1.Neuroplasticity Mechanisms of Exercise-induced Brain Protection
Li-Juan HOU ; Lan-Qun MAO ; Wei CHEN ; Ke LI ; Xu-Dong ZHAO ; Yin-Hao WANG ; Zi-Zheng YANG ; Tian-He WEI
Progress in Biochemistry and Biophysics 2025;52(6):1435-1452
Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection.
2.The Critical Roles of GABAergic Interneurons in The Pathological Progression of Alzheimer’s Disease
Ke-Han CHEN ; Zheng-Jiang YANG ; Zi-Xin GAO ; Yuan YAO ; De-Zhong YAO ; Yin YANG ; Ke CHEN
Progress in Biochemistry and Biophysics 2025;52(9):2233-2240
Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV+) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST+) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP+) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV+ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV+ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV+, SST+, and VIP+ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.
3.Results of one-year blood pressure follow-up after proximal and total renal artery denervation
Yi-Wen REN ; Hao ZHOU ; Wei-Jie CHEN ; Hua-An DU ; Bo ZHANG ; Dan LI ; Ming-Yang XIAO ; Zi-Hao WANG ; Zhi-Yu LING ; Yue-Hui YIN
Chinese Journal of Interventional Cardiology 2024;32(6):305-310
Objective To compare the efficacy of renal proximal renal artery denervation(pRDN)and full-length renal artery denervation(fRDN)for treatment of hypertension.Methods Fifty-six hypertensive patients were enrolled and randomly assigned to full-length renal artery denervation group(n=25)and proximal renal artery denervation group(n=31).After the procedure,24-hour ambulatory blood pressure monitoring(24 h-ABPM)at 6 months and office blood pressure at 12 months was recorded for statistical analysis.Results The blood pressure at follow-up reduced significantly in both groups,while there was no significant difference between groups.The baseline office blood pressure in fRDN group and pRDN group was(180±15)/(104±10)mmHg and(180±12)/(103±8)mmHg,respectively,which decreased to(142±9)/(82±7)mmHg and(143±10)/(83±6)mmHg at 12 months postoperatively(P<0.001 within groups and P>0.05 between groups).The baseline 24 h-ABPM in the two groups was(162±13)/(95±8)mmHg and(160±12)/(94±8)mmHg,respectively,which decreased to(142±11)/(83±7)mmHg and(141±8)/(81±7)mmHg at 6 months postoperatively(P<0.001 within groups and P>0.05 between groups).However,there was no significant difference in the reduction of office blood pressure and ambulatory blood pressure between the two groups.No treatment-related adverse events were observed.Conclusions pRDN has similar antihypertensive effect to fRDN.
4.Clinical Characteristics and Diagnostic Methods of Pulmonary Mucormycosis
Hai-hong CHEN ; Wei-ping TAN ; Hui-min YANG ; Peng-hao GUO ; Zi-yin YE ; Yang-li LIU ; Yu-biao GUO
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):175-180
ObjectiveTo summarize the clinical features and prognosis of pulmonary mucormycosis (PM) in southern China, and to explore the diagnostic value of metagenomic next generation sequencing (mNGS) in PM. MethodsThe clinical manifestations, diagnosis, treatment and prognosis of patients diagnosed with PM in The First Affiliated Hospital of Sun Yat-sen University from January 1, 2019 to January 31, 2022 who had undergone mNGS detection in lung tissue or alveolar lavage fluid were collected retrospectively. A total of 14 patients with PM were included, including 4 patients with confirmed diagnosis and 10 patients with clinical diagnosis. ResultsAll patients had underlying medical conditions, with hematological malignancies and diabetes being the most common. The most common symptoms were fever (n = 10), cough (n = 9) and shortness of breath (n = 9). Consolidation was the most common sign of chest CT, followed by mass, mostly with cavity. On laboratory tests, decreased CD4+T lymphocytes, elevated CD8+T lymphocytes, and decreased CD4+/CD8+ ratio, and presentation with pleural effusion indicate poor prognosis. The positive rate of mNGS diagnosis was 78.5%, which was significantly higher than that of histopathology (50%), fungus rapid fluorescence staining (61.5%) and fungal culture (23.1%) of bronchoalveolar lavage fluid. ConclusionsPulmonary mucormycosis is more likely to occur in patients with underlying diseases or who are immunocompromised. The clinical manifestations lack specificity. The low CD4/CD8 ratio and presentation of pleural effusion on CT imaging indicate poor prognosis of patients. mNGS is a rapid, convenient and sensitive method for the diagnosis of PM, which has advantages in the diagnosis of pulmonary mucormycosis.
