MicroRNA-200 family members are weakly expressed in the neurosensory epithelia of the developing zebrafish (Danio rerio) inner ear.

MicroRNA-200 family members are expressed in the developing mouse inner ear and in zebrafish (Danio rerio) olfactory epithelia, taste buds, and neuromasts, and have also been shown to be associated with differentiation of olfactory and taste buds. However, the role of the miR-200 family in the inner ear of zebrafish had not been studied. We investigated the expression and function of the miR-200 family in the zebrafish inner ear via in situ hybridization and loss-of-function methods. Expression of the miR-200 family was weak and dispersed throughout the developing zebrafish inner ear. After knockdown of miR-200 family members in the developing inner ear, no significant differences in development were observed compared to the controls. Otic vesicles, otoliths, and semicircular canals appeared normal. Compared with less differentiated olfactory filaments in olfactory epithelia, the development of hair cells and statoacoustic ganglion neurons were normal. The kinocilia and stereocilia of hair cells, the innervation of hair cells, and the formation of ribbon synapses were also unaffected. Overall, we conclude that the miR-200 family has a negligible role in the development of zebrafish inner ear; the functions of the miR- 200 family may be organ-specific.

MicroRNA-23b promotes tolerogenic properties of dendritic cells in vitro through inhibiting Notch1/NF-κB signalling pathways.

BACKGROUND: MicroRNAs (miRNAs) are known to regulate the inflammatory response in various cell types. However, the ability of miRNAs to modulate dendritic cells (DCs) function for allergen immunotherapy is unclear. OBJECTIVE: To assess the role of miR-23b in the regulation of ovalbumin (OVA)-induced DC differentiation and function and to investigate the related molecular mechanisms. METHODS: Bone marrow-derived dendritic cells (BMDCs) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of miRNA expression. After transfection with miR-23b reagents, DCs were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD4+ T-cell differentiation. The possible roles of the Notch and NF-κB signalling pathways were also evaluated. Human monocyte-derived dendritic cells (MDDCs) were similarly evaluated as well. RESULTS: Significant upregulation of miR-23b was observed in BMDCs pulsed with OVA. Following miR-23b transfection, BMDCs showed decreased OVA uptake, increased IL-10 production, decreased IL-12 production and an enhanced capacity to promote FoxP3+ CD4+ T regulatory cells (Tregs) differentiation. In addition, inactivation of the Notch1 and NF-κB signalling pathways were observed. Conversely, inhibition of miR-23b in BMDCs resulted in the opposite effects. In human MDDCs, miRNA23b transfection similarly increased IL-10 and decreased IL-12 production, and that treated human MDDCs induced increased FoxP3+ CD4+ T cells. CONCLUSION: Our findings provide evidence that miR-23b is capable of inducing tolerogenic DC activity and Treg responses in vitro through the inhibition of the Notch1 and NF-κB signalling pathways; thus, miR-23b might represent a therapeutic target for the management of allergic diseases.

[Efficacy comparison of robotic and laparoscopic radical resection of rectal cancer for overweight and obese patients].

