Objective To evaluate the distribution of Enterococcus isolated from clinical samples and bacterial resistance to antimicrobial agents. Methods Two hundred and six strains of Enterococcus were isolated, identification and antimicrobial susceptibility tests were performed. Results The majority of 206 strains of Enterococcus were E.faecalis ( 80.10% ) and E.faecium ( 11.65% ), strains were mainly isolated from sputum ( 21.84% ), prostatic fluid (20.87%) ; pus ( 20.39% ) and urine (10.68%) . The isolation rate of vancomycin resistant strains of E.faecalis, E.faecium, E.avium and E.gallinarum were 1.82% , 4.17% , 14.29% and 100%, respectively. Among strains of E.faecalis, 56.36% and 54.55% were highly resistant to gentamycin and streptomycin respectively; and among strain of E.faecium, 79.17% and 45.83% were highly resistant to gentamycin and streptomycin respectively. Conclusion The main nosocomial infection caused by Enterococcus are lower respiratory infection, there are significant differences in antimicrobial susceptibilily among different species, the correct identification and antimicrobial susceptibility tests of strains ought to be performed to provide reference for rational antimicrobial application in clinic.
Mitochondrial homeostasis has been increasingly viewed as a potential target of cancer therapy, and mitochondrial fission is a novel regulator of mitochondrial function and apoptosis. The aim of our study was to determine the detailed role of mitochondrial fission in SW837 colorectal cancer cell viability, mobility and proliferation. In addition, the current study also investigated the therapeutic impact of Tanshinone IIA (Tan IIA), a type of anticancer adjuvant drug, on cancer mitochondrial homeostasis. The results of our data illustrated that Tan IIA promoted SW837 cell death, impaired cell migration and mediated cancer proliferation arrest in a dose-dependent manner. Functional investigation exhibited that Tan IIA treatment evoked mitochondrial injury, as witnessed by mitochondrial ROS overproduction, mitochondrial potential collapse, antioxidant factor downregulation, mitochondrial pro-apoptotic protein upregulation, and caspase-9-dependent apoptotic pathway activation. Furthermore, we confirmed that Tan IIA mediated mitochondrial damage by activating mitochondrial fission, and the inhibition of mitochondrial fission abrogated the proapoptotic effects of Tan IIA on SW837 cells. To this end, our results demonstrated that Tan IIA modulated mitochondrial fission via the JNK-Mff pathways. The blockade of the JNK-Mff axis inhibited Tan IIA-mediated mitochondrial fission and promoted the survival of SW837 cells. Altogether, our results identified mitochondrial fission as a new potential target to control cancer viability, mobility and proliferation. Furthermore, our findings demonstrate that Tan IIA is an effective drug to treat colorectal cancer by activating JNK-Mff-mitochondrial fission pathways.
Objective:To observe the efficacy of mitoxantrone based combinative chemotherapy and hematopoietic growth factor on autologous peripheral blood stem cells(APBSC) mobilization.Methods:MA mobilization regimen MOED mobilization regimen granulocyte colony-stimulating factor (G CSF) or G CSF and granulocyte macrophage colony stimulating factor (GM CSF) each,subcutaneously injected from the day of WBC recovery from nadir to the day of APBSC harvesting. APBSC harvesting started when WBC recovery to 2.5×10 9/L and CD + 34 cells percentage 1 % and finished when accumulated mononuclear cells(MNC)4×10 8/kg.CFU GM assay and CD + 34 cells detection of the APBSC were performed.Results:Twenty cases underwent the APBSC mobilization with mitoxantrone based chemotherapy combined with hematopoietic growth factor. Accumulated MNC for two successive days was(4.35±2.08)×10 8/kg,CD + 34 cells(9.87±4.30) ×10 6/kg and CFU GM(2.86±2.10)×10 4/kg. No severe toxicity was observed.Hematopoietic reconstitution was very well in 18 patients received the APBSC transplantation.Conclusion:Mitoxantrone based chemotherapy combined with hematopoietic growth factor was a safe and highly effective method for APBSC mobilization.
