A morphine reward generalization mouse model based on conditioned place preference and aversion.

BACKGROUND: Conditioned place preference (CPP) is a common behavioral paradigm for studying the association of unconditioned stimulus reward memory with context. Generalization is a flexible memory recall pattern developed on the basis of original memory. Drug-seeking behaviors in substance use disorders (SUDs) exhibit diversity, which we generally attribute to the highly generalized features of SUD memory. However, to date, there are no animal models for SUD generalization studies. METHODS: We design the generalization box (G-box) and the generalization retrieval process based on the conditioned place preference (CPP) model. In the memory retrieval stage, we replaced the conditioning CPP box (T-box) with a generalization box (G-box) to study drug generalization memory. For appearance, the generalized boxes have different angles and numbers of sides compared to the conditioning boxes. For the visual cues, the shapes of the symbols are different (triangle icons for the hexagonal chamber and dot icons for the round chamber), but the orientation information remains the same. To establish CPP generalization, the mice received morphine on the vertical or horizontal side of a conditioning box (T-box) and saline on the other side. Then, after CPP conditioning, the generalization test was performed in a generalization box (G-box: hexagonal chamber and Gr-box: round chamber) 21 days later. RESULTS: CPP-conditioned mice still displayed a clear preference for similar visual information in the G-box. CPA-conditioned mice behaved similarly to CPP, with mice consistently avoiding similar visual information in the G-box. We further observed that the generalization results are similar using two generalization boxes (G-box and Gr-box). CONCLUSION: In this study, we succeeded in creating a simple and effective generalization model for morphine reward. The establishment of this model provides a new tool for generalization studies of SUD and therapy in humans.

SNAI2 Attenuated the Stem-like Phenotype by Reducing the Expansion of EPCAMhigh Cells in Cervical Cancer Cells.

SNAI2 (Snai2) is a zinc-finger transcriptional repressor that belongs to the Snail family. The accumulated evidence suggests that SNAI2 exhibits biphasic effects on regulating a stem-like phenotype in various types of cells, both normal and malignant. In this study, by exogenously expressing SNAI2 in SiHa cells, SNAI2 exhibited the capacity to inhibit a stem-like phenotype in cervical cancer cells. The SNAI2-overexpressing cells inhibited cell growth, tumorsphere formation, tumor growth, enhanced sensitivity to cisplatin, reduced stem cell-related factors' expression, and lowered tumor initiating frequency. In addition, the EPCAMhigh cells sorted from SiHa cells exhibited an enhanced capacity to maintain a stem-like phenotype. Further study demonstrated that the trans-suppression of EPCAM expression by SNAI2 led to blockage of the nuclear translocation of ß-catenin, as well as reduction in SOX2 and c-Myc expression in SiHa and HeLa cells, but induction in SNAI2 knockdown cells (CaSki), which would be responsible for the attenuation of the stem-like phenotype in cervical cancer cells mediated by SNAI2. All of these results demonstrated that SNAI2 could attenuate the stem-like phenotype in cervical cancer cells through the EPCAM/ß-catenin axis.

Achilles tendon thickening does not affect elasticity and functional outcome after surgical repair of Achilles rupture: A retrospective study / 中华创伤杂志(英文版)

