Memory effect of spider major ampullate silk in loading-unloading cycles and the structural connotations.

Spider silk is repeatedly stretched while performing biological functions. There is a close relationship between the shape change of the fibre materials and their mechanical properties. However, the effect of the deformation and interval time on the structure and tensile behaviour properties of spider silk after repeatedly stretching by given strain value has been rarely reported. Here we found that major ampullate silk (MAS) can revert its tensile behaviour independent of its previous loading history via intervals of approximately 8 s to 5 min with constant and increased elongation, respectively, after being subjected to yield and hardening regions. The true stress-true strain curve beyond a given value of true strain is independent from the previous loading history of the sample. Even after longer intervals (≥1 h), MAS can reproduce the last tensile behaviour via one stretched. Despite recognizing the development of irreversible deformations in the material when tested in air, the reversible change in tensile behaviour outside the spider silk's elastic region has rarely been observed before. MAS has at least one proper ground state that allows it to present good shape and mechanical behaviour memory in terms of longitudinal stretching, functioning as a new strategy to achieve certain tensile properties. The analysis of the true stress-true strain curves was performed from a series of loading‒unloading tests to evaluate the evolution of those mechanical parameters with the cycle number. The elastic modulus measured in the loading steps increases monotonously with increasing values of true strain reached in the cycles. In contrast, a marginal variation is found in the values of the yield stress measured in the different cycles. The memory and variation in the mechanical behaviour and performance of MAS can be accounted for through the irreversible and reversible deformation micromechanisms and its combination in which the viscoelasticity of the material plays a leading role. These findings may be helpful to guide the biomimetic design of novel fibre materials such as spider silk gut via artificially stretching spider silk glands.

Factors Associated With Participation Rate and Predictive of Improvement After Cardiac Rehabilitation in Patients With Heart Failure.

PURPOSE: Patients with heart failure (HF) are often limited in their ability to perform exercise. Cardiac rehabilitation (CR) improves aerobic capacity and quality of life (QOL) and is recommended for patients with clinically stable HF; however, it is underutilized. The aim of this study was to investigate the factors associated with participation and completion rates and predictive of improvement after phase II CR in patients with HF. METHODS: Participation and completion rates were calculated for all patients with HF enrolled in a multidisciplinary management program from October 2008 to December 2018. Functional capacity and QOL were estimated. In patients undergoing CR, changes in peak oxygen uptake (V˙ o2peak ) were measured. RESULTS: Of 662 patients enrolled, 448 (68%) completed the cardiopulmonary exercise test (CPX). Phase II CR was recommended in 411 patients, of whom 291 (71%) participated in CR. Participation was significantly related to sex and the time interval in days between hospital discharge and the CPX. Overall, 171 patients completed 36 sessions of CR (with a completion rate of 59%). During CR, there were 18 (6%) adverse events. Cardiac rehabilitation was associated with improvement in V˙ o2peak from 1153 ± 393 to 1342 ± 470 mL/min (a 16% improvement; P < .001) and in QOL. The independent predictors of increase in V˙ o2peak included sex, age, diabetes mellitus, and entry V˙ o2peak . CONCLUSIONS: In patients with HF, factors associated with CR participation rate included sex and days between hospital discharge and the CPX. Participation in CR improved V˙ o2peak and QOL. The improvement was related to male sex, younger age, no diabetes mellitus, and higher entry V˙ o2peak .

Clinical efficacy analysis of mesenchymal stem cell therapy in patients with COVID-19: A systematic review.

BACKGROUND: Currently, ongoing trials of mesenchymal stem cells (MSC) therapies for coronavirus disease 2019 (COVID-19) have been reported. AIM: In this study, we investigated whether MSCs have therapeutic efficacy in novel COVID-19 patients. METHODS: Search terms included stem cell, MSC, umbilical cord blood, novel coronavirus, severe acute respiratory syndrome coronavirus-2 and COVID-19, applied to PubMed, the Cochrane Controlled Trials Register, EMBASE and Web of Science. RESULTS: A total of 13 eligible clinical trials met our inclusion criteria with a total of 548 patients. The analysis showed no significant decrease in C-reactive protein (CRP) levels after stem cell therapy (P = 0.11). A reduction of D-dimer levels was also not observed in patients after stem cell administration (P = 0.82). Furthermore, interleukin 6 (IL-6) demonstrated no decrease after stem cell therapy (P = 0.45). Finally, we investigated the overall survival (OS) rate after stem cell therapy in COVID-19 patients. There was a significant improvement in OS after stem cell therapy; the OS of enrolled patients who received stem cell therapy was 90.3%, whereas that of the control group was 79.8% (P = 0.02). CONCLUSION: Overall, our analysis suggests that while MSC therapy for COVID-19 patients does not significantly decrease inflammatory markers such as CRP, D-dimer and IL-6, OS is improved.

