Early warning of systemic risk in stock market based on EEMD-LSTM.

With the increasing importance of the stock market, it is of great practical significance to accurately describe the systemic risk of the stock market and conduct more accurate early warning research on it. However, the existing research on the systemic risk of the stock market lacks multi-dimensional factors, and there is still room for improvement in the forecasting model. Therefore, to further measure the systemic risk profile of the Chinese stock market, establish a risk early warning system suitable for the Chinese stock market, and improve the risk management awareness of investors and regulators. This paper proposes a combination model of EEMD-LSTM, which can describe the complex nonlinear interaction. Firstly, 35 stock market systemic risk indicators are selected from the perspectives of macroeconomic operation, market cross-contagion and the stock market itself to build a comprehensive indicator system that conforms to the reality of China. Furthermore, based on TEI@I complex system methodology, an EEMD-LSTM model is proposed. The EEMD method is adopted to decompose the composite index sequence into intrinsic mode function components (IMF) of different scales and one trend term. Then the LSTM algorithm is used to predicted and model the decomposed sub-sequences. Finally, the forecast result of the composite index is obtained through integration. The empirical results show that the stock market systemic risk index constructed in this paper can effectively identify important risk events within the sample period. In addition, compared with the benchmark model, the EEMD-LSTM model constructed in this paper shows a stronger early warning ability for systemic financial risks in the stock market.

Total Synthesis of Quebrachamine and Kopsiyunnanine D.

The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.

Risk factors for lateral pelvic lymph node metastasis in patients with lower rectal cancer: a systematic review and meta-analysis.

Background and objective: Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods. Methods: We searched relevant databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 05 October 2022 to evaluate the risk factors for LPLN metastasis in patients with RC in this meta-analysis. Results: A total of 24 articles with 5843 patients were included in this study. The overall results showed that female sex, age <60 years, pretherapeutic CEA level >5 ng/ml, clinical T4 stage (cT4), clinical M1 stage (cM1), distance of the tumour from the anal verge (AV) <50 mm, tumour centre located below the peritoneal reflection (Rb), short axis (SA) of LPLN ≥8 mm before nCRT, short axis (SA) of LPLN ≥5 mm after nCRT, border irregularity of LPLN, tumour size ≥50 mm, pathological T3-4 stage (pT3-4), pathological N2 stage (pN2), mesorectal lymph node metastasis (MLNM), lymphatic invasion (LI), venous invasion (VI), CRM (+) and poor differentiation were significant risk factors for LPLN metastasis (P <0.05). Conclusion: This study summarized almost all potential risk factors of LPLN metastasis and expected to provide effective treatment strategies for patients with LRC. According to the risk factors of lateral lymph node metastasis, we can adopt different comprehensive treatment strategies. High-risk patients can perform lateral lymph node dissection to effectively reduce local recurrence; In low-risk patients, we can avoid overtreatment, reduce complications and trauma caused by lateral lymph node dissection, and maximize patient survival and quality of life.

Application value of modified magnetic bead screening for enrichment of cell-free fetal DNA from maternal peripheral blood in non-invasive prenatal testing / 中华围产医学杂志

