Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscular atrophy and pyramidal deficit,due to the degeneration of upper and lower motor neurons,with an average survival of approximately 3-5 years from symptom onset.The pathogenesis of the disease is not yet clear.Riluzole and edaravone are the only FDA-approved drugs to treat ALS.Riluzole prolongs life by only a few months and edaravone improves patient functionality scores in a subset of patients.Due to the unavailability of effective drugs,there is an urgent need for new treatment modalities in ALS.A growing body of evidence shows dysregulated energy metabolism in ALS patients and models.Studies also found that eating behaviors and metabolic changes correlate with the change of structure and function of the hypothalamic melanocortin system.In addition,enhancement of mitochondrial function in ATP production and/or utilization could bring some kinds of benefit to the ALS patients or models.Here,we review disturbances in energy metabolism in ALS patients and models,and provide an overview of new energy metabolism approaches in ALS.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Coronary microcirculation disorder after myocardial ischemia reperfusion （MIR） is a prominent problem in the treatment of coronary heart disease. According to the physiological commonality between “collaterals-sweat pore qi and fluid” and coronary microcirculation， and the evolution of the course of MIR， it is believed that “heart collateral stasis obstruction， sweat pore constraint and block” is the cause of coronary microcirculation disorder. The evolution of the pathogenesis can be divided into three periods. During the myocardial ischemia period， the pathogenesis is heart collaterals obstruction and sweat pores empty， while during the ischemia reperfusion period， it is internal formulation of deficiency wind， spasms of collaterals or slight heart collaterals obstruction； in the coronary microcirculation disorder period， sweat pores constraint and block， constraint transforming into heat， qi and fluid failing to diffuse are the pathogenesis. The corresponding treatment principle is assisting dredge with supplementation， and supplementing deficiency to dispel stasis； treating wind and blood simultaneously， and extinguishing wind to arrest convulsion； clearing heat and cooling blood， and diffusing qi and unblocking qi and fluid. Moreover， it is recommended to treat the heart and lungs simultaneously， and regulate the heart and liver at the same time.