1.Risk factors and resistance patterns of invasive Acinetobacter Baumannii infection in Children.
Yan Ling GE ; Qing Wen SHAN ; Yue QIU ; Shu Ping ZHOU ; Yi Bing CHENG ; Fang WANG ; Jun Wen YANG ; Chao Min WAN ; Yu ZHU ; Yi XU ; Min Xia CHEN ; Dao Jiong LIN ; Chun Hui ZHU ; Mei ZENG
Chinese Journal of Pediatrics 2022;60(8):762-768
Objective: To understand the risk factors and antibiotics-resistant patterns of invasive Acinetobacter baumannii infection in Children. Methods: This retrospective study was conducted in 6 tertiary hospitals from January 2016 to December 2018. The basic information, clinical data and the results of antimicrobial susceptibility testing were collected from the 98 pediatric inpatients with Acinetobacter baumannii isolated from blood or cerebrospinal fluid and analyzed. According to the susceptibility of the infected strains to carbapenems, they were divided into carbapenem-sensitive Acinetobacter baumannii (CSAB) group and carbapenem-resistant Acinetobacter baumannii (CRAB) group. According to the possible sources of infection, they were divided into nosocomial infection group and community infection group. Chi-square test or Fisher exact test were used to analyze categorical variables and rank sum test were used to analyze continuous variables. The risk factors of invasive CRAB infection in children were analyzed by Logistic regression. Result: There were 56 males and 42 females in 98 cases. The onset age of patients was 8 (2, 24) months. There were 62 cases (63%) from rural area. A total of 87 cases (89%) were confirmed with bloodstream infection, and 12 cases (12%) confirmed with meningitis (1 case was accompanied with bloodstream infection). In these patients, 66 cases (67%) received invasive medical procedures or surgery, 54 cases (55%) received carbapenems-containing therapy. Twenty-four cases were infected with CRAB, and 74 cases with CSAB. The onset age of cases in CRAB group was lower than that in CSAB group (4 (1, 9) vs. 10 (4, 24) months, Z=-2.16, P=0.031). The proportions of hospitalization in intensive care unit, carbapenem antibiotics using, pneumonia and adverse prognosis in CRAB group were higher than those in CSAB group (6 cases (25%) vs. 4 cases (5%), 18 cases (75%) vs. 36 cases (49%), 17 cases (71%) vs. 17 cases (23%), 6 cases (25%) vs. 4 cases (5%), χ2=5.61, 5.09, 18.32, 5.61, all P<0.05). Seventy-seven cases were nosocomial infection and 21 cases were hospital-acquired infection. The proportion of children hospitalized in high-risk wards for nosocomial infections, length of hospitalization, number of antimicrobial therapy received and duration of antimicrobial therapy were higher in the hospital associated infection group than those in the community acquired infection group (all P<0.05). Logistic regression analysis showed that children from rural area (OR=8.42, 95%CI 1.45-48.88), prior mechanical ventilation (OR=12.62, 95%CI 1.31-121.76), and prior antibiotic therapy (OR=4.90, 95%CI 1.35-17.72) were independent risk factors for CRAB infection. The resistance percentage of CSAB isolates to many classes of antibiotics was <6% except to gentamicin, which was as high as 20% (13/65). All CRAB isolates of resistant to ampicillin-sulbactam (20/20), cefepime (23/23), piperacillin (17/17), meropenem (23/23) and imipenem (24/24) were 100%. The resistance percentage to other antibiotics were up to 42%-96%. Conclusions: Most of invasive Acinetobacter baumannii infection in children in China are hospital-acquired. The outcome of invasive CRAB infection was poorer than that of CSAB infection. The drug resistance rate of CRAB strains isolated is high. Living in rural area, prior invasive mechanical ventilation and prior antibiotic therapy were independent risk factors for invasive CRAB infection. The prevention and control of nosocomial infection and appropriate use of antibiotics to reduce Acinetobacter baumannii infection.
Acinetobacter Infections/epidemiology*
;
Acinetobacter baumannii
;
Anti-Bacterial Agents/therapeutic use*
;
Carbapenems/therapeutic use*
;
Child
;
Cross Infection/epidemiology*
;
Drug Resistance, Multiple, Bacterial
;
Female
;
Humans
;
Infant
;
Male
;
Microbial Sensitivity Tests
;
Retrospective Studies
;
Risk Factors
;
Sepsis
2.Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China.
