Insights into control over cognitive flexibility from studies of task-switching.

Cognitive flexibility denotes the ability to disengage from a current task and shift one's focus to a different activity. An individual's level of flexibility is not fixed; rather, people adapt their readiness to switch tasks to changing circumstances. We here review recent studies in the task-switching literature that have produced new insights into the contextual factors that drive this adaptation of flexibility, as well as proposals regarding the underlying cognitive mechanisms and learning processes. A fast-growing literature suggests that there are several different means of learning the need for, and implementing, changes in one's level of flexibility. These, in turn, have distinct consequences for the degree to which adjustments in cognitive flexibility are transferrable to new stimuli and tasks.

Task sets define boundaries of learned cognitive flexibility in list-wide proportion switch manipulations.

Different contexts in daily life often require varying levels of cognitive flexibility. Previous research has shown that people adapt their level of flexibility to match changing contextual demands for task switching in cued-switching paradigms that vary the proportion of switch trials within lists of trials. Specifically, the behavioral costs of switching as opposed to repeating tasks scale inversely with the proportion of switches-a finding referred to as the list-wide proportion switch (LWPS) effect. Previous research found that flexibility adaptations transferred across stimuli, but were specifically tied to task sets, rather than block-wide changes in flexibility state. In the current study, we conducted additional tests of the hypothesis that flexibility learning is task specific in the LWPS paradigm. In Experiments 1 and 2, we used trial-unique stimuli and unbiased task cues to control for associative learning tied to stimulus or cue features. Experiment 3 further tested whether task-specific learning occurred even for tasks performed on integrated features of the same stimuli. Across these three experiments, we found robust task-specific flexibility learning, which transferred across novel stimuli and unbiased cues and occurred regardless of stimulus-feature overlap between tasks. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

High-fat intake alleviates lung injury induced by Paragonimus proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues / 中国血吸虫病防治杂志

Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Selective contributions of executive function ability to the P3.

The P3 component (P300, P3b) is considered to be an effective index of attention and categorization processes when elicited in a visual oddball task, specifically reflecting the selection of a rare target item among frequent non-targets. Researchers have proposed that target categorization is guided by representations of target features held in working memory (WM), thus guiding attention and categorization processes to distinguish targets from non-targets. Although WM is theorized to have visuospatial, verbal and executive function components, most studies do not investigate how these WM components contribute to the P3. This study uses an individual differences approach to determine whether correlations between WM capabilities and P3 amplitudes indicate a common underlying cognitive construct. Participants (n = 140) completed an 80/20 visual oddball task to elicit the P3 as well as independent visual working memory (VWM), spatial working memory (SPWM), and executive function (task switching (TS) and digit symbol substitution (DSS)) tests. Results indicated that measures of executive function, DSS and TS, but not VWM or SPWM ability, correlated with and predicted faster task response times and greater P3 amplitudes. RT and WM measures were not correlated with P3 fractional area latencies. These results support context updating theory. Executive function WM availability, whether as a property of the participant's processing system or based on task demands, plays a functional role in the P3 and an important role in efficient visual categorization and goal-directed learning.

Neural Dynamics of Context-sensitive Adjustments in Cognitive Flexibility.

To adaptively interact with the uncertainties of daily life, we must match our level of cognitive flexibility to situations that place different demands on our ability to focus on the current task while remaining sensitive to cues that signal other, more urgent tasks. Such cognitive-flexibility adjustments in response to changing contextual demands (metaflexibility) have been observed in cued task-switching paradigms, where the performance cost incurred by switching versus repeating tasks (switch cost) scales inversely with the proportion of switches (PS) within a block of trials. However, the neural underpinnings of these adjustments in cognitive flexibility are not well understood. Here, we recorded 64-channel EEG measures of electrical brain activity as participants switched between letter and digit categorization tasks in varying PS contexts, from which we extracted ERPs elicited by the task cue and EEG alpha-power differences during both the cue-to-target interval and the resting precue period. The temporal resolution of EEG/ERPs allowed us to test whether contextual adjustments in cognitive flexibility are mediated by tonic changes in processing mode, or by changes in phasic, task-cue-triggered processes. We observed reliable modulation of behavioral switch cost by PS context that were mirrored in both cue-evoked ERP and time-frequency effects, but not in blockwide precue EEG changes. These results indicate that different levels of cognitive flexibility are instantiated in response to the presentation of task cues, rather than by being maintained as a tonic neural-activity state difference between low- and high-switch contexts.

