Enhancing medical education in respiratory diseases: efficacy of a 3D printing, problem-based, and case-based learning approach.

OBJECTIVES: The present study aims to investigate the efficacy of utilizing three-dimensional (3D) printing technology in concert with Problem-Based Learning (PBL) and Case-Based Learning (CBL) pedagogical approaches in educating senior undergraduate clinical medical students on respiratory diseases. METHODS: A cohort of 422 fourth-year clinical medicical students of from Anhui Medical University, pursuing a five-year program, were arbitrarily segregated into two distinct groups. The experimental group was subjected to a combined pedagogical approach, which included 3D printing technology, PBL and CBL (referred to as DPC). Conversely, the control group was exposed to conventional teaching methodologies for respiratory disease education. The effectiveness of the teaching methods was subsequently appraised using both theoretical test scores and custom questionnaires. RESULTS: Post-quiz scores indicated a statistically significant improvement in the DPC group as compared to the traditional group (P < 0.01). Self-evaluation and satisfaction questionnaires revealed that the DPC group's self-assessment scores outperformed the traditional group in several aspects, including clinical thinking ability, learning initiative, self-study ability, anatomical knowledge mastery, confidence in learning, ability to analyze and solve problems, comprehension of the knowledge, help to clinical thinking and level of satisfaction on the teaching methods (P < 0.01). However, within the unsatisfied DPC sub-group, none of these self-assessment aspects, except for comprehension of the knowledge, impacted the learning efficacy (P > 0.05). CONCLUSION: The deployment of the DPC pedagogical approach may confer unique experiential learning opportunities for students, potentially enhancing theoretical test scores and promoting self-evaluation and satisfaction in the context of respiratory disease education. Hence, it may be instrumental in augmenting the overall teaching efficacy.

Sarcoidosis Stage II: a Case Report and Review of the Literature.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown origin characterized by non-caseous necrotizing epithelial cell granuloma that affects the lung and lymphatic system. Sarcoidosis mainly occurs in young and middle-aged people, usually manifested as bilateral hilar lymph node enlargement, lung infiltration, and eye and skin lesions. Sarcoidosis has a high natural remission rate, but patients with progressive imaging or pulmonary function accompanied by significant clinical symptoms or extrapulmonary lesions need to be treated. METHODS: The sarcoidosis patient had received a 3-month methylprednisolone treatment which significantly improved clinical manifestations including cough and sputum, and extrapulmonary presentation, such as skin nodules and enlargement of parotid glands. RESULTS: A 52-year-old female reporting repeated cough and sputum, with scattered skin rashes and nodules on the extremities, accompanied by nasal congestion, enlargement of abdominal and retroperitoneal lymph nodes and parotid glands was studied. Computed tomography (CT) showed miliary nodules diffusely distributed in both lungs, multiple enlarged lymph nodes in mediastinum, bilateral enlarged hilar lymph nodes, and right pleural effusion. Bronchoscopy with lung biopsy showed granuloma formation, special staining including acid resistance was negative, but signet ring cell carcinoma and tuberculosis cannot be excluded. Biopsy of a skin nodule also showed granulomatosis. PET-CT reported all considered as inflammatory lesions, with a high possibility of tuberculosis. Based on all the information, we confirmed the diagnosis of sarcoidosis stage II. She was then successfully treated with a steroid monotherapy, which resulted in a satisfactory clinical outcome without serious complications. CONCLUSIONS: Clinical manifestations of this patient are unspecific. Based on the pathological finding, clinical and radiological manifestation, and evidence of no alternative diseases, sarcoidosis stage II is diagnosed. Treatment with a steroid was of benefit in this sarcoidosis patient.

Histone deacetylase-2 expression and activity in children with nephrotic syndrome with different glucocorticoid response.