Objective:To evaluate the value of modified magnetic bead screening for enrichment of cell-free fetal DNA (cffDNA) in non-invasive prenatal testing (NIPT).Methods:This study retrospectively recruited 31 cases with low concentration of cffDNA (<6.00%), Z value in the gray zone (3.00-4.00) at the first detection, or false-positive (confirmed by invasive prenatal diagnosis) or false-negative (confirmed by postnatal chromosome test) results among 11 000 pregnant women who underwent routine NIPT in Beijing Haidian District Maternal and Child Health Care Hospital from October 2017 to December 2019. Plasma samples collected for the first-time routine NIPT were used to enrich cffDNA using modified magnetic beads for NIPT (modified NIPT). Wilcoxon rank sum test was used to compare the modified NIPT with the routine NIPT in detecting the cffDNA concentrations of male fetuses.Results:Among the 31 pregnant women, there were 13 cases with low cffDNA concentration in routine NIPT, 11 having false-positive results in the routine NIPT (three for trisomy 13, four for trisomy 18 and four for trisomy 21, all were confirmed by invasive prenatal diagnosis), six with gray-zone Z values in the first-time NIPT (retesting indicating low risk) and one having false negative result for trisomy 21 (confirmed by postnatal chromosome test). Cell-free DNA (cfDNA) fragments less than 150 bp were effectively enriched using the modified magnetic bead screening and the concentration of cffDNA was increased from 4.43% (2.45%-17.61%) in routine NIPT to 13.46% (7.75%-36.64%) in the modified NIPT ( Z=-14.22, P<0.01). Results of the modified NIPT indicated that 13 cases with low cffDNA concentration of routine NIPT were successfully detected as low risk, as well as the risks in the six cases with gray-zone Z value and six of the 11 false-positive cases in the routine NIPT were low, which were consistent with the retest results of the routine NIPT, while high risk was found in one false-negative case. Conclusions:The modified NIPT could reduce the false positive rate by lowering the failure rate caused by low concentration of cffDNA and is able to identify false-negative cases. Compared with the routine NIPT, it shows a higher success rate and a lower false positive rate.

Remote ischemic conditioning-induced hyperacute and acute responses of plasma proteome in healthy young male adults: a quantitative proteomic analysis / 中华医学杂志(英文版)

BACKGROUND@#Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender.@*METHODS@#Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method.@*RESULTS@#Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades.@*CONCLUSIONS@#One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.

Re-evaluation of systematic reviews of acupuncture and moxibustion for childhood autism / 中国针灸

OBJECTIVE@#To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment.@*METHODS@#The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence.@*RESULTS@#A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias.@*CONCLUSION@#Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.

Comparison of the prognosis of four different surgical strategies for proximal gastric cancer: a network meta-analysis.

BACKGROUND: There is controversy regarding the long-term prognosis and short-term postoperative complications of different surgical strategies for proximal gastric cancer (PGC). METHODS: We searched for articles published in Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science between January 1, 1990, and February 1, 2021. We screened out the literature comparing different surgical strategies. We then evaluated the long-term and short-term outcome of different surgical strategies using a network meta-analysis, which summarizes the hazard ratio, odds ratio, mean difference, and 95% confidence interval. RESULTS: There were no significant differences between different surgical strategies for 5-year overall survival (OS), anastomotic leakage, or weight loss after 1 year. Compared with total gastrectomy with Roux-en-Y reconstruction (TG-RY) and proximal gastrectomy with double tract reconstruction (PG-DTR), the proximal gastrectomy with esophagogastrostomy (PG-EG) strategy significantly increased the incidence of reflux esophagitis; and the operation time and blood loss of the PG-EG strategy were significantly less than those of the other surgical strategies. The anastomotic stenosis rates of the PG-EG and proximal gastrectomy with jejunum interstitial (PG-JI) strategies were significantly higher than those of TG-RY and PG-DTR; the hemoglobin level after 1 year for the PG-DTR strategy was significantly higher than that of the TG-RY strategy. CONCLUSION: Our comprehensive literature research found that different surgical strategies had no significant difference in the long-term survival of PGC, but the incidence of reflux esophagitis and anastomotic stenosis after PG-DTR and TG-RY was significantly reduced.

Boosting in-plane anisotropy by periodic phase engineering in two-dimensional VO2 single crystals.