Joint Detection of Community and Structural Hole Spanner of Networks in Hyperbolic Space.

Community detection and structural hole spanner (the node bridging different communities) identification, revealing the mesoscopic and microscopic structural properties of complex networks, have drawn much attention in recent years. As the determinant of mesoscopic structure, communities and structural hole spanners discover the clustering and hierarchy of networks, which has a key impact on transmission phenomena such as epidemic transmission, information diffusion, etc. However, most existing studies address the two tasks independently, which ignores the structural correlation between mesoscale and microscale and suffers from high computational costs. In this article, we propose an algorithm for simultaneously detecting communities and structural hole spanners via hyperbolic embedding (SDHE). Specifically, we first embed networks into a hyperbolic plane, in which, the angular distribution of the nodes reveals community structures of the embedded network. Then, we analyze the critical gap to detect communities and the angular region where structural hole spanners may exist. Finally, we identify structural hole spanners via two-step connectivity. Experimental results on synthetic networks and real networks demonstrate the effectiveness of our proposed algorithm compared with several state-of-the-art methods.

Effect of positive airway pressure on cardiac troponins in patients with sleep-disordered breathing: A meta-analysis.

BACKGROUND: Cardiac troponins are highly sensitive and specific biomarkers for cardiac injury. Previous studies evaluating the effect of positive airway pressure (PAP) on cardiac troponins in patients with sleep-disordered breathing (SDB) have yielded conflicting results. The meta-analysis was performed to examine the effect of PAP on cardiac troponins in SDB patients. METHODS: PubMed, Web of Science, and EMBASE before September 2021 on original English language studies were searched. The data on cardiac troponins in both baseline and post-PAP treatment were extracted from all studies. The data on the change of cardiac troponins in both PAP and control group were extracted from randomized controlled trials. Standardized mean difference (SMD) was used to synthesize quantitative results. RESULTS: A total of 11 studies were included. PAP treatment was not associated with a significant change in cardiac troponin T between the baseline and post-PAP treatment (SMD = -0.163, 95% confidence interval [CI] = -0.652 to 0.326, z = 0.65, p = .514). The pooled estimate of SMD of cardiac troponin I between the pre- and post-PAP treatment was 0.287, and the 95% CI was -0.586 to 1.160 (z = 0.64, p = .519). The pooled SMD of change of cardiac troponin T between the PAP group and control group was -0.473 (95% CI = -1.198 to 0.252, z = 1.28, p = .201). CONCLUSIONS: This meta-analysis revealed that PAP treatment was not associated with any change of cardiac troponin in SDB patients.

[Characteristics of nutrient accumulation and vertical spatial distribution in Cunninghamia lanceolata plantation with different stand densities]. / ä¸åŒæž—åˆ†å¯†åº¦æ‰æœ¨æž—å »åˆ†ç§¯ç´¯ä¸Žåž‚ç›´ç©ºé—´åˆ†é .