PURPOSE@#Previous studies have confirmed that Achilles tendon occurs Achilles thickening after repair surgery of the rupture. Although this mechanism has been elucidated in the laboratory, there are few reports on its impact on clinical function. We designed a retrospective study to investigate the Achilles thickening after Achilles tendon rupture repair and its correlation between the elasticity and postoperative function.@*METHODS@#In this retrospective analysis, patients who underwent surgical treatment for acute Achilles tendon rupture from April 2016 to April 2020 were included. All the patients were regularly followed up at 3 months, 1 year, and 2 years after surgery. American Orthopaedic Foot Ankle Surgeon (AOFAS) scale and Leppilahti score were used to evaluate functional outcomes. Achilles elasticity was measured by ultrasound shear wave of elasticity. Achilles thickening was calculated as maximal transverse and longitudinal diameter in cross-sectional plane of magnetic resonance scan. Sample t-tests was used for different follow-up periods. Correlation between Achilles thickening and other factors were analyzed using Pearson's method. p < 0.05 indicates a statistically significant difference.@*RESULTS@#AOFAS scale and Leppilahti score at 1 year were significantly higher than at 3 months postoperatively (both p < 0.001). These functional scales were also improved at 2-year follow-up significantly (both p < 0.001). The dorsiflexion difference showed gradually recovery in each follow-up period (t = -17.907, p < 0.001). The elasticity of the Achilles appeared to continuously decreases during the postoperative follow-up period in all position sets (p < 0.001). In thickening evaluation, the cross-sectional area of the thickest plane of Achilles was significantly higher at 1 year postoperatively (310.5 ± 25.2) mm2 than that at 3 months postoperatively ((278.0 ± 26.2) mm2, t = -8.219, p < 0.001) and became thinner in 2-year magnetic resonance scan ((256.1 ± 15.1) mm2, t = 16.769, p < 0.001). The correlations between Achilles thickening, elasticity, and functional outcome did not show statistical significance (p > 0.05) in every follow-up period.@*CONCLUSION@#Achilles tendon thickens after surgery in the 1st year, but begins to gradually return to thinning about 2 years after surgery. There was no significant correlation between the increase and decrease of thickening and the patients' clinical function scores, Achilles elasticity, and bilateral ankle dorsiflexion difference.

High Morphine Use Disorder Susceptibility Is Predicted by Impaired Learning Ability in Mice.

An obvious reason for substance uses disorders (SUDs) is drug craving and seeking behavior induced by conditioned context, which is an abnormal solid context memory. The relationship between susceptibility to SUD and learning ability remains unclear in humans and animal models. In this study, we found that susceptibility to morphine use disorder (MUD) was negatively correlated with learning ability in conditioned place preference (CPP) in C57 mice. By using behavioral tests, we identified the FVB mouse as learning impaired. In addition, we discovered that learning-relevant proteins, such as the glutamate receptor subunits GluA1, NR1, and NR2A, were decreased in FVB mice. Finally, we assessed the context learning ability of FVB mice using the CPP test and priming. We found that FVB mice had lower learning performance with respect to normal memory but higher performance of morphine-reinstatement memory. Compared to C57 mice, FVB mice are highly sensitive to MUDs. Our results suggest that SUD susceptibility is predicted by impaired learning ability in mice; therefore, learning ability can play a simple and practical role in identifying high-risk SUD groups.

Mechanism of valproic acid-induced dendritic spine and synaptic impairment in the prefrontal cortex for causing core autistic symptoms in mice / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism of valproic acid (VPA) -induced impairment of the dendritic spines and synapses in the prefrontal cortex (PFC) for causing core symptoms of autism spectrum disorder (ASD) in mice.@*METHODS@#Female C57 mice were subjected to injections of saline or VPA on gestational days 10 and 12, and the male offspring mice in the two groups were used as the normal control group and ASD model group (n=10), respectively. Another 20 male mice with fetal exposure to VPA were randomized into two groups for stereotactic injection of DMSO or Wortmannin into the PFC (n=10). Open field test, juvenile play test and 3-chamber test were used to evaluate autistic behaviors of the mice. The density of dendrite spines in the PFC was observed with Golgi staining. Western blotting and immunofluorescence staining were used to detect the expressions of p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and the synaptic proteins PSD95, p-Syn, and Syn in the PFC of the mice.@*RESULTS@#Compared with the normal control mice, the mice with fetal exposure to VPA exhibited obvious autism-like behaviors with significantly decreased density of total, mushroom and stubby dendritic spines (P < 0.05) and increased filopodia dendritic spines (P < 0.05) in the PFC. The VPA-exposed mice also showed significantly increased expressions of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR (P < 0.01) and lowered expressions of PSD95 and p-Syn/Syn in the PFC (P < 0.05 or 0.001). Wortmannin injection into the PFC obviously improved the ASD-like phenotype and dendritic spine development, down-regulated PI3K/Akt/mTOR signaling pathway and up-regulated the synaptic proteins in VPA-exposed mice.@*CONCLUSION@#In male mice with fetal exposure to VPA, excessive activation of PI3K/Akt/mTOR signaling pathway and decreased expressions of the synaptic proteins PSD95 and p-Syn cause dendritic spine damage and synaptic development disturbance in the PFC, which eventually leads to ASD-like phenotype.