Bi-Jun SHI ; Ying LI ; Fan WU ; Zhou-Shan FENG ; Qi-Liang CUI ; Chuan-Zhong YANG ; Xiao-Tong YE ; Yi-Heng DAI ; Wei-Yi LIANG ; Xiu-Zhen YE ; Jing MO ; Lu DING ; Ben-Qing WU ; Hong-Xiang CHEN ; Chi-Wang LI ; Zhe ZHANG ; Xiao RONG ; Wei SHEN ; Wei-Min HUANG ; Bing-Yan YANG ; Jun-Feng LYU ; Hui-Wen HUANG ; Le-Ying HUO ; Hong-Ping RAO ; Wen-Kang YAN ; Xue-Jun REN ; Yong YANG ; Fang-Fang WANG ; Dong LIU ; Shi-Guang DIAO ; Xiao-Yan LIU ; Qiong MENG ; Yu WANG ; Bin WANG ; Li-Juan ZHANG ; Yu-Ge HUANG ; Dang AO ; Wei-Zhong LI ; Jie-Ling CHEN ; Yan-Ling CHEN ; Wei LI ; Zhi-Feng CHEN ; Yue-Qin DING ; Xiao-Yu LI ; Yue-Fang HUANG ; Ni-Yang LIN ; Yang-Fan CAI ; Sha-Sha HAN ; Ya JIN ; Guo-Sheng LIU ; Zhong-He WAN ; Yi BAN ; Bo BAI ; Guang-Hong LI ; Yue-Xiu YAN
Chinese Journal of Contemporary Pediatrics 2022;24(1):33-40
OBJECTIVES:
To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.
METHODS:
A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.
RESULTS:
Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).
CONCLUSIONS
There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology*
;
Female
;
Gestational Age
;
Humans
;
Infant
;
Infant, Extremely Premature
;
Infant, Newborn
;
Pregnancy
;
Respiratory Distress Syndrome, Newborn/epidemiology*
;
Retrospective Studies
;
Treatment Outcome
3.Induction of peripheral blood mononuclear cells to hepatocyte-like cells and preliminary study of cell response to injury under the effect of acetaminophen.
Ping LIU ; Biao ZHANG ; Quan ZENG ; Si Wen CHEN ; Chen GE ; Wei Hua WANG ; Chang Zheng WANG ; Wen YUE ; Jun WAN
Chinese Journal of Hepatology 2022;30(1):87-93
Objective: To establish a method for the induction of peripheral blood mononuclear cells to hepatocyte-like cells, and preliminarily investigate cell response to injury under the effect of acetaminophen (APAP). Methods: The surface marker CD45 of peripheral blood mononuclear cells wase detected cells by using flow cytometry and immunofluorescence methods. The cellular morphology of induced hepatocyte-like cells was observed under an inverted microscope. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the expression level of hepatocyte-specific genes, such as cytochrome (CY) P1A2, CYP3A4, CYP2C9, albumin (ALB), alpha-fetoprotein (AFP), and hepatocyte nuclear factor (HNF)4α mRNA. Immunofluorescence method was used to detect intracellular hepatocyte markers AFP, HNF4α, and ALB expression at the protein level. Biochemical analyzer was used to detect hepatocyte-specific secretory functions of AFP, ALB, and urea. Luciferase chemiluminescence method was used to detect the activity of key drug metabolizing enzyme CYP3A4. Colorimetric assay was used to detect the effect of the drug acetaminophen on hepatocyte-like cells, and alanine aminotransferase (ALT) was used as an indicator of liver cell injury. The statistical differences between the data were compared with t-test and rank-sum test. Results: The positive expression rate of CD45 cell surface markers isolated from peripheral blood mononuclear cells was about 98%, and hepatocyte-like cell morphology changes appeared on 15th day of induction. Compared with isolated mononuclear cells, CYP1A2, CYP3A4, CYP2C9, ALB, AFP and HNF4α mRNA was markedly elevated. The expression level of AFP, ALB and HNF4α protein were equally increased, and the secretory function of AFP, ALB and urea were enhanced. Compared with primary hepatocytes, CYP1A2, CYP2C9, AFP, HNF4α mRNA, and CYP3A4 mRNA did not decrease. The expression levels of AFP, ALB, and HNF4α proteins in the cells did not decrease, and the secretory function of AFP, ALB, and urea did not decrease. In addition, the CYP3A4 enzyme activity produced by hepatocyte-like cells was similar to that of primary hepatocytes. Compared with hepatocyte-like cells incubated without APAP, hepatocyte-like cells incubated with APAP had higher ALT level. Under the effect of APAP, the ALT level of hepatocyte-like cells was higher than isolated mononuclear cells. Conclusion: Peripheral blood mononuclear cells can be induced into hepatocyte-like cells with partial characteristics of hepatocytes, including the activity of CYP3A4, a key enzyme of hepatocyte drug metabolism. Additionally, preliminarily ALT secretory features reflect the hepatocytes injury under the effect of acetaminophen.