The growth, biomass, nutrient content and accumulation as well as the vertical distribution of nutrient accumulation in Cunninghamia lanceolata plantation across densities of 1800, 3000, 4500 trees·hm-2 were stu-died in order to provide scientific basis for efficient cultivation of C. lanceolata plantation. The total amounts of nutrients accumulated in C. lanceolata plantation with 1800, 3000, 4500 trees·hm-2 were 1311.57, 2531.55 and 2307.33 kg·hm-2, respectively. There were significant variations among different densities. Under the same density, the order of nutrient content and accumulation in C. lanceolata plantation was total N > total K > total Ca > total Mg > total P. Moreover, the amount of nutrients in trunk and bark decreased with the increases of tree height. The amount of nutrient accumulation in persistent withered branch and leaf were allocated from middle to the upper part of tree, while the opposite was observed for fresh branch and leaf. N accumulation increased with the increases of stand densities, while the other nutrients first increased then decreased. The order of the amount of nutrient accumulation in trunk, bark, root, persistent withered branch, persistent withered leaf and litter among different densities was 4500 > 3000 > 1800 trees·hm-2, and was 3000 > 1800 > 4500 trees·hm-2 in fresh branch and leaf, and 1800 > 3000 > 4500 trees·hm-2 in understory. Under the densities of 1800 and 4500 trees·hm-2, the nutrient distribution ratio in bark was the largest, accounting for 21.6% and 19.4%. In 3000 trees·hm-2, the distribution ratio of fresh leaves reached its maximum, accounting for about 22.9%, and the next was fresh branches, which had a distribution ratio of about 17.8%. 3000 trees·hm-2 was the most appropriate density for nutrient accumulation and distribution in C. lanceolata plantation.

Madelung's disease with alcoholic liver disease and acute kidney injury: A case report.

BACKGROUND: Madelung's disease (MD) is a rare disorder of lipid metabolism, characterized by the growth of unencapsulated masses of adipose tissue symmetrically deposited around the neck, shoulders, or other sites around the body. Its pathological mechanism is not yet known. One of the most common comorbidities in MD patients is liver disease, especially chronic alcoholic liver disease (CALD); however, no reports exist of acute kidney injury (AKI) with MD. CASE SUMMARY: We report a 60-year-old man who presented with complaint of edema in the lower limbs that had persisted for 3 d. Physical examination showed subcutaneous masses around the neck, and history-taking revealed the masses to have been present for 2 years and long-term heavy drinking. Considering the clinical symptoms, along with various laboratory test results and imaging characteristics, a diagnosis was made of MD with acute exacerbation of CALD and AKI. The patient was treated with liver function protection and traditional Chinese medicine, without surgical intervention. He was advised to quit drinking. After 10 d, the edema had subsided, renal function indicators returned to normal, liver function significantly improved, and size of subcutaneous masses remained stable. CONCLUSION: In MD, concomitant liver or kidney complications are possible and monitoring of liver and kidney functions can be beneficial.

The incidence of cytokine release syndrome and neurotoxicity of CD19 chimeric antigen receptor-T cell therapy in the patient with acute lymphoblastic leukemia and lymphoma.

Our objective was to summarize the side effect of chimeric antigen receptor (CAR)-T cell therapy in patients with acute lymphocytic leukemia (ALL) and lymphoma. Two independent reviewers extracted relevant data. A total of 35 hematologic malignancy studies with CD19 CAR-T cell were included (1412 participants). Severe cytokine release syndrome (sCRS) proportion was experienced by 18.5% (95% confidence interval [CI], 0.128-0.259; P = 0.000) of 982 patients with the National Cancer Institute/Lee/common terminology criteria for adverse events grading system. The pooled neurotoxicity proportion was 21.7% (95% CI, 0.167-0.287; P = 0.000) of 747 patients with the same grading system. For all of the 25 clinical trials with the same grading system, subgroup analysis was performed. Based on the different disease type, a pooled prevalence of 35.7% was observed with event rate (ER) of 0.358 (95% CI, 0.289-0.434; P = 0.000) for ALL in 12 clinical trials. For lymphoma, a pooled prevalence of 13% was observed with ER of 0.073 (95% CI, 0.028-0.179; P = 0.000) in eight clinical trials. It was demonstrated that the patients who were older than 18 years of age have the lower sCRS incidence of 16.1% (95% CI, 0.110-0.250; P = 0.000) compared with 28.6% of the remaining population who were younger than 18 years of age (95% CI, 0.117-0.462: P = 0.023) in our analysis. Based on the different co-stimulatory domain, the sCRS of 16.5% was observed with ER of 0.175 (95% CI, 0.090-0.312; P = 0.000) for 4-1BB. The sCRS of 22.2% was observed with ER of 0.193 (95% CI, 0.107-0.322; P = 0.000) for CD28. For both the CD28 and 4-1BB, the sCRS of 17.3% was observed with ER of 0.170 (95% CI, 0.067-0.369; P = 0.003). Sub-analysis sCRS of the impact with cell dose and specific disease indication were also demonstrated. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. These results are helpful for physicians, patients and the other stakeholders to understand the adverse events and to further promote the improvement of CAR-T cell therapy in the future.

