The main function of mitochondria is to produce energy, and the respiratory chain complex embedded in theinner membrane of mitochondria is the site of energy production. Its disorder leads to dysfunction in variousorgans, a condition called mitochondrial respiratory chain complex deficiency (MRCD), or simply, mitochondrialdisease. Over 1,500 proteins are involved in respiratory chain reactions, and only 13 of them are encoded bymitochondrial DNA (mtDNA). The rest are coded by nuclear genes. Currently, there are more than 420 genes recognized to cause MRCD, and many of them are nuclear. MRCD caused by mtDNA mutations is maternally inherited, while that caused by nuclear genes is inherited in an autosomal recessive, autosomal dominant, or X-linkedmanner. Over 3,000 cases of pediatric MRCD have been analyzed in Japan since 2007, and over 480 cases havebeen genetically diagnosed. The most frequent genetic causes of MRCD in Japan are MT-TL1, MT-ATP6, PDHA1,ECHS1, and MT-ND6. Cases with younger onset are more likely to be caused by mutations in nuclear genes.Recently, novel nuclear genes such as GTPBP3, IARS and ATAD3 have been reported to cause MRCD. We arenow aware that MRCD may be the cause of many diseases in children, including cardiomyopathies, neonatal fatalhyperlactatemia, and hepatopathies. Neonatal-onset mitochondrial disease is defined as any MRCD with onsetin the neonatal period. Since initial symptoms often appear within the first two days of life, MRCD should besuspected in any neonates not doing well in this period. Mitochondrial nephropathy is also gaining attention, andit can be suspected by a characteristic pathological finding called granular swollen epithelial cells. Large-scaleepidemiologic studies have revealed outcomes and risk factors for mitochondrial cardiomyopathies, neonatalonset mitochondrial disease, and Leigh disease. With genetic analysis of MRCD now covered by public healthinsurance, research is expected to accelerate even more in the near future.

Idiopathic nephrotic syndrome (NS) is the most common incurable chronic kidney disease in children, and 20–30% of patients experience repeated recurrence over a long period of time. The pathophysiology of NS remainsunclear, and there are cases of frequent relapsing NS and steroid-resistant NS. This paper outlines the followingitems.The “MCD/FSGS spectrum”, a concept that encompasses minimal change type and focal segmental glomerulosclerosis in NS, has been proposed in recent years.As the role of molecular targeted drugs such as rituximab is increasing in the treatment of frequent relapsingNS, trials of combination drugs to maintain remission and safer methods of rituximab treatment are being investigated.It has recently been reported that the etiological gene NPHS1 of Finnish type NS, which is a representativedisease of congenital NS, is a disease susceptibility gene for steroid-sensitive NS.

Novel scientific discoveries must be published; otherwise, they become personal experiences. In the field ofmedicine, original papers report the results of new experimental findings, clinical analyses of specific diseases orother medical phenomena, case reports describe the progression, diagnosis, and treatment of significant cases, andreview articles summarize the medical community’s current understanding of specific phenomena, diseases, andtreatment policies. There is a universal standard for writing both Japanese and English articles. Thus, residents,postgraduate students, and other novices are requested to learn how to write according to this standard.

Background: Although the associations between periodontitis (PD) and acute myocardial infarctions (AMIs) are known, it is unclear whether the severity of PD is correlated with atherosclerotic cardiovascular status (ASCVS) in patients with AMIs. Methods: This was a cross-sectional study. We investigated 50 patients with AMI admitted to Nihon University Itabashi Hospital from July 2019 to May 2022. All patients were classified according to the presence and severity of PD. The periodontal status was defined by radiographic bone loss in accordance with previous studies (healthy; ≥ 80% remaining bone [RB], mild-moderate PD; 66 ≤ RB < 80%, and severe PD; RB < 66%), and the degree of ASCVS was compared. Results: The frequency of tooth loss ≥ 5 was significantly higher, and the mean probing pocket depth was numerically higher from healthy to mild-moderate PD to severe PD. The low-density lipoprotein/high-density lipoprotein ratio significantly increased from healthy to mild-moderate PD to severe PD. The carotid intima-media thickness was numerically higher in the severe PD group. The early diastolic velocity to early diastolic myocardial velocity (E/e’) ratio was significantly higher in severe PD and had a weak negative correlation with the severity of PD (r = −0.411, p = 0.003). Conclusions: We found that the severity of PD was correlated with the E/e’ ratio in AMI patients.