BACKGROUND: Glucocorticosteroid (GC) is one of the most effective drugs available for the treatment of primary nephrotic syndrome (PNS) in children. However, some patients show little or no response to GC. The purpose of our research was to observe and describe the different levels of histone deacetylase-2 (HDAC2) expression in peripheral blood lymphocytes in children with PNS compared with various responses to the GC treatment, with the primary aim to assess the correlation between HDAC2 and GC resistance in PNS children. METHODS: Forty-eight patients with PNS suffering from their first attack prior to GC treatment were chosen as subjects. They were divided into two groups, those who had steroid-sensitive nephrotic syndrome (SSNS; n = 25) and those with steroid-resistant NS (SRNS; n = 23), according to their response to a 6-week course of oral prednisone. Twenty healthy children from the Physical Examination Center in the hospital served as the control group; Peripheral blood was collected at different time points prior to GC treatment and after regular therapy. RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA) techniques were adopted to analyze HDAC2 mRNA, protein expression, and activity, respectively, in peripheral blood lymphocytes. The level of interleukin-8 (IL-8) in serum was measured by an ELISA. RESULTS: Prior to GC treatment, HDAC2 expression level and activity were lower in the SRNS group than in the SSNS and control group. A statistically significant difference in HDAC2 expression and activity were observed after GC treatment between these groups, with HDAC2 expression and activity lower in the SRNS group than in the SSNS and control groups. In the SSNS group, the expression and activity of HDAC2 were higher following GC treatment than prior to GC treatment. There was a clear difference in HDAC2 expression and activity of SRNS at the different time points. No statistically significant difference was found between the two groups. The pre-treatment and post-treatment serum IL-8 levels in the SRNS group were significantly higher than those in the SSNS group. HDAC2 from children with PNS before GC treatment and after regular therapy for 6 weeks was negatively correlated with serum IL-8 level. CONCLUSION: The GC effect was influenced by the HDAC2 expression and activity, leading to decreased serum IL-8 levels in children with PNS. HDAC2 seems to be one of the markers of GC resistance in children with PNS.

Invasive pulmonary aspergillosis accompanied by soft tissue lesions during treatment of a patient with hyperthyroidism: a case report.

Invasive pulmonary aspergillosis (IPA) is difficult to diagnose because it requires histopathology and tissue culture, as well as due to its rapid progression. Invasive pulmonary aspergillosis is the primary cause of pulmonary mycosis in China, which can occur in patients with neutrophil deficiency, leukaemia or lymphoma, malignant tumours, or chronic obstructive pulmonary disease with long-term corticosteroid use or bacterial exacerbations. Such fungal infections can lead to disseminated disease and death within weeks, and the mortality rate for untreated invasive aspergillosis is high. Therefore, increased awareness of invasive aspergillosis in non-traditional hosts is warranted due to the high mortality rate experienced by patients with this disease. Invasive pulmonary aspergillosis has become a principal cause of life-threatening infections in immunocompromised patients. Invasive aspergillosis frequently involves the lung parenchyma and is infrequently accompanied by soft tissue lesions. We present an unusual case of a patient with agranulocytosis that was caused by methimazole that was given to control his hyperthyroidism, and IPA that was accompanied by unusual maxillofacial soft tissue swelling that required treatment with voriconazole. Upon follow-up 11 months later, a chest computed tomography scan (CT) revealed that most lesions had been completely absorbed. Moreover, his maxillofacial ulcers had become encrusted, and the soft tissue swelling had subsided.

Engineered myocardial tissues constructed in vivo using cardiomyocyte-like cells derived from bone marrow mesenchymal stem cells in rats.

BACKGROUND: To explore the feasibility of constructing engineered myocardial tissues (EMTs) in vivo, using polylactic acid -co-glycolic acid (PLGA) for scaffold and cardiomyocyte-like cells derived from bone marrow mesenchymal stem cells (BMMSCs) for seeded cells. METHODS: BMMSCs were isolated from femur and tibia of Sprague-Dawley (SD) rats by density-gradient centrifugation. The third passage cells were treated with 10 µmol/L 5-azacytidine (5-aza) and 0.1 µmol/L angiotensin II (Ang II) for 24 h, followed by culturing in complete medium for 3 weeks to differentiated into cardiomyocyte-like cells. The cardiomyocyte-like cells were seeded into PLGA scaffolds to form the grafts. The grafts were cultured in the incubator for three days and then implanted into the peritoneal cavity of SD rats. Four weeks later, routine hematoxylin-eosin (HE) staining, immunohistochemical staining for myocardium-specific cardiac troponin I (cTnI), scanning electron microscopy and transmission electron microscopy were used to analyze the morphology and microconstruction of the EMTs in host rats. RESULTS: HE staining showed that the cardiomyocyte-like cells distributed equally in the PLGA scaffold, and the nuclei arranged in the spindle shape. Immunohistochemical staining revealed that majority of engrafted cells in the PLGA -Cardiomyocyte-like cells group were positive for cTnI. Scanning electron microscopy showed that the inoculated cells well attached to PLGA and grew in 3 dimensions in construct. Transmission electron microscopy showed that the EMTs contained well arranged myofilaments paralleled to the longitudinal cell axis, the cells were rich in endoplasmic reticulum and mitochondria, while desmosomes, gap junction and Z line-like substances were also can be observed as well within the engrafted cells. CONCLUSION: We have developed an in vivo method to construct engineered myocardial tissue. The in vivo microenvironment helped engrafted cells/tissue survive and share similarities with the native heart tissue.

