1.Application evaluation of cardiopulmonary exercise test to guide comprehensive pulmonary rehabilitation in patients with pneumoconiosis
Congxia YAN ; Baoping LI ; Fuhai SHEN ; Hong CAO ; Jing LI ; Lirong ZHANG ; Zhiping SUN ; Bowen HOU ; Lini GAO ; Xinyu LI ; Chaoyi MA ; Xiaolu LIU
Journal of Environmental and Occupational Medicine 2024;41(1):47-53
Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO2/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO2), maximum metabolic equivalent (METs), and maximum work (Wmax). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO2/kg, AT, EqCO2, METs, or Wmax between the two groups (P>0.05). At the end of the trail, the indicators like pVO2/kg [(19.81±2.38) mL·(min·kg)−1], AT [(14.48±2.33) mL·(min·kg)−1], METs (5.64±0.69), and Wmax [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)−1, (11.70±1.94) mL·(min kg)−1, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO2 between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.
2.Progress of Nimotuzumab Application in Nasopharyngeal Carcinoma
Tianci LIANG ; Yue ZHAO ; Chenchen SONG ; Chaoyi ZHANG ; Chen CHEN ; Qiaoran LI ; Biaoxue RONG
Cancer Research on Prevention and Treatment 2024;51(11):956-961
Compared with the global average, the incidence rate of nasopharyngeal carcinoma (NPC) in China is higher, particularly in the southern regions where the mortality rate has remained persistently high. Nimotuzumab, a targeted therapy that acts on the epidermal growth factor receptor, has prompted continuous progress in NPC treatment. The combination of nimotuzumab with traditional radiotherapy and chemotherapy can enhance treatment efficacy, reduce adverse reactions, and improve patients’ quality of life. This article summarizes current research findings from this perspective to provide diagnostic and therapeutic strategies for NPC treatment.
3.Bibliometric analysis of ESKAPE drug‑resistant bacteria
Chaoyi GUO ; Min LI ; Yongzhang ZHU ; Xiaokui GUO
Shanghai Journal of Preventive Medicine 2024;36(2):207-215
ObjectiveTo conduct a bibliometric visual analysis of studies on Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (ESKAPE) in the past 10 years at home and abroad, and to analyze current research status and future research directions in this field based on the concept of “One health”. MethodsRelated literature on ESKAPE drug resistant bacteria from 2013 to 2022 was searched on CNKI and WoS, respectively. Furthermore, a metrological visualization analysis of authors, source of agencies, countries, and keywords was conducted by the CiteSpace 6.1.R6 software. ResultsA total of 2 991 pieces of Chinese-language and 24 497 pieces of English-language literature were included in this study. Although the number and growth rate of English-language publications were higher than those of Chinese-language publications, the number of English-language papers authored by Chinese scholars showed a significant upward trend. The level of collaboration between authors and institutions in Chinese-language publications was weaker than that in English-language publications. Overall, the country with the highest number of publications was the United States (6 623), followed by China (3 776). However, China’s annual publication volume (851) exceeded that of the United States (600) in 2022. China had collaborations with 25 countries, indicating good global cooperation, but its level of international cooperation was still slightly weaker than that of the United States. High-frequency keywords in Chinese-language literature mainly included drug resistance, nosocomial infection, and antibiotics, while high-frequency keywords in English-language literature included Staphylococcus aureus, Klebsiella pneumoniae, and methicillin-resistant. ConclusionCarbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, and "One health" are research hotspots. In the future, cross-sectoral and multi-regional collaboration should be deepened to strengthen the control of infections of important drug-resistant bacteria, and infection treatment strategies should be optimized as well.
4.Differential metabolites of bronchoalveolar lavage fluid from coal worker's pneumoconiosis patients
Chaoyi MA ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Gang CHEN ; Guoxuan MA ; Yongmei ZHAO ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xiaolu LIU ; Xinyu LI
Journal of Environmental and Occupational Medicine 2024;41(6):617-624
Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.
