1.Harnessing chemical communication in plant-microbiome and intra-microbiome interactions.
Hongfu LI ; Yaxin HU ; Siqi CHEN ; Yusufjon GAFFOROV ; Mengcen WANG ; Xiaoyu LIU
Journal of Zhejiang University. Science. B 2025;26(10):923-934
Chemical communication in plant-microbiome and intra-microbiome interactions weaves a complex network, critically shaping ecosystem stability and agricultural productivity. This non-contact interaction is driven by small-molecule signals that orchestrate crosstalk dynamics and beneficial association. Plants leverage these signals to distinguish between pathogens and beneficial microbes, dynamically modulate immune responses, and secrete exudates to recruit a beneficial microbiome, while microbes in turn influence plant nutrient acquisition and stress resilience. Such bidirectional chemical dialogues underpin nutrient cycling, co-evolution, microbiome assembly, and plant resistance. However, knowledge gaps persist regarding validating the key molecules involved in plant-microbe interactions. Interpreting chemical communication requires multi-omics integration to predict key information, genome editing and click chemistry to verify the function of biomolecules, and artificial intelligence (AI) models to improve resolution and accuracy. This review helps advance the understanding of chemical communication and provides theoretical support for agriculture to cope with food insecurity and climate challenges.
Microbiota/physiology*
;
Plants/microbiology*
;
Artificial Intelligence
;
Ecosystem
2.How to avoid misdiagnosis of rosacea
Chinese Journal of Dermatology 2024;57(2):119-122
In recent years, with the in-depth research on rosacea, dermatologists′ understanding of rosacea has gradually increased. However, misdiagnosis and overdiagnosis emerge as a tendency because some doctors roughly equate erythema with rosacea, neglecting the differential diagnosis with other similar skin problems. This article discusses clinical manifestations and diagnostic criteria of rosacea, elaborates on how to make a correct diagnosis, and lists key points in differential diagnosis between rosacea and other skin diseases, with a view to providing a reference for clinicians in the treatment of rosacea, and to reducing its misdiagnosis and overdiagnosis.
3.Small intestinal bacterial overgrowth in patients with rosacea: prevalence and clinical features
Guangrong MA ; Hongfu XIE ; Jiashuang LIU ; Zhonglian ZHOU ; Songqi ZOU ; Yingxue HUANG ; Ji LI
Chinese Journal of Dermatology 2024;57(2):134-140
Objective:To investigate the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with rosacea, and to analyze the relationship between breath test results and the occurrence of rosacea.Methods:Patients with rosacea were enrolled from the outpatient department of Xiangya Hospital from March 2022 to June 2023. The methane-hydrogen breath test was used to detect intestinal levels of methane and hydrogen in all patients to investigate the prevalence of SIBO. The basic information, clinical symptoms and severity, quality of life scores, gastrointestinal symptoms, and past medical history of the patients were collected. Statistical analysis was carried out by using the chi-square test, nonparametric test and multivariate logistic regression models to investigate the relationship between SIBO and the occurrence of rosacea.Results:A total of 116 patients with rosacea completed the methane-hydrogen breath test. They were aged 18 to 56 years (median [ Q1, Q3]: 25 [22, 33] years), and included 7 males (6.0%) and 109 females (94.0%) ; there were 43 cases (37.1%) of erythematotelangiectatic rosacea, and 73 (62.9%) of papulopustular rosacea. As the breath test showed, 94 patients were diagnosed with SIBO (81.0%, 95% CI: 72.7% - 87.7%) based on the breath tests, 84 showed positive hydrogen breath test results (72.4%, 95% CI: 63.3% - 80.3%), and 47 had positive methane breath test results (40.5%, 95% CI: 31.5% - 50%). Among the 67 patients with moderate to severe erythema, 33 (49.3%) showed positive methane breath test results, and 14 of 49 (28.6%) patients with mild erythema showed positive methane breath test results, with a rate difference of 20.7% ( P = 0.025, 95% CI: 13.9% - 27.5%) ; there were no significant differences in the positive rates of SIBO and hydrogen breath test results between the patients with moderate to severe erythema and those with mild erythema (both P > 0.05). No significant differences were observed in the age, gender, clinical subtypes, severity of papulopustules, flushing and burning sensation, or rosacea quality of life index scores between the SIBO-positive and -negative groups, between hydrogen-positive and -negative groups, and between methane-positive and -negative groups (all P > 0.05). Multivariate logistic regression analysis showed that methane positivity on breath test was associated with the severity of erythema in rosacea ( OR = 2.495, 95% CI: 1.102 - 5.649, P < 0.05) . Conclusions:The prevalence of SIBO was relatively high in the patients with rosacea. However, only the positive rate of methane breath test differed between the rosacea patients and non-rosacea controls, and there was some correlation between methane positivity on breath test and increased severity of rosacea erythema.
