[Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF)].

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Relationship of resting heart rate and blood pressure with all-cause and cardiovascular disease mortality.

OBJECTIVES: This study aimed to investigate associations of resting heart rate (RHR) and blood pressure (BP) with all-cause and cardiovascular disease (CVD) mortality. STUDY DESIGN: A retrospective cohort study. METHODS: A total of 67,028 Chinese participants aged ≥60 years were included in the analysis. RHR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were evaluated according to quartiles ([41-69, 70-74, 75-79, 80-127 beats/min], [80-119, 120-129, 130-139, 140-238 mm Hg], and [40-70, 71-79, 80-84, 85-133 mm Hg]). Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and CVD mortality with RHR, SBP, and DBP. Restricted cubic splines were used to evaluate the dose-response association. RESULTS: During the 361,975 person-year follow-up, 9326 deaths were recorded, of which 5039 deaths were due to CVD. The risk of all-cause mortality was increased by 25% with the quartiles four vs quartile one of RHR (HR [95% CI]:1.25 [1.17-1.33]), and CVD mortality was increased by 32% (HR [95% CI]: 1.32 [1.22-1.44]). Similar results were observed when comparing the quartiles four vs quartile one of SBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.14 [1.07, 1.22] and 1.23 [1.12. 1.34]) and DBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.17 [1.11. 1.24] and 1.36 [1.26. 1.47]). We found linear associations of RHR, SBP, and DBP with all-cause and CVD mortality (Pnon-linearity >0.05), except for the approximately J-shaped association between DBP and all-cause mortality (Pnon-linearity = 0.008). There was a significant interaction of RHR and SBP with all-cause and CVD mortality (Pinteraction <0.05). CONCLUSIONS: RHR and BP increased the risk of all-cause and CVD mortality, especially fast RHR combined with high SBP.

Confronting implicit bias toward patients: a scoping review of post-graduate physician curricula.

BACKGROUND: Physicians' behavior may unknowingly be impacted by prejudice and thereby contribute to healthcare inequities. Despite increasingly robust data demonstrating physician implicit bias (The Office of Minority Health. Minority Population Profiles, 2021; COVID-19 Shines Light on Health Disparities, National Conference of State Legislatures 2021), the evidence behind how to change this with training programs remains unclear. This scoping review therefore reports on the implementation, outcomes, and characteristics of post-graduate physician implicit bias curricula. METHODS: The authors conducted a literature review using scoping review methodology. They searched 7 databases in February and November 2020 for English-language academic and gray literature on implicit bias curricula for physicians at all levels of post-graduate training. Ten reviewers screened studies for eligibility independently, then extracted data from these studies and compiled it into a chart and analytical summary. RESULTS: Of the 4,599 articles screened, this review identified 90 articles on implicit bias interventions for post-graduate physicians. Inductive data analysis revealed a spectrum of educational approaches, which were categorized int o 4 educational models called Competence, Skills-Based, Social Contact, and Critical Models. The most commonly reported strength was the interactive nature of the curricula (26%), and the most frequently identified challenges were related to time and resources available (53%). Half of the interventions discussed facilitator preparation, and the majority (62%) evaluated outcomes using pre and post self-assessments. CONCLUSIONS: This review provides a comprehensive synthesis of the literature on physician implicit bias curricula. It is our goal that this supports medical educators in applying and improving aspects of these interventions in their own programs.

[Application of ROC and PR curves in the evaluation of clinical diagnostic testing].

This study reviewed the concepts and properties of the receiver operating characteristic (ROC) curve and precision recall (PR) curve, and made suggestions on the application of two curves based on the prevalence in combination with the results of simulation data. This study demonstrated that the ROC curve and PR curve had different properties, which could reflect the performance of diagnostic methods from various aspects. These two curves should be selected with a consideration of prevalence and clinical scenarios. When the prevalence was less than 20%, especially less than 5%, the PR curve could be adopted.

[Efficacy and safety of alirocumab versus ezetimibe in high cardiovascular risk Chinese patients with hyperlipidemia: ODYSSEY EAST Study-Chinese sub-population analysis].