Long-term prediction of sea surface chlorophyll-a concentration based on the combination of spatio-temporal features.

Harmful algal blooms (HABs) events have a serious impact on marine fisheries and marine management. They occur globally with high frequency and are characterized by a long duration and difficult governance. HABs incidents have occurred in the South China Sea (SCS), and the frequency of occurrence has been on the rise in recent decades. Predicting the long-term chlorophyll-a (Chl-a) concentration has the potential to facilitate long-term monitoring and early warning of HABs events. Currently, long-term predictions of ocean circulation and temperature are common, while long-term predictions of marine biochemistry are still in their infancy. Traditional Chl-a prediction methods have problems, such as low accuracy and the inability to carry out long-term predictions. This research improved the CNN-LSTM model by combining spatio-temporal features to predict Chl-a concentrations. This model can extract both the temporal and spatial features of Chl-a, expand the dataset, and improve the prediction accuracy and training speed. The predictions were made using a Chl-a dataset for the Reed Tablemount in the SCS. The time series of Chl-a used was the satellite data of NASA's official website from January 2002 to June 2020. The results indicate that the predictions of the CNN-LSTM model are better than those of the LSTM and SARIMA models. The five-year long-term rolling prediction of Chl-a was carried out, and the three-year Pearson correlation coefficient reached 0.5. The novelty of this study is the realization of a three-year long-term prediction of Chl-a concentrations. The Mann-Kendall trend test method and the least square method were used to fit the straight line to detect the trend of the five-year predicted value and the true value, respectively. The results indicated that the prediction value and true value of the sea surface Chl-a from 2015 to 2020 both exhibited an overall upward trend. In addition, the prediction performance of the model in large-scale prediction is better than that in small-scale prediction.

Investigation and analysis of influencing factors of the needs for smart elderly care services among community older adults in main urban areas of Chongqing / 中国实用护理杂志

Objective:To investigate status quo of smart elderly care needs of community older adults in main urban areas of Chongqing, and to analyze the influencing factors.Methods:A survey, using convenience sampling method, involving 452 community older adults in 9 districts in urban areas of Chongqing, was conducted by the General questionnaire and Smart Elderly Care Needs questionnaire from October to December, 2021. And analyze the influencing factors of the demand for smart elderly care needs.Results:In the demand for smart elderly care needs of the community elderly in the main urban area of Chongqing, the scores of needs for daily life care, social and emotional support, daily medical care and emergency medical assistance were 3.39 ± 1.45, 3.60 ± 1.28, 3.80 ± 1.19 and 3.87 ± 1.27, respectively. The results of ordinal Logistic analysis showed that gender, age, living alone and education level were the influencing factors of daily life care needs( P<0.05). Age and living alone were the influencing factors of social and emotional support and emergency medical assistance needs( P<0.05). Daily medical care needs were influenced by living alone( P<0.05). Conclusions:Community older adults in main urban areas of Chongqing have high level of needs for smart elderly care. Smart elderly care should focus on the ones with higher demand, namely those living alone, older, male and poorly educated, so as to promote active aging.