4.Clinical application of MR-guided radiotherapy based on MR-linac in esophageal cancer patients
Xinyu GAO ; Zhenjiang LI ; Hongfu SUN ; Dan HAN ; Qian ZHAO ; Chengxin LIU ; Wei HUANG
Journal of International Oncology 2024;51(1):37-42
Objective:To explore the application process, efficacy and safety of MR-guided radiotherapy based on MR-linac in esophageal cancer.Methods:The clinical data of patients with esophageal cancer treated with MR-linac at Shandong Cancer Hospital and Institute from September 2021 to July 2022 were retrospectively analyzed, to investigate the treatment process of esophageal cancer with MR-linac, and to analyze the efficacy and safety of patients. All patients received MR-guided radiotherapy, underwent CT and MR localization, target area delineation, and design of the Monaco treatment planning system plan. Adaptation-to-position adjustment was conducted during the pre-treatment evaluation. The median number of fractions was 25, the median single dose of planning target volume was 1.8 Gy, and the median total dose was 50.2 Gy. Median follow-up was 16 months.Results:Among the 12 patients in the whole group, there were 1 case of cervical esophageal cancer, 3 cases of upper thoracic esophageal cancer, 4 cases of middle thoracic esophageal cancer and 4 cases of lower thoracic esophageal cancer, including 3 cases of neoadjuvant radiotherapy and 9 cases of radical radiotherapy. All patients had a smooth treatment process. The median treatment time was 33 min, and the patients had good compliance. For patients with radical radiotherapy, one month after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 9; six months after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 6. All patients treated with neoadjuvant radiotherapy underwent surgery within 2 months, and one patient achieved pathological complete remission. The most common acute adverse reactions were radiation esophagitis (7 cases) and leukopenia in bone marrow suppression (8 cases), with late-stage adverse reactions being radiation pneumonia (1 case). The adverse reactions to radiotherapy were slight, and no grade 4 or above adverse reactions were observed.Conclusion:The clinical treatment process for esophageal cancer under MR-guided radiotherapy based on MR-linac is feasible, with good curative effects and mild adverse reactions.
5.Role and mechanisms of disulfiram in improving cardiac function and re-ducing myocardial inflammation in HFpEF rats based on NLRP3/cas-pase-1/GSDMD signaling pathway
Xuanyang SHEN ; Weidong LI ; Xiaolu JIANG ; Meiqi ZHANG ; Wentao TAN ; Yuan SHEN ; Hongfu WEN
Chinese Journal of Pathophysiology 2024;40(10):1891-1897
AIM:To investigate the role and possible mechanisms of disulfiram(DSF)in a rat model of heart failure with preserved ejection fraction(HFpEF)induced by high-fat diet(HFD)and nitric oxide blocker Nω-nitro-L-argi-nine methyl ester(L-NAME).METHODS:The HFpEF rat model was constructed using HFD and L-NAME.Sprague-Dawley rats were randomly divided into 3 groups:control group(fed with a normal diet and water),HFpEF group(fed with HFD and drinking water containing 0.5 g/L L-NAME),and DSF+HFpEF group(treated with DSF in addition to HFD and L-NAME).After 5 weeks,cardiac function of the rats was examined using echocardiography and exercise test.Myo-cardial pathological changes were detected using hematoxylin-eosin and wheat germ agglutinin staining,the degree of car-diac fibrosis was assessed using Masson staining,and apoptosis levels were observed using TUNEL staining.Western blot was performed to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),cleaved caspase-1,gasdermin D N-terminal fragment(GSDMD-N)in the myocardium,and serum level of N-terminal pro-brain natriuretic