Objective: To compare the efficacy and safety profile of alirocumab (PCSK9 inhibitor) versus ezetimibe on top of maximally tolerated statin dose in high cardiovascular risk Chinese patients with hyperlipidemia. Methods: The ODYSSEY EAST study was a randomized, double-blinded, double dummy, active-control, parallel group, multi-centers clinical trial, the Chinese sub-population included 456 patients with hyperlipidemia and high cardiovascular risk on maximally tolerated statin dose. Patients were randomized (2∶1) to receive the subcutaneous injection of alirocumab (75 mg Q2W; with dose up titration to 150 mg Q2W at week 12 if low-density lipoprotein cholesterol (LDL-C) was ≥1.81 mmol/L at week 8) or the oral administration of ezetimibe (10 mg daily) for 24 weeks. The primary endpoint was percentage change in calculated LDL-C from baseline to week 24. Key secondary efficacy endpoints included percentage change from baseline to week 12 or 24 in LDL-C (week 12) and other lipid parameters, including apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), TC, lipoprotein(a) (Lp(a)), HDL-C, fasting triglycerides (TG), and Apo A1, and the proportion of patients reaching LDL-C<1.81 mmol/L at week 24. Safety profile of therapeutic drugs was also assessed during the treatment period. Results: The mean age of 456 Chinese patients was (59.5±10.9) years, 341(74.8%) patients were male, 303 patients (66.4%) in alirocumab group and 153 patients (33.5%) in ezetimibe group. Demographic characteristics, disease characteristics, and lipid parameters at baseline were similar between the two groups. LDL-C was reduced more from baseline to week 12 and 24 in alirocumab group versus ezetimibe group, the difference of their least-squares mean (standard error) percent change were(-35.2±2.2)% and (-36.9±2.5)% (both P<0.001). At 12 weeks, alirocumab had significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-40.3±2.8)%, (-27.7±1.8)%, (-19.6±1.5)% and (-27.7±1.9)%, respectively (all P<0.001). At 24 weeks, the percent of patients who reached LDL-C<1.81 mmol/L and LDL-C<1.42 mmol/L was significantly higher in alirocumab group (85.3% and 70.5%) than in ezetimibe group (42.2% and 17.0%, both P<0.001), and alirocumab use was also associated with significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-37.2±2.8)%, (-29.1±2.0)%, (-21.6±1.6)% and (-29.6±2.2)%, respectively (all P<0.001). The incidence of treatment related adverse events was similar between the two treatment groups (223/302 patients (73.8%) in alirocumab group and 109/153 patients (71.2%) in ezetimibe group). Respiratory infection, urinary infection, dizziness and local injection-site reactions were the most frequently reported adverse events. Conclusions: In high cardiovascular risk patients with hyperlipidemia from China on maximally tolerated statin dose, the reduction of LDL-C induced by alirocumab is more significant than that induced by ezetimibe. Both treatments were generally safe during the observation period of study.

Influences of position of ytterbium-doped fiber and ASE pump on spectral properties of random fiber laser.

The influences of the position of the ytterbium-doped fiber and the parasitic lasing in the amplified spontaneous emission (ASE) pump source on the spectral properties of the random fiber laser are analyzed and discussed in this paper. The experimental results show that putting ytterbium-doped fiber in the random fiber laser's cavity and using an ASE pump source with parasitic lasing are beneficial for the generation of high-order Stokes. A near-infrared supercontinuum with 20 dB bandwidth of more than 500 nm can be generated directly from a random fiber laser, which proved that a random laser fiber cannot only works as a traditional random fiber laser, but also can be a novel, simple, low-cost, low-coherence and robust near-infrared supercontinuum generation method.

A systemic lupus erythematosus patient with thunderclap headache: reversible cerebral vasoconstriction syndrome.

Headaches are common in patients with systemic lupus erythematosus (SLE). It is important to identify the exact cause of headaches in SLE to avoid unnecessary steroid or immunosuppressive therapy like in neuropsychiatric SLE. A 35-year-old woman with SLE suddenly developed severe headache. Magnetic resonance angiography showed multifocal segmental narrowing of cerebral arteries, suggestive of central nervous system vasculitis. However, lack of abnormal enhancement in vessel wall imaging indicated reversible cerebral vasoconstriction syndrome (RCVS) rather than central nervous system vasculitis. The patient was treated with oral nimodipine and she recovered over a period of two months. Following magnetic resonance angiography on day 90 was normal. Herein we report a case of reversible cerebral vasoconstriction syndrome in an SLE patient with literature review.