Assessment of the efficacy of passive cellular immunotherapy for glioma patients.

To evaluate the therapeutic efficacy of passive cellular immunotherapy for glioma, a total of 979 patients were assigned to the meta-analysis. PubMed and the Cochrane Central Register of Controlled Trials were searched initially from February 2018 and updated in April 2019. The overall survival (OS) rates and Karnofsky performance status (KPS) values of patients who underwent passive cellular immunotherapy were compared to those of patients who did not undergo immunotherapy. The proportion of survival rates was also evaluated in one group of clinical trials. Pooled analysis was performed with random- or fixed-effects models. Clinical trials of lymphokine-activated killer cells, cytotoxic T lymphocytes, autologous tumor-specific T lymphocytes, chimeric antigen receptor T cells, cytokine-induced killer cells, cytomegalovirus-specific T cells, and natural killer cell therapies were selected. Results showed that treatment of glioma with passive cellular immunotherapy was associated with a significantly improved 0.5-year OS (p = 0.003) as well as improved 1-, 1.5-, and 3-year OS (p ≤ 0.05). A meta-analysis of 206 patients in one group of clinical trials with 12-month follow-up showed that the overall pooled survival rate was 37.9% (p = 0.003). Analysis of KPS values demonstrated favorable results for the immunotherapy arm (p < 0.001). Thus, the present meta-analysis showed that passive cellular immunotherapy prolongs survival and improves quality of life for glioma patients, suggesting that it has some clinical benefits.

Hirsutella sinensis inhibits NLRP3 inflammasome activation to block aristolochic acid-induced renal tubular epithelial cell transdifferentiation.

In recent years, kidney damage caused by ingestion of Chinese medicinal herbs containing Aristolochic acid (AA) has attracted extensive attention. However, whether the nephrotoxicity of AA is related to NLRP3 inflammasome has not been reported. Hirsutella sinensis (HS) has a certain therapeutic effect on aristolochic acid nephropathy (AAN) and is related to NLRP3 inflammasome. Therefore, this study explores whether HS plays a role in renal injury induced by AA through NLRP3 inflammasome pathway. AA-stimulated renal tubular epithelial cells showed that AA could promote the expression of NLRP3, ASC, and α-SMA, increase the secretion and expression of caspase-1, IL-1ß, and IL-18, and inhibit the expression of E-cadherin in a dose- and time-dependent manner. When NLRP3 was down-regulated, the expression of α-SMA and E-cadherin did not change significantly, but significantly blocked the regulation of α-SMA and E-cadherin expression by AA. When AA and HS were added to renal tubular epithelial cells at the same time, the effects of AA on the expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18, and α-SMA gradually decreased to the level of control group with the increase of HS dosage. At the same time, HS can reduce the transdifferentiation of renal tubular epithelial cells by inhibiting the activation of NLRP3 inflammasome. These findings will provide important pharmacological references for the treatment of AAN and the clinical application of HS.

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies.

Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proved remarkably effective in recently published clinical trials. In this meta-analysis, we performed a systematic review in terms of the clinical response treated with CAR-T cells in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and lymphomas patients. Thirty-eight published clinical studies including 665 patients were eligible for response rate (RR) evaluation. The overall pooled RR of CD19-CAR-T cells was 72% (95% confidence interval: 62-77%). The various clinical parameters were analyzed. RR was 81% in ALL, 68% in lymphoma and 70% in CLL. RR in patients who received interleukin (IL)-2 was 70%, whereas in those who did not receive IL-2, it was 74%. RR was 75% with lymphodepletion and 56% without lymphodepletion. RR with autologous cells was 76% and 57% with allogeneic cells. In conclusion, this meta-analysis showed a high clinical RR of CD19-CAR-T cell-based immunotherapy in patients with refractory B-cell malignancies.

[The Clinical Study of Comorbidities and Systemic Inflammation in COPD].