In Reply We reported on an unusual patient who presented in the emergency room with symptoms and signs of an exceptional hBPPV (1): acute spontaneous and spinning vertigo, nausea, vomiting, spontaneous nystagmus, and VOR gain deficit on the right side. After being treated with liberatory maneuvers, the patient was free of symptoms and nystagmus and was released from the emergency unit. This case was special in 4 respects: 1) gravity dependence of spontaneous nystagmus, 2) recovery of the horizontal VOR gain on the affected right side immediately after treatment, 3) asymmetry of VEMP (both cVEMP and oVEMP) to air-conducted sound (ACS) before and 2 days after treatment, and 4) VEMP recovery 30 days after treatment. We hypothesized that the most plausible explanation for all effects is a reversible horizontal canal dysfunction due to the presence of a plug. The Commentary by Curthoys (this issue) on our case report (1) reveals the ongoing controversy surrounding the hypothesis of a canal origin of VEMP to ACS. At the heart of the controversy lies the challenge, which this hypothesis poses to the widely accepted interpretation that VEMP responses to ACS are purely of otolithic origin. The Commentary raised a number of issues related to Luis et al. (1) and Zhu et al. (2). Therefore, this joint reply by the authors of both studies aims to address the concerns inthe Commentary by Curthoys and to clarify several important issues related to the technical aspects of VEMP testing, the time course of VEMP and VOR gain recovery in the reported patient, the observed eye velocity saturation as a possible sign for a canal plug, and to the literature on human and animal VEMP neurophysiology. VEMP TESTING First, the Commentary by Curthoys raised doubts as to whether we met the minimum requirements for interpreting VEMPs to ACS. Both VEMP and audiometry (pure tone and acoustic impedance, i.e., tympanometry with stapedial reflexes) are always evaluated as bundle tests in the lab of the first author. All tests were performed on all occasions from Day 1 on and were unremarkable. The phones were correctly inserted by an experienced otologist under direct viewing conditions with headlight. Nevertheless, as in all cases of absent or asymmetric response, the patient was asked if he could hear the stimulus; the examiner himself heard the stimulus, and the cables were double checked and swapped. A technical failure can therefore be excluded as a possible explanation for the simultaneous absence and recovery of both cVEMP and oVEMP. To avoid redundant information and to keep the article, a Clinical Capsule Report, as short as possible, the information provided was formulated simply: “the neurootological examination was otherwise unremarkable.” ASSOCIATION OF VOR WITH VEMP RECOVERY In view of the apparent dissociation between VOR and VEMP recovery times in the reported patient, the authors of the Commentary raised the issue of a “logical problem” in our conclusion (1). The VOR gain recovered early after treatment, whereas the recovery of both oVEMP and cVEMP was delayed. In our Discussion (1), we emphasized that “this differentially delayed normalization (…) remains to be explained.” Here, we provide the following more detailed considerations: A possible but admittedly speculative explanation might be the residual mild gain asymmetry of 15% (0.81 on the right versus 1.09 on the left) reported for Day 3, that is, 48 hours after the treatment. As can be seen in the eye and head velocity regression diagram in figure 1, this mild gain asymmetry is the result of a right gain deficit occurring only at head velocities above 150 degrees per second. In the Discussion, this was attributed to “continuing changes in biomechanical semicircular canal properties.” It might well be that such a mildly reduced gain is already a sufficient condition to have an effect on the VEMPs. The interpretation in the Commentary that “canal function and VEMPs returned independently” is therefore not supported by the data we presented (1). On the contrary: after complete recovery 80 days after treatment, a second episode with a right geotropic hBBPV, which occurred 8 months later, again showed a mild asymmetry of both VOR gain and cVEMP, which eventually recovered 30 days later. The recovery pattern in the 2 episodes shows that VEMPs and horizontal VOR gain are not independent, as suggested by the Commentary, but that they are