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1.
J Am Assoc Lab Anim Sci ; 59(2): 212-220, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32059757

RESUMEN

Ulcerative dermatitis in laboratory mice remains an ongoing clinical problem and animal welfare issue. Many products have been used to treat dermatitis in mice, with varying success. Recently, the topical administration of healing clays, such as bentonite and green clays, has been explored as a viable, natural treatment. We found high concentrations of arsenic and lead in experimental samples of therapeutic clay. Given the known toxic effects of these environmental heavy metals, we sought to determine whether the topical administration of a clay product containing bioavailable arsenic and lead exerted a biologic effect in mice that potentially could introduce unwanted research variability. Two cohorts of 20 singly housed, shaved, dermatitis free, adult male CD1 mice were dosed daily for 2 wk by topical application of saline or green clay paste. Samples of liver, kidney and whole blood were collected and analyzed for total arsenic and lead concentrations. Hepatic and renal concentrations of arsenic were not different between treated and control mice in either cohort; however, hepatic and renal concentrations of lead were elevated in clay treated mice compared to controls in both cohorts. In addition, in both cohorts, the activity of δ-aminolevulinate acid dehydratase, an enzyme involved with heme biosynthesis and a marker of lead toxicity, did not differ significantly between the clay-treated mice and controls. We have demonstrated that these clay products contain high concentrations of arsenic and lead and that topical application can result in the accumulation of lead in the liver and kidneys; however, these concentrations did not result in measurable biologic effects. These products should be used with caution, especially in studies of lead toxicity, heme biosynthesis, and renal α2 microglobulin function.

2.
Neurosci Bull ; 2020 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-32096114

RESUMEN

Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states. Identifying the neural mechanisms by which the state-dependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep-wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.

3.
Med Biol Eng Comput ; 2020 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-32086764

RESUMEN

Since more and more elderly people suffer from lower extremity movement problems, it is of great social significance to assist persons with motor dysfunction to walk independently again and reduce the burden on caregivers. The self-paced walking intention, which could increase the ability of self-control on the start and stop of motion, was studied by applying brain-computer interface (BCI) technology, a novel research field. The cerebral hemoglobin signal, which was obtained from 30 subjects by applying functional near-infrared spectroscopy (fNIRS) technology, was processed to detect self-paced walking intention in this paper. Teager-Kaiser energy was extracted at each sampling point for five sub-bands (0.0095~0.021 Hz, 0.021~0.052 Hz, 0.052~0.145 Hz, 0.145~0.6 Hz, and 0.6~2.0 Hz). Gradient boosting decision tree (GBDT) was then utilized to establish the detecting model in real-time. The proposed method had a good performance to detect the walking intention and passed the pseudo-online test with a true positive rate of 100% (80/80), a false positive rate of 2.91% (4822/165171), and a detection latency of 0.39 ± 1.06 s. GBDT method had an area under the curve value of 0.944 and was 0.125 (p < 0.001) higher than linear discriminant analysis (LDA). The results reflected that it is feasible to decode self-paced walking intention by applying fNIRS technology. This study lays a foundation for applying fNIRS-based BCI technology to control walking assistive devices practically. Graphical abstract Graphical representation of the detecting process for pseudo-online test. The lower figure is a partial enlargement of the upper figure. In the lower figure, the blue line represents the probability of walking predicted by GBDT without smoothing and the orange-red line represents the smoothed probability. The dark-red ellipse shows the effect of the smoothing-threshold method.

