Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence.

BACKGROUND: Endothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory network, including genome-wide alternative splicing machinery, involved in endothelial cell senescence is lacking. RESULTS: We thoroughly described the transcriptome landscape of replicative senescent human umbilical vein endothelial cells. Genes with high connectivity showing a monotonic expression increase or decrease with the culture period were defined as hub genes in the co-expression network. Computational network analysis of