Adult hemophagocytic syndrome in emergency department setting: the implications of hormone therapy on diagnosis and prognosis / 中华急诊医学杂志

Objective:To assess the implications of hormone therapy on confirmation of clinical diagnosis and prognosis of adult hemophagocytic syndrome (HPS) in the emergency department setting.Methods:The eligible 34 patients admitted with suspected HPS in the Emergency Department of Peking University People's Hospital from September 2019 to August 2021 were respectively collected. The patients were divided into the death group and survival group according to the prognosis and divided into early hormone therapy group and standard hormone therapy group according to the timing of hormone application. Patients in the early hormone therapy group were divided into the routine 4 criteria group and non-routine 4 criteria group according to the conditions of meeting the four HLH-2004 diagnostic criteria. Medical records of the following were collected and statistically analyzed: complete blood count, blood biochemical index, coagulation function, serum ferritin, NK cell activity, sCD25 level, peripheral blood smear, bone marrow biopsy, abdominal ultrasound scan, and abdominal CT on admission, and recheck the clinical indicators such as blood count, blood biochemical index and blood coagulation dunction 5-7 days later.Results:①Patients from the death group were older, with higher APACHEⅡ scores and SOFA scores, higher total bilirubin, and lower serum albumin. ② Univariate Logistic analysis showed age ( OR=1.098, CI: 1.019-1.183, P=0.014), APACHE Ⅱ score ( OR=1.144, CI: 1.017-1.285, P=0.024), SOFA score ( OR=1.441, CI: 1.079-1.925, P=0.013) were associated with the risk of death. Multivariate Logistic analysis showed that age ( OR=1.099, CI: 1.014-1.190, P=0.021) was associated with the risk of death. There was no significant correlation between early hormone therapy and clinical prognosis. Kaplan-Meier survival curves showed that there was no difference in the 60-day survival rate between the early hormone therapy group and the standard hormone therapy group. ③ The level of triglyceride still increased after early hormone therapy, and the number of indexes meeting the diagnostic criteria of HLH-2004 increased significantly. All patients met the criteria of Hscore>169, and 3 patients did not meet at least 5 diagnostic criteria of HLH-2004, accounting for 16.7% of the total cases of early hormone therapy. ④ Starting hormone therapy when the four HLH-2004 diagnostic criteria were met could reduce the length of hospital stay. Prothrombin time and activited partial thomboplastin time were closer to normal levels in patients 5-7 days after treatment. Early hormone therapy had no significant effect on treatment response and in-hospital death risk. There were no significant differences in APACHE Ⅱ score, SOFA score, confirmation of diagnosis, treatment response, clinical prognosis, and related clinical indicators after hormone therapy between the routine 4 criteria and non-routine 4 criteria groups. Conclusions:Initiation of early hormone therapy has no significant effect on the confirmation of clinical diagnosis, treatment response, in-hospital mortality, and 60-day survival rate of patients with HPS, and can quickly correct coagulation dysfunction and effectively reduce the length of hospital stay. An earlier start of hormonal therapy (meeting the four HLH-2004 diagnostic criteria) may be considered by the emergency physician when a patient is highly suspected of HPS diagnosis

Minimal impact of consolidation on learned switch-readiness.

Adaptive behavior is characterized by our ability to create, maintain, and update (or switch) rules by which we categorize and respond to stimuli across changing contexts (cognitive flexibility). Recent research suggests that people can link the control process of task-switching to contextual cues through associative learning, whereby the behavioral cost of switching is reduced for contexts that require frequent switching. One example is the listwide proportion switch (LWPS) effect, denoting smaller switch costs in blocks of trials where switching is more frequent. However, the conditions that govern such learned cognitive flexibility are poorly understood. One major unanswered question is whether this type of learning benefits from memory consolidation effects. To address this question, we manipulated whether task-sets and/or specific task stimuli were more frequently linked with task-switching (vs. repeating), and ran participants over two experimental sessions, separated by a 24-hr delay. We expected that consolidation would facilitate learned cognitive flexibility, resulting in a greater reduction of switch costs with increasing task-switch likelihood on Session 2 compared with Session 1. Across two experiments, we observed robust LWPS effects in both sessions. However, we found little evidence for effects of consolidation on learned cognitive flexibility: The magnitude of the LWPS effect did not change from Session 1 to 2. Altogether our results suggest that people reliably and quickly acquire task-set and stimulus-based switch associations, but this form of control learning-unlike many instances of reward-based learning-does not benefit from long-term memory consolidation. Possible reasons for these findings are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neural Dynamics of Conflict Control in Working Memory.