4.
Artículo en Inglés | MEDLINE | ID: mdl-32101494

RESUMEN

Objective: The aim of the present study was to investigate the clinical treatment effect on oral venous lakes (OVL) treated with neodymium-doped yttrium aluminum garnet (Nd:YAG) laser or a combination of erbium-yttrium aluminum garnet (Er:YAG) laser. Patients and methods: Between June 2015 and March 2017, nine patients, suffering from OVL in the mandibular regions, were treated with Nd:YAG laser or combination of Nd:YAG laser and Er:YAG laser in our department. The Nd:YAG laser was mainly performed for the treatment of nine initial lesions. The preset parameters were as follows: average power of 5 W, frequency of 100 Hz, microshort pulse (MSP), tip size of 300 µm, spot size of 3 mm, irradiation distance of 3-4 mm, and speed of 1-2 mm/s, sequential treatment. The power density at work was 57 W/cm2. If postoperative scars occurred after the Nd:YAG treatment, the Er:YAG laser was used. The parameters were set as follows: power of 3.75 W, energy of 150 mJ, frequency of 25 Hz, very long pulse (VLP), tip size of 0.6 mm, 40% water, and 60% gas. The patients were followed up for 4-8 weeks. The therapeutic results were graded on a 4-point scale system. Adverse effects after laser treatment were evaluated and managed accordingly. Results: With single Nd:YAG laser, the therapeutic outcome was excellent in seven patients (77.8%) and good in two patients (22.2%). Scar tissue was encountered in two patients 2 weeks after Nd:YAG laser therapy, and then Er:YAG laser was used for the scar removal. No mucosal necrosis was found in any of the patients. Conclusions: The Nd:YAG laser or combined with Er:YAG laser was an effective and safe treatment for patients with OVL in the mandibular region.

5.
ACS Appl Mater Interfaces ; 12(5): 5680-5694, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-31944660

RESUMEN

Photodynamic therapy (PDT), a clinically approved cancer treatment, has faced many drawbacks that restricted its applications. For example, the hypoxia-induced elevated hypoxia-inducible factor-1α (HIF-1α) may desensitize tumors to PDT, and the high concentration of glutathione (GSH) in cancer cells can also neutralize the generated reactive oxygen species (ROS) during PDT, resulting in insufficient therapy. Moreover, extra probes for imaging-guided visualization therapy are always needed to track drug release or distribution, while it may decrease the drug loading of the drug delivery system (DDS). In the present study, we have designed and prepared a novel multifunctional combined therapy nanoparticle (ZnPc@Cur-S-OA NPs), in which curcumin (Cur) was not only used as a chemotherapy drug to achieve a combination therapy with PDT via downregulating HIF-1α and depleting GSH in B16F10 cells but also designed as a small-molecule ROS-triggered release prodrug to deliver the photosensitizer (PS). The red fluorescence of PS in the nanoparticles (NPs) can be used to track the NPs distribution, while the green fluorescence of Cur showed an "OFF-ON" activation, which enables additional imaging and real-time self-monitoring capabilities. These results proved that the prepared combined therapy NPs were more effective to inhibit the growth of B16F10 mouse melanoma tumor than was monotherapy without eliciting systemic toxicity either in vitro or in vivo, which indicated the combined therapy NPs as an effective way to improve the PDT efficacy via downregulation of HIF-1α and depletion of GSH. Thus, the strategy of using a multifunctional natural product as the stimuli-responsive carrier as well as the synergist with PDT for enhancing antitumor efficacy via multiple pathways may open an alternative avenue to fabricate new self-delivery combination therapy nanodrugs. Besides, the fluorescence emitted from the drug can be used for real-time self-monitoring of drug release and distribution, which has great potential in clinic to adjust the administration dose and irradiation time for different tumor types and stages for individual therapy.

6.
Future Med Chem ; 12(3): 243-267, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31950858

RESUMEN

The basic leucine zipper transcription factor Nrf2 is the primary regulator of cellular oxidative stress. Activation of Nrf2 is regarded as a potential preventive and therapeutic strategy. However, aberrant hyperactivation of Nrf2 is found in a variety of cancers and promotes cancer progression and metastasis. Moreover, constitutive activation of Nrf2 confers cancer cells resistance to chemo- and radio-therapy. Thus, inhibiting Nrf2 could be a new therapeutic strategy for cancer. With the aim of accelerating the discovery and development of novel Nrf2 inhibitors, we summarize the biological and pathological functions of Nrf2 in cancer. Furthermore, the recent studies of small molecular Nrf2 inhibitors and potential Nrf2 inhibitory mechanisms are also summarized in this review.