Objective: During laparoscopic pelvic operational procedure for obese patients with rectal cancer, the large amount of fat in the abdominal cavity often impairs the exposure of the surgical field, resulting in technical difficulty. In contrast, robotic surgery has the advantages of being more minimally invasive, precise, and flexible. This study compared the clinical efficacy of robotic and laparoscopic radical resection of rectal cancer for overweight and obese patients. Methods: A retrospective cohort study was conducted. Clinical data of 173 patients with rectal cancer and a body mass index (BMI) ≥ 25 kg/m(2) who received robotic or laparoscopic radical rectal resection at the First Affiliated Hospital of Nanchang University from January 2015 to February 2019 were retrospectively collected. Of 173 patients, 90 underwent robotic surgery and 83 underwent laparoscopic surgery. The intraoperative parameters, postoperative short-term and follow-up status were analyzed and compared between the two groups. The follow-up ended in December 2019. Results: Of 173 patients, 103 were male and 70 were female with a median age of 62 (range 29 to 86) years. The average BMI was (27.2±1.6) kg/m(2) in the robotic group and (27.3±1.5) kg/m(2) in the laparoscopic group. No significant differences in baseline data were observed between two groups (all P>0.05). As compared to the laparoscopic group, the robotic group had less intraoperative blood loss [(73.0±46.8) ml vs. (120.9±59.9) ml, t=-5.881, P<0.001] and higher postoperative hospitalization expense [(61±15) thousand yuan vs (52±13) thousand yuan, t=3.468, P=0.026]. The conversion rate in the robotic group was 1.1% (1/90), which was lower than 6.0% (5/83) in the laparoscopic group, but the difference was not statistically significant (P=0.106). There were no statistically significant differences between the two groups in operative time, number of intraoperative blood transfusion, number of harvested lymph nodes, time to the first flatus, postoperative hospital stay and morbidity of total postoperative complications (all P>0.05). Five (6.0%) patients in the laparoscopic group developed urinary dysfunction, while no case in the robotic group developed postoperative urinary dysfunction (P=0.024). The 173 patients were followed up for 8-59 months, with a median follow-up of 36 months. The 3-year overall survival rate of robotic group and laparoscopic group was 89.8% and 86.6%, respectively without significant difference between the two groups (P=0.638). The 3-year disease-free survival rate of the robotic group and the laparoscopic group was 85.6% and 81.5%, respectively without significant difference as well (P=0.638). Conclusions: Robotic radical surgery is safe and feasible for overweight and obese patients with rectal cancer. Compared with laparoscopic radical surgery, it has advantages of clear vision of surgical exposure, less intraoperative blood loss, less pelvic autonomic nerve damage, and operation in a narrow space.

[Key points and skills of assistant in robotic radical gastrectomy for gastric cancer].

An excellent assistant for robotic radical gastrectomy can play an important role in the operation, especially in a initial team. In robotic gastric cancer surgery, an excellent assistant should actively participate in the operation process, choose the appropriate trocar position according to patient's body habitus. Moreover, he should master various surgical instruments skillfully and switch instruments fluently to assist the surgeon to expose key parts during operation, and provide effective help in the operative details, so that the whole operation process can run more smoothly and the operation efficiency and quality will be greatly improved. The growth of the assistants needs constant practice and summary of experience. Meanwhile, the encouragement of the chief surgeon also plays a positive role in promoting the development of the assistants.

Congenital Partial Absence of Pericardium: A Mimic of Arrhythmogenic Right Ventricular Cardiomyopathy.

Congenital absence of pericardium is a rare condition with electrocardiogram, chest X-ray, and echocardiographic findings which may mimic those of other cardiac conditions. We present a case of a 19-year-old asymptomatic female with incidental cardiomegaly on chest X-ray and electrocardiographic and echocardiographic changes, which meet the revised task force criteria for definite arrhythmogenic right ventricular cardiomyopathy but subsequently confirmed to have congenital partial absence of pericardium on cardiac magnetic resonance imaging.

A Review of Three Commonly Used Herbs Which Enhance Memory and New Evidences Which Show Their Combination Could Improve Memory in Young Animals.