5.Efficacy and safety of acupuncture for polycystic ovary syndrome: An overview of systematic reviews.
Han YANG ; Zhi-Yong XIAO ; Zi-Han YIN ; Zheng YU ; Jia-Jia LIU ; Yan-Qun XIAO ; Yao ZHOU ; Juan LI ; Jie YANG ; Fan-Rong LIANG
Journal of Integrative Medicine 2023;21(2):136-148
BACKGROUND:
Polycystic ovary syndrome (PCOS) is the primary cause of anovulatory infertility, bringing serious harm to women's physical and mental health. Acupuncture may be an effective treatment for PCOS. However, systematic reviews (SRs) on the efficacy and safety of acupuncture for PCOS have reported inconsistent results, and the quality of these studies has not been adequately assessed.
OBJECTIVE:
To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS, as well as to assess the quality and risks of bias of the available SRs.
SEARCH STRATEGY:
Nine electronic databases (Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, Chinese National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Chinese Science and Technology Periodical Database, and China Biology Medicine disc) were searched from their establishment to July 27, 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "acupuncture," "polycystic ovary syndrome," and "systematic review."
INCLUSION CRITERIA:
SRs of randomized controlled trials that explored the efficacy and (or) safety of acupuncture for treating patients with PCOS were included.
DATA EXTRACTION AND ANALYSIS:
Two authors independently extracted study data according to a predesigned form. Tools for evaluating the methodological quality, risk of bias, reporting quality, and confidence in study outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), were used to score the included SRs.
RESULTS:
A total of 885 studies were retrieved, and 11 eligible SRs were finally included in this review. The methodological quality of 2 SRs (18.18%) was low, while the other 9 SRs (81.82%) were scored as extremely low. Four SRs (36.36%) were considered to be of low risk of bias. As for reporting quality, the reporting completeness of 9 SRs (81.82%) was more than 70%. Concerning the confidence in study results, 2 study results were considered to have a high quality of evidence (3.13%), 14 (21.88%) a "moderate" quality, 28 (43.75%) a "low" quality, and 20 (31.24%) considered a "very low" quality. Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate (CPR) and ovulation rate, and reduce luteinizing hormone/follicle-stimulating hormone ratio, homeostasis model assessment of insulin resistance, and body mass index (BMI). When compared with medicine alone, acupuncture alone also can improve CPR. Further, when compared with no intervention, acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI. Acupuncture was reported to cause no adverse events or some adverse events without serious harm.
CONCLUSION
The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence. More high-quality studies are needed to support the use of acupuncture in PCOS.