7.
Biomed Pharmacother ; 124: 109740, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31972361

RESUMEN

On account of the acquired drug resistance, the potency of cisplatin-based chemotherapy is far from satisfactory in rectal cancer. Increasing evidence has highlighted the crucial function of aberrantly expressed lncRNAs on the cisplatin resistance in multiple cancers. This research was the first attempt to decipher the underlying function and mechanism of long intergenic non-protein coding RNA 461 (LINC00461) in rectal cancer and also its relation to cisplatin resistance of rectal cancer. Data from this study revealed that LINC00461 expression was upregulated in rectal cancer cells. LINC00461 depletion restrained rectal cancer progression and sensitized rectal cancer cells to cisplatin. Molecular mechanism assays testified that LINC00461 bound with miR-593-5p. Besides, miR-593-5p upregulation improved the sensitivity of rectal cancer cells to cisplatin. Additionally, cyclin D1 (CCND1) was manifested to be a downstream target of miR-593-5p. Furthermore, CCND1 upregulation could reverse the effect of LINC00461 downregulation on rectal cancer progression and cisplatin resistance of rectal cancer. To sum up, LINC00461 mediates cisplatin resistance of rectal cancer by targeting miR-593-5p/CCND1 axis, shedding new light on the treatment of rectal cancer.

8.
Biomed Pharmacother ; 124: 109855, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31986410

RESUMEN

MGN-3 is an arabinoxylan from rice bran that has been shown to be an excellent antioxidant and radioprotector. This study examined the protective effects of MGN-3 on radiation-induced intestinal injury. Mice were treated with MGN-3 prior to irradiation, then continued to receive MGN-3 for 4 weeks thereafter. MGN-3 increased the activity of mitochondrial respiratory chain complexes Ⅰ, Ⅲ, Ⅳ and Ⅴ, the intercellular ATP content, the mitochondria-encoded gene expression and mitochondrial copy numbers in the jejunal and colonic mucosa. MGN-3 reduced the oxidative stress levels and inflammatory response indicators in the serum and jejunal and colonic mucosa. Antioxidant indicators such as superoxide dismutase, glutathione peroxidase, catalase and total antioxidant capacity were significantly increased in the serum and jejunal and colonic mucosa in the MGN-3 group. Moreover, MGN-3 decreased the gene abundances and enzymatic activities of caspase-3, 8, 9 and 10 in the jejunal and colonic mucosa. The endotoxin, diamine peroxidase, d-lactate and zonulin levels were significantly reduced in the serum and jejunal and colonic mucosa in the MGN-3 group. MGN-3 also markedly upregulated the gene abundances of ZO-1, occludin, claudin-1 and mucin 2. MGN-3 effectively attenuated radiation-induced changes in the intestinal epithelial mitochondrial function, oxidative stress, inflammatory response, apoptosis, intestinal permeability and barrier function in mice. These findings add to our understanding of the potential mechanisms by which MGN-3 alleviates radioactive intestinal injury.