Attention and working memory (WM) have classically been considered as two separate cognitive functions, but more recent theories have conceptualized them as operating on shared representations and being distinguished primarily by whether attention is directed internally (WM) or externally (attention, traditionally defined). Supporting this idea, a recent behavioral study documented a "WM Stroop effect," showing that maintaining a color word in WM impacts perceptual color-naming performance to the same degree as presenting the color word externally in the classic Stroop task. Here, we employed ERPs to examine the neural processes underlying this WM Stroop task compared to those in the classic Stroop and in a WM-control task. Based on the assumption that holding a color word in WM would (pre-)activate the same color representation as by externally presenting that color word, we hypothesized that the neural cascade of conflict-control processes would occur more rapidly in the WM Stroop than in the classic Stroop task. Our behavioral results replicated equivalent interference behavioral effects for the WM and classic Stroop tasks. Importantly, however, the ERP signatures of conflict detection and resolution displayed substantially shorter latencies in the WM Stroop task. Moreover, delay-period conflict in the WM Stroop task, but not in the WM control task, impacted the ERP and performance measures for the WM probe stimuli. Together, these findings provide new insights into how the brain processes conflict between internal representations and external stimuli, and they support the view of shared representations between internally held WM content and attentional processing of external stimuli.

Adhere to the people-centered approach and actively respond to the aging of the population—there is a lot to be done for nursing / 中国实用护理杂志

Effective response to the aging of China′s population bears on the overall development of the country and the well-being of hundreds of millions of people. From the elderly social participation, intelligent media use and calm better death as the entry point actively promote healthy aging, happy aging through the community nursing, information nursing, hospice care and other perspectives. Nursing has always adhered to the people-centered, social reality needs as the guidance. It is expected to provide reference for improving the welfare construction of the broad masses of people represented by the elderly and facilitating the all-round promotion of the Healthy China strategy.

Comparison of cognitive function in children with different subtypes of attention deficit hyperactivity disorder / 中华行为医学与脑科学杂志

Objective:To explore the heterogeneity of behavioral problems and cognitive function of three subtypes of attention deficit hyperactivity disorder(ADHD), and to analyze the related factors of cognitive function.Methods:The outpatients with ADHD were evaluated by Wechsler children′s intelligence test (C-WISC), SNAP-Ⅳ parental rating scale (SNAP-Ⅳ), Conners parental symptom questionnaire (PSQ) and 12 online cognitive function tests. The differences of behavioral problems and cognitive function of children with different subtypes of ADHD, and the correlation between their intelligence level, PSQ, SNAP-Ⅳ and cognitive function were compared by SPSS 22.0 software.Results:The results of PSQ questionnaire showed that ADHD-C ((1.11±0.59), (1.59±0.58), (1.62±0.50)) had higher behavior problems, impulse-hyperactivity and hyperactivity index than ADHD-I ((0.64±0.27), (1.01±0.54), (1.09±0.32)) and ADHD-HI ((0.75±0.35), (1.22±0.58), (1.05±0.38)) ( F=9.374, F=7.644, F=15.176, P<0.05), while ADHD-C (2.01±0.55) had higher learning problems than ADHD-I (1.66±0.58) and ADHD-HI (1.16±0.43) ( F=11.709, P<0.05). In terms of cognitive function, there were differences in language understanding ability, digital reasoning ability, sequence relationship and short-term memory ability ( χ2=6.734, 7.192, 7.822, 8.646, all P<0.05) among the three groups of ADHD children. ADHD-HI (4.00(4.00, 5.00), 5.00(4.25, 6.00), 5.00(4.00, 7.00)) had better language understanding ability, digital reasoning ability and sequence relationship than ADHD-I (3.00(2.00, 5.00), 3.00(2.50, 6.00), 4.00(3.00, 5.50)). The short-term memory ability of ADHD-HI (5.00(4.00, 6.00)) and ADHD-C (5.00(4.00, 6.00)) were better than that of ADHD-I (4.00(3.00, 5.00)). The intellectual structure of ADHD children was positively correlated with spatial cognitive ability, sequential relationship, Raven reasoning test, short term memory span and Wisconsin card sorting test ( r=0.25-0.57, all P<0.05). Children′s learning problems and psychosomatic problems were negatively correlated with their digital comprehension ability ( r=-0.26, -0.25, both P<0.05). Conclusion:The behavioral problems and cognitive function of children with different subtypes of ADHD are different and have a certain correlation.