The combination of angiotensin II and 5-azacytidine promotes cardiomyocyte differentiation of rat bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMMSCs) are ideal seed cells for tissue engineering and regenerative medicine. Many studies have shown that 5-azacytidine (5-aza) can induce BMMSCs to differentiate into cardiomyogenic cells, but some issues still remain to be resolved. In this study, we investigated the effects of angiotensin II (Ang II) on the proliferation and differentiation of BMMSCs induced by 5-aza in vitro. BMMSCs were isolated from the bone marrow of Sprague-Dawley rats by density gradient centrifugation. The third-passage cells were divided into four groups: the Ang II group (0. 1 µmol/l) (group A), the 5-aza group (10 µmol/l) (group B), the Ang II combined with 5-aza group (0.1 and 10 µmol/l) (group C), and the untreated group as control. After 24 h of induction, the medium was changed to the complete culture medium without any inductor, and the cells were cultured for 3 weeks. Morphological changes were observed under a phase contrast microscope. The effect of Ang II and 5-aza on BMMSC proliferation was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. Cardiomyogenic cells were identified through immunofluorescence staining, and the induction ratio was examined by flow cytometry. The level of cardiac troponin I (cTnI) was examined by western blotting, and the ultrastructures of the induced cells were viewed with a transmission electron microscope. The MTT assay showed that the cell proliferation in group C outweighed that in either group A or group B, but no significant difference existed between group A and group B. The expression of specific proteins, namely, cTnI and sarcomeric α-actin in induced BMMSCs was verified as positive. Flow cytometry showed that the induction ratio in group C was higher than that in group A or group B. The protein levels of cTnI in groups A, B, and C were significantly higher than those in the control group. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions. Angiotensin II and 5-azacytidine can promote the proliferation and differentiation of BMMSCs into cardiomyocyte-like cells.

Decreased expression of Beclin-1 and LC3 in human lung cancer.

Autophagy, a conversed response to stress, has recently been studied in human cancers. Two important autophagic genes-Beclin-1 and LC3 are reported in several human cancers. However, the expressions of Beclin-1 and LC3 in lung cancer have not yet been investigated. In the present study, we investigated the expression of Beclin-1 and LC3, and the relationship between the expression profile and the clinical or pathological changes in human lung cancer. 40 primary lung cancer patients are involved in present study. mRNA expressions of Beclin-1 and LC3-II were detected by Real Time PCR and the protein levels were assessed by immunohistochemistry and western blot. Relative lower expressions of Beclin-1 and LC3-II mRNA were found in the lung cancer tissues compared to counterpart normal tissues. Consistently, the lower amount of Beclin-1 and LC3-II protein was found in lung cancer tissues. However, the expressions of Beclin-1 and LC3-II in lung cancer tissues were not affected by patients' age, gender, smoking, histological type, lymph node metastasis and tumor-node-metastasis (TNM) stage. Both mRNA and protein levels of Beclin-1 and LC3-II were significantly decreased in lung cancer tissues which suggested that autophagy may be involved in the pathogenesis of lung cancer.

Emotion Recognition Algorithm Application Financial Development and Economic Growth Status and Development Trend.