Characterization and phylogenomics of the complete mitochondrial genome of the polyzoic cestode Gangesia oligonchis (Platyhelminthes: Onchoproteocephalidea).

The order Onchoproteocephalidea (Eucestoda) was recently erected to accommodate the hook-bearing tetraphyllideans and the proteocephalideans, which are characterized by internal proglottization and a tetra-acetabulate scolex. The recognized subfamilies in the Proteocephalidae appeared to be non-monophyletic based on 28S recombinant DNA (rDNA) sequence data. Other molecular markers with higher phylogenetic resolution, such as large mitochondrial DNA fragments and multiple genes, are obviously needed. Thus the mitochondrial genome of Gangesia oligonchis, belonging to the putative earliest diverging group of the Proteocephalidae, was sequenced. The circular mitogenome of G. oligonchis was 13,958 bp in size, and contained the standard 36 genes: 22 transfer RNA genes, two rRNA genes and 12 protein-coding genes, as well as two major non-coding regions. A short NCR and a large NCR (lNCR) region were 216 bp and 419 bp in size, respectively. Highly repetitive regions in the lNCR region were detected with that of 11 repeat units. The mitogenome of G. oligonchis shared 71.1% nucleotide identity with Testudotaenia sp. WL-2016. Phylogenetic analyses of the complete mitochondrial genomes with Bayesian inference and maximum likelihood methods indicated that G. oligonchis formed a sister clade with Testudotaenia sp. WL-2016 with maximum support. The ordinal topology is (Caryophyllidea, (Diphyllobothriidea, (Bothriocephalidea, (Onchoproteocephalidea, Cyclophyllidea)))). The mitogenomic gene arrangement of G. oligonchis was identical to that of Testudotaenia sp. WL-2016. Both mitogenomic and nuclear sequence data for many more taxa are required to effectively explore the inter-relationships among the Onchoproteocephalidea.

[Effects of nasogastric and percutaneous endoscopic gastrostomy tube feeding on the susceptibility of pulmonary infection in long-term coma patients with stroke or traumatic brain injury].

Objective: To investigate the effects of nasogastric tube (NGT) and percutaneous endoscopic gastrostomy (PEG) tube feeding on the susceptibility of pulmonary infection in long-term coma patients with stroke or traumatic brain injury. Methods: A total of 295 candidates who were in long-term coma after stroke or traumatic brain injury but without pulmonary infection and eligible for PEG catheterization were screened prospectively between January 2014 and February 2018. The patients were divided into PEG group (86 patients) and NGT group (209 patients) according to the choice of next-of-kin. Data related to the susceptibility of pulmonary infection were collected and analyzed in the two groups one month after the catheterization. Results: After follow-up for one month, compared with NGT group, patients in PEG group had a lower incidence of pulmonary infection (23.3% vs 37.8%, P=0.023), a later occurrence of pulmonary infection (average time: 21 days vs 13 days, P=0.034), and a less severe pulmonary infection (7.0% vs 12.9%, P=0.029). The following characteristics made patients more susceptible to pulmonary infection: age ≥ 70 years (HR=1.619, 95% CI 1.054-2.172), Charlson comorbidity index ≥ 2 points (HR=1.647, 95% CI 1.043-2.485), using of proton pump inhibitor ≥ 7 days (HR=1.725, 95% CI 1.214-2.738), and number of pressure ulcers ≥ 3 (HR=2.109, 95% CI 1.128-3.844). However, serum albumin concentration ≥35 g/L (HR=0.670, 95% CI 0.375-0.963) was a protective factor for pulmonary infections. The number of consistent pathogens cultivated from saliva, gastric juice and sputum simultaneously in NGT and PEG group was 35 strains (27.8%) and 8 strains (13.3%), respectively (P=0.029). The mortality of pulmonary infection was similar in the two groups (3.5% vs 4.3%, P=1.000), but the death due to pulmonary infection in the PEG group occur later (median time: 20 days vs 11 days, P=0.012). Conclusions: PEG feeding was a preferred nutrition way which could reduce the risk of pulmonary infection more effectively than NGT feeding which might favored a retrograde gastro-pulmonary route by which pathogens colonized in stomach migrated to respiratory tract. Patients with characteristics mentioned above had the susceptibility of pulmonary infection, thus risk assessment of pulmonary infection should be conducted before selecting the catheterization method.