peptide(NT-proBNP),and interleukin(IL)-1β and IL-18 in the myocardium were detected by ELISA.RESULTS:Compared with control group,the rats in HFpEF group showed increased body weight,systolic blood pres-sure,diastolic blood pressure,E/E′ ratio,left ventricular anterior wall thickness at diastole and serum NT-proBNP level(P<0.05),and decreased E/A ratio and absolute value of global longitudinal strain(GLS;P<0.05).In contrast,the rats in DSF+HFpEF group showed decreased body weight,E/E′ ratio,diastolic blood pressure and serum NT-proBNP level(P<0.05),and increased E/A ratio and absolute value of GLS(P<0.05),with no significant changes in systolic blood pressure,left ventricular posterior wall thickness at diastole and left ventricular ejection fraction(P>0.05).The rats in HFpEF group had increased myocardial fibrosis area,cardiomyocyte cross-sectional area,and apoptotic rate compared with control group(P<0.05),while these indexes were reduced in DSF+HFpEF group(P<0.05).The results of Western blot and ELISA showed that the levels of NLRP3,cleaved caspase-1,GSDMD-N,IL-1β and IL-18 were increased in the myocardium of rats in HFpEF group compared with control group(P<0.05),but decreased in DSF+HFpEF group com-pared with HFpEF group(P<0.05).CONCLUSION:Disulfiram improves cardiac function and attenuates myocardial remodeling in HFpEF rats.The mechanism may be related to the modulation of NLRP3/caspase-1/GSDMD signaling path-way and the reduction of myocardial inflammatory response.
6.Paroxysmal kinesigenic dyskinesia
Chinese Journal of Neurology 2024;57(9):1020-1024
Paroxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal movement disorders, characterized by the chorea and dystonia triggered by sudden changes in movement or posture. The condition can be effectively controlled by medications such as carbamazepine and oxcarbazepine. PKD is an autosomal dominant inherited disorder, with causative genes identified as PRRT2 and TMEM151A. Due to insufficient understanding of this condition among clinicians, it is frequently misdiagnosed as epilepsy or hysteria, leading to delay of treatment. The systematic overview about the etiology, pathogenesis, epidemiology, clinical manifestations, auxiliary investigations, diagnostic criteria, differential diagnosis, therapeutic approaches, and prognosis of PKD is provided in this article.
7.Prognostic evaluation of coagulation indicators for patients with acute fatty liver of pregnancy.
Hongfu YANG ; Ming LIANG ; Pingna LI ; Ning MA ; Qilong LIU ; Rongqing SUN
Chinese Critical Care Medicine 2023;35(6):610-614
OBJECTIVE:
To explore the relevant clinical test indicators that affect the prognosis of patients with acute fatty liver of pregnancy (AFLP), and to provide a basis for early diagnosis and correct selection of treatment methods.
METHODS:
A retrospective analysis was conducted. Clinical data of AFLP patients in the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2010 to May 2021 were collected. According to the 28-day prognosis, the patients were divided into death group and survival group. The clinical data, laboratory examination indicators, and prognosis of the two groups were compared, and further binary Logistic regression analysis was used to analyze the risk factors affecting the prognosis of patients. At the same time, the values of related indicators at each time point (24, 48, 72 hours) after the start of treatment were recorded. The receiver operator characteristic curve (ROC curve) of prothrombin time (PT) and international normalized ratio (INR) for evaluating the prognosis of patients at each time point was drawn, and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of relevant indicators at each time point for the prognosis of AFLP patients.