Developing of Focal Ischemia in the Hippocampus or the Amygdala Reveals a Regional Compensation Rule for Fear Memory Acquisition.

Circuit compensation is often observed in patients with acute ischemic stroke, suggesting the importance of the interaction between brain regions. Also, contextual fear memory is an association between multisensory contexts and fearful stimuli, for which the interaction between the hippocampus and the amygdala is believed to be critical. To understand how focal ischemia in one region could influence the other region, we used a modified photo-thrombosis to induce focal ischemia in the hippocampus or the amygdala or both in freely-moving rats. We found that the learning curve and short-term memory (STM) were not affected in the rats although focal ischemia was induced 5 h before learning in either the hippocampus or the amygdala; these were impaired by the induction of ischemia in both the regions. Furthermore, the learning curve and STM were impaired when ischemia was induced 24 h before learning in either the hippocampus or the amygdala when the synaptic transmission was altered in one region because of ischemia in the other region. These results suggest that the circuit compensation between the hippocampus and the amygdala is critical for fear memory acquisition.

LncRNA TTN-AS1 intensifies sorafenib resistance in hepatocellular carcinoma by sponging miR-16-5p and upregulation of cyclin E1.

Drug resistance has always been an important problem affecting the therapeutic effect of hepatocellular carcinoma (HCC). To investigate the potential role of lncRNA TTN-AS1 in HCC cells with sorafenib (SOR) resistance, and explore the underlying pathways, quantitative real time polymerase chain reaction (qRT-PCR) was used to test the expression of TTN-AS1 in HCC tissues and cells. Then, the expression of TTN-AS1 was down-regulated by shRNA, the activity changes, apoptosis and related protein expression in HCC cells with/without SOR treatment were observed in succession. Expression levels of the downstream target of TTN-AS1, miR-16-5p were studied by dual-luciferase binding assay, cell proliferation, and western blotting analysis. Nude mice models of human HCC with TTN-AS1 gene knockdown were established to observe the tumor growth. As the results revealed, TTN-AS1 silencing in HCC cells induced apoptosis by enhancing the sensitivity of cells to SOR, and the tumor in nude mice became smaller. The mechanism study showed that miR-16-5p was affected by TTN-AS1 sponge, up-regulated cyclin E1 expression, and regulated PTEN/Akt signaling pathway, thereby significantly alleviating the inhibition of apoptosis of HCC cells induced by TTN-AS1 gene. Collectively, our results provided TTN-AS1 as a potential therapeutic target for sorafenib resistance in HCC.

Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Prognostic Implications of Immune-Related Genes' (IRGs) Signature Models in Cervical Cancer and Endometrial Cancer.