The Trans-omics Landscape of COVID-19

System-wide molecular characteristics of COVID-19, especially in those patients without comorbidities, have not been fully investigated. We compared extensive molecular profiles of blood samples from 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Amongst the major findings, asymptomatic patients were characterized by highly activated anti-virus interferon, T/natural killer (NK) cell activation, and transcriptional upregulation of inflammatory cytokine mRNAs. However, given very abundant RNA binding proteins (RBPs), these cytokine mRNAs could be effectively destabilized hence preserving normal cytokine levels. In contrast, in critically ill patients, cytokine storm due to RBPs inhibition and tryptophan metabolites accumulation contributed to T/NK cell dysfunction. A machine-learning model was constructed which accurately stratified the COVID-19 severities based on their multi-omics features. Overall, our analysis provides insights into COVID-19 pathogenesis and identifies targets for intervening in treatment.

Contextual Adaptation of Cognitive Flexibility is driven by Task- and Item-Level Learning.

Adaptive behavior requires finding, and adjusting, an optimal tradeoff between focusing on a current task-set (cognitive stability) and updating that task-set when the environment changes (cognitive flexibility). Such dynamic adjustments of cognitive flexibility are observed in cued task-switching paradigms, where switch costs tend to decrease as the proportion of switch trials over blocks increases. However, the learning mechanisms underlying this phenomenon, here referred to as the list-wide proportion switch effect (LWPSE), are currently unknown. We addressed this question across four behavioral experiments. Experiment 1 replicated the basic LWPSE reported in previous studies. Having participants switch between three instead of two tasks, Experiment 2 demonstrated that the LWPSE is preserved even when the specific alternate task to switch to cannot be anticipated. Experiments 3a and 3b tested for the generalization of list-wide switch-readiness to an unbiased "transfer task," presented equally often as switch and repeat trials, by intermixing the transfer task with biased tasks. Despite the list-wide bias, the LWPSE was only found for biased tasks, suggesting that the modulations of switch costs are task set and/or task stimulus (item)-specific. To evaluate these two possibilities, Experiment 4 employed biased versus unbiased stimuli within biased task sets and found switch-cost modulations for both stimuli sets. These results establish how people adapt their stability-flexibility tradeoff to different contexts. Specifically, our findings show that people learn to associate context-appropriate levels of switch readiness with switch-predictive cues, provided by task sets as well as specific task stimuli.

Optimized anaesthetic strategy for laparoscopic pancreaticoduodenectomy: erector spinae plane block combined with general anesthesia / 中华麻醉学杂志