[Significance of monitoring the gradients between transcutaneous PCO(2) and end-tidal PCO(2) in patients with septic shock].

Objective: To investigate the significance of monitoring the gradients between transcutaneous PCO(2) and end-tidal PCO(2) [P(c-et)CO(2)] in patients with septic shock. Method: Thirty-five mechanically ventilated patients with early septic shock were enrolled as the study group and 18 non-septic shock patients with stable hemodynamics as the control group between May 2014 and October 2016. The patients with septic shock were treated by early goal-directed therapy (EGDT) within 6 hours since hospitalization. The differences of baseline level of P(c-et)CO(2) and arterial lactate concentration (LAC) between the two groups and the variations of these indexes after EGDT in the study group were compared respectively. Results: The baseline levels of P(c-et)CO(2) and LAC in patients with septic shock were significantly higher than those of the control group [(26.0±16.2) mmHg vs (11.0±5.6) mmHg (1 mmHg=0.133 kPa) and (4.0±1.7) mmol/L vs (1.6±0.6)mmol/L, all P=0.000]. The area under receiver operator characteristic (ROC) curve (AUC) for baseline P(c-et)CO(2) and LAC was 0.924 (95%CI: 0.851-0.996) and 0.931 (95%CI: 0.872-1.000), respectively. P(c-et)CO(2) >12.6 mmHg and LAC >2.5 mmol/L could discriminate septic shock patients from those without shock with the same sensibility of 97% and the specificity of 83% and 78% respectively. With regard to the prognosis (Day 28) of the patients with septic shock, AUC for baseline P(c-et)CO(2) and LAC was 0.709 (95%CI: 0.533-0.886) and 0.714 (95%CI: 0.545-0.883), respectively. P(c-et)CO(2) >20.0 mmHg and LAC>3.6 mmol/L could discriminate survivors from non-survivors with the same sensibility of 92% and the same specificity of 76%. All the patients in the study group completed EGDT within 6 hours after admission, 20 (57.1%) passed EGDT and 17 (85.0%) survived, 15 (42.9%) failed EGDT and 4 (26.7%) survived, and the survival rates were significantly different (F=9.844, P=0.001). After EGDT, P(c-et)CO(2) (21.0±9.5 mmHg) and LAC(3.3±2.5 mmol/L)reduced significantly compared with the baselines (P=0.008 and P=0.046), and the associated AUC was 0.905(95%CI: 0.792-1.000) and 0.747 (95%CI: 0.576-0.917)respectively. P(c-et)CO(2) > 16.5 mmHg and LAC > 3.1 mmol/L could discriminate survivors from non-survivors with the sensibility of 97% and 91%, and the specificity of 78% and 69%, respectively. Conclusions: P(c-et)CO(2) >12.6 mmHg could play the same role as LAC in recognizing early septic shock. EGDT was an effective therapy for the septic shock and P(c-et)CO(2) reflected efficacy. P(c-et)CO(2)>20 mmHg before EGDT and >16.5 mmHg after EGDT both could predict the 28 d prognosis of patients with septic shock, and the effect of the former was equal to that of LAC, but the latter was better than LAC.

[Impact of Myocardial Infarction and Abnormalities of Cardiac Conduction System on Sudden Cardiac Death].

Sudden cardiac death （SCD）, most commonly seen in coronary heart disease, is a kind of sudden death caused by series of cardiac parameters, which usually combines with myocardial infarction. However, some SCDs （including early myocardial infarction） happen suddenly and cause death in a very short time. In these circumstances, typical morphological changes are lack in macroscopic or microscopic fields, which make such SCDs become the emphasis and difficulty in the present research. SCD caused by myocardial infarction and abnormalities of cardiac conduction system （CCS） is related to atherosclerosis of coronary artery closely. This paper reviews cardiac dysfunction caused by myocardial infarction and diseases of CCS from morphology and molecular biology, and explores potential relationship between them. This paper aims to provide clues to the mechanism of myocardial infarction related sudden death and possible assistance for forensic diagnosis of SCD.

Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody.

Reliable risk assessment for biotherapeutics requires accurate evaluation of risk factors associated with immunogenicity. Immunogenicity risk assessment tools were developed and applied to investigate the immunogenicity of a fully human therapeutic monoclonal antibody, ATR-107 [anti-interleukin (IL)-21 receptor] that elicited anti-drug antibodies (ADA) in 76% of healthy subjects in a Phase 1 study. Because the ATR-107 target is expressed on dendritic cells (DCs), the immunogenicity risk related to engagement with DC and antigen presentation pathways was studied. Despite the presence of IL-21R on DCs, ATR-107 did not bind to the DCs more extensively than the control therapeutic antibody (PF-1) that had elicited low clinical ADA incidence. However, ATR-107, but not the control therapeutic antibody, was translocated to the DC late endosomes, co-localized with intracellular antigen-D related (HLA-DR) molecules and presented a dominant T cell epitope overlapping the complementarity determining region 2 (CDR2) of the light chain. ATR-107 induced increased DC activation exemplified by up-regulation of DC surface expression of CD86, CD274 (PD-L1) and CD40, increased expansion of activated DC populations expressing CD86(hi), CD40(hi), CD83(hi), programmed death ligand 1 (PD-L1)(hi), HLA-DR(hi) or CCR7(hi), as well as elevated secretion of tumour necrosis factor (TNF)-α by DCs. DCs exposed to ATR-107 stimulated an autologous T cell proliferative response in human donor cells, in concert with the detection of immunoglobulin (Ig)G-type anti-ATR-107 antibody response in clinical samples. Collectively, the enhanced engagement of antigen presentation machinery by ATR-107 was suggested. The approaches and findings described in this study may be relevant to identifying lower immunogenicity risk targets and therapeutic molecules.

The differential impact of natural killer (NK) cell education via KIR2DL3 and KIR3DL1 on CCL4 secretion in the context of in-vitro HIV infection.

Carriage of certain inhibitory natural killer (NK) cell receptor (iNKR)/HLA ligand pairs is associated with protection from infection and slow time to AIDS implicating NK cells in HIV control. NK cells acquire functional potential through education, which requires the engagement of iNKRs by their human leucocyte antigen (HLA) ligands. HIV infection down-regulates cell surface HLA-A/B, but not HLA-C/E. We investigated how NK cell populations expressing combinations of the iNKRs NKG2A, KIR2DL3 (2DL3) and KIR3DL1 (3DL1) responded to autologous HIV infected CD4 (iCD4) cells. Purified NK cells from HIV-uninfected individuals were stimulated with autologous HIV iCD4 or uninfected CD4 T cells. Using flow cytometry we gated on each of the 8 NKG2A+/- 2DL3+/- 3DL1+/- populations and analysed all possible combinations of interferon (IFN)-γ, CCL4 and CD107a functional subsets responding to iCD4 cells. Infected CD4 cells induced differential frequencies of NKG2A+/- 2DL3+/- 3DL1+/- populations with total IFN-γ+ , CCL4+ and CD107a+ functional profiles. 2DL3+ NKG2A+ NK cells had a higher frequency of responses to iCD4 than other populations studied. A higher frequency of 2DL3+ NK cells responded to iCD4 from individuals that were not HLA-C1 homozygotes. These results show that 2DL3+ NK cells are mediators of HIV-specific responses. Furthermore, responses of NK cell populations to iCD4 are influenced not only by NK cell education through specific KIR/HLA pairs, but also by differential HIV-mediated changes in HLA expression.

Identification and comparative proteomic study of quail and duck egg white protein using 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry analysis.