In-plane anisotropy (IPA) due to asymmetry in lattice structures provides an additional parameter for the precise tuning of characteristic polarization-dependent properties in two-dimensional (2D) materials, but the narrow range within which such method can modulate properties hinders significant development of related devices. Herein we present a novel periodic phase engineering strategy that can remarkably enhance the intrinsic IPA obtainable from minor variations in asymmetric structures. By introducing alternant monoclinic and rutile phases in 2D VO2 single crystals through the regulation of interfacial thermal strain, the IPA in electrical conductivity can be reversibly modulated in a range spanning two orders of magnitude, reaching an unprecedented IPA of 113. Such an intriguing local phase engineering in 2D materials can be well depicted and predicted by a theoretical model consisting of phase transformation, thermal expansion, and friction force at the interface, creating a framework applicable to other 2D materials. Ultimately, the considerable adjustability and reversibility of the presented strategy provide opportunities for future polarization-dependent photoelectric and optoelectronic devices.

Analysis of current status and influencing factors of lactation initiation delay in women with vaginal delivery / 中国实用护理杂志

Objective:To investigate cases of delayed lactation initiation in women with transvaginal delivery and the influencing factors, in order to provide a basis for effective control of delayed lactation initiation and promotion of breastfeeding.Methods:Inpatients who were admitted to the obstetric ward of Affiliated Hospital of Jining Medical College from November 6, 2020 to January 16, 2021 were selected for the study using convenience sampling method and investigated by general information questionnaire and Chindbirth Experience Questionnaire (CEQ). Binary Logistic regression analysis was used to determine the factors influencing delayed lactation initiation.Results:The incidence of delayed lactation initiation in 622 women with transvaginal delivery was 38.75% (241/622). Binary Logistic regression analysis showed that age 20-35 years, full-term delivery, labor and delivery, use of labor analgesia, and good experience of transvaginal delivery were protective factors for delayed lactation initiation ( OR values were 0.012 to 0.868, all P<0.05); age >35 years, excessive weight gain during pregnancy, presence of pregnancy complications, use of induction of labor during delivery, long labor process, and damage to perineal skin after delivery were risk factors for delayed lactation initiation ( OR values were 1.097 to 13.235, all P<0.05). Conclusions:The high incidence of delayed lactation initiation in women with transvaginal delivery is influenced by a number of factors, which reminds the clinic that lactation in women after transvaginal delivery also needs to be taken into account, with priority assessment and prevention for those who are elderly (age≥35 years), primiparous, have other diseases during pregnancy, have gained too much weight during pregnancy, have preterm delivery, have a long duration of labor, have not received labor analgesia, have had a single or combined induction of labor, have had an episiotomy or perineal laceration during labor, and have a poor transvaginal delivery experience.

Advance in the relationship between allergic rhinitis and ADHD in children / 国际儿科学杂志

In recent years, more and more researchers at home and abroad have realized that there is a certain relationship between allergic rhinitis(AR) and attention deficit hyperactivity disorder(ADHD) in children.Children with AR had higher ADHD related symptom scores than healthy children; ADHD children have a significantly increased risk of allergic diseases, such as asthma, eczema and atopic dermatitis.At present, it has been clear that they have the common characteristics of increasing prevalence year by year, genetic tendency, environmental and neuropsychological factors, and similar clinical manifestations.However, there is no final conclusion whether they are mutual cause and effect or comorbidities.This artide reviews the similarities between AR and ADHD in epidemiology, etiology, clinical manifestations and drug treatment, so as to further explore the correlation between AR and ADHD.

Comparison of the prognosis of four different treatment strategies for acute left malignant colonic obstruction: a systematic review and network meta-analysis.