Acetaminophen/pharmacology*
;
Cell Differentiation
;
Cells, Cultured
;
Hepatocytes
;
Leukocytes, Mononuclear
;
RNA, Messenger
4.Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation.
Zeng-Qin WANG ; Yan GAO ; Xiao-Yue DONG ; Huai-Yan WANG ; Hong-Yan LU ; Xiao-Qing CHEN ; Mei XUE ; Jia ZHANG ; Ming-Fu WU ; Jun WAN ; Xin-Ping WU ; Zhao-Jun PAN ; Xiao-Yi DENG ; Shu-Ping HAN ; Yu QIAO ; Li YANG ; Zhang-Bin YU
Chinese Journal of Contemporary Pediatrics 2022;24(6):669-674
OBJECTIVES:
To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance.
METHODS:
A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission.
RESULTS:
A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05).
CONCLUSIONS
Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.
Case-Control Studies
;
Female
;
Follow-Up Studies
;
Humans
;
Hyperbilirubinemia, Neonatal/therapy*
;
Infant, Newborn
;
Obstetrics
;
Patient Discharge
;
Pregnancy
;
Retrospective Studies
5.Effect of Health Locus of Control on Early Rehabilitation After Anterior Cruciate Ligament Reconstruction
Yue XU ; Wei-ping LI ; Bin SONG ; Hua-mei CAI ; Wan-ting YANG ; Chuan JIANG ; Zheng-zheng ZHANG ; Zhong CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(6):1028-1034
ObjectiveTo explore the effect of health locus of control on the early rehabilitation after anterior cruciate ligament(ACL) reconstruction. MethodsFrom July 2019 to October 2019, a prospective cohort study of 155 ACL patients receiving reconstruction (male=124 and female=31) in our hospital was conducted. The general data questionnaire, MHLC-C, Tegner activity score, IKDC Score, Lysholm Score and Y-Balance Test were used for further analysis. The correlation between HLC and early rehabilitation after ACL reconstruction was explored by Wilcoxon signed-rank tests, correlation analysis and Logistics regression analysis. ResultsPositive correlations were found between the internality health locus of control (IHLC) and the IKDC score (r3m=0.77, r6m=0.70, P<0.001), as well as the Lysholm scores (r3m=0.68, r6m=0.64, P<0.001) and the Tegner activity score (r3m=0.24, r6m=0.46, P<0.05) in 3 and 6 months after surgery, and higher IHLC score indicated a better y-balance test outcome[OR 95%CI=0.86(0.76, 0.97), P=0.016]. Chance health locus of control (CHLC) was negatively correlated with the IKDC score (r3m=-0.71, r6m=-0.67, P<0.001), the Lysholm score (r3m=-0.49, r6m=-0.43, P<0.001) and the Tegner activity score (r3m=-0.22, r6m=-0.35, P<0.05) in 3 and 6 months after surgery, and higher CHLC score indicated worse outcome of y-balance test [OR 95%CI=1.26(1.12, 1.41), P<0.001]. There was a negative correlation between the Powerful others health locus of control (PHLC) and the IKDC score (r3m=-0.51, r6m=-0.50, P<0.001), the Lysholm scores (r3m=-0.36, r6m=-0.40, P<0.001), but there was no correlation with the Tegner activity score in 3 and 6 months after surgery(P>0.05). The risk of poor y-balance test increased by higher score of PHLC [OR 95%CI=1.74(1.29, 2.34), P<0.001]. ConclusionA significant correlation was found between the health locus of control and the early rehabilitation effect after ACL reconstruction. Higher internality health locus of control scores indicated a better rehabilitation outcome, while higher scores of external loci of control indicated higher risk of worse rehabilitation outcome.
6.Association between serum uric acid and subclinical cardiac damage in children with primary hypertension.
Miao HOU ; Ling SUN ; Wan-Ping ZHOU ; Yue-Yue DING ; Qiu-Qin XU ; Lei CAO ; Jie SHEN ; Dao-Ping YANG ; Hai-Tao LYU
Chinese Journal of Contemporary Pediatrics 2021;23(2):174-179
OBJECTIVE:
To evaluate the condition of subclinical cardiac damage in children with primary hypertension and the association between serum uric acid and subclinical cardiac damage.
METHODS:
A retrospective analysis was performed on the medical data of 55 children who were hospitalized and diagnosed with primary hypertension in the Department of Cardiology, Children's Hospital of Soochow University from January 2015 to June 2020. Forty-five healthy children, matched for age and sex, were enrolled as the control group. The two groups were compared in terms of clinical features, laboratory examination, and parameters for left ventricular structure, systolic function, and diastolic function. The correlation of serum uric acid with the parameters for left ventricular structure, systolic function, and diastolic function in children with primary hypertension was analyzed.