OBJECTIVE: To assess the association between chronic obstructive pulmonary disease (COPD) comorbidities and clinical characteristics, and to explore the inflammation mechanism. METHODS: 220 stable COPD patients were included. Clinical characteristics and comorbidities were recorded, and blood samples were collected. The relationship among the number and type of comorbidities, Charlson comorbidity index (CCI), clinical characteristics and the levels of plasma inflammatory markers [interleukin (IL)-6, high sensitivity C-reaction protein (hs-CRP), tumor necrosis factor-α (TNF-α), IL-8] were studied. RESULTS: The top five comorbidities were hypertension, metabolic syndrome and diabetes osteoporosis, bronchiectasis and peripheral vascular diseases. The level of plasma IL-6 was greater in higher CCI score (≥4) group compared with lower CCI score (<4) group ( P=0.011). Levels of IL-6 and IL-8 and the number of hospitalization in prior year were positively correlated with CCI and age adjusted CCI (r<0.03, P<0.05). There was a correlation between the COPD comorbidities and systemic inflammatory response (r<0.3, P<0.05). CONCLUSION: Patients with a higher CCI score had more severe symptoms, functional impairment and higher level of inflammatory factors and high frequency of hospital admission due to acute exacerbation. The mechanism by which COPD may play a role in systemic inflammatory response deserves further study.

99mTc-Phy portal perfusion index imaging helps predict the severity of hepatitis B virus cirrhosis: a preliminary study.

OBJECTIVE: The aim was to perform exploratory research on the application of technetium phytate (Tc-Phy) portal perfusion index (PPI) imaging in predicting the complications of hepatitis B cirrhosis and their severity. PATIENTS AND METHODS: A total of 65 hepatitis B cirrhosis patients were stratified, respectively, into three groups from classes A to C according to Child-Pugh scores and five groups from stages 1 to 5 according to the five-stage prognostic system. PPIs were compared and analyzed, respectively, among the three and five groups. The correlations between PPIs and major biochemical indices of liver function were also analyzed. One-way analysis of variance was used to compare the PPIs among the various groups and a nonparametric Spearman test was used to analyze the correlations between PPIs and various biochemical indices. RESULTS: PPIs of the five groups decreased gradually from stage 1 to stage 5 (73.03±8.49, 52.96±16.22, 46.24±15.25, 29.99±17.36, and 11.50±6.37, respectively); with the exception of the difference between stages 2 and 3 (P=0.252), the differences between the remaining groups were statistically significant (P<0.05). The PPI showed positive correlations with serum total protein, serum albumin, and albumin/globulin results (r=0.292, 0.559, 0.520, respectively; P<0.05), and negative correlations with serum globulin (r=-0.366, P<0.05). CONCLUSION: Technetium phytate PPI could be a promising noninvasive and effective method for predicting the complications of hepatitis B cirrhosis and their severity; a lower PPI value indicates a higher severity of complications for hepatitis B cirrhosis patients. PPI can provide very meaningful reference data for clinical practice.

Genetic screening and functional analysis of CASP9 mutations in a Chinese cohort with neural tube defects.

AIM: Neural tube defects (NTDs) are birth defects of the nervous system and are the second most frequent cause of birth defects worldwide. The etiology of NTDs is complicated and involves both genetic and environmental factors. CASP9 is an initiator caspase in the intrinsic apoptosis pathway, which in Casp9-/- mice has been shown to result in NTDs because of decreased apoptosis. The aim of this study was to evaluate the potential genetic contribution of the CASP9 gene in human NTDs. METHODS: High-throughput sequencing was performed to screen genetic variants of CASP9 genes in 355 NTD cases and 225 matched controls. Apoptosis-relevant assays were performed on transiently transfected E9 neuroepithelial cells or human embryonic kidney 293T cells, to determine the functional characteristics of NTD-specific rare variants under complete or low folic acid (FA) status. RESULTS: We found significant expression of CASP9 rare variants in NTDs and identified 4 NTD-specific missense variants. Functional assays demonstrated that a p.Y251C variant attenuates apoptosis by reducing CASP9 protein expression and decreasing activity of the intrinsic apoptosis pathway. From this, we conclude that this variant may represent a loss-of-function mutation. A 4-time recurrent p.R191G variant did not affect intrinsic apoptosis in complete medium, while it completely inhibited apoptosis induced by low FA medium. CONCLUSION: Our findings identify a genetic link for apoptosis in human NTDs and highlight the effect of gene-environment interactions in a complex disease.

Melatonin receptor 1B gene polymorphism rs10830963 and gestational diabetes mellitus among a Chinese population - a meta-analysis of association studies.