Cervical cancer and endometrial cancer remain serious threats to women's health. Even though some patients can be treated with surgery plus chemoradiotherapy as a conventional option, the overall efficacy is deemed unsatisfactory. As such, the development for new treatment approaches is truly necessary. In recent years, immunotherapy has been widely used in clinical practice and it is an area of great interest that researchers are keeping attention on. However, a thorough immune-related genes (IRGs) study for cervical cancer and endometrial cancer is still lacking. We therefore aim to make a comprehensive evaluation of IRGs through bioinformatics and large databases, and also investigate the relationship between the two types of cancer. We reviewed the transcriptome RNAs of IRGs and clinical data based on the TCGA database. Survival-associated IRGs in cervical/endometrial cancer were identified using univariable and multivariable Cox proportional-hazard regression analysis for developing an IRG signature model to evaluate the risk of patients. In the end, this model was validated based on the enrichment analyses through GO, KEGG, and GSEA pathways, Kaplan-Meier survival curve, ROC curves, and immune cell infiltration. Our results showed that out of 25/23 survival-associated IRGs for cervical/endometrial cancer, 13/12 warranted further examination by multivariate Cox proportional-hazard regression analysis and were selected to develop an IRGs signature model. As a result, enrichment analyses for high-risk groups indicated main enriched pathways were associated with tumor development and progression, and statistical differences were found between high-risk and low-risk groups as shown by Kaplan-Meier survival curve. This model could be used as an independent measure for risk assessment and was considered relevant to immune cell infiltration, but it had nothing to do with clinicopathological characteristics. In summary, based on comprehensive analysis, we obtained the IRGs signature model in cervical cancer (LTA, TFRC, TYK2, DLL4, CSK, JUND, NFATC4, SBDS, FLT1, IL17RD, IL3RA, SDC1, PLAU) and endometrial cancer (LTA, PSMC4, KAL1, TNF, SBDS, HDGF, LTB, HTR3E, NR2F1, NR3C1, PGR, CBLC), which can effectively evaluate the prognosis and risk of patients and provide justification in immunology for further researches.

The New Biomarker for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Based on Public Database Mining.

To reconstruct the ceRNA biological network of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and to select an appropriate mRNA as a biomarker that could be used for CESC early diagnosis and prognosis evaluation. We downloaded CESC data from the TCGA public database, and statistical analysis was conducted with the R software to find out differential expressed genes encoding for lncRNAs, miRNAs, and mRNAs. The differentially expressed mRNAs (DEmRNAs) screened in the ceRNA network were analyzed for survival to find the mRNAs with significantly linked to the survival prognosis. These mRNAs were searched in the Pathological Atlas to identify the final appropriate mRNAs. Differential expression analysis revealed 773 lncRNAs, 94 miRNAs, and 2466 mRNAs. Survival analysis of DEmRNAs in the ceRNA network indicated that ADGRF4, ANXA8L1, HCAR3, IRF6, and PDE2A (P < 0.05) were negatively correlated with survival time. Verification of these six DEmRNAs in the Pathology Atlas indicated that PDE2A was a possible biomarker for CESC patients. PDE2A might be a biomarker for early diagnosis and prognosis evaluation of CESC patients, but due to the lack of available data, further studies may be needed for confirmation.

Celebrex adjuvant therapy on COVID-19: An experimental study

BackgroundThe world is under serious threat with the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). However, there is no effective drug for the treatment of COVID-19. Based on analyses of available data, we deduced that the excessive prostaglandins E2 (PGE2) accumulation mediated by cyclooxygenase-2 (COX-2) was the key pathological basis of COVID-19. MethodsThe urine PGE2 levels were measured by mass spectrometry. An experimental study about Celebrex to treat COVID-19 was conducted based on routine treatment. A total of 44 confirmed COVID-19 patients were enrolled (Experimental group n=37, Control group n=7). Patients in experimental group were given Celebrex once or twice a day (0.2 g/time) for 7-14 days. The dosage or duration was modified for individuals. Clinical outcomes of Celebrex adjuvant therapy were evaluated by vital signs, laboratory tests, and computed tomography upon the discontinuance of Celebrex. ResultsWe found that the concentrations of PGE2 in urine samples of COVID-19 patients were significantly higher than that of healthy individuals (mean value is 170 ng/ml vs 18.8 ng/ml, p<0.01) and positively correlated with the progression of COVID-19. Among the experimental group (ordinary n=29, severe n=7, critical n=1), 25 cases were treated with full dose and 11 cases with half dose of Celebrex, and 1 case with Ibuprofen. The remission rate were 100%, 82% and 57% in full dose, half dose and control group respectively. Celebrex significantly reduced the PGE2 levels and promoted recovery of ordinary or severe COVID-19. ConclusionOur study suggests that Celebrex adjuvant treatment may be helpful for the therapy of COVID-19.