9.
Pain ; 161(2): 288-299, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31651580

RESUMEN

Patients with chronic pain often report being sensitive to pain at night before falling asleep, a time when the synchronization of cortical activity is initiated. However, how cortical activity relates to pain sensitivity is still unclear. Because sleep is characterized by enhanced cortical delta power, we hypothesized that enhanced cortical delta power may be an indicator of intensified pain. To test this hypothesis, we used pain thresholds tests, EEG/electromyogram recordings, c-Fos staining, and chemogenetic and pharmacological techniques in mice. We found that sleep deprivation or pharmacologic enhancement of EEG delta power by reserpine and scopolamine dramatically decreased mechanical pain thresholds, but not thermal withdrawal latency, in a partial sciatic nerve ligation model of neuropathic pain mice. On the contrary, suppression of EEG delta power using a wake-promoting agent modafinil significantly attenuated mechanical allodynia. Moreover, when EEG delta power was enhanced, c-Fos expression decreased in most regions of the cortex, except the anterior cingulate cortex (ACC), where c-Fos was increased in the somatostatin- and parvalbumin-positive GABAergic neurons. Chemogenetic activation of GABAergic neurons in ACC enhanced EEG delta power and lowered mechanical pain thresholds simultaneously in naive mice. However, chemogenetic inhibition of ACC GABAergic neurons could not block mechanical allodynia. These results provided compelling evidence that elevated EEG delta power is accompanied with aggravated neuropathic pain, whereas decreased delta power attenuated it, suggesting that enhanced delta power can be a specific marker of rising chronic neuropathic pain and that wake-promoting compounds could be used as analgesics in the clinic.

10.
Sleep ; 43(2)2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-31552427

RESUMEN

Light has immediate effects on sleep in rodents, but the neural pathways underlying the effect remain to be elucidated. The intergeniculate leaflet (IGL) containing GABAergic neurons receives direct retinal inputs. We hypothesized that IGL GABAergic neurons may mediate light-induced sleep. EEG/electromyogram recording, immunohistochemistry, electrophysiology, optogenetics, fiber photometry, behavioral tests, and cell-specific destruction were employed to investigate the role of IGL GABAergic neurons in the regulation of acute light-induced sleep. Here, EEG/electromyogram recordings revealed that acute light exposure during the nocturnal active phase in mice induced a significant increase in non-rapid eye movement and rapid eye movement sleep compared with controls. Immunohistochemistry showed that acute light exposure for 2 hours in the active phase induced an increase in c-Fos expression in the IGL, whereas lights-off in the rest phase inhibited it. Patch clamp coupled with optogenetics demonstrated that retinal ganglion cells had monosynaptic functional connections to IGL GABAergic neurons. Calcium activity by fiber photometry in freely behaving mice showed that light exposure increased the activity of IGL GABAergic neurons. Furthermore, lesion of IGL GABAergic neurons by caspase-3 virus significantly attenuated the sleep-promoting effect of light exposure during active phases. Collectively, these results clearly indicated that the IGL is one of key nuclei mediating light-induced sleep in mice.

11.
Biochem Pharmacol ; 172: 113753, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31837310

RESUMEN

Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), is a crucial substance metabolism and elimination process that mostly occurs in the liver to protect the body from toxic substances and maintain homeostasis. The reaction functions well in a uridine diphosphate glucuronic acid (UDPGA) -dependent manner in vivo. However, the mechanism for recognizing UDPGA or analog has not been reported so far. Here, through X-ray crystallography, we present a 1.78 Å cocrystal structure of the C-terminal domain of UDP-glucuronosyltransferase 2B15 (2B15CTD, K284-H451) bound by tartrate, which reveals the detailed recognition mechanism of UDPGA analog at the active site. Using surface plasmon resonance techniques, protein thermal shift studies, and limited proteolysis, we determine that tartrate stabilizes the conformation of 2B15CTD thermodynamically. The biochemical analysis further elucidates that two residues, S312 and T374, are essential for the interactions between 2B15CTD and tartrate. We also investigate the pharmacological effects of tartrate on UGTs based on the cocrystal structure of UGT2B15 and experiments performed in vitro and in vivo. In brief, the LC-MS/MS analysis shows that tartrate has a significant inhibitory effect towards UGT2B15 (Ki = 91 µM), and oral administration of tartrate to FVB mice can reduce the relative plasma concentration of glucuronide. These results reveal an unexpected physiological role of tartrate in the maintenance of UGTs function. Therefore, tartrate is a potential inhibitor of UGTs, and the excess tartrate in the diet may disturb body homeostasis and inhibit the metabolism of UGT substrates by interfering with glucuronidation.