INTRODUCTION: Studies have been conducted to investigate the association between rs10830963 of MTNR1B and the risk of gestational diabetes mellitus (GDM), but with inconclusive results. We aimed to clarify these controversies, especially with regard to the association in the Chinese population. MATERIAL AND METHODS: A systemic literature reference search inclusive to August 12, 2016 yielded 35 articles, from which 11 studies met the inclusion criteria for the final meta-analysis, including 3889 patients with GDM and 6708 controls. RESULTS: We found statistically significant associations between rs10830963 and GDM using odds ratios (ORs) and 95% confidence intervals (CIs) [GG genotype vs. CC genotype: OR = 1.70, 95% CI: 1.38-2.10; G allele vs C allele: OR = 1.27, 95% CI: 1.20-1.36; GG+CG vs. CC (dominant model): OR = 1.31, 95% CI: 1.20-1.44; GG vs CG+CC (recessive model): OR = 1.41, 95% CI: 1.26-1.58]. In subgroup analyses stratified by ethnicity, we also observed rs10830963 to be associated with significantly increased risk of GDM in all genetic models in the Chinese population. CONCLUSIONS: Our meta-analysis indicated that the rs10830963 polymorphism might serve as a risk factor of GDM in the Chinese population.

High-intensity Interval Training Improves Mitochondrial Function and Suppresses Thrombin Generation in Platelets undergoing Hypoxic Stress.

This study elucidates how high-intensity interval training (HIT) and moderate-intensity continuous training (MCT) affect mitochondrial functionality and thrombin generation (TG) in platelets following hypoxic exercise (HE, 100 W under 12% O2 for 30 min). Forty-five healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n = 15) or MCT (sustained 60%VO2max, n = 15) for 30 minutes/day, 5 days/week for 6 weeks, or to a control group (CTL, n = 15) that did not received exercise intervention. Before the intervention, HE (i) reduced the ATP-linked O2 consumption rate (OCR), the reserve capacity of OCR, and the activities of citrate synthase (CS) and succinate dehydrogenase (SDH), (ii) lowered mitochondrial membrane potential (MP) and elevated matrix oxidant burden (MOB) in platelets, and (iii) enhanced dynamic TG in platelet-rich plasma (PRP), which responses were attenuated by pretreating PRP with oligomycin or rotenone/antimycin A. However, 6-week HIT (i) increased mitochondrial OCR capacity with enhancing the CS and SDH activities and (ii) heightened mitochondrial MP with depressing MOB in platelets following HE, compared to those of MCT and CTL. Moreover, the HIT suppressed the HE-promoted dynamic TG in PRP. Hence, we conclude that the HIT simultaneously improves mitochondrial bioenergetics and suppresses dynamic TG in platelets undergoing hypoxia.

[Efficacy Comparison of Different Salvage Treatment Regimens for Patients with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively. According to the treatment regimens, 156 patients were divided into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete remission(CR), partial remissison(PR), overall survival(OS), disease-free survival(DFS) and adverse events during the treatment were analyzed, so as to compare and evaluate the efficacy and safety of the 3 different regimens. RESULTS: After 1 course of re-induction chemotherapy, CR in MAC group was significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs 34.0%)(P<0.05). The OS was not statistically significantly different among 3 groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months, respectively. The myelosuppression was the main adverse event with no significant difference among the groups(P>0.05). More patients treated with MAC regimen underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the incidence of fatal infections was not signicantly different among 3 groups(5% vs 8.9% vs 5.9%)(P>0.05). CONCLUSION: Compared with FLAG and CAG regimen, the MAC regimen can enable more AML patients with primary induction failure and refractory to achieve CR without increasing severe adverse events,therefore,this regimen may provide a opportunity for patients to recieve hematopoietic stem cell transplantation.

Assessment of Upper-Airway Configuration in Obstructive Sleep Apnea Syndrome With Computed Tomography Imaging During Müller Maneuver.