We have investigated the potential of the antiviral drugs ribavirin (RBV) and interferon-beta (IFN-β) for drugrepositioning and have described the antitumor effect of combination therapy of temozolomide (TMZ), RBV andIFN-β for glioblastoma (GBM) cells in vitro. However, sufficient data, including in vivo experiments for clinicalapplication, are incomplete. We conducted both in vitro and in vivo experiments to validate the antitumor effect of TMZ, RBV and IFN-β combination therapy on the commercialized human GBM cell line U-87MG and the originally established patient-derived GBM cell line 0125-GSC. In vitro experiments counting viable U-87MG and0125-GSC cells after combined administration of TMZ and RBV and/or TMZ, RBV and IFN-β indicated that cellproliferation was strongly inhibited by both combination therapies compared to single drugs. However, no significant difference was found between these combination therapies. The expression of apoptosis-related proteins wasenhanced after the combined administration of TMZ and RBV and/or TMZ, RBV and IFN-β compared with theadministration of single drugs. In vivo experiments implanted U-87MG cells into nude mouse brains, and singledrugs or combination therapy were administered. Survival time in mice was significantly prolonged by systemictreatment with combination therapy of TMZ and RBV and/or TMZ, RBV and IFN-β compared to single drugtreatment, but no significant difference was found between the two combination therapies. The present resultsdemonstrated that TMZ, RBV and IFN-β and/or TMZ and RBV combination therapy showed antitumor effectsagainst GBM cells both in vitro and in vivo. TMZ and RBV combination therapy may be the most promisingnovel treatment for clinical application.

血友病 A は凝固第Ⅷ因子の異常により出血傾向を呈する疾患である．観血的処置時は経静脈的補充療法が推奨されるが，肝切除時における周術期管理の報告は少ない．今回，血友病 A 患者に発症した肝細胞癌に対し周術期に第Ⅷ因子製剤の持続投与で管理した症例を経験した．症例は 82 歳男性，左腎癌に対し腎摘出術の既往あり．慢性 C 型肝炎の経過観察中，肝 S8 に 32 mm の肝細胞癌を指摘された．肝障害度は A であったが，APTT が62.3 秒と延長し，第Ⅷ因子活性は 7％と低下していた．第Ⅷ因子製剤を術前 5000 単位投与し凝固能の改善を確認後，肝 S8 部分切除術を施行した．術後は第Ⅷ因子製剤必要量を APTT 値で推定後，術後 2 日目まで約 5.8U/kg/h（1 日総量 7000 単 位 ）， 術 後 7 日目まで約 4.2U/kg/h（1 日総量 5000 単位）で持続投与し合併症なく術後 10 日目に退院した．第Ⅷ因子活性の即時測定が困難な場合は APTT のモニターリング下に凝固因子製剤を持続投与する事で周術期管理が可能であった．

症例は 56 歳の女性で，健康診断にて便潜血と貧血を指摘され当院を受診した．上部消化管内視鏡検査及び腹部造影 CT 検査を施行したところ，下十二指腸角に 33mm 大の腫瘤性病変を認めた．生検病理検査にて十二指腸 GIST の診断のもと，十二指腸局所切除および十二指腸空腸側々吻合を施行した．術後経過は良好で術後 10日目に退院となった．十二指腸 GIST の外科治療は，可能な限り機能温存が望まれる．十二指腸が解剖学的に複雑である点と，リンパ節転移が稀である点から，術式と再建方法の選択が重要となる．