Pregnancy
;
Humans
;
Female
;
Polycystic Ovary Syndrome/etiology*
;
Acupuncture Therapy/adverse effects*
;
Infertility, Female/etiology*
;
China
6.Smart Hip Ultrasound Technology in Screening for Infant Developmental Dysplasia of the Hip
Ying XU ; Hong-kui YU ; Xiao-ying LIN ; Yang ZHAO ; Xing-yi YANG ; Zi-yin HUANG ; Xiao XU
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(5):870-877
ObjectiveTo develop a deep learning system for early ultrasound screening of developmental dysplasia of the hip (DDH), a new smart-hip ultrasound technique (S-hip), and to validate its clinical application. MethodsWe selected 11,100 annotated and reviewed coronal ultrasound images of infant hips between November 2021 and August 2022, 8,100 of which were used for the training set and 3,000 for the test set, to build a S-hip deep learning system. To verify the consistency between the automated measurement by S-hip and the manual measurements by sonographers, 174 standard coronal ultrasound images of 87 infants' bilateral hips were acquired, then α angle, β angle and femoral head coverage (FHC) were measured by S-hip, an ultrasound expert and a resident. The measurement data and the time required for the measurements were recorded and statistically analyzed. Another 100 standard coronal ultrasound images of the hips were randomly selected and measured twice respectively by the ultrasound expert and resident to assess the intra-sonographer repeatability. ResultsThe intraclass correlation coefficient (ICC) (95% CI) values of α angle, β angle and FHC results measured by S-hip and ultrasound expert were 0.799 (0.738, 0.847), 0.798 (0.737, 0.846) and 0.934 (0.954, 0.975), respectively. Those values measured by the ultrasound expert and resident were 0.725 (0.645, 0.789), 0.674 (0.583, 0.748) and 0.931 (0.908, 0.949), respectively. The mean absolute errors (MAE) of α angle, β angle and FHC results between measurements by S-hip and ultrasound expert were 2.69 °, 4.43 ° and 2.47%, respectively. The time required for measurements by S-hip, ultrasound expert and resident was (1.59±0.36) s, (18.76±2.23) s and (19.45±2.76) s, respectively. The automated measurement by S-hip cost much shorter time than the manual measurements by sonographers and the difference was statistically significant (P<0.001). The ICC (95% CI) values of α angle, β angle and FHC results between two measurements by the ultrasound expert were 0.943 (0.916, 0.961), 0.959 (0.940, 0.972), and 0.981 (0.971, 0.987), respectively. Those values by the ultrasound resident were 0.884 (0.833, 0.921), 0.921 (0.884, 0.946), and 0.962 (0.944, 0.974). ConclusionThe S-hip based on a deep learning system is a highly reliable automated technique to accurately measure α angle, β angle and FHC. Compared with ultrasound residents, S-hip allows for a more simplified and significantly quicker measurement, which may enhance the widespread use of hip ultrasound screening in infants.
7.Research on anti-tumor mechanism of attenuated Salmonella typhimurium VNP20009
Te YIN ; Li-na LIU ; Shi-da DONG ; Bao-lian HUANG ; Chen-yang LI ; Zhi-ting CAO ; Zi-chun HUA
Acta Pharmaceutica Sinica 2023;58(9):2700-2706
Attenuated
8.Risk factors of systemic allergic reactions caused by subcutaneous allergen immunotherapy.
Li Sha LI ; Kai GUAN ; Jia YIN ; Liang Lu WANG ; Yu Xiang ZHI ; Jin Lü SUN ; Hong LI ; Li Ping WEN ; Rui TANG ; Jian Qing GU ; Zi Xi WANG ; Le CUI ; Ying Yang XU ; Sai Nan BIAN
Chinese Journal of Preventive Medicine 2023;57(12):1972-1977
Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans
;
Allergens
;
Asian People
;
Desensitization, Immunologic/adverse effects*
;
Hypersensitivity/epidemiology*
;
Retrospective Studies
9.Antimicrobial resistance and genomic characterization of Campylobacter isolates recovered from retailed poultry meat samples in 20 provinces of China in 2020.