RESULTS:
Compared with the control group, the hypertension group had significantly higher left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT) (
CONCLUSIONS
Children with primary hypertension may have subclinical cardiac damage such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial enlargement, and proximal aortic dilation. Elevated serum uric acid is significantly associated with cardiac damage in children with primary hypertension.
Blood Pressure
;
Child
;
Humans
;
Hypertension/complications*
;
Hypertrophy, Left Ventricular/etiology*
;
Retrospective Studies
;
Uric Acid
7.Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis.
Miao QIAN ; Zhang-Bin YU ; Xiao-Hui CHEN ; Yan XU ; Yue-Lan MA ; Shan-Yu JIANG ; Huai-Yan WANG ; Zeng-Qin WANG ; Liang-Rong HAN ; Shuang-Shuang LI ; Hong-Yan LU ; Jun WAN ; Yan GAO ; Xiao-Qing CHEN ; Li ZHAO ; Ming-Fu WU ; Hong-Juan ZHANG ; Mei XUE ; Ling-Ling ZHU ; Zhao-Fang TIAN ; Wen-Juan TU ; Xin-Ping WU ; Shu-Ping HAN ; Xiao-Qi GU
Chinese Journal of Contemporary Pediatrics 2021;23(6):593-598
OBJECTIVE:
To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation.
METHODS:
A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (
RESULTS:
Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (
CONCLUSIONS
For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.
Birth Weight
;
Cesarean Section
;
China
;
Female
;
Gestational Age
;
Humans
;
Infant
;
Infant, Newborn
;
Infant, Premature
;
Pregnancy
;
Retrospective Studies
8.An investigation of severe neonatal hyperbilirubinemia in 13 hospitals of Jiangsu Province, China.
Qian-Qian LI ; Xiao-Yue DONG ; Yu QIAO ; Yu-Jie YIN ; Yan GAO ; Jin-Jun ZHOU ; Li YANG ; Rong-Ping ZHU ; Fu-Dong WANG ; Jun WAN ; Yan XU ; Zhao-Jun PAN ; Wei-Yuan WANG ; Jun-Mei YAN ; Shu-Ping HAN ; Hong-Yan LU ; Yu-Hua HU ; Shuang-Shuang LI ; Jin-Xiu WANG ; Ming-Fu WU ; Jun WANG ; Xiao-Yi DENG ; Zhang-Bin YU
Chinese Journal of Contemporary Pediatrics 2020;22(7):690-695
OBJECTIVE:
To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China.
METHODS:
The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data.
RESULTS:
In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates.
CONCLUSIONS
Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.
Bilirubin
;
China
;
Evoked Potentials, Auditory, Brain Stem
;
Humans
;
Hyperbilirubinemia, Neonatal
;
Infant, Newborn
;
Retrospective Studies
9.Seroprevalence of and Identification of Risk Factors in China.
Xiu Ping SONG ; Hai Bin ZHANG ; Qi Yong LIU ; Ji Min SUN ; Lei XU ; Shao Hua GU ; Wan Wan SUN ; Yu Juan YUE ; Dong Sheng REN ; Jun WANG ; Dong Mei LI
Biomedical and Environmental Sciences 2020;33(1):72-75
Serum samples were tested for IgG antibodies using indirect immunofluorescence assays. We then analyzed associated risk factors. Serum samples were considered positive when reactive at a dilution of more than 1:320. Differences between groups and risk factors associated with exposure were statistically analyzed using Chi-square tests and the generalized linear model. 122 of 1,260 samples (9.68%) were positive for infection. The infection rate ranged from 0% to 30.43% and differed significantly among age groups ( < 0.01); infection rate in the 50-59 years group was significantly higher than that in other age groups. The seroprevalence of varied significantly among sites within the four provinces, and the infection rate of field workers was significantly higher than that of urban workers.
10.Advance in Physical Activity for Brain Plasticity (review)
Ming-yue WAN ; Rui XIA ; Hui-ying LIN ; Ping-ting QIU ; Cheng-wu HUANG ; Guo-hua ZHENG
Chinese Journal of Rehabilitation Theory and Practice 2020;26(9):1071-1075
Brain plasticity is adaptability of brain to environment and experience in neural structure and function. Physical activity, such as aerobic exercise, resistance exercise, balance, and Taiji Quan, etc., can improve brain plasticity, involved various brain regions, and the mechanisms of neuronal and molecular pathways.

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