BACKGROUND: This review looks into the herbs Gingko biloba, Polygala tenuifolia, and Lycii fructus for their widely studied neuroprotective properties. In particular, we investigated memory enhancing effect of these herbs, and their potential synergetic effect on memory with new data. Sixmonth treated mice demonstrated shorter escape latency in water maze and shorter arrival time in a consolidated memory task. Immunochemistry showed evident increase in superoxide dismutase activities in the prefrontal cortex, implying protection against free radicals during aging. Discrete increase of catecholaminergic neurons was found in the prefrontal cortex, hippocampus, corpus striatum, and midbrain, suggesting better memory and better control on mood and behavior. Necrotic cells in the brain decreased as indicated by immunocytochemistry of lactic dehydrogenase. Terminal deoxynucleotidyl transferase dUTP nick end labeling showed no apoptotic cells in most brain areas in high dose group. Biochemistry revealed increase of dopaminergic cells in treatment groups at prefrontal cortex, and in the hippocampus and cerebellum of the high dose group. Most 6-month groups showed increase of serotonin in all three areas. For the high dose group, GABA increased in the hippocampus but not prefrontal cortex, which would help induce sleep at night. Protein kinase C increased in most groups at prefrontal cortex, hippocampus and cerebellum, signifying increase of possible signal transduction pathways for memory or other nervous activations. CONCLUSION: Our results intimate that the interaction of the three herbs exerts beneficial effects on memory, associated cognitive function, and necrosis. Future investigations based on the present data shall aid development of clinically relevant medication.

Mutated tau, amyloid and neuroinflammation in Alzheimer disease-A brief review.

This review discussed the importance of mutated tau, amyloid and neuroinflammatory factors and microglia in Alzheimer disease. In particular tau, CD4 and TNF alpha were included in the review and the colocalizations of these factors were highlighted. It is important to realize the Alzheimer disease may result from the interactions of these factors. Some of these factors may coexist at the same region and at the same time e.g. mutated tau and amyloid in plaques. A summary scheme of etiology leading to the disease was included.

Mitsuokella Jalaludinii Supplementation Improved Nutrient Utilization of Broilers Fed Low-Available Phosphorus Diet

Phytase enzyme is supplemented to poultry feed to improve phosphorus (P) availability. Mitsuokella jalaludinii, bacteria isolated from the rumen of cattle, has been reported as a cheaper alternative source of phytase. As much nutrients are trapped within the phytate complex, we hypothesized that the supplementation of M. jalaludinii phytase to poultry feed would enhance nutrient utilization by poultry. In the current study, the efficacy of freeze-dried M. jalaludinii cells (Mj) as feed supplement for broilers fed low-available phosphorus (low-aP) diet was evaluated. Day-old male Cobb raised in battery cages were assigned to three treatment groups [normal-available phosphorus diet with heat-deactivated Mj (DMj); low-aP diet with DMj; and low-aP diet with Mj], each consisting of four replicates (10 birds per replicate) for a 3-weeks feeding period. Feed intake was recorded daily from day 1-21, whereas broilers were weighted at day 1, 7, 14, and 21. Total excreta were collected at day 11-13 and 18-20. At day 21, twelve broilers from each treatment group were slaughtered to collect plasma and tibia. The results showed that Mj significantly enhanced broilers live weight and feed conversion ratio compared to the control groups (p 0.05). Supplementation with Mj have also enhanced the level of P, Ca, Mn, Cu, and Zn in the sera; and Ca and Mn in the tibia at day 18-20 sampling period (p 0.05). As Mj supplementation can enhance nutrient utilization particularly in broilers fed with low-aP diet, it could provide the market with another option in improving broilers growth rate at a lower cost.(AU)

Mitsuokella Jalaludinii Supplementation Improved Nutrient Utilization of Broilers Fed Low-Available Phosphorus Diet