A proteomic study of egg white proteins from 2 major poultry species, namely quail (Coturnix coturnix) and duck (Anas platyrhynchos), was performed with comparison to those of chicken (Gallus gallus) through 2-dimensional polyacrylamide gel electrophoresis (2-DE) analysis. By using matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF MS/MS), 29 protein spots representing 10 different kinds of proteins as well as 17 protein spots designating 9 proteins were successfully identified in quail and duck egg white, respectively. This report suggested a closer relationship between quail and chicken egg white proteome patterns, whereas the duck egg white protein distribution on the 2-DE map was more distinct. In duck egg white, some well-known major proteins, such as ovomucoid, clusterin, extracellular fatty acid-binding protein precursor (ex-FABP), and prostaglandin D2 synthase (PG D2 synthase), were not detected, while two major protein spots identified as "deleted in malignant brain tumors 1" protein (DMBT1) and vitellogenin-2 were found specific to duck in the corresponding range on the 2-DE gel map. These interspecies diversities may be associated with the egg white protein functions in cell defense or regulating/supporting the embryonic development to adapt to the inhabiting environment or reproduction demand during long-term evolution. The findings of this work will give insight into the advantages involved in the application on egg white proteins from various egg sources, which may present novel beneficial properties in the food industry or related to human health.

[Effects of functional electrical stimulation based on normal gait pattern on walking function in subjects with recovery of stroke].

OBJECTIVE: To observe the effects of functional electrical stimulation(FES) based on normal gait pattern on walking function in subjects with recovery of stroke. METHODS: From December 2010 to January 2013, 58 patients with recovery of stroke were recruited from the Rehabilitation Medicine Departments of Sun Yat-sen Memorial Hospital and the Guangdong Provincial Traditional Chinese Medicine Hospital. And the Minimize software was used to divide them randomly into 1 of the 3 groups: four-channel FES group (n=29), single-channel FES group (n=15) and placebo electrical group (n=14) at the rate of 2∶1∶1. All received standardized rehabilitation program. The four-channel FES group received four-channel FES treatment based on normal gait pattern, the single-channel FES group received single-channel FES treatment, the placebo electrical group received the same electrical stimulation as the four-channel FES group, but without current output when stimulating. Stimulation lasted for 30 min/d, 1 session / d, 5 d/w for 3 weeks. All subjects in the three groups received Fugl-Meyer Assessment scale (FMA), Berg Balance scale (BBS), gait speed during a 10-meter walking test, muscle co-activation index (CI) of the lower extremity during walking and the Modified Barthel index (MBI) assessments before and after 3 weeks treatment. RESULTS: Before treatment, the FMA, BBS and gait speed during a 10-meter walking test of the four-channel FES group were (23.0±2.2), (31±71) and (0.23±0.10), respectively. After 3 weeks treatment, the scores were improved to (28.4±1.5), (42±6)and(0.43±0.09), respectively. And the FMA, BBS and gait speed during a 10-meter walking test of the ingle-channel FES group increased from (21.9±3.4), (31±6) and (0.24±0.09) to (26.6±1.8), (38±5) and (0.34±0.08), respectively. The placebo electrical group increased from (23.6±3.0), (33±5) and (0.25±0.09) respectively to (26.0±2.4), (36±4) and (0.29±0.08). And the FMA, BBS and gait speed during a 10-meter walking test of the three groups were significantly higher than those in pre-treatment (P<0.05), and the scores in four-channel FES group were significantly higher than the single-channel group and the placebo electrical group's (P<0.05). The MBI score of the three groups were all improved, but it didn't show difference among the three groups (P>0.05). The results of surface electromyography showed significant decrease in CI of quadriceps / hamstring of the 3 groups, and the four-channel FES group had more significant decrease than the other two groups (P<0.05). CONCLUSION: Functional electrical stimulation based on normal gait pattern could improve walking function in subjects with recovery of stroke.

Influence of surgical resection of hepatocellular carcinoma(HCC) for hematogenous dissemination of HCC cells and its effect on recurrence and metastasis: 3 years prospective study.