5.Changes in intestinal flora of coal workers' pneumoconiosis patients after tetrandrine intervention
Xiaolu LIU ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Yongmei ZHAO ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xinyu LI ; Chaoyi MA
Journal of Environmental and Occupational Medicine 2024;41(6):625-631
Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P<0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P<0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P<0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P<0.05), but the differences in Chao1 index were not statistically significant (P>0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P>0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P<0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P<0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.
6.Multi-slice spiral computerized tomography image characteristics of coal workers with pneumoconiosis
Xinyu LI ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xiaolu LIU ; Chaoyi MA
Journal of Environmental and Occupational Medicine 2024;41(7):774-779
Background Multi-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. Objective To present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. Methods From June 2022 to June 2023, a total of
7.Analysis of clinical characteristics and treatment of patients with perianal necrotizing fasciitis
Shaoban ZHU ; Dehui LI ; Da'en LIU ; Jun WEI ; Chaoyi ZHONG ; Yajun WU ; Qingwen NONG ; Shumei QIU ; Shuntang LI
Chinese Journal of Burns 2024;40(10):955-962
Objective:To investigate the clinical characteristics and treatment of patients with perianal necrotizing fasciitis.Methods:This study was a retrospective cohort study. Twenty patients with perianal necrotizing fasciitis who met the inclusion criteria were admitted to the Department of Burn and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University (hereinafter referred to as our department) from August 2013 to September 2023, including 19 males and 1 female, aged 24-74 (56±11) years. Based on the spreading route of perianal infection to the lower abdomen, the patients were divided into perianal-inguinal-lower abdominal wall group (12 cases) and perianal-pelvic cavity-retroperitoneal group (8 cases). The following clinical data were compared between the two groups of patients: general data, including gender, age, combined underlying diseases, blood glucose level and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score when admitted to our department, and laboratory risk indicator for necrotizing fasciitis (LRINEC) score when admitted to our department and at 14 d after admitted to our department; infection indicators when admitted to our department, including C-reactive protein level, white blood cell count, lymphocyte count, procalcitonin level, and lactic acid level; clinical outcome-related indicators, including time from onset to definite infection range, number of surgery, treatment in intensive care unit (ICU), length of hospital stay, treatment outcome, and recurrence of necrotizing fasciitis during follow-up; detection of pathogen and bacterial drug resistance in wound necrotic tissue specimen when admitted to our department.Results:Compared with those in perianal-inguinal-lower abdominal wall group, the APACHE Ⅱ score and lactic acid level when admitted to our department and LRINEC score at 14 d after admitted to our department (with t values of -5.98, -5.01, and -2.86, respectively, P<0.05) and ICU treatment ratio ( P<0.05) were significantly increased, the time from onset to definite infection range was significantly prolonged ( Z=-3.75, P<0.05), and the number of surgery was significantly increased ( Z=2.80, P<0.05) in patients in perianal-pelvic cavity-retroperitoneal group. There were no statistically significant differences in other data between the two groups of patients ( P>0.05). Eighteen patients were cured, and no recurrence of perianal necrotizing fasciitis was observed during follow-up of 6 months in 18 cured patients. The main bacteria were Escherichia coliand Klebsiella pneumoniae, and the fungui were Aspergillus and Candida albicans detected in wound necrotic tissue specimens in two groups of patients when admitted to our department. The ratio of multiple drug resistance of bacteria in wound necrotic tissue specimens in perianal-pelvic cavity-retroperitoneal group of patients was significantly higher than that in perianal-inguinal-lower abdominal wall group ( P<0.05). Conclusions:Perianal necrotizing fasciitis can spread to the lower abdomen through two routes: the perianal-inguinal-lower abdominal wall route and the perianal-pelvic cavity-retroperitoneal route. The latter is more insidious in disease progression and more challenging in treatment. Establishing a mechanism of multi-disciplinary team diagnosis and treatment can achieve the goal of early diagnosis and precise treatment of perianal necrotizing fasciitis.