12.
Bioorg Med Chem Lett ; 30(2): 126853, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31859162

RESUMEN

Oxidative stress plays vital roles in virous neurodegenerative diseases including Alzheimer's disease. Activation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), the key regulator of oxidative stress, may provide a new therapeutic strategy for these diseases. Herein we synthesized and evaluated a series of 1,3,4-oxa/thiadiazole core Nrf2 activators as neuroprotective agents. The representative compound 8 exhibited cytoprotective and Nrf2 activation effects in a neuron-like PC-12 cells. Additionally, compound 8 showed good membrane permeability, indicating this compound could penetrate blood-brain barrier (BBB) to reach central nervous system (CNS) as a neuro-protective agent. These results indicated that these Nrf2 activators with 1,3,4-oxa/thiadiazole core could serve as a new chemotype against oxidative stress in neurodegenerative diseases.

13.
Orthop Surg ; 12(1): 3-15, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31880083

RESUMEN

To investigate whether high body mass index (BMI) had adverse effects on the postoperative outcomes for patients who underwent anterior or posterior cervical fusion procedures. A literature search were conducted in PubMed, Embase, and Web of Science. Comparative or controlled studies that examined the influences of high BMI on postoperative outcomes after cervical fusion procedures were included. Using a fixed-effect model or random-effect model, the effects of high BMI were determined by weight mean difference (WMD) with 95% confidence interval (95% CI) or risk ratio (RR) with 95% CI. A total of seven studies were included in this meta-analysis. The pooled estimate showed that high BMI was associated with longer hospital stay (WMD = 1.61 days, 95% CI: 0.51, 2.71; P = 0.004), longer surgical time (WMD = 4.55, 95% CI: 1.04, 8.07; P = 0.011), higher mortality rate (RR = 3.01, 95% CI: 2.75, 3.29; P < 0.001), and higher postoperative rates of cardiac complication (RR = 1.30, 95% CI: 1.11, 1.52; P = 0.001), deep venous thromboembolism (RR = 2.29, 95% CI: 1.36, 3.86; P = 0.002), and wound complication (RR = 1.69, 95% CI: 1.26, 2.28; P < 0.001). However, there was no significant differences between high and normal BMI groups in terms of Neck Disability Index (WMD = 1.49, 95% CI: -2.34, 5.32; P = 0.447), SF-36 Mental Component Score (MCS) (WMD = -0.87, 95% CI: -2.09, 0.35; P = 0.164), overall complications (RR = 1.18, 95% CI: 0.80, 1.76; P = 0.399), central nervous system (CNS) complications (RR = 0.68, 95% CI: 0.17, 2.76; P = 0.586), pulmonary complications (RR = 1.46, 95% CI: 0.87, 2.46; P = 0.150), and septic complications (RR = 0.87, 95% CI: 0.32, 2.38; P = 0.785).High BMI seemed to be associated with longer hospital stay, surgical time, and higher postoperative complication rates compared to normal BMI. Therefore, high BMI patients should be counseled carefully regarding the risk of postoperative complications and surgical outcomes after cervical fusion procedures.