associated; whenever the horizontal VOR was even mildly affected, this also had an effect on the VEMPs. What “remains to be explained” in future work is the observation that the association of horizontal VOR with VEMPs does not seem to be a metrical one, that is, the immediate partial recovery of VOR gain after treatment from 0.29 to 0.81 is not reflected in a comparable VEMP recovery. This might be due to a number of mechanisms, for example, a threshold in semicircular canal biomechanics, central compensation, or frequency-dependent differences in response to 500 Hz ACS versus head impulses with a frequency content of 5 Hz. In addition, the 2 episodes are different in that the first event was characterized by an unusual horizontal canal plug and the second event by a more common hBPPV, which might be a reason for the dissociation of oVEMP and cVEMP between the 2 episodes. A Clinical Capsule Report like ours (1) cannot provide conclusive explanations for all these observations. The observed association and its alternative explanations, however, demonstrate that the rigid assumption of an otolithic origin of VEMP responses as the only possible interpretation for the arguable independence of VOR gain and VEMP recovery does not justify a falsification of our conclusion. The controversy ensuing in both the Commentary and in this reply shows how important it is for the clinical interpretation of ACS-induced VEMPs to clarify these questions in future work. The Commentary continues to cite three publications by Manzari et al. (3–5) in support of the view that a dissociation of VOR gains and bone-conducted vibration induced VEMPs demonstrates the different vestibular origins of the 2 outcomes, with VOR gains reflecting canal and VEMPs reflecting otolith function. The first difficulty that arises from comparing our VEMP results with those of Manzari et al. (3–5) is the difference between stimulation methods: we used ACS (1) and the latter used bone-conducted vibration. The Commentary further claims that “all 59 patients in Manzari et al. (3) had normal horizontal canal function during both vHIT and caloric testing.” However, Manzari et al (3) did not report that All 59 patients were examined with vHIT, but only that “many patients were also tested by video recording of horizontal head impulses,” without specifying how many patients were tested by vHIT and what their VOR gains were. Apparently, only the presence of a corrective saccade was assessed by vHIT and not the gain. From the few vHIT details reported by Manzari et al. (3), it is difficult to compare their results with our quantitative vHIT analysis of VOR gain (1). Apart from VOR gain, another missing detail is head impulse velocity. In figure 1 of our case report (1), VEMP asymmetry on Day 3 was associated with a mild VOR gain asymmetry of 15%, which was unmasked only at head velocities between 150 and 300 degrees per second. Whether the head impulses used by Manzari et al. (3,4) were too slow to unmask such a gain asymmetry is not clear. In the case report on a 4-year-old boy by Manzari et al. (5), head impulse velocity was indeed too slow to unmask even a more pronounced asymmetry. Head velocity on the affected right side reached its peak of about 80 degrees per second at about 90 ms after movement onset (fig. 1). This corresponds to an estimated acceleration of roughly 1,400 degrees per square second, which is well below the accelerations typically used in previous studies on head impulse testing. For example, Aw et al. (6) used accelerations of 3,000 to 4,000 degrees per square second and Schmid-Priscoveanu et al. (7) reported 10,000 degrees per square second, with peak velocities of 250 degrees per second. In contrast, Manzari et al. (5) stimulated with less than a third of this peak velocity, although it is well known that only “rapid, … unlike slow” head movements demonstrate the VOR gain asymmetry “that is expressed by Ewald’s Second Law” (8). Because this law is fundamental to head impulse testing, a possible consequence of ignoring it is a false-negative vHIT outcome, as recently demonstrated by Machner et al. (9) in a patient with unstable gait and oscillopsia after left-side mastoidectomy for cholesteatoma. vHIT outcome in this patient was indeed negative as long as peak head velocities remained below 200 degrees per second. In accordance with Ewald’s Second Law, gain asymmetry was only unmasked with head