Aims was to study whether hepatal surgery leads to hematogenous dissemination of hepatocellular carcinoma (HCC) cells and determine period of its persistence by nested reverse transcription-polymerase chain reaction (RT-PCR). Peripheral vein blood (5ml) samples were obtained from 54 HCC patients of T1N0M0 and 6 HCC patients of T2N0M0 stage and 20 patients with liver cavernous hemangioma(LCH) before operation and 48h,72h and 1 week after surgical resection of hepatoma between Janurary 1st, 2007 and December 31th, 2010. We detected alpha-fetoprotein (AFP) messenger RNA(mRNA) by nested RT-PCR perioperatively.FPmRNA of all 60 cases of HCC patients and 20 cases of LCH were negative before hepatal surgery, 28 of 60 HCC cases became positve at 48h after surgery (46.7%), 16 of 60 HCC cases remained positive at 72h postoperatively(26.7%), none of 60 HCC patients AFPmRNA was detected at 1 week after hepatal surgery(0.0%). None of LCH patients were detected AFPmRNA after hepatal surgery(0.0%). For 28 HCC patients with AFPmRNA positive after hepatal surgery, 4 HCC patients developed intrahepatic tumor recurrences in 1st year (4/28, 14.3%),6 HCC patients relapsed in the second year(6/28,21.4%),10 HCC patients relapsed in the third year(10/28,35.7%). For 32 HCC patients with AFPmRNA negative group postoperation, 5 cases relapsed in 1st year (5/32, 15.6%),7 cases developed intrahepatic tumor recurrences in the second year (7/32, 21.9%),11 cases relasped in the third year (11/32, 34.4%,P>0.05),none of HCC patients occured distal metastasis after surgical resection of hepatoma. None of LCH patients relapsed postoperation within three years.Hepatal surgery may cause HCC cells spreading into peripheral blood shortly, but it may be not concerning with recurrence or metastasis of HCC.

Expression changes in epithelial cell adhesion molecule during colorectal cancer tumorigenesis.

We investigated the relationship between the expression of epithelial cell adhesion molecule (EpCAM) and the occurrence and development of colon cancer. Fifty colon cancer tissues and adjacent normal tissues were collected, while 40 normal intestinal mucosa tissues were collected as the blank group. EpCAM expression was detected by immunohistochemistry and the patients were followed-up to evaluate the prognosis. The positive expression rate of EpCAM reached 93.7% in patients with colorectal carcinoma, which was significantly higher than that in the negative control group and blank group (14.8 and 12.7%, P < 0.05, respectively). There was no significant difference between the control group and blank group regarding EpCAM expression. No direct relationship was observed between EpCAM expression and patient age, gender, and other characteristics. EpCAM was overexpressed in colorectal cancer and had a high detection rate. EpCAM can be used as a diagnostic biomarker for clinical detection of colorectal cancer.

Cloning and functional analysis of the chitinase gene promoter in peanut.

Chitinase is an important pathogenesis-related protein in plants, and it can accumulate when induced by salicylic acid (SA) or other elicitors. Here, we found that chitinase mRNA levels were 4.5-times greater when peanut seedlings were sprayed with 1.5 mM SA, as compared to water. The upstream promoter sequence of the chitinase gene was cloned by TAIL-PCR and the potential cis-regulatory elements in this promoter were predicted by the cis-element databases PLACE and plantCARE. Elements in the promoter related to SA induction and disease resistance response included AS-1, GT1-motif, GRWAAW, TGTCA, W-box, and WB-box. The full-length promoter (P) and a series of 5'-deleted promoters (P1-P5) were cloned and then substituted for the 35S promoter of pCAMBIA1301-xylA, which carries the xylose isomerase gene as the selectable marker and GUS as the reporter gene. Six plant expression vectors (pCAMBIA1301-xylA-P-pCAMBIA1301-xylA-P5) were obtained. The six expression vectors were then transferred into onion epidermal cells and peanut plants by Agrobacterium-mediated transformation. Both the full-length and deleted promoters resulted in GUS staining of the onion epidermis cells when induced by SA. In onion epidermis cells, GUS enzyme activity was greater after SA induction. In transgenic peanut plants, GUS mRNA levels were greater after SA induction. Consideration of the cis-regulatory elements predicted by PLACE and plantCARE suggested that AS-1, GRWAAW, and W-box are positive regulatory elements in P2 and P3 and that GT1-motif and TGTCA are negative regulatory elements between P and P2.