14.
J Musculoskelet Neuronal Interact ; 19(4): 516-520, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31789303

RESUMEN

OBJECTIVE: To study the effect of comprehensive nursing based on the concept of feedforward control on postoperative FMA (Fugl-Meyer Assessment) and SF-36 (health status questionnaire) in patients with femoral trochanteric fracture. METHODS: 114 patients with femoral intertrochanteric fracture were enrolled in the study. Patients were divided into control group and observation group according to order of admission, 57 cases in each group. Both groups of patients received proximal femoral nail antirotation surgery, conventional nursing and feedforward control based comprehensive nursing. Nursing effects of the two groups of patients were compared. RESULTS: Anus first exhaust time, the time of getting out of bed and hospitalization time, and after nursing, SAS (Self-Rating Anxiety) and SDS (Self-Rating Depression) score of the observation group were significantly lower than those of the control group (p<0.05). FMA and SF-36 score of the observation group after surgical nursing were significantly higher than those of the control group (p<0.05). The total incidence of complications in the observation group was lower than that in the control group (p<0.05). CONCLUSIONS: Comprehensive care based on the concept of feedforward control has a better nursing effect for patients with intertrochanteric fracture, which can shorten the time of patient getting out of bed and hospitalization and reduce the incidence of post-complications.

15.
Med Sci Monit ; 25: 9483-9489, 2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31829312

RESUMEN

BACKGROUND Short-segment pedicle screw instrumentation provides superior outcomes in treating thoracolumbar fractures. Nevertheless, the effect of intermediate screws on the outcome of short-segment instrumentation at the fracture level has not been specifically analyzed. We performed an update meta-analysis of the effect of additional vertebroplasty on the outcome of short-segment instrumentation to determine the role of screws for patients with fractured vertebra. MATERIAL AND METHODS A systematic literature search was conducted, updated to January 2019, in terms of the efficacy of additional vertebroplasty on the outcome of short-segment instrumentation at the fracture level. After rigorous quality review, we extracted the data from qualified clinical studies. We further analyzed odds ratios (ORs) of the endpoints of interest based on the included trials. RESULTS Compared with the control group, short-segmental fixation combined with intermediate screws restored Cobb angle (P<0.001) and reduced anterior vertebral height compression (P=0.001). However, our results did not reveal statistically significant differences in operative time (P=0.28) or estimated blood loss (P=0.23). A statistically significant difference was observed in mean hospital stay (P=0.02). CONCLUSIONS Reinforcement with fracture-level screw combination can help stabilize the fractures and restore the anatomy. Nevertheless, additional trials and studies with longer follow-ups and on larger populations are warranted to confirm the current findings.

16.
Aging (Albany NY) ; 11(23): 11111-11123, 2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31829979

RESUMEN

BACKGROUND: Mixed evidence challenges preoperative alpha-fetoprotein (AFP) as an independent prognostic factor for patients with hepatocellular carcinoma (HCC) after hepatectomy. RESULTS: Daily post-operative decrease of AFP by 9% as compared to the preoperative level (A09) were selected as the Cut-off. The Kaplan-Meier curve showed that A09 was significantly different for OS (P=0.043) and RFS (P=0.03). A decrease in risk by 54% was observed for OS and 32% for RFS in the at-risk population (A09>9%). A better concordance was observed after adding A09 into TNM and BCLC staging systems. Moreover, a consistent concordance was observed in the internal (FDZS5:0.63; FDZS3:0.608) and external (FDZS5:0.85; FDZS3:0.762) validation cohorts, suggesting its prognostic value in HCC population with elevated AFP. CONCLUSIONS: Decrease in perioperative serum AFP rather than preoperative AFP is an independent prognostic factor for HCC patients after hepatectomy. Cut-off A09 significantly discriminates overall and recurrence-free survival and could be interpret into TNM and BCLC staging systems to improve the stratification power for HCC patients with elevated AFP. METHODS: Kaplan-Meier curve depicted the differences of overall survival (OS) and recurrence-free survival (RFS). Nomogram and concordance were employed to evaluate the superiority of the current staging system.

17.
Trials ; 20(1): 719, 2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31831051

RESUMEN

BACKGROUND: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction. METHODS/DESIGN: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine. DISCUSSION: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.