impulse velocities of 300 degrees per second. Therefore, the dissociation between VEMP and vHIT responses in Manzari et al. (3,5) might be due to false-negative vHIT outcomes. In the case report by Manzari et al. (4), the vHIT results in figure 2A do not support the conclusion in the Commentary that the patient had normal horizontal canal function. On the contrary, the gain on the affected right side (mean = 1.14, SD = 0.08, n = 24) was significantly smaller (p = 7 × 10−9, one-tailed t test) than the gain on the left side (mean = 1.35, SD = 0.08, n = 12). Both gains were above the normative range of 0.78 to 1.1 (8). The gain asymmetry of 8.4% was beyond the range of normal values of less than 5.6% (7). VELOCITY SATURATION BY A CANAL PLUG The most puzzling remark in the Commentary concerns the “final error” that we (1) are said to have made by not citing Manzari et al. (10) as the first to “describe” the velocity saturation. This comment is puzzling because in the whole text there is indeed no description of any velocity saturation. The authors of the Commentary point to a velocity saturation in figure 1, which, however, is characterized by the occurrence of many saccades, by slow phase eye velocities that are difficult to distinguish from saccades and “bump artifacts” (11), by a considerable noise content, by a low image resolution, and by image compression artifacts. A velocity saturation is therefore difficult to detect. Only on the basis of this figure and without the raw data, it is impossible to assess the claim in the Commentary that this figure shows a velocity saturation. If there was a velocity saturation, it went unnoticed. Interestingly, a similar velocity saturation also went unnoticed in a surgical canal plugging (see figure S1 in (11)), which clearly supports our conclusion that this particular velocity profile might be a specific sign of a canal plug. This profile was documented both with search coil and with vHIT. The search coil recording, however, showed a clearer image of this saturation than did the vHIT recording. The difference might be due to the recognized “bump artifact” (11) present in the vHIT device that the authors used. Could the contralateral inhibitory saturation be responsible for the saturation in the eye velocity profile?Evidence from vHIT testing in unilateral vestibular loss after schwannoma surgery contradicts this, as thereis clearly no velocity saturation (see fig. 4 in (11)). The reason for this probably relies on the fact that each contralateral firing cell has its own firing discharge and velocity-firing characteristic. Therefore each would hit the firing rate saturation boundary at 0 Hz at another velocity. vHIT velocity saturation in vestibular neuritis seems unlikely. Instead, for us (1) the most plausible explanation for the saturation of the eye velocity response (and the nystagmus pattern) observed in the reported BPPV patient was the presence of an otoconial canal plug, since such a plug would cause a negative cupular pressure and block endolymph flow, thus modifying the cupular-endolymph biomechanical dynamics. VEMP PHYSIOLOGY Curthoys’ group was the first to specifically examine the neural basis of VEMP testing by studying the responses of vestibular afferents to clinical VEMP stimuli. They reported that sound primarily activated the saccule (12–14) and utricle (15), but not the canals, even at intensities of 80 or 90 dB SL re ABR threshold. These seminal works have been widely cited to support the current saccular theory of cervical VEMP. While the simplicity of the saccular theory has played an important role in the rapid development of the field, it has been challenged by accumulating evidence that shows sound activation of the semicircular canals (for literature review, see (2)). To address the neural basis of sound activation of the vestibular system, which is essential for interpreting clinical VEMP testing results, Zhu and Zhou at the University of Mississippi Medical Center have conducted a series of studies over the past decade to further characterize the responses of the vestibular system to clinical VEMP stimuli in monkeys (16–19) and rats (2,20–23). Their efforts are motivated by 3 aims. The first aim is to develop a quantitative measurement of sound sensitivity of an individual vestibular neuron. This is achieved by computing the cumulative probability of evoking a spike (CPE) that measures how a transient