BACKGROUND: There is controversy regarding the efficacy of different treatment strategies for acute left malignant colonic obstruction. This study investigated the 5-year overall survival (OS) and disease-free survival (DFS) of several treatment strategies for acute left malignant colonic obstruction. METHODS: We searched for articles published in PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library between January 1, 2000, and July 1, 2020. We screened out the literature comparing different treatment strategies. Evaluate the primary and secondary outcomes of different treatment strategies. The network meta-analysis summarizes the hazard ratio, odds ratio, mean difference, and its 95% confidence interval. RESULTS: The network meta-analysis involved 48 articles, including 8 (randomized controlled trials) RCTs and 40 non-RCTs. Primary outcomes: the 5-year overall survival (OS) and disease-free survival (DFS) of the CS-BTS strategy and the DS-BTS strategy were significantly better than those of the ES strategy, and the 5-year OS of the DS-BTS strategy was significantly better than that of CS-BTS. The long-term survival of TCT-BTS was not significantly different from those of CS-BTS and ES. SECONDARY OUTCOMES: compared with emergency resection (ER) strategies, colonic stent-bridge to surgery (CS-BTS) and transanal colorectal tube-bridge to surgery (TCT-BTS) strategies can significantly increase the primary anastomosis rate, CS-BTS and decompressing stoma-bridge to surgery (DS-BTS) strategies can significantly reduce mortality, and CS-BTS strategies can significantly reduce the permanent stoma rate. The hospital stay of DS-BTS is significantly longer than that of other strategies. There was no significant difference in the anastomotic leakage levels of several treatment strategies. CONCLUSION: Comprehensive literature research, we find that CS-BTS and DS-BTS strategies can bring better 5-year OS and DFS than ER. DS-BTS strategies have a better 5-year OS than CS-BTS strategies. Without considering the hospital stays, DS-BTS strategy is the best choice.

Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells / 中国天然药物

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.

Mechanism of Fluspirilene suppressing HCC through decreasing Akt expression / 中国药理学通报

Aim To explore the mechanism of Fluspirilene inhibiting HCC through decreasing the expression of Akt.Methods The difference of mRNA was verified by the test of protein expression between Fluspirilenc treatment group and control group by HCC experiment in vivo and vitro, including Western blot, IHC after mRNA array.Results Akt expression was lower in Fluspirilene treatment group than that in control group by mRNA array.Protein expression of Akt, phosphorylate-CDK2 and phos- phorylate-Rb decreased massively in Fluspirilene treatment group in a concentration-dependent manner in HepG2 and Huh7 cells by Western blotting compared with those in control group.Declined expression of phosphorylate-Akt was proved in a concen- tration-dependent manner in xenograft tumor tissues in Fluspirilene treatment group compared with that in control group in IHC test.Conclusions Fluspirilene inhibits HCC by decreasing significantly the protein expression of Akt, phosphorylat-Akt, phos- phorylate-CDK2 and phosphorylate-Rb.

Study on the effects and mechanism of Linc01278 on the biological behavior of prostate cancer cells / 中华内分泌外科杂志

Objective:To investigate the effect and molecular mechanism of long non-coding RNA (Linc01278) on the proliferation, invasion and migration, and tumor phenotype of prostate cancer cells.Methods:Prostate cancer tissues and corresponding normal tissues adjacent to the cancer were obtained in 46 patients with prostate cancer confirmed by the hospital from Dec. 2018 to Dec. 2019. Real-time fluorescence quantitative PCR (qPCR) was used to detect the expression levels of Linc01278 and miR-145 in prostate cancer tissues and adjacent normal tissues. The prostate cancer PC-3 cells were transfected with plasmids and cells were divided into four groups: blank group, control group, overexpression group and rescue group. The blank group was not given any treatment; the control group was transfected with blank control vector and miRNA Control; the overexpression group was transfected with Linc01278 overexpression vector and miRNA Control; the rescue group was transfected with Linc01278 overexpression vector and miR-145 mimics. Bioinformatics analysis was used to predict the binding site of Linc01278 to miR-145. Dual Luciferase Reporter Gene Assay was used to analyze the adsorption of Linc01278 on miR-145; Transwell experiment was used to detect the invasion and migration ability of the four groups of cells; CCK-8 method was used to detect the cell proliferation ability of the four groups of cells. Western blot was used to detect the expression of OCT4 and SOX2 in the four groups of cells; qPCR was used to detect the expression of OCT4, SOX2 and miR-145 in the four groups of cells.Results:Compared with adjacent normal tissues, Linc01278 was significantly higher in prostate cancer tissues (adjacent normal tissues: 0.012±0.002 vs prostate cancer tissues: 0.022±0.002, P=0.0072) , while miR-145 was significantly lower (adjacent normal tissues: 0.117±0.011 vs prostate cancer tissues: 0.081±0.007, P=0.0005) . Correlation of both was negative significantly ( P=0.0012) . Targetscan analysis revealed that the 804-825 position of the Linc01278 transcript had a complementary base pairing with miR-145. The results of the double luciferase reporter gene showed that miR-145 mimics could significantly reduce the luciferase activity of Linc01278 ( P<0.01) . Compared with the blank group and the control group, the invasion and migration cells, the relative proliferation ability, the expression of Oct4 and Sox2 mRNA and protein were significantly increased, and the expression of miR-145 was significantly decreased in the overexpression group ( P<0.05) . While compared with the overexpression group, the invasion and migration cells, the relative proliferation ability, Oct4 and Sox2 were significantly decreased in the rescue group, and the expression of miR-145 was significantly increased ( P<0.01) . Conclusion:Linc01278 may promote the proliferation, invasion and migration of prostate cancer cells by specifically adsorbing miR-145.