18.
Neuropharmacology ; 168: 107923, 2019 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-31874169

RESUMEN

The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known about the physiological role and mechanism of the OT in sleep-wake regulation. The OT expresses abundant adenosine A2A receptors (A2ARs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A2ARs. This study examined sleep-wake profiles through electroencephalography and electromyography recordings with pharmacological and chemogenetic manipulations in freely moving rodents. Compared with their controls, activation of OT A2ARs pharmacologically and OT A2AR neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A2ARs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A2AR neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A2ARs in the OT play an important role in sleep regulation.

19.
Hepatobiliary Surg Nutr ; 8(5): 470-479, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31673536

RESUMEN

Background: There are few detailed consensus and guidelines on perioperative clinical characteristics of liver transplantation (LT) in patients with methylmalonic acidemia (MMA). This retrospective study investigated details of the clinical course and individualized treatment plan of the center with largest experience in China. Methods: A total of 7 MMA patients undergoing LT in Beijing Friendship Hospital from June 2013 to December 2017 were enrolled in the study, whose clinical data (clinical characteristics, laboratory findings, chronological changes in urine MMA levels, treatment, etc.) during perioperative period were analyzed retrospectively. All the patients received strict postoperative management. Results: All the 7 cases were confirmed to have isolated MMA, among which, 3 cases received living donor liver transplantation (LDLT), 4 cases received deceased donor liver transplantation (DDLT). A wild fluctuate of metabolic condition was observed within the first few days after surgery and two weeks after LT, the mean base excess of blood value (BE-B) restored to normal whereas plasma bicarbonate (HCO3 -) was still below normal value even with intermittent sodium bicarbonate correction. It also showed marked reduction in propionylcarnitine (C3) and C3/C2 level and the mean urine MMA by gas chromatography-mass spectrometry (GC-MS) was reduced by 81.7% (P<0.01) but remained >72× higher than upper limit of normal. The metabolism-correcting medications were administered as before. The renal function of one case with renal insufficiency before LT (serum creatinine rising) maintained stable by adjusting the immunosuppressive regimen during the observation period. All patients survive to date. Conclusions: LT is an effective treatment to prevent metabolic crisis, but patients with MMA tend to be metabolically fragile even after surgery. During perioperative period, close monitoring should be given for acidosis episodes so as to implement sodium bicarbonate correction. Metabolism-correcting medications are still needed. Special immunosuppressive regimen is an effective way of maintaining renal function for those with kidney dysfunction.

20.
Biomater Sci ; 8(1): 212-223, 2019 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-31674634

RESUMEN

Gambogic acid (GA) is a natural anti-tumor drug whose application is restricted by its poor aqueous solubility and inefficient bioavailability. Developing nanomaterials with excellent biocompatibility can amplify the therapeutic effects of GA. In this study, a tumor-targeted redox controllable self-assembled nano-system with magnetic enhanced EPR effects (mPEG-HA/CSO-SS-Hex/SPION/GA) was developed to improve the anticancer efficacy of GA. The nano-system is constituted by three layers: the outer layer is mono-aminated poly(ethylene glycol) grafted hyaluronic acid (mPEG-HA), which can target the CD44 receptor in breast cancer cells; the middle layer consists of disulfide linked hexadecanol (Hex) and chitosan oligosaccharide (CSO) to control the drug release by reduction response; the core layer is superparamagnetic iron oxide nanoparticles (SPION), which can enhance the EPR effect by magnetic guidance and contribute to GA entrapment. Different experiments were performed to characterize the complex self-assembly, and the cytotoxicity, pharmacokinetics, and in vivo antitumor activity of the self-assembly were investigated to evaluate its anti-tumor effects. The results revealed that mPEG-HA/CSO-SS-Hex/SPION/GA is an excellent nanosystem with appropriate size and sensitive responsiveness; it can accumulate in tumor sites and achieve excellent therapeutic effects on triple-negative breast cancer (TNBC). In summary, a CD44-targeted redox-triggered self-assembly nanosystem with magnetic enhanced EPR effects was developed for effective amplification of GA; it has potential to act as an effective carrier in drug delivery for chemotherapy of TNBC.

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