8.Predictive value of glucose metabolism and lipid metabolism indexes for in-stent restenosis in patients with arteriosclerosis obliterans of lower limbs after surgery
Chengwen WU ; Chaoyi CUI ; Haihan KANG ; Fei LI
Journal of Xinxiang Medical College 2024;41(7):657-662
Objective To explore the predictive value of glucose metabolism and lipid metabolism indexes for in-stent restenosis(ISR)in patients with arteriosclerosis obliterans(ASO)of lower limbs after surgery.Methods A total of 160 patients with ASO of lower limbs admitted to the Second Affiliated Hospital of Zhengzhou University and Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2018 to October 2021 were selected as the research subjects.All patients were treated with percutaneous transluminal angioplasty combined with stent implantation and were followed up for 1 year.Patients were divided into the ISR group(n=59)and the non-ISR group(n=101),according to the incidence of ISR during the follow-up period.General clinical data of patients in the two groups were collected.Univariate analysis was performed to preliminarily screen out the influencing factors for ISR,and the selected indexes were further analyzed by multivariate logistic regression to analyze the influencing factors for the occurrence of ISR in patients with ASO of lower limbs after surgery.The receiver operating characteristic(ROC)curve was used to analyze the value of the glucose metabolism and lipid metabolism indexes one day before discharge alone and their combination in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery.The net benefit rate of predicting the occurrence of ISR in patients with ASO of lower limbs by the levels of glucose metabolism and lipid metabolism indexes one day before discharge alone and their combination was analyzed through the decision curve.Results Among the 160 patients,59 developed ISR,with an incidence rate of 36.88%.There was no significant difference in age,gender,alcohol consumption,complications,affected side,Fontaine stage,fasting plasma glucose,and serum triglycerides of patients between the ISR group and the non-ISR group(P>0.05);the proportion of smokers and the levels of glycosylated hemoglobin A1c(HbA1c)in peripheral blood and low-density lipoprotein(LDL)in serum of patients in the ISR group were significantly higher than those in the non-ISR group,while the level of high-density lipoprotein(HDL)in serum was significantly lower than that in the non-ISR group(P<0.05).Multivariate logistic regression analysis showed that the elevated levels of HbA1 c in peripheral blood and LDL in serum were risk factors for ISR in patients with ASO of lower limbs after surgery(odds ratio>1.00,P<0.05),and the increased level of HDL in serum was the protective factor for ISR in patients with ASO of limbs after surgery(odds ratio<1.00,P<0.05).The ROC curve showed that the area under the curve of peripheral blood HbA1c,serum LDL and HDL levels alone and their combination in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery was 0.717,0.761,0.654,and 0.824,respectively;the specificity was 0.861,0.792,0.851,and 0.663,respectively;and the sensitivity was 0.525,0.678,0.424,and 0.864,respectively.The decision curve showed that the net benefit rate for the combination of peripheral blood HbA1c,serum LDL and HDL levels one day before discharge in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery was higher than that of prediction by the said indexes alone.Conclusion Glucose metabolism index peripheral blood HbA1c and lipid metabolism indexes serum LDL and HDL have certain predictive values for the occurrence of ISR in patients with ASO of lower limbs after surgery,and the net benefit rate of the joint prediction of the three indexes is higher.
9.The Main Mechanisms of Mesenchymal Stem Cell-Based Treatments against COVID-19
Jinling LI ; Shipei HE ; Hang YANG ; Lizeai ZHANG ; Jie XIAO ; Chaoyi LIANG ; Sijia LIU
Tissue Engineering and Regenerative Medicine 2024;21(4):545-556
BACKGROUND:
Coronavirus disease 2019 (COVID-19) has a clinical manifestation of hypoxic respiratory failure and acute respiratory distress syndrome. However, COVID-19 still lacks of effective clinical treatments so far. As a promising potential treatment against COVID-19, stem cell therapy raised recently and had attracted much attention. Here we review the mechanisms of mesenchymal stem cell-based treatments against COVID-19, and provide potential cues for the effective control of COVID-19 in the future.