Chang Wei WANG ; Yao BAI ; Shao Ting LI ; Zi Xin PENG ; Da Jin YANG ; Yin Ping DONG ; Jing XIAO ; Wei WANG ; Feng Qin LI
Chinese Journal of Preventive Medicine 2023;57(12):2086-2094
Objective: To understand the antimicrobial resistance and genome characteristics of Campylobacter isolates recovered from retailed poultry meat samples in 20 provinces in China in 2020. Methods: In 2020, 265 Campylobacter strains including 244 Campylobacter jejuni and 21 Campylobacter coli collected from retailed poultry meat samples in China were tested for antimicrobial resistance to 9 antimicrobial compounds by using the agar dilution method. Forty-two selected isolates were sent for whole genome sequencing and 38 high-quality genomes were analyzed for their antimicrobial resistance genes, virulence genes, sequence types and genetic diversity. Results: The resistance rates of Campylobacter isolates from poultry meats to tetracycline, nalidixic acid and ciprofloxacin were the highest (84%-100%), with 53.2% of the isolates showing multidrug resistance in this study. The resistance rates of C. coli to erythromycin, azithromycin, telithromycin, gentamicin and clindamycin were significantly higher than those of C. jejuni (P<0.05). The resistance genes conferring resistance to β-lactams (100%, 38/38), quinolones (94.7%, 36/38), tetracycline (81.6%, 31/38) and aminoglycosides (50%, 19/38) were the most frequently detected among 38 Campylobacter genomes. C. jejuni carried more virulence genes than C. coli. In total, 19 and 17 sequence types (ST) were obtained from 20 sequenced C. jejuni and 18 C. coli isolates, respectively, including 5 novel STs. The isolates showed a high genetic diversity based on their sequence types. Conclusion: The phenomenon of antimicrobial resistance in Campylobacter from poultry meat sources in China is relatively serious, and resistance and virulence genes are widely distributed in Campylobacter. There is genetic diversity in Campylobacter.
Humans
;
Animals
;
Anti-Bacterial Agents/pharmacology*
;
Campylobacter/genetics*
;
Poultry
;
Drug Resistance, Bacterial/genetics*
;
Genomics
;
China
;
Tetracycline
10.Clinical features of children with febrile seizures caused by Omicron variant infection.
Jian-Zhao ZHANG ; Zi-Qi LIU ; Zhuo-Tang ZHONG ; Xiao-Yin PENG ; Sheng-Hai YANG ; Shuo FENG ; Xin-Na JI ; Jian YANG
Chinese Journal of Contemporary Pediatrics 2023;25(6):595-599
OBJECTIVES:
To study the clinical features of children with febrile seizures after Omicron variant infection.
METHODS:
A retrospective analysis was performed on the clinical data of children with febrile seizures after Omicron variant infection who were admitted to the Department of Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, from December 1 to 31, 2022 (during the epidemic of Omicron variant; Omicron group), and the children with febrile seizures (without Omicron variant infection) who were admitted from December 1 to 31, in 2021 were included as the non-Omicron group. Clinical features were compared between the two groups.
RESULTS:
There were 381 children in the Omicron group (250 boys and 131 girls), with a mean age of (3.2±2.4) years. There were 112 children in the non-Omicron group (72 boys and 40 girls), with a mean age of (3.5±1.8) years. The number of children in the Omicron group was 3.4 times that in the non-Omicron group. The proportion of children in two age groups, aged 1 to <2 years and 6-10.83 years, in the Omicron group was higher than that in the non-Omicron group, while the proportion of children in two age groups, aged 4 to <5 years and 5 to <6 years, was lower in the Omicron group than that in the non-Omicron group (P<0.05).The Omicron group had a significantly higher proportion of children with cluster seizures and status convulsion than the non-Omicron group (P<0.05). Among the children with recurrence of febrile seizures, the proportion of children aged 6-10.83 years in the Omicron group was higher than that in the non-Omicron group, while the proportion of children aged 3 years, 4 years, and 5 years in the Omicron group was lower than that in the non-Omicron group (P<0.05).
CONCLUSIONS
Children with febrile seizures after Omicron variant infection tend to have a wider age range, with an increase in the proportion of children with cluster seizures and status convulsion during the course of fever.
Male
;
Female
;
Humans
;
Child
;
Infant
;
Child, Preschool
;
Seizures, Febrile/etiology*
;
Retrospective Studies
;
Seizures
;
Fever
;
Epidemics
;
Epilepsy, Generalized

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