Objective:To evaluate the optimized effect of erector spinae plane block (ESPB) combined with general anesthesia when used for the patients undergoing laparoscopic pancreaticoduodenectomy.Methods:Sixty-eight American Society of Anesthesiologists physical status Ⅱ orⅢ patients of both sexes, aged 18-64 yr, with body mass index of 18-24 kg/m 2, scheduled for elective laparoscopic pancreaticoduodenectomy, were divided into general anesthesia group (group G, n=34) and ESPB combined with general anesthesia group (group EG, n=34) using a random number table method.In group E, ultrasound-guided ESPB was performed before induction with general anesthesia, and 0.375% ropivacaine 20 ml was injected into both sides.Total intravenous anesthesia was applied in both groups.Patient-controlled intravenous analgesia (PCIA) with sufentanil 1.5 g/kg in 100 ml of normal saline was performed after surgery.The PCIA pump was set up to deliver a 2 ml bolus dose with a 5-min lockout interval and background infusion at 3 ml/h.Analgesia was performed until 24 h after operation, and the visual analogue scale score at rest was maintained at ≤4.Sufentanil 0.1 g/kg was intravenously injected as rescue analgesic when visual analogue scale score >4.The extubation time and occurrence of intraoperative cardiovascular events were recorded.The amount of sufentanil used during operation and within 24 h after operation was recorded.The time to first pressing the analgesia pump after operation and effective pressing times of PCA within 24 h after operation were recorded.Time to first flatus, first ambulation time and length of postoperative hospital stay were recorded.The development of postoperative adverse reactions such as nausea and vomiting, irritability and respiratory depression within 24 h after operation was recorded. Results:Compared with group G, the incidence of intraoperative hypertension and tachycardia was significantly decreased, the extubation time was shortened, the consumption of sufentanil during operation and within 24 h after operation was reduced, the time to first pressing the analgesia pump was prolonged, the effective pressing times of PCA within 24 h after operation were reduced, time to first flatus, first ambulation time and length of postoperative hospital stay were shortened, and the incidence of nausea and vomiting, irritability and respiratory depression within 24 h after operation was decreased in group EG ( P<0.05). Conclusion:The combination of ESPB and general anesthesia is helpful in achieving an anesthesia mode of lower opioid consumption and more helpful for inhibition of postoperative pain responses and for early postoperative recovery than general anesthesia alone when used for the patients undergoing laparoscopic pancreaticoduodenectomy.

Clinical characteristics and genetic analysis of a combined inherited antithrombin and factor Ⅶ deficiency pedigree / 中华检验医学杂志

Objective:To study the clinical characteristics and gene mutations in a family with combined inherited antithrombin (AT) and factor Ⅶ (FⅦ) deficiency, and explore the relationship between AT gene, F7 gene mutations and diseases. Methods:Pedigree investigation. Blood samplesand clinical dataswere collected fromthe proband and her family members (a total of 16 people in 3 generations) who admitted to the First Affiliated Hospital of Wenzhou Medical University in November 2018. The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), antithrombin activity (AT: A), antithrombin antigen (AT: Ag), protein C activity (PC: A), protein S activity (PS: A), FⅦ activity (FⅦ: C), FⅦ antigen (FⅦ: Ag) and other indicators were detectedto confirm the diagnosis. DNA direct sequencing analysis of all exons, flanking sequences, 5′ and 3′ untranslated regions of AT genes and F7 genes, and the mutation sites were confirmed by clone sequencingor reverse sequencing. Results:The AT: A and AT: Ag of the proband were 46% and 135 mg/L, respectively (reference range: 250-360 mg/L), some of her family members′ s (father, aunt, two cousins, younger brother and nephew) AT: A and AT: Ag were reduced to 50% of normal range. Her father (Ⅰ 2), aunt (Ⅰ 4), elder brother (Ⅱ 7), younger brother (Ⅱ 8), and nephew (Ⅲ 3)′s FⅦ: C were 45%, 50%, 48%, 47% and 48%, respectively; and their FⅦ:Ag was within the normal range. Genetic analysis revealed that the proband(Ⅱ 6) and some of her family members (father, aunt, two cousins, younger brother and nephew) took rs3138521 polymorphism in the 5′ untranslated region of AT gene. Her father (Ⅰ 2), aunt (Ⅰ 4), elder brother (Ⅱ 7), younger brother (Ⅱ 8), nephew (Ⅲ 3) took c.1091G>A heterozygous missense mutationin exon 8 of F7 gene, resulting in p.Arg304Gln. Conclusion:The rs3138521 in AT gene and c.1091G>A in F7 gene, which may be the molecular mechanism leading to combined inherited AT and FⅦ deficiency in this family.