Stress Concentration Induced by the Crystal Orientation in the Transient-Liquid-Phase Bonded Joint of Single-Crystalline Ni3Al.

Single-crystalline Ni3Al-based superalloys have been widely used in aviation, aerospace, and military fields because of their excellent mechanical properties, especially at extremely high temperatures. Usually, single-crystalline Ni3Al-based superalloys are welded together by a Ni3Al-based polycrystalline alloy via transient liquid phase (TLP) bonding. In this study, the elastic constants of single-crystalline Ni3Al were calculated via density functional theory (DFT) and the elastic modulus, shear modulus, and Poisson's ratio of the polycrystalline Ni3Al were evaluated by the Voigt-Reuss approximation method. The results are in good agreement with previously reported experimental values. Based on the calculated mechanical properties of single-crystalline and polycrystalline Ni3Al, three-dimensional finite element analysis (FEA) was used to characterize the mechanical behavior of the TLP bonded joint of single-crystalline Ni3Al. The simulation results reveal obvious stress concentration in the joint because of the different states of crystal orientation between single crystals and polycrystals, which may induce failure in the polycrystalline Ni3Al and weaken the mechanical strength of the TLP bonded joint. Furthermore, results also show that the decrease in the elastic modulus of the intermediate layer (i.e., polycrystalline Ni3Al) can relieve the stress concentration and improve the mechanical strength in the TLP bonded joint.

A comparative study of ultrasonic scalpel (US) versus conventional metal clips for closure of the cystic duct in laparoscopic cholecystectomy (LC): A meta-analysis.

BACKGROUND: laparoscopic cholecystectomy (LC) has become the gold standard surgery for benign gallbladder diseases. Metal clips are conventionally used to secure the cystic duct and artery, while monopolar electrocautery (ME) predominates during laparoscopic dissection. ultrasonic scalpel (US) has already been explored for sealing the cystic duct and artery as a sole instrument, which has been regarded as a reasonable alternative to clips. The aim of this study was to investigate the safety and effectiveness of US versus clips for securing the cystic duct during LC. METHODS: We identified eligible studies in PubMed, Medline, Cochrane Library, Embase, and SpringerLink up to 1st May 2018, together with the reference lists of original studies. Meta-analysis was conducted using STATA 14.0. Q-based chi-square test and the I statistics were utilized to assess heterogeneity among the included studies. A P-value below .05 was set for statistical significance. Forest plots of combined Hazard ratios (HRs) with 95% confidence intervals (CIs) were also generated. RESULTS: Eight studies met eligibility criteria in this meta-analysis eventually. A total of 1131 patients were included, of whom 529 were contained in the US group, compared to 602 in the clips group, which showed a significant difference (P = .025) without substantial statistical heterogeneity (I = 0.0%). No statistical significance was revealed regarding age (I = 0.0%, P = .957), and sex (I = 0.0%, P = .578) between both groups. The operative time and hospital stay in the US group were significantly shorter than that in the clips group, with I = 95.0%, P = .000 and I = 72.8%, P = .005, respectively. Concerning conversion (I = 48.6%, P = .084), perforation (I = 12.0%, P = .338), along with bile leakage (I = 0.0% P = .594), and overall morbidity (I = 19.1%, P = .289), comparison between both groups exhibited no statistical significance. CONCLUSIONS: US enabled shorter operative time and hospital stay during LC, compared with clips. Additionally, US was comparable to clips regarding conversion, perforation, along with bile leakage and overall morbidity. Therefore, our meta-analysis concluded that US is clinically superior to the conventional clips in some aspects, or is at least as safe and effective as them, concerning closure of the cystic duct and artery.

The role of splenectomy in lipid metabolism and atherosclerosis (AS).