Phytase enzyme is supplemented to poultry feed to improve phosphorus (P) availability. Mitsuokella jalaludinii, bacteria isolated from the rumen of cattle, has been reported as a cheaper alternative source of phytase. As much nutrients are trapped within the phytate complex, we hypothesized that the supplementation of M. jalaludinii phytase to poultry feed would enhance nutrient utilization by poultry. In the current study, the efficacy of freeze-dried M. jalaludinii cells (Mj) as feed supplement for broilers fed low-available phosphorus (low-aP) diet was evaluated. Day-old male Cobb raised in battery cages were assigned to three treatment groups [normal-available phosphorus diet with heat-deactivated Mj (DMj); low-aP diet with DMj; and low-aP diet with Mj], each consisting of four replicates (10 birds per replicate) for a 3-weeks feeding period. Feed intake was recorded daily from day 1-21, whereas broilers were weighted at day 1, 7, 14, and 21. Total excreta were collected at day 11-13 and 18-20. At day 21, twelve broilers from each treatment group were slaughtered to collect plasma and tibia. The results showed that Mj significantly enhanced broilers live weight and feed conversion ratio compared to the control groups (p 0.05). Supplementation with Mj have also enhanced the level of P, Ca, Mn, Cu, and Zn in the sera; and Ca and Mn in the tibia at day 18-20 sampling period (p 0.05). As Mj supplementation can enhance nutrient utilization particularly in broilers fed with low-aP diet, it could provide the market with another option in improving broilers growth rate at a lower cost.

[Therapy of adult-onset laryngeal papilloma: integrallty submucosal dissection of the tumor by CO2 laser].

Objective: To evaluate the feasibility and efficacy of the integrallty submucosal resection of adult-onset laryngeal papilloma by CO2 laser. Methods: A group of 64 cases (36 males and 28 females, multipe lesions 54 cases and single lesion 10 cases, aged 18-75 years, mean age 43.13 years) with adult-onset laryngeal papilloma encountered in the first affliated hospital of Sun Yatsen university from 2009 to 2015 was retrospectively analyzed. All cases were treated with integrallty submucosal dissection of the tumor by CO2 laser, and observed the changes of tumor integral scope, inter-operative, operative processes, postoperative voice quality, postoperative scarring, and the tracheotomy conditions, which were analysed and evaluated. Results: A total of 64 patients were followed up from 1 year to 5 years. Preoperative tumor integral scope of these patients averaged of 7.00. A total of 62 cases kept 0 score of the tumor integral scope for at least one year, which lead to a clinical cure rate of 96.9%. The inter-operative averaged of 25.7 months. The total operative processes of these patients were 87 times (mean time 1.36). Four cases resulted in postoperative scarring. However these was a good result in postoperative voice quality with a mean score 4.25. As to the changes of tumor integral scope, all cases got a declining score (mean score 6.72), which resulted in a remission rate of 100%. Conclusion: The integrallty submucosal dissection of adult-onset 1aryngeal papilloma by CO2 laser was an effective way to reduce the tumor integral scope; lengthen their inter-operative; decrease the operative processes, avoid the occurrence of tracheotomy; and improve the postoperative voice quality. Most of the patients could even be cured ultimately.

Optimal low dosage of acetylsalicylic acid (ASA) for the prevention and treatment of ischemic cerebrovascular disease in geriatric patients.

A series of 108 geriatric patients with ischemic cerebrovascular disease were treated with low dose aspirin (acetylsalicylic acid, ASA). Daily doses of 100 mg, 50 mg and 25 mg were administered to three groups of 36 patients. Changes in platelet aggregation responses were dynamically observed in 64 (22 normal subjects, 42 patients). Monitoring of 22 normal subjects revealed inhibition of platelet aggregation at a dose of 300 mg or 100 mg which could last as long as 7 days. This suggests that 100 mg or less could be clinically effective. Satisfactory inhibitory effects on platelet aggregation were observed in all three groups, with 14 patients in each group given daily doses of 100 mg, 50 mg and 25 mg during four weeks' observation. The most effective inhibition was obtained in the 50 mg group. Therefore, the authors recommend 50 mg/d as the optimal dosage for low dose aspirin therapy in geriatric patients.

[Analysis of 59 cases of non-traumatic sudden death in various neurological diseases].