Financial market and economic growth and development trends can be regarded as an extremely complex system, and the in-depth study and prediction of this complex system has always been the focus of attention of economists and other scholars. Emotion recognition algorithm is a pattern recognition technology that integrates a number of emerging science and technology, and has good non-linear system fitting capabilities. However, using emotion recognition algorithm models to analyze and predict financial market and economic growth and development trends can yield more accurate prediction results. This article first gives a detailed introduction to the existing financial development and economic growth status and development trend forecasting problems, and then gives a brief overview of the concept of emotion recognition algorithms. Then, it describes the emotion recognition methods, including statistical emotion recognition methods, mixed emotion recognition methods, and emotion recognition methods based on knowledge technology, and conducts in-depth research on the three algorithm models of statistical emotion recognition methods, they are the support vector machine algorithm model, the artificial neural network algorithm model, and the long and short-term memory network algorithm model. Finally, these three algorithm models are applied to the financial market and economic growth and development trend prediction experiments. Experimental results show that the average absolute error of the three algorithms is below 25, which verifies that the emotion recognition algorithm has good operability and feasibility for the prediction of financial market and economic growth and development trends.

Circ_0016760 Acts as a Sponge of MicroRNA-4295 to Enhance E2F Transcription Factor 3 Expression and Facilitates Cell Proliferation and Glycolysis in Non-Small Cell Lung Cancer.

Background: Circular RNAs (circRNAs) have been validated as important regulators of non-small cell lung cancer (NSCLC), but the role and potential mechanism of circ_0016760 in NSCLC remain largely unclear. Materials and Methods: Quantitative real-time polymerase chain reaction was performed to detect the levels of circ_0016760, microRNA-4295 (miR-4295), and E2F transcription factor 3 (E2F3). The cell proliferation was measured by methyl-thiazolyl diphenyl-tetrazolium bromide assay. The protein levels of proliferating cell nuclear antigen and E2F3 were examined by Western blot. Xenograft mice model was constructed to explore the effect of circ_0016760 on tumor growth in vivo. The relationship among circ_0016760, miR-4295, and E2F3 was evaluated using dual-luciferase reporter assay. Glucose consumption of NSCLC cells was assessed by the glucose assay kit. Results: Circ_0016760 and E2F3 expression levels were upregulated in NSCLC tissues and cells, while miR-4295 was downregulated. Circ_0016760 could bind to miR-4295, and negatively modulate its expression in NSCLC cells. Besides, miR-4295 directly targeted E2F3 and inversely regulated E2F3 expression. More importantly, Circ_0016760 facilitated proliferation and glycolysis of NSCLC cells by increasing E2F3 by sponging miR-4295 as well as promoted the tumor growth in vivo. Conclusion: Circ_0016760 served as a growth-promoting circRNA in NSCLC by facilitating cell proliferation and glycolysis by regulating the miR-4295/E2F3 axis, providing a novel potential target for NSCLC treatment.

Excellent response of lung adenocarcinoma harboring a rare SLC8A1 downstream intergenic region ALK fusion to ceritinib treatment: A case report.

RATIONALE: Anaplastic lymphoma kinase (ALK) gene fusion, an important driver gene alteration leading to the development of lung cancer, occurs in 5% of nonsmall cell lung cancer (NSCLC) cases in China. In addition to echinoderm microtubule-associated protein-like 4 (EML4)-ALK, which is the most common type of ALK fusion, various fusion partner genes have been identified in recent years. However, ALK intergenic breakpoint fusions confound fusion detection and targeted treatment. PATIENT CONCERNS: A 40-year-old woman presented to our hospital with a 2-month history of a cough. DIAGNOSIS: Based on the right hilar lymph node biopsy and positron emission tomography computed tomography (PET-CT) examination, the patient was diagnosed with "stage IV lung adenocarcinoma" showing metastases in the mediastina, right hilar lymph nodes, and C7 vertebral body. A rare solute carrier family 8 member A1 (SLC8A1) downstream intergenic region ALK fusion was identified in biopsy specimens using next-generation sequencing (NGS). INTERVENTIONS: The patient received first-line molecular-targeted therapy (ceritinib). OUTCOMES: After nearly 9 months, the best evaluation of partial remission (PR) was obtained. LESSONS: This is the first clinical evidence of advanced NSCLC due to a rare SLC8A1 downstream intergenic region ALK fusion that has been effectively treated with ceritinib. Whether this finding represents an inherent property of this fusion protein or its unique clinicopathological characteristics in patients carrying this fusion protein remains to be investigated. Moreover, the patient's durable response to ceritinib and future resistance mechanisms require further follow-up.

Inhibition of p53-p21 pathway promotes the differentiation of rat bone marrow mesenchymal stem cells into cardiomyocytes.