The extensive performance of splenectomy worldwide for patients suffered from splenic trauma has given rise to high risks of postoperative complications, which has been attracting increasing attention in recent years. Nowadays the spleen is regarded as a versatile organ of the human body, invested with various excellent properties. The spleen has been recognized to take a great part in lipid metabolism. While removal of the spleen intends to alter lipid values, especially with an elevated LDL, splenic autotransplantation is able to normalize these lipid alterations. What is more, conservative surgical procedures like subtotal or partial splenectomy, could as well, afford a correction of dyslipidemia. At the same time, clinically, splenectomy demonstrates a high rate of atherosclerosis (AS), whereas non-surgical treatment after splenic trauma shows unchanged propagation of AS. Based on the intimate relationship between serum lipids and AS, the lipid changes modulated by splenectomy are believed to be responsible for the development of AS. Therefore, a "splenic factor" is most likely present in the regulation of lipidation and AS. Several theories have been postulated to elucidate the possible mechanism involved, among which most are primarily based on its forceful natural immune function, that is to say, the mononuclear phagocytic system.However, the accurate mechanisms behind this mysterious phenomenon still remain unclear so far. Of importance, lipid fractions should be monitored consecutively in case of inevitable splenectomy.

Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry / 中华医学杂志(英文版)

<p><b>Background</b>Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and it's diagnosis is difficult. The aim of this study was to investigate the metabolic profiles of PCOS patients by analyzing urine samples and identify useful biomarkers for diagnosis of PCOS.</p><p><b>Methods</b>This study was carried out in the Department of Obstetrics and Gynecology of the Maternal and Child Health Hospital of Hunan Province from December 2014 to July 2016. In this study, the urine samples of 21 women with PCOS and 16 healthy controls were assessed through gas chromatography-mass spectrometry to investigate the urine metabolite characteristics of PCOS and identify useful biomarkers for the diagnosis of this disorder. The Student's t-test and rank sum test were applied to validate the statistical significance of the between the two groups.</p><p><b>Results</b>In total, 35 urine metabolites were found to be significantly different between the PCOS patients and the controls. In particular, a significant increase in the levels of lactose (10.01 [0,13.99] mmol/mol creatinine vs. 2.35 [0.16, 3.26] mmol/mol creatinine, P = 0.042), stearic acid (2.35 [1.47, 3.14] mmol/mol creatinine vs. 0.05 [0, 0.14] mmol/mol creatinine, P < 0.001), and palmitic acid (2.13 [1.07, 2.79] mmol/mol creatinine vs. 0 [0, 0] mmol/mol creatinine, P < 0.001) and a decrease in the levels of succinic acid (0 [0, 0] mmol/mol creatinine vs. 38.94 [4.16, 51.30] mmol/mol creatinine, P < 0.001) were found in the PCOS patients compared with the controls. It was possible to cluster the PCOS patients and the healthy controls into two distinct regions based on a principal component analysis model. Of the differentially expressed metabolites, four compounds, including stearic acid, palmitic acid, benzoylglycine, and threonine, were selected as potential biomarkers.</p><p><b>Conclusions</b>This study offers new insight into the pathogenesis of PCOS, and the discriminating urine metabolites may provide a prospect for the diagnosis of PCOS.</p>

Protective efficacy of a single salvianolic acid A treatment on photothrombosis-induced sustained spatial memory impairments.