Associations between Lesion Locations and Stroke Recurrence in Survivors of First-ever Ischemic Stroke: A Prospective Cohort Study.

Several studies have indicated that stroke survivors with multiple lesions or with larger lesion volumes have a higher risk of stroke recurrence. However, the relationship between lesion locations and stroke recurrence is unclear. We conducted a prospective cohort study of first-ever ischemic stroke survivors who were consecutively enrolled from January 2010 to December 2015. Stroke recurrence was assessed every 3 months after post-discharge via telephone interviews by trained interviewers. Lesion locations were obtained from hospital-based MRI or CT scans and classified using two classification systems that were based on cerebral hemisphere or vascular territory and brain anatomical structures. Flexible parametric survival models using the proportional hazards scale (PH model) were used to analyze the time-to-event data. Among 633 survivors, 63.51% (n=402) had anterior circulation ischemia (ACI), and more than half of all ACIs occurred in the subcortex. After a median follow-up of 2.5 years, 117 (18.48%) survivors developed a recurrent stroke. The results of the multivariate PH model showed that survivors with non-brain lesions were at higher risk of recurrence than those with right-side lesions (HR, 2.79; 95%CI, 1.53, 5.08; P=0.001). There was no increase in risk among survivors with left-side lesions (HR, 0.97; 95%CI, 0.53, 1.75; P=0.914) or both-side lesions (HR, 1.24; 95%CI, 0.75, 2.07; P=0.401) compared to those with right-side lesions. Additionally, there were no associations between stroke recurrence and lesion locations that were classified based on vascular territory and brain anatomical structures. It was concluded that first-ever ischemic stroke survivors with non-brain lesion had higher recurrence risk than those with right-side lesion, although no significant associations were found when the lesion locations were classified by vascular territory and brain anatomical structures.

The mechanism of the modulation of electronic anisotropy in two-dimensional ReS2.

Although the anisotropy and strategies for the modulation of the anisotropy in ReS2 have been widely reported, a comprehensive study on the inherent electronic anisotropy of ReS2 is still absent to date; therefore, the mechanism of anisotropy evolution is ambiguous as well. In this study, we have conducted a systematic investigation on the evolution of electronic anisotropy in bilayer ReS2, under the modulation of charge doping levels and temperature. It is found that the adjustability of electronic anisotropy is largely attributed to the angle-dependent scattering from defects or vacancies at a low doping level. At a high doping level, in contrast, the inherent electronic anisotropy can be recovered by filling the traps to attenuate the influence of scattering. This work renders insights into the exploration of electronic anisotropy in 2D materials.