P53 is shown recently to play an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells (BMMSCs). In this study, by inhibiting p53-p21 pathway with p53 inhibitor (p-fifty three inhibitor-alpha, PFT-α), we investigated the resulting effects on the differentiation of rat BMMSCs into cardiomyocyte-like cells. BMMSCs were isolated from bone marrow of SD rats by density gradient centrifugation. The fourth passage cells were divided into four groups: control group, PFT-α group, 5-AZA group, and PFT-α + 5-AZA group. The purified BMMSCs were identified by surface antigens and the proliferation and apoptosis of BMMSCs were examined by MTT and flow cytometry analysis. The expression of cTnI and CX-43 in BMMSCs after induction was detected by immunofluorescence and that of cTnI, p53, and p21 was detected by western blot. Our results demonstrated that PFT-α at 20 µmol/l significantly reduced the apoptosis and promoted the proliferation of BMMSCs, and induced BMMSCs to differentiate into cardiomyocyte-like cells. In conclusion, these data open up new possibility of modulating p53-p21 pathway for directed differentiation of BMMSCs into cardiomyocytes, which will be valuable for cardiovascular regenerative medicine.

Alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA is regulated by SRp40.

Increasing evidence indicates that alternative splicing of human glucocorticoid receptor (GR) transcripts is implicated in the development of glucocorticoid resistance but the underlying mechanism was not well known. Serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 play an important role in the spliceosome assembly. In this study, we analyzed the effects of different SR proteins and hnRNP A1 on the alternative splicing of GR pre-mRNA in HeLa and 293T cells using a minigene transfection assay. Our results revealed that only SRp40 could induce a GRalpha to GRbeta shift of pre-mRNA splicing in exon 9 in HeLa cells and this effect induced by SRp40 was further confirmed by small interfering RNA study. However, in 293T cells, SRp40 could not induce this shift. These results indicated that SRp40 may influence the alternative splicing of GR pre-mRNA to regulate the ratio of GRalpha to GRbeta, and this effect is cell-dependent.

TLR9 mediates the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation.

Toll-like receptor 9 (TLR9) has been reported to mediate airway inflammation, however, the underlying mechanism is poorly understood. In the present study, our objective was to reveal whether TLR9 regulates NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation and Raw264.7 cells. Female wild type(WT)and TLR9-/-mice on C57BL/6 background were used to induce allergic airway inflammation by challenge of OVA, and Raw264.7 cells with or without TLR9 knockdown by small interfering RNA (siRNA) were stimulated by S.aureus. The results demonstrated that deletion of TLR9 effectively attenuated OVA-induced allergic airway inflammation including inflammatory cells infiltration and goblet cell hyperplasia. Meanwhile, OVA-induced protein expression of NLRP3, caspase-1(p20) and mature IL-1ß, as well as secretion of IL-1ß and IL-18 in wild type mice (WT) was obviously suppressed by TLR9 deficiency. Concomitantly, the expression of oxidative markers 8-OhDG and nitrotyrosine was increased in OVA-challenged WT mice, while TLR9 deficiency significantly inhibited such increase. Similarly, in the in vitro study, we found that knockdown of TLR9 markedly suppressed S.aureus-induced activation of NLRP3 inflammasome and oxidative stress in Raw264.7 cells. Collectively, our findings indicated that TLR9 may mediate allergic airway inflammation via activating NLRP3 inflammasome and oxidative stress.

TLR2 favors OVA-induced allergic airway inflammation in mice through JNK signaling pathway with activation of autophagy.