With respect to the high burden of ischemic stroke and the absence of pharmacological treatment for promoting rehabilitation, promising candidates with specific effects on long-term functional recovery are highly desired. Candidates need reasonable experimental paradigms to evaluate the long-term functional outcome focused on ischemia-induced sensorimotor and memory deficits. "Danshen", a traditional Chinese herb, has long been used to treat coronary and cerebral vascular diseases as well as dementia. Salvianolic acid A (SAA), one of the major active ingredients of Danshen, was demonstrated to be effective in protecting against cerebral ischemic injury. Here, employing an experimental stroke model induced by photothrombosis in the unilateral frontal cortex of rats, we investigated whether SAA has long-term protective effects on ischemia-induced sensorimotor and memory deficits in our behavioral tests. The results indicated that a single SAA treatment improved the cortical ischemia-induced sensorimotor deficits during 15 days' cylinder test period, and alleviated ischemia-induced sustained spatial memory impairments during the 2 months' dependent Morris Water Maze (MWM) tests. In addition, either ischemic injury or SAA treatment did not show any changes compared with sham group in other behavioral tests including rotarod tests, swimming speed in MWM tests, open field tests, elevated plus maze tests, treadmill tests and forced swimming tests. The results reveal that the cognitive deficits are not the results of animal's anxiety or confounding motor impairments. Overall, the present paradigm appears suitable for the preclinical evaluation of the long-term effects of pharmacological treatments on ischemic stroke. Meanwhile, SAA might have therapeutic potential for the treatment of memory deficits associated with ischemic stroke.

[Treatment and analysis of the early postoperative complications of tibial plateau fractures].

OBJECTIVE: To analysis the early complications of tibial fracture and its related factors, and propose a solution. METHODS: From December 2003 to December 2013,38 patients with early complications of tibial plateau fracture after operation were retrospectively analyzed. There were 35 males and 3 females, aged from 37 to 69 years old (averaged 42.3 years). According to Schatzker classification, 3 cases were classified as type II, 2 cases as type III, 2 cases as type IV, 19 cases as type V, 12 cases as type VI. The intervals between injury and operation ranged from 9 hours to 9 days, 26 cases within 3 days. Fifteen cases were treated with internal fixation of plates and 23 were treated by plate fixation and bone transplantation. Early complications included skin necrosis in 15 cases, infection in 6 cases, osteofascial compartment syndrome in 3 cases, common peroneal nerve injury in 2 cases, the superficial peroneal nerve injury in 3 cases, popliteal artery injury in 2 cases, loss of reduction in 7 cases. RESULTS: The wound of 14 cases healed at the first stage and 24 cases healed delay. Hospitalization days ranged from 7 to 67 days (averaged 25.6 days). All patients were followed up for 12 to 36 months with an average of 16.4 months. The fracture healing time ranged from 3 to 9 months (averaged 6.9 months). According to Merchant knee function evaluation criteria, the results were excellent in 19 cases, good in 12, fair in 5 and poor in 2. CONCLUSION: Early complications of tibial fracture after operation is closely associated with the severe fracture complexity and related with preoperative preparation, surgical timing, operation incision selection and surgical technique. Early detection and timely processing reduce damage.

Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms.

The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair.

Chronic constant light-induced hippocampal late-phase long-term potentiation impairment in vitro is attenuated by antagonist of D1/D5 receptors.

Previous study reported that chronic constant light exposure caused hippocampus-dependent long-term memory deficit. However, the underlying cellular mechanism of this impairment is still unclear. Multiple lines of evidence indicated that long-term potentiation (LTP) is a cellular model for memory formation. Here we found that, by recording of field excitatory postsynaptic potential (fEPSP) in vitro, chronic constant light (CCL, 3 weeks) exposure impaired the late long-term potentiation (L-LTP), but not early long-term potentiation (E-LTP) and basal transmission in Schaffer collateral (SC)-CA1 synapses of hippocampal slices from rats. Because L-LTP depends on D1/D5 receptors, we examined whether interference of D1/D5 receptors can modulate L-LTP of CCL rats. Bath application of D1/D5 receptors antagonist SCH23390 (1µM) blocked L-LTP in control rats and attenuated the impaired L-LTP in CCL rats. In contrast, pre-incubation of D1/D5 receptors agonist SKF38393 (25µM) occluded further L-LTP in control rats while exacerbated the L-LTP impairment in CCL rats. These results suggested that CCL-induced L-LTP impairment can be modulated by D1/D5 receptors. Our findings may contribute to the further understanding of synaptic plasticity mechanism underlying hippocampal long-term memory impairment induced by circadian rhythm disruption.