stimulus (e.g., a brief click) induces a change of firing probability of a neuron (24). Instead of simply classifying an afferent as sound sensitive or nonsound sensitive, the CPE analysis provides a quantitative assessment of sound sensitivity of a vestibular neuron. The second aim is to employ the CPE approach to record a large number of vestibular afferents from all the 5 vestibular end organs to test the saccular theory of VEMPs. The third aim is to seek sound parameters that can selectively activate certain vestibular end organs, which will serve as the neural basis of discriminative VEMP testing protocols and interpretation guidelines. Zhu et al., cited by Luis et al. (1) as reference 15 and in the Commentary as reference 2, surveyed the sound sensitivity of over 900 vestibular afferents in anesthetized rats. In addition to activating 81% of irregular otolith afferents, acoustic clicks [80 dB SL re ABR threshold (∼130 dB pSPL)] activate a substantial number of irregular anterior canal afferents (AC, 59%) and horizontal canal afferents (HC, 47%). Among them, ∼50% of sound sensitive AC afferents and ∼20% of sound-sensitive HC afferents are high sound-sensitive afferents (i.e., CPE > 0.5; figs. 2 and 3 in (2)), which are considered to contribute to generating VEMPs. It should be noted that the canal afferents with lower CPE values may also contribute to VEMPs because summation of synchronous activation of a population of sound-sensitive afferents may result in measurable VEMP responses. In addition to the neurophysiologic evidence of sound activation of the canals, a recent intra-axonal recording/labeling study shows that click sensitive afferents innervate the HC and AC cristae as well as the saccular and utricular maculae (22), therefore, providing direct anatomic evidence for sound activation of both the canals andotoliths. Because motoneurons of the sternocleidomastoid muscles (SCM) receive inputs from both the canals and the otoliths (for reviews, (25,26)), these new data suggest that the contribution of canal afferents to VEMPs should not be ruled out in clinical VEMP testing. However, given the distinct physical and geometrical properties of the otoliths and the canals, it is possible to achieve selective activation of a set of vestibular end organs by employing appropriate sound parameters (20,21,27–30). Their ongoing experiments have this aim. The Commentary also mentioned an issue related to identifying the end organ innervated by an otolith afferent. In intact animals, otolith afferents can be reliably identified by their responses to static head tilts because canal afferents do not respond to changes in head orientation with respect to gravity. In animals that undergo surgical procedures for vestibular nerve recording, however, Goldberg and Fernandez (1975) (31) showed that the vertical canal afferents are sensitive to static head tilts because removal of the brain tissue overlying the vestibular nerves and ganglion exposes the bony labyrinth to room temperature. This results in a thermal gradient across the labyrinths, which makes the vertical canals sensitive to gravitational changes. To avoid this ambiguity, it is important to use turntables that provide adequate rotational stimulation to the vertical canals. CONCLUSION In summary, we addressed the arguments of the Commentary in the following points: 1) We have demonstrated that a technical failure can be excluded as a possible explanation for the simultaneous absence and recovery of both cVEMP and oVEMP. Very basic technical aspects, are not the most plausible causes for our findings; 2) vHIT and VEMP responses did not return independently but were associated. Whenever the horizontal VOR was even mildly affected, this also had an effect on VEMPs; 3) To the best of our knowledge vHIT was used for the first time to document a high-frequency VOR hypofunction during BPPV. Moreover, it documented an eye velocity saturation profile as was later demonstrated in a surgical canal plug (11); 4) our case showed that a patient with BPPV might present with spontaneous nystagmus. BPPV must be ruled out in acute vestibular syndrome patients. Not only the direction but also the intensity of the nystagmus position dependency should be tested in every patient with spontaneous nystagmus, just as the vHIT velocity profile; 5) as there is solid and growing evidence of sound canal activation, canal contributions to