RESULTS:
A total of 64 AFLP patients were selected. The patients developed the AFLP during pregnancy (34.5±6.8) weeks, with 14 deaths (mortality of 21.9%) and 50 survivors (survival rate of 78.1%). There was no statistically significant difference in general clinical data between the two groups of patients, including age, time from onset to visit, time from visit to cessation of pregnancy, acute physiology and chronic health evaluations II (APACHE II), hospitalization time in ICU, and total hospitalization cost. However, the proportion of male fetuses and stillbirths in the death group was higher than that in the survival group. The laboratory examination indicators including the white blood cell count (WBC), alanine transaminase (ALT), serum creatinine (SCr), PT extension, INR elevation, and hyperammonia in the death group were significantly higher than those in the survival group (all P < 0.05). Through Logistic regression analysis of the above indicators showed that PT > 14 s and INR > 1.5 were risk factors affecting the prognosis of AFLP patients [PT > 14 s: odds ratio (OR) = 1.215, 95% confidence interval (95%CI) was 1.076-1.371, INR > 1.5: OR = 0.719, 95%CI was 0.624-0.829, both P < 0.01]. ROC curve analysis showed that both PT and INR at ICU admission and 24, 48, and 72 hours of treatment can evaluate the prognosis of AFLP patients [AUC and 95%CI of PT were 0.772 (0.599-0.945), 0.763 (0.608-0.918), 0.879 (0.795-0.963), and 0.957 (0.904-1.000), respectively; AUC and 95%CI of INR were 0.808 (0.650-0.966), 0.730 (0.564-0.896), 0.854 (0.761-0.947), and 0.952 (0.896-1.000), respectively; all P < 0.05], the AUC of PT and INR after 72 hours of treatment was the highest, with higher sensitivity (93.5%, 91.8%) and specificity (90.9%, 90.9%).
CONCLUSIONS
AFLP often occurs in the middle and late stages of pregnancy, and the initial symptoms are mainly gastrointestinal symptoms. Once discovered, pregnancy should be terminated immediately. PT and INR are good indicators for evaluating AFLP patient efficacy and prognosis, and PT and INR are the best prognostic indicators after 72 hours of treatment.
Humans
;
Male
;
Prognosis
;
ROC Curve
;
Retrospective Studies
;
Intensive Care Units
;
Sepsis/diagnosis*
8.Analysis of lymphocyte subsets in patients with sepsis and its impact on prognosis.
Hongfu YANG ; Pingna LI ; Qiumin CUI ; Ning MA ; Qilong LIU ; Xiaoge SUN ; Rongqing SUN
Chinese Critical Care Medicine 2023;35(7):702-706
OBJECTIVE:
To explore the characteristics of changes in peripheral blood lymphocyte subsets in patients with sepsis in intensive care unit (ICU) and analyze their predictive value for prognosis.
METHODS:
The clinical data of sepsis patients admitted to the surgical intensive care unit (SICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were analyzed retrospectively. The patients met the diagnostic criteria of Sepsis-3 and were ≥ 18 years old. Peripheral venous blood samples were collected from all patients on the next morning after admission to SICU for routine blood test and peripheral blood lymphocyte subsets. According to the 28-day survival, the patients were divided into two groups, and the differences in immune indexes between the two groups were compared. Logistic regression analysis was used to analyze the risk factors of immune indexes that affect prognosis.
RESULTS:
(1) A total of 279 patients with sepsis were enrolled in the experiment, of which 198 patients survived at 28 days (28-day survival rate 71.0%), and 81 patients died (28-day mortality 29.0%). There were no significant differences in age (years old: 57.81±1.71 vs. 54.99±1.05) and gender (male: 60.5% vs. 63.6%) between the death group and the survival group (both P > 0.05), and the baseline data was comparable.(2) Acute physiology and chronic health evalution II (APACHE II: 22.06±0.08 vs. 14.08±0.52, P < 0.001), neutrophil percentage [NEU%: (88.90±1.09)% vs. (84.12±0.77)%, P = 0.001], procalcitonin [PCT (μg/L): 11.97±2.73 vs. 5.76±1.08, P = 0.011], platelet distribution width (fL: 16.81±0.10 vs. 16.57±0.06, P = 0.029) were higher than those in the survival group, while lymphocyte percentage [LYM%: (6.98±0.78)% vs. (10.59±0.86)%, P = 0.012], lymphocyte count [LYM (×109/L): 0.70±0.06 vs. 0.98±0.49, P = 0.002], and platelet count [PLT (×109/L): 151.38±13.96 vs. 205.80±9.38, P = 0.002], and thrombocytocrit [(0.15±0.01)% vs. (0.19±0.07)%, P = 0.012] were lower than those in the survival group. (3) There was no statistically significant difference in the percentage of lymphocyte subsets between the death group and the survival group, but the absolute value of LYM (pieces/μL: 650.24±84.67 vs. 876.64±38.02, P = 0.005), CD3+ absolute value (pieces/μL: 445.30±57.33 vs. 606.84±29.25, P = 0.006), CD3+CD4+ absolute value (pieces/μL: 239.97±26.96 vs. 353.49±18.59, P = 0.001), CD19+ absolute value (pieces/μL: 111.10±18.66 vs. 150.30±10.15, P = 0.049) in the death group was lower than those in the survival group. Other lymphocyte subsets in the death group, such as CD3+CD8+ absolute value (pieces/μL: 172.40±24.34 vs. 211.22±11.95, P = 0.112), absolute value of natural killer cell [NK (pieces/μL): 101.26±18.15 vs. 114.72±7.64, P = 0.420], absolute value of natural killer T cell [NKT (pieces/μL): 33.22±5.13 vs. 39.43±2.85, P = 0.262], CD4-CD8- absolute value (pieces/μL: 41.07±11.07 vs. 48.84±3.31, P = 0.510), CD4+CD8+ absolute value (pieces/μL: 3.39±1.45 vs. 3.47±0.36, P = 0.943) were not significantly different from those in the survival group. (4)Logistic regression analysis showed that lymphocyte subsets were not selected as immune markers with statistical significance for the prognosis of sepsis.
CONCLUSIONS
The changes of immune indexes in sepsis patients are closely related to their prognosis. Early monitoring of the above indexes can accurately evaluate the condition and prognosis of sepsis patients.
Humans
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Male
;
Adolescent
;
Retrospective Studies
;
ROC Curve
;
Sepsis/diagnosis*
;
Lymphocyte Count
;
Lymphocyte Subsets
;
Prognosis
;
Killer Cells, Natural
9.Expression level of cytokines in patients with sepsis and its effect on prognosis.
Pingna LI ; Hongfu YANG ; Qiumin CUI ; Ning MA ; Qilong LIU ; Xiaoge SUN ; Rongqing SUN
Chinese Critical Care Medicine 2023;35(12):1250-1254
OBJECTIVE:
To observe the expression level of cytokines in patients with sepsis and its effect on prognosis.
METHODS:
The clinical data of sepsis patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were analyzed retrospectively, including gender, age, and acute physiology and chronic health evaluation II (APACHE II), blood routine, procalcitonin (PCT), C-reactive protein (CRP), and cytokines levels [interleukins (IL-2, IL-4, IL-6, IL-10, IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)] within 24 hours of admission to ICU. The 28-day prognosis of the patients was followed up. The patients were divided into survival group and death group according to the prognosis. The clinical data between the two groups of sepsis patients with different prognosis were compared. Binary Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of patients with sepsis, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each risk factor for the prognosis of patients with sepsis.
RESULTS:
(1) A total of 227 patients with sepsis were enrolled, including 168 patients in the survival group (survival rate 74.0%) and 59 patients in the death group (mortality 26.0%). There were no significant differences in age (years old: 55.97±2.13 vs. 54.67±1.11) and gender (male: 71.2% vs. 57.1%) between the death group and the survival group (both P > 0.05), indicating that the baseline data of the two groups were comparable. (2) The APACHE II (19.37±0.99 vs. 14.88±0.61, P < 0.001) and PCT (μg/L: 12.39±2.94 vs. 4.14±0.90, P < 0.001) in the death group were significantly higher than those in the survival group, while the platelet count [PLT (×109/L): 144.75±12.50 vs. 215.99±11.26, P = 0.001] and thrombocytocrit [(0.14±0.01)% vs. (0.19±0.01)%, P = 0.001] were significantly lower than those in the survival group. (3) The level of IL-6 in the death group was significantly higher than that in the survival group (ng/L: 577.66±143.16 vs. 99.74±33.84, P < 0.001). There were no statistically significant differences in other cytokines, IL-2, IL-4, IL-10, TNF-α, IFN-γ and IL-17 between the death group and the survival group [IL-2 (ng/L): 2.44±0.38 vs. 2.63±0.27, P = 0.708; IL-4 (ng/L): 3.26±0.67 vs. 3.18±0.34, P = 0.913; IL-10 (ng/L): 33.22±5.13 vs. 39.43±2.85, P = 0.262; TNF-α (ng/L): 59.33±19.21 vs. 48.79±29.87, P = 0.839; IFN-γ (ng/L): 6.69±5.18 vs. 1.81±0.16, P = 0.100; IL-17 (ng/L): 2.05±0.29 vs. 2.58±0.33, P = 0.369]. (4) Binary Logistic regression analysis showed that APACHE II and IL-6 were independent risk factors affecting the prognosis of patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.050 (1.008-1.093) and 1.001 (1.000-1.002), P values were 0.019 and 0.026, respectively]. (5) ROC curve analysis showed that APACHE II and IL-6 had certain predictive value for the prognosis of patients with sepsis, the area under the ROC curve (AUC) was 0.754 (95%CI was 0.681-0.827) and 0.592 (95%CI was 0.511-0.673), P values were < 0.001 and 0.035, respectively. When the optimal cut-off value of APACHE II was 16.50 score, the sensitivity was 72.6% and the specificity was 69.9%. When the optimal cut-off value of IL-6 was 27.87 ng/L, the sensitivity was 67.2% and the specificity was 52.8%.