Effect of repetitive normobaric hypoxic preconditioning on white matter lesions and cognitive impairment in chronic cerebral ischemia rats / 中华老年心脑血管病杂志

Objective To study the effect of repetitive normobaric hypoxic preconditioning (RNHP) on white matter lesions (WMLs) and cognitive impairment in chronic cerebral ischemia rats.Methods Twenty-four healthy adult male SD rats were divided into sham operation group,model group,and RNHP group (8 in each group).The bilateral common carotid arteries in sham operation group were isolated but not ligated in ambient air,those in model group were ligated in ambient air,and those in RNHP group were preconditioned for 2 weeks before ligation.Their cognitive function was assessed in Morris water maze test,their WMLs were caluculated with KlüverBarrera staining.The astroglia,microglia and oligodendrocyte in cerebral white matter were stained with immunolabelling technique using antibodies to glial fibrillary acidic protein,Iba-1 and CNPase.Results The percentage of target quadrant swimming time was significantly higher in RNHP group and sham operation group than in model group (27.26％ ± 2.06％,29.06％ ± 1.72％ vs 20.58％±2.23％,P＜0.05,P＜0.01).The scores of WMLs in corpus callosum,caudate putamen and anterior commissure were significantly lower,the number of astrocytes and microglias was significantly smaller while that of oligodendrocytes was significantly greater in RNHP group and sham operation group than in model group (P＜0.05,P＜0.01).Conclusion RNHP can improve WMLs and cognitive impairment in chronic cerebral ischemia rats.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA.</p><p><b>METHODS</b>This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes.</p><p><b>CONCLUSIONS</b>The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820.</p>

Ubiquitin S65 phosphorylation engenders a pH-sensitive conformational switch.

Ubiquitin (Ub) is an important signaling protein. Recent studies have shown that Ub can be enzymatically phosphorylated at S65, and that the resulting pUb exhibits two conformational states-a relaxed state and a retracted state. However, crystallization efforts have yielded only the structure for the relaxed state, which was found similar to that of unmodified Ub. Here we present the solution structures of pUb in both states obtained through refinement against state-specific NMR restraints. We show that the retracted state differs from the relaxed state by the retraction of the last ß-strand and by the extension of the second α-helix. Further, we show that at 7.2, the pKa value for the phosphoryl group in the relaxed state is higher by 1.4 units than that in the retracted state. Consequently, pUb exists in equilibrium between protonated and deprotonated forms and between retracted and relaxed states, with protonated/relaxed species enriched at slightly acidic pH and deprotonated/retracted species enriched at slightly basic pH. The heterogeneity of pUb explains the inability of phosphomimetic mutants to fully mimic pUb. The pH-sensitive conformational switch is likely preserved for polyubiquitin, as single-molecule FRET data indicate that pH change leads to quaternary rearrangement of a phosphorylated K63-linked diubiquitin. Because cellular pH varies among compartments and changes upon pathophysiological insults, our finding suggests that pH and Ub phosphorylation confer additional target specificities and enable an additional layer of modulation for Ub signals.

Effect of miR-196 on endocrine therapy for breast cancer by targeting p27 / 中华内分泌外科杂志

Objective To determine the effect of miR-196 on sensitivity of endocrine therapy for breast cancer and to explore its possible molecular mechanism.Methods The expression of miR-196 was detected by real-time quantitative PCR (RT-qPCR) in MCF7 (ER+) and BT549 (ER-).The sensitivity of tamoxifen on MCF7 cells was evaluated by MTT and colony formation.Dual-luciferase,RT-qPCR and western blot assays were used to determine the regulation of miR-196 on p27.Results The expression of miR-196 was up-regulated in BT549 compared to that in MCF7 cells.The cell viability and colony formation were increased in miR-196-overexpressed MCF7 cells compared to those in the control cells after treatment with tamoxifen.The luciferase activity and expression of p27 were decreased in miR-196-overexpressed MCF7 cells compared to those in the control cells.Overexpression of p27 eliminated the effect of miR-196-induced endocrine therapy resistance in MCF7 cell.Conclusion miR-196 promotes breast cancer endocrine resistance by targeting p27.