fibers. In our nerve stimulation system, quasitrapezoidal-shaped current pulses were delivered through a tripolar cuff electrode to effect differential block by membrane hyperpolarization. The quasitrapezoidal-shaped pulses with a square leading edge, a 350 microsecond(s) plateau, and an exponential trailing phase ensured the block of propagating action potentials and prevented the occurrence of anodal break excitation. The tripolar cuff electrode design restricted current flow inside the cuff and thus eliminated the undesired nerve stimulation due to a "virtual cathode." Experiments were performed on 13 cats. The cuff electrode was placed on the medial gastrocnemius nerve. Both compound and single fiber action potentials were recorded from L7 ventral root filaments. The results demonstrated that larger alpha motor axons could be blocked at lower current levels than smaller alpha motor axons, and that all alpha fibers could be blocked at lower current levels than gamma fibers. A statistical analysis indicated that the blocking threshold was correlated with the axonal conduction velocity or fiber diameter. This method could be used in physiological experiments and neural prostheses to achieve a small-to-large recruitment order in motor or sensory systems.

A method to effect physiological recruitment order in electrically activated muscle.

A new stimulation method has been utilized to achieve physiological recruitment order of small-to-large motor units in electrically activated muscles. The use of quasitrapezoidal-shaped pulses and a tripolar cuff electrode made selective activation of small motor axons possible, thus recruiting slow-twitch, fatigue-resistant muscle units before fast-twitch, fatigable units in a heterogeneous muscle. Isometric contraction force from the medial gastrocnemius muscle was measured in five cats. The physiological recruitment order was evidenced by larger twitch widths at lower force levels and smaller twitch widths at higher force levels in the muscles tested. In addition, force modulation process was more gradual and fused contractions were obtained at lower stimulation frequencies when the new stimulation method was employed. Furthermore, muscles activated by the new method were more fatigue-resistant under repetitive activation at low force levels. This stimulation method is simpler to implement and has fewer adverse effects on the neuromuscular system than previous blocking methods. Therefore, it may have applications in future functional neuromuscular stimulation systems.

[Isolation and identification of flavonoids and organic acids from Gynostemma pentaphyllum Makino].

Three constituents were isolated from the aerial parts of Gynostemma pentaphyllum. They were identified as rutin (I), ombuoside (II) and malonic acid (III) by physico-chemical properties and spectroscopic methods. They are reported present in G.pentaphyllum for the first time.