CONCLUSIONS
APACHE II score and IL-6 level have certain predictive value for the prognosis of patients with sepsis, the higher APACHE II score and IL-6 level, the greater the probability of death in patients with sepsis.
Humans
;
Male
;
Interleukin-10
;
Interleukin-17
;
Cytokines
;
Tumor Necrosis Factor-alpha
;
Interleukin-6
;
Retrospective Studies
;
Interleukin-2
;
Interleukin-4
;
ROC Curve
;
Sepsis/diagnosis*
;
Prognosis
;
Procalcitonin
;
Interferon-gamma
;
Intensive Care Units
10.Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations.
Peishan WANG ; Qiao WEI ; Hongfu LI ; Zhi-Ying WU
Chinese Medical Journal 2023;136(2):176-183
BACKGROUND:
Juvenile amyotrophic lateral sclerosis (JALS) is an uncommon form of amyotrophic lateral sclerosis whose age at onset (AAO) is defined as prior to 25 years. FUS mutations are the most common cause of JALS. SPTLC1 was recently identified as a disease-causative gene for JALS, which has rarely been reported in Asian populations. Little is known regarding the difference in clinical features between JALS patients carrying FUS and SPTLC1 mutations. This study aimed to screen mutations in JALS patients and to compare the clinical features between JALS patients with FUS and SPTLC1 mutations.
METHODS:
Sixteen JALS patients were enrolled, including three newly recruited patients between July 2015 and August 2018 from the Second Affiliated Hospital, Zhejiang University School of Medicine. Mutations were screened by whole-exome sequencing. In addition, clinical features such as AAO, onset site and disease duration were extracted and compared between JALS patients carrying FUS and SPTLC1 mutations through a literature review.
RESULTS:
A novel and de novo SPTLC1 mutation (c.58G>A, p.A20T) was identified in a sporadic patient. Among 16 JALS patients, 7/16 carried FUS mutations and 5/16 carried respective SPTLC1 , SETX , NEFH , DCTN1 , and TARDBP mutations. Compared with FUS mutation patients, those with SPTLC1 mutations had an earlier AAO (7.9 ± 4.6 years vs. 18.1 ± 3.9 years, P < 0.01), much longer disease duration (512.0 [416.7-607.3] months vs. 33.4 [21.6-45.1] months, P < 0.01), and no onset of bulbar.
CONCLUSION
Our findings expand the genetic and phenotypic spectrum of JALS and help to better understand the genotype-phenotype correlation of JALS.
Humans
;
Amyotrophic Lateral Sclerosis/genetics*
;
DNA Helicases/genetics*
;
Genetic Association Studies
;
Multifunctional Enzymes/genetics*
;
Mutation/genetics*
;
RNA Helicases/genetics*
;
RNA-Binding Protein FUS/genetics*
;
Serine C-Palmitoyltransferase/genetics*
;
Child, Preschool
;
Child
;
Adolescent
;
Young Adult

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