BACKGROUND: The purpose of this observational study was to investigate the relationship between upper-airway configuration assessed by CT imaging during the Müller maneuver state and the severity of obstructive sleep apnea syndrome (OSAS). METHODS: A total of 358 snoring subjects who underwent standard polysomnography and upper-airway configuration by using CT imaging were enrolled. According to the apnea-hypopnea index (AHI), subjects were classified into 4 groups: snoring group (simple snoring), AHI < 5; mild OSAS, 5 ≤ AHI < 15; moderate OSAS, 15 ≤ AHI < 30; and severe OSAS, AHI ≥ 30. We also divided the upper airway into 3 parts, named the nasopharynx, oropharynx, and hypopharynx, from the CT scan and evaluated the minimal cross-sectional area (mCSA) and the shape of each airway level and calculated upper-airway length and distance from mandibular plane to hyoid bone (MPH). RESULTS: Multivariate logistic stepwise regression analysis identified body mass index (BMI), mCSA of nasopharynx, upper-airway length, and MPH as risk factors for the severity of OSAS. When subdivided for BMI and sex, upper-airway length was a risk factor for OSAS in non-obese (BMI < 27 kg/m2) and male subjects, and MPH was a risk factor only in obese (BMI ≥ 27 kg/m2) subjects. Meanwhile, mCSA of nasopharynx was significantly associated with the severity of OSAS independent of BMI. CONCLUSIONS: Subjects with severe OSAS have more significant abnormalities of the upper airway. Obesity, mCSA of nasopharynx, upper-airway length, and MPH may contribute to the severity of OSAS. Obesity and sex should be taken into account when evaluating the abnormalities of upper-airway anatomy in snorers and patients with OSAS.

[Preliminary Clinical Efficiency of Autologous Peripheral Blood Mononuclear Cells for Treating Critical Limb Ischemia of Thromboangiitis Obliterans].

OBJECTIVE: To evaluate the long-term clinical effect of autologous peripheral blood mononuclear cells (PB-MNC) on critical limb ischemia (CLI) in patients with thromboangiitis obliterans (TAO) patients. METHODS: The clinical data of 22 patients with CLI caused by TAO from July 2004 to May 2013 were analyzed retrospectively, 22 patients were divided into 2 groups; out of them 12 cases in one group were treated with granulocyte colony-stimulating factor (G-CSF)-mobilized autologous peripheral blood mononuclear cells (auto-PBMNC group), 10 cases in another group received conservative treatment (CT group). The log-rank test was used to compare the long-term outcomes in auto-PBMNC group and CT group. RESULTS: The wound healing rate (P=0.016) and CLI-free rate (P=0.013) were significantly higher in PB-MNC group compared with that in CT group. No difference was found in amputation rates between the 2 groups (major amputation: P=0.361, minor and major amputation: P=0.867). No patients died or no serious adverse events occurred during the follow-up period. CONCLUSION: The auto-PBMNC therapy can significantly promote the wound healing, and protect against CLI in TAO patients, but the risk of amputation is not low in comparison with conservative treatment.

Sonic Hedgehog Signaling Affected by Promoter Hypermethylation Induces Aberrant Gli2 Expression in Spina Bifida.

GLI2 is a key mediator of the sonic hedgehog (Shh) signaling pathway and plays an important role in neural tube development during vertebrate embryogenesis; however, the role of gli2 in human folate-related neural tube defects remains unclear. In this study, we compared methylation status and polymorphisms of gli2 between spina bifida patients and a control group to explore the underlying mechanisms related to folate deficiency in spina bifida. No single nucleotide polymorphism was found to be significantly different between the two groups, although gli2 methylation levels were significantly increased in spina bifida samples, accompanied by aberrant GLI2 expression. Moreover, a prominent negative correlation was found between the folate level in brain tissue and the gli2 methylation status (r = -0.41, P = 0.014), and gli2 hypermethylation increased the risk of spina bifida with an odds ratio of 12.45 (95 % confidence interval: 2.71-57.22, P = 0.001). In addition, we established a cell model to illustrate the effect of gli2 expression and the accessibility of chromatin affected by methylation. High gli2 and gli1 mRNA expression was detected in 5-Aza-treated cells, while gli2 hypermethylation resulted in chromatin inaccessibility and a reduced association with nuclear proteins containing transcriptional factors. More meaningful to the pathway, the effect gene of the Shh pathway, gli1, was found to have a reduced level of expression along with a decreased expression of gli2 in our cell model. Aberrant high methylation resulted in the low expression of gli2 in spina bifida, which was affected by the change in chromatin status and the capacity of transcription factor binding.