METHODS:
Literature is obtained from databases PubMed and Web of Science. Key words were chosen for COVID- 19, acute respiratory syndrome coronavirus 2, mesenchymal stem cells, stem cell therapy, and therapeutic mechanism. Then we summarize and critically analyze the relevant articles retrieved.
RESULTS:
Mesenchymal stem cell therapy is a potential effective treatment against COVID-19. Its therapeutic efficacy is mainly reflected in reducing severe pulmonary inflammation, reducing lung injury, improving pulmonary function, protecting and repairing lung tissue of the patients. Possible therapeutic mechanisms might include immunoregulation, antiinflammatory effect, tissue regeneration, anti-apoptosis effect, antiviral, and antibacterial effect, MSC - EVs, and so on.
CONCLUSION
Mesenchymal stem cells can effectively treat COVID-19 through immunoregulation, anti-inflammatory, tissue regeneration, anti-apoptosis, anti-virus and antibacterial, MSC - EVs, and other ways. Systematically elucidating the mechanisms of mesenchymal stem cell-based treatments for COVID-19 will provide novel insights into the follow-up research and development of new therapeutic strategies in next step.
10.Mechanism of Bugansan Decoction in ameliorating learning and memory impairment in D-galactose-induced aging rats based on AGEs/RAGE/NF-κB pathway
Wei LI ; Shuo WANG ; Jiepeng WANG ; Fang FANG ; Chaoyi FANG
Digital Chinese Medicine 2023;6(3):317-327
:
Objective To investigate the underlying mechanism of the compound Bugansan Decoction
(补肝散, BGSD) in intervening learning and memory in D-galactose (D-gal)-induced aging rats.
Methods:
A total of 40 rats were randomly assigned to four groups: control, model, BGSD [14.06 g/(kg·d)], and piracetam [0.4 g/(kg·d)] groups, with 10 rats in each group. D-gal [400 mg/(kg·d)] was injected intraperitoneally to establish the aging rat model. The rats' body weight, water intake, food intake, and gripping strength were recorded each week. The eightarm maze and step-down test were used to measure the rats' capacity for learning and memory. Liver, thymus, spleen, and brain tissues were weighed to calculate the corresponding organ indices; serum malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Hematoxylin and eosin (HE) staining was adopted to observe the pathological changes of the hippocampus; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the hippocampus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of receptors for advanced glycation end products (RAGE), nuclear factor-κB (NF-κB), TNF-α, IL-6, and IL-1β mRNA in the hippocampus. Western blot (WB) was employed to detect the expression levels of advanced glycation end products (AGEs), RAGE, and NF-κB protein in the hippocampus.
Results:
In D-gal-induced aging rats, BGSD significantly increased food intake, water intake, body weight, gripping strength, and organ indices (P < 0.05), and significantly decreased working memory error (WME), reference memory error (RME), and total memory errors (TE) in an eight-arm maze (P < 0.05). In the step-down test, step-down latency was prolonged and the frequency of errors dropped (P < 0.05). Additionally, BGSD could lessen the harm done to hippocampus neurons, increase serum SOD activity, lower MDA levels, and down-regulate the expression levels of the pro-inflammatory molecules TNF-α, IL-6, and IL-1β (P < 0.05). Further findings showed that BGSD significantly decreased hippocampal AGEs, RAGE, and NF-κB expression (P < 0.05).
Conclusion
By blocking the AGEs/RAGE/NF-κB signaling pathway, BGSD may regulate the neuroinflammatory damage in D-gal-induced aging rats, and thus improve learning and memory.

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