VEMPs should not be ruled out before the neurophysiologic basis of sound activation of the vestibular system is fully understood. Leonel Luis, M.D. Health Sciences Institute Portuguese Catholic University Clinical Physiology Translational Unit Institute of Molecular Medicine Faculty of Medicine University of Lisbon Lisbon, Portugal [email protected] Hong Zhu, M.D., Ph.D. Departments of Otolaryngology and Communicative Sciences and Neurobiology & Anatomical Sciences University of Mississippi Medical Center Jackson, Mississippi, U.S.A. João Costa, M.D., Ph.D. Clinical Physiology Translational Unit Institute of Molecular Medicine Faculty of Medicine University of Lisbon EMG and Motor Control Unit Neurology Department, Hospital Clinic Universitat de Barcelona, IDIBAPS Barcelona, Spain Josep Valls-Solé, M.D., Ph.D. EMG and Motor Control Unit Neurology Department, Hospital Clinic Universitat de Barcelona, IDIBAPS Barcelona, Spain Thomas Brandt, M.D. German Center for Vertigo and Balance Disorders Ludwig-Maximilians University Munich Munich, Germany Wu Zhou, Ph.D. Departments of Otolaryngology and Communicative Sciences and Neurobiology & Anatomical Sciences University of Mississippi Medical Center Jackson, Mississippi, U.S.A. Erich Schneider, Ph.D. German Center for Vertigo and Balance Disorders Ludwig-Maximilians University Munich, Germany Brandenburg University of Technology, Cottbus Senftenberg, Germany Thomas Brandt is shareholder and Erich Schneider is general manager and shareholder of EyeSeeTec GmbH. All other authors disclose no conflicts of interest. Acknowledgments: The authors thank Judy Benson for critically reading the manuscript. Supported by the German Federal Ministry of Education and Research (Grant 01 EO 0901) and NIH R01DC012060 (HZ), NIH R01DC008585 (WZ) and NIH R01 DC05785 (WZ).
In order to determine the genetic structure and possible origin of ancient human in Zhengzishan cemetery of Upper Capital site of the Yuan Dynasty in Inner Mongolia,DNA was extracted from the ancient human in the cemetery.Through amplifying and sequencing,the mtDNA hypervariable region I(HVRI) sequences of 10 ancient individuals were obtained.Combining with the human mtDNA data from modern eastern Asian,northern Asian,central Asian and European,phylogenetic analysis and multidimensional scaling analysis were performed.The research results show that the ancient human from Zhenzishan cemetery belongs to Han Chinese and they are northern Han.This study provides a new method for revealing the complicated social structure and social history of the Yuan Dynasty.
Abstract Pathogenesis of cardiac microvascular ischemia‐reperfusion (IR) injury is associated with excessive mitochondrial fission. However, the upstream mediator of mitochondrial fission remains obscure. Bax inhibitor 1 (BI1) is linked to multiple mitochondrial functions, and there have been no studies investigating the contribution of BI1 on mitochondrial fission in the setting of cardiac microvascular IR injury. This study was undertaken to establish the action of BI1 on the cardiac microvascular reperfusion injury and figure out whether BI1 sustained endothelial viability via inhibiting mitochondrial fission. Our observation indicated that BI1 was downregulated in reperfused hearts and overexpression of BI1 attenuated microvascular IR injury. Mechanistically, reperfusion injury elevated the levels of xanthine oxidase (XO), an effect that was followed by increased reactive oxygen species (ROS) production. Subsequently, oxidative stress mediated F‐actin depolymerization and the latter promoted mitochondrial fission. Aberrant fission caused mitochondrial dysfunction and ultimately activated mitochondrial apoptosis in cardiac microvascular endothelial cells. By comparison, BI1 overexpression repressed XO expression and thus neutralized ROS, interrupting F‐actin‐mediated mitochondrial fission. The inhibitory effect of BI1 on mitochondrial fission sustained endothelial viability, reversed endothelial barrier integrity, attenuated the microvascular inflammation response, and maintained microcirculation patency. Altogether, we conclude that BI1 is essential in maintaining mitochondrial homeostasis and alleviating cardiac microvascular IR injury. Deregulated BI1 via the XO/ROS/F‐actin pathways plays a causative role in the development of cardiac microvascular reperfusion injury.
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