Sudden death is a common complication of myocardial infarction, necrotic pancreatitis and other diseases. Physicians usually neglect the possibility of neurological disorders. 59 cases of sudden death among 314 autopsied cases with neurological diseases were analyzed. The most frequent cause of neurological sudden death was cerebrovascular disease (CVD). It was present in 53 (89.9%) cases. 48 of them had hemorrhagic CVD. 37 of these 48 cases were due to hypothalamic lesions. In 37 cases general autopsy was performed; pathological abnormalities of heart, lungs, stomach etc, were found in 28 of them. In conclusion, the size and location of the lesion correlated with the prognosis of the disease. Concomitant multiple organ damage may deteriorate the lesion. Awareness of sudden death resulting from CVD may elevate the rate of correct diagnosis.

Three months of methoxetamine administration is associated with significant bladder and renal toxicity in mice.

UNLABELLED: CONTEXT.: Methoxetamine is a ketamine analogue that has recently emerged as a novel psychoactive substance. Chronic ketamine use is associated with significant bladder and renal toxicity. Methoxetamine has been marketed as "bladder friendly", but there is no data to be able to substantiate this claim. OBJECTIVE: To characterise the patterns of bladder and renal toxicity associated with 3 months of methoxetamine administration in an animal model. MATERIALS AND METHODS: Two-month-old Institute of Cancer Research mice were administered 30 mg/kg methoxetamine intraperitoneally (n = 5) or saline (n = 3 control) for 3 months. The animals were then sacrificed and histological examination, immuno-cytochemistry using polyclonal anti-CD4 antibodies and sirius-red staining for collagen were performed. RESULTS: The kidneys of methoxetamine-treated animals showed inflammatory cell infiltration, tubular cell necrosis and glomerular damage (1.9 ± 0.3% shrunken glomeruli in control, 9.8 ± 0.8% in methoxetamine-treated mice (p < 0.0001); 2.9 ± 0.3% tubular cell degeneration in control, 20.4 ± 1.1% in methoxetamine-treated mice (p < 0.0001)). There was a greater density of mononuclear cells in the bladder lamina propria and submucosa in methoxetamine-treated mice (43.0 ± 2.1 per 250 × 250 µm) than controls (7.1 ± 1.2 per 250 × 250 µm), p < 0.001. CD4-positive staining was seen in the bladder submucosa and lamina propria of all methoxetamine-treated mice and muscle-layer of two methoxetamine-treated mice; these changes were not seen in the control mice. There was an increase in sirius-red collagen in the bladder sub-mucosa and muscle-layer in the methoxetamine-treated mice compared with control mice. DISCUSSION: This study has shown that 3 months of daily 30 mg/kg intra-peritoneal methoxetamine results in significant bladder and renal toxicity in mice. Changes in the bladder included inflammatory changes with subsequent fibrosis and changes in the kidney were seen at both a tubular and glomerular level. These changes are similar to those seen in comparable animal models of chronic ketamine administration. Further work is required to determine the time course of the onset of these effects and whether the effects are reversible with methoxetamine cessation.

Long term ketamine and ketamine plus alcohol toxicity - what can we learn from animal models?

This review addressed the adverse effects of the frequently-used recreational drug, ketamine through using mice and monkey models. Our laboratory has documented initially that ketamine can induce the formation of hyperphosphorlated tau (hypertau), which is a hallmark of Alzheimer's disease (AD), in the cerebral cortex of both mice and monkeys as well as apoptosis in neurons in these species. Besides the cerebral cortex, other centers in the central nervous system (CNS) and peripheral nervous system (PNS) are also influenced by ketamine. Cerebellum was found to be down-regulated in both mice and humans after long-term of ketamine administration and it was caused by the apoptosis of Purkinje cells. Deleterious effects in other organs reported in long-term ketamine users include of kidney dysfunction leading to proteinuria, fibrosis of the urinary bladder and reduction in size of the urinary bladder leading to frequent urination, increase of liver fibrosis and cardiac problems such as premature ventricular beats. Moreover, ketamine is usually co-administrated with other chemicals such as caffeine or alcohol. It has been reported increased harmful effects when ketamine was used in combination with the above substances. Mechanisms of damages of ketamine might be due to 1) up-regulation of NMDA receptors leading to overestimation of glutamatergic system or 2) the metabolite of ketamine which was a hydroquinone exerted toxicity.