AIMS: Numerous studies indicate that toll-like receptor 2 (TLR2) led to divergent effects in asthma. The occurrence of autophagy in asthma pathogenesis is still incompletely understood. Here, we aimed to investigate the role of TLR2 and the underlying mechanisms in allergic airway inflammation and autophagy activation. MAIN METHODS: C57BL/6 and TLR2 knockout (TLR2-/-) mice were subjected to an ovalbumin (OVA)-immunized allergic airway model, and were treated with SP600125. Differential cell counts in bronchoalveolar lavage fluid were determined by Wright's staining. Histological analysis of airway inflammation was determined by haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. The levels of OVA-specific immunoglobulin E (IgE), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme-linked immunosorbent assay (ELISA). Proteins expression in lung tissues was detected by western blot, expression of TLR2 was further observed by immunofluorescence. Autophagy activation was determined by western blot and transmission electron microscopy (TEM). KEY FINDINGS: TLR2 expression was increased upon OVA challenge, and TLR2 deficiency was associated with decreased allergic airway inflammation. Meanwhile, TLR2 deficiency weakened autophagy activation. Moreover, inhibition of c-Jun N-terminal kinase (JNK) by SP600125 also suppressed OVA-induced allergic airway inflammation and autophagy activation. Interestingly, treating TLR2-/- mice with SP600125 showed similar OVA-induced allergic airway inflammation and autophagy activation compared to that in vehicle-treated TLR2-/- mice. SIGNIFICANCE: TLR2 might contribute to the maintenance of allergic airway inflammation through JNK signaling pathway accompanying with autophagy activation. These findings may provide a novel signal target for prevention of allergic airway inflammation.

Several interleukin-4 and interleukin-13 gene single nucleotide polymorphisms among Chinese asthmatic patients.

Asthma is a common respiratory disease associated with airway hyperactivity and high total serum immunoglobulin E (IgE) levels. The asthmatic phenotypes are widely considered to be caused by environmental effects on genetically predisposed individuals. Interleukin (IL)-4 and IL-13 act on B cells and regulate the IgE production, and the single nucleotide polymorphisms (SNPs) in the IL-4 and IL-13 genes are implicated in the pathogenesis of asthma. To study the association of IL-4 and IL-13 gene polymorphisms with asthma, we sequenced the promoter regions and exons of IL-4 and IL-13 genes in two groups: one (spouses group) consisted of 13 pairs of asthmatic patients (cases) and their unaffected spouses (controls); the other (parents group) consisted of 11 pairs of asthmatic children (cases) and their unaffected father/mother (controls). In total, seven polymorphisms were identified, one novel and six previously reported. However, according to the results of the statistical analysis we performed, no statistically significant association of these SNPs and asthma was observed (p > 0.05). Asthma is largely determined by the accumulation of several certain genetic variations other than one or two SNPs. Future function studies may be able to help us reveal the significance of genetic variants we identified in this study.

Targeting the BDNF/TrkB pathway for the treatment of tumors.

Neurotrophins are a family of growth factors that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4. Among them, BDNF is the most studied due to its high expression in the brain. Over the past two decades, BDNF and its receptor tropomyosin receptor kinase B (TrkB) have been reported to be upregulated in a wide range of tumors. This activated signal stimulates a series of downstream pathways, including phosphoinositide 3-kinase/protein kinase B, Ras-Raf-mitogen activated protein kinase kinase-extracellular signal-regulated kinases, the phospholipase-C-γ pathway and the transactivation of epidermal growth factor receptor. Activation of these signaling pathways induces oncogenic effects by increasing cancer cell growth, proliferation, survival, migration and epithelial to mesenchymal transition, and decreasing anoikis, relapse and chemotherapeutic sensitivity. The present review summarizes recent findings to discuss the role of BDNF in tumors, the underlying molecular mechanism, targeting Trk receptors for treatment of cancers and its potential risk.

Mifepristone repairs region-dependent alteration of synapsin I in hippocampus in rat model of depression.

Clinical investigations present much evidence that the glucocorticoid receptor (GR) antagonist mifepristone leads to a rapid amelioration of depression. The molecular mechanisms of mifepristone involved in the treatment of depression are not fully understood. Depression is associated with hippocampal plasticity, for which increased excitatory amino acid (EAA) release in CA3 induced by chronic stress is responsible, and glucocorticoids have a permissive role and act synergistically with EAAs in producing neuronal damage. Moreover, glucocorticoids increase synapsin I, which has a key role in the release of neurotransmitter, including EAAs. Hereby, we hypothesize that major depression involves synapsin I alteration and that mifepristone blocks this alteration. In the present study, we observed both the expression of hippocampal synapsin I and depression-associated behavior in a rat model of depression induced by chronic unpredictable mild stress (CUMS). The result showed that a region-dependent synapsin I alteration occurs in the rat hippocampus after 21 days of CUMS, that is, it increases in dentate gyrus (DG)/CA3 and decreases in the CA1 region. Correlation analysis indicated that the decrease of synapsin I in CA1 is highly correlated with the increase in the DG/CA3 subfield. Simultaneously, the region-dependent alteration of synapsin I is correlated with depression-associated behaviors. Both the alteration of synapsin I and the depression-associated behavior were rapidly restored after treatment with mifepristone for 1 week. The result suggests that the molecular mechanism underlying the treatment of depression with mifepristone is associated with the rapid repair of the synaptic alteration.

Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia.

Recent studies have demonstrated that lithium has a neuroprotective effect against brain ischemia. Whether this effect is mediated by hippocampal neurogenesis remains unknown. The ERK (extracellular signal-regulated kinase) pathway plays an essential role in regulating neurogenesis. The present study was undertaken to investigate whether lithium regulates hippocampal neurogenesis by the ERK pathway and improves spatial learning and memory deficits in rats after ischemia. Rats were daily injected with lithium (1 mmol/kg) and 2 weeks later subjected to 15-min ischemia induced by four-vessel occlusion method. 5-bromo-2'-deoxyuridine (Brdu; 50mg/kg) was administrated twice daily at postischemic day 6, or for 3 days from postischemic day 6 to 8. We found that lithium increased the ERK1/2 activation after ischemia by western blotting analysis. There was a significant increase in Brdu-positive cells in the hippocampal dentate gyrus after lithium treatment, compared with ischemia group at postischemic days 7 and 21; furthermore, the survival rate of Brdu-positive cells was elevated by lithium. Inhibition of the ERK1/2 activation by U0126 diminished these effects of lithium. The percentages of Brdu-positive cells that expressed a neuronal marker or an astrocytic marker were not significantly influenced by lithium. Moreover, lithium improved the impaired spatial learning and memory ability in Morris water maze, and U0126 attenuated the behavioral improvement by lithium. These results suggest that lithium up-regulates the generation and survival of new-born cells in the hippocampus by the ERK pathway and improves the behavioral disorder in rats after transient global cerebral ischemia.

Lithium improves the behavioral disorder in rats subjected to transient global cerebral ischemia.

Previous study has indicated that chronic treatment with lithium protects brain against ischemic injury by reducing apoptotic death. To investigate whether lithium improves the behavioral disorder induced by transient global cerebral ischemia, we examined the effects of lithium treatment on the performance of rats in a set of behavioral tests, i.e. beam balance, elevated plus maze (EPM), open field and Morris water maze. Our results showed that lithium attenuated the worse general 'well-being' and the worse performance in beam balance, and hyperactivity in EPM and open field, including increased open arm entries, time spent in the open arms, squares crossed, rearing and grooming over 7 days after 15min ischemia, which were induced by four-vessel occlusion in Sprague-Dawley rats. Moreover, lithium improved the injured spatial learning and memory ability in Morris water maze at post-ischemic days 8 and 9. Histological analysis displayed that it decreased obviously cell death in hippocampal CA1 region. Our study further confirmed the protective role of lithium in the ischemia-reperfusion injury and suggested that lithium might be a helpful therapeutic approach to the treatment of stroke combining with other neuroprotective agents.

Sequential invasive-noninvasive mechanical ventilation weaning strategy for patients after tracheostomy.

BACKGROUND: Because the continuity and integrity of the trachea are likely damaged to some extent after tracheostomy, the implementation of sequential ventilation has certain difficulties, and sequential invasive-noninvasive ventilation on patients after tracheostomy is less common in practice. The present study aimed to investigate the feasibility of invasive-noninvasive sequential weaning strategy in patients after tracheostomy. METHODS: Fifty patients including 24 patients with withdrawal of mechanical ventilation (conventional group) and 26 patients with sequential invasive-noninvasive weaning by directly plugging of tracheostomy (sequential group) were analyzed retrospectively after appearance of pulmonary infection control (PIC) window. The analysis of arterial blood gases, ventilator-associated pneumonia (VAP) incidence, the total duration of mechanical ventilation, the success rate of weaning and total cost of hospitalization were compared between the two groups. RESULTS: Arterial blood gas analysis showed that the sequential weaning group was better than the conventional weaning group 1 and 24 hours after invasive ventilation. The VAP incidence was lowered, the duration of mechanical ventilation shortened, the success rate of weaning increased, and the total cost of hospitalization decreased. CONCLUSION: Sequential invasive-noninvasive ventilator weaning is feasible in patients after tracheostomy.