Comparison of Endocrine Therapies in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer:A Network Meta-Analysis / 한국유방암학회지

We aimed to explore what kind of endocrine treatments are optimal for hormone receptorpositive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

Phenotypic and genotypic analysis of a pedigree affected with hereditary protein C deficiency due to heterozygous deletional mutation of PROC gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the phenotype and genetic variants of a pedigree affected with hereditary protein C (PC) deficiency.@*METHODS@#The protein C activity (PC:A) of the proband and her family members (a four-generation pedigree including 11 individuals) were tested by chromogenic substrate method, and the protein C antigen (PC:Ag) was detected with an enzyme-linked immunosorbent assay(ELISA). The 9 exons and flanking sequences of the protein C (PROC) gene were amplified by PCR and directly sequenced. Suspected mutation was validated by clone sequencing and in other members of the family. MutationTaster and ClustalX-2.1-win was used to analyze the pathogenicity and conservation of the mutation site,respectively. Three-dimentional protein model and amino acids interaction were analyzed with Swiss-PdbViewer software.@*RESULTS@#The PC: A and PC: Ag of the proband were decreased to 46% (reference range: 70%-130%) and 50% (referencerange:70%-140%), respectively. Her grandmother,aunt, cousin and younger brother also showed declined PC:A and PC:Ag by approximately 50%. Genetic analysis revealed that the above individuals have all carried a deletional mutation c.1212-1212delG (p.Met364TrpfsX15) in exon 9 of the PROC gene which can cause replacement of Methionine at position 364 by Tryptophan and alteration of 15 downstream amino acids, and produce a premature stop codon at position 378. The score of MutationTaster was 1.000, indicating that the variant is pathogenic. Conservative analysis showed that the 15 altered amino acids are located in a conserved region across nine homologous species. Protein model analysis showed that the mutation has disrupted a catalytic domain of protein C thereby affected its function.@*CONCLUSION@#The heterozygous c.1212-1212delG deletional mutation in exon 9 of the PROC gene, which was unreported previously,probably accounts for the decrease of PC:A and PC:Ag in this pedigree.

Diagnosis and treatment of posttransplant lymphoproliferative diseases in liver transplant recipients: a single-center experience / 器官移植

Objective To summarize the incidence, diagnosis and treatment experience of posttransplant lymphoproliferative diseases (PTLD) in the liver transplant recipients. Methods Clinical data of 734 liver transplant recipients were retrospectively analyzed. The incidence, clinical symptoms, laboratory and imaging data of PTLD in liver transplant recipients were collected. The pathological results and treatment methods of PTLD recipients were analyzed. The prognosis of PTLD recipients was evaluated. Results The incidence of PTLD in liver transplant recipients was 2.2% (16/734). The median time of onset after operation was 8(3, 46) months. The main clinical manifestations of PTLD were fever and lymph nodes enlargement. Some patients developed anemia, hepatosplenomegaly, abnormal liver function and digestive system symptoms, etc. Among 16 PTLD recipients, 1 case showed abnormal increase in blood concentration of tacrolimus, 6 cases of elevated transaminase levels, 14 cases of increased Epstein-Barr virus (EBV) DNA load and 5 cases of increased cytomegalovirus (CMV) DNA load. Positron emission tomography and computed tomography (PET/CT) showed hypermetabolism of 18F-flurodeoxyglucose in the enlarged lymph nodes of 13 recipients. CT scan of the neck and abdomen indicated multiple lymph node enlargement in the corresponding area of 2 recipients. Lymph nodes enlargement of 1 recipient showed on ultrasound only. All 16 PTLD recipients received pathological examination. In situ hybridization showed that EBV-encoded small RNA (EBER) was positive in 13 recipients. Reducing the immunosuppressant level was the basal treatment plan for PTLD recipients, and it can be combined with rituximab-targeted therapy and chemotherapy according to different pathological types of PTLD. Surgery and radiotherapy were used for enlarged lymph nodes. One recipient died of transplant liver failure due to PTLD treatment. Conclusions Administration of immunosuppressants after liver transplantation can increase the risk of PTLD. The incidence of PTLD is higher in pediatric liver transplant recipients than in adults. Early diagnosis and reasonable treatment can significantly improve the prognosis of PTLD recipients.