Intestinal and liver changes after chronic ketamine and ketamine plus alcohol treatment.

The effects of long-term chronic ketamine treatment on the intestine and the liver were studied in the ICR mice which had daily intraperitoneal injection of ketamine at 30 mg/kg per day for 7 months. The intestine showed no significant pathology after treatment but had a decrease of the positive sites of proliferative cell nuclear antigen in the mucosae of the intestines after ketamine and ketamine plus alcohol (added in the last month) treatment. No significant apoptosis (via TUNEL) nor necrosis (via lactic acid dehydrogenase) was detected in the intestines of all control and ketamine-treated groups, with the exception of an increase of lactic acid dehydrogenase in the mucosae of the intestines of the ketamine plus alcohol group. In the liver, loss of glycogen was observed in animals after ketamine and ketamine plus alcohol treatment, in addition to the pathology reported in a previous work. The decrease in quantity of glycogen in the liver reflected either a failure of glycogen synthesis from glucose or an increase of glycogenolysis in the liver.

Extract of white button mushroom affects skin healing and angiogenesis.

White button mushroom extract was examined in this study on (1) its potential effect on angiogenesis in chorioallantoic culture and (2) its recovering effect on the skin after injury in the ICR mice. Methods used included TUNEL assay on apoptosis, immunohistochemistry for vascular endothelial growth factor (VEGF), proliferative cell nuclear antigen (PCNA), epidermal growth factor (EGF), transforming growth factor ß (TGF-ß), and immune factor CD4 and western blotting. The results of chorioallantoic culture showed that the mushroom treatment led to significant increase in densities of VEGF sites. In the skin injury, ICR mice model increased EGF, PCNA, and collagen fibers, along with decrease of TUNEL positive apoptotic cells and limited reaction of TGF-ß and CD4 indicated that white button mushroom extract appeared to have beneficial effects on skin in regeneration and after injury.

Permanent deficits in brain functions caused by long-term ketamine treatment in mice.

Ketamine, an injectable anesthetic, is also a popular recreational drug used by young adults worldwide. Ketamine is a non-competitive antagonist of N-methyl-d-aspartate receptor, which plays important roles in synaptic plasticity and neuronal learning. Most previous studies have examined the immediate and short-term effects of ketamine, which include learning and cognitive deficits plus impairment of working memory, whereas little is known about the long-term effects of repeated ketamine injections of common or usual recreational doses. Therefore, we aimed to evaluate the deficits in brain functions with behavioral tests, including wire hang, hot plate and water maze tests, plus examine prefrontal cortex apoptotic markers, including Bax, Bcl-2 and caspase-3, in mice treated with 6 months of daily ketamine administration. In our study, following 6 months of ketamine injection, mice showed significant deterioration in neuromuscular strength and nociception 4 hours post-dose, but learning and working memory were not affected nor was there significant apoptosis in the prefrontal cortex. Our research revealed the important clinical finding that long-term ketamine abuse with usual recreational doses can detrimentally affect neuromuscular strength and nociception as part of measurable, stable and persistent deficits in brain function.

How would composite traditional Chinese medicine protect the brain--an example of the composite formula "Pien Tze Huang".

Chinese medicine has a long history of several thousand years. The main form of Traditional Chinese Medicine (TCM) is composite, i.e. a mixture of up to 10 medicinal products. Thus a composite prescription of 4-5 kinds of Chinese medicinal products may contain several hundred kinds of chemical composition. The active ingredients and clinical efficacy of which are difficult to characterize. We aim to review the Chinese literature of TCMs with neuroprotective effects. We illustrate with our study on Pien Tze Huang (PZH) the use of in vivo tests in the study of composite TCM. Our results show evidence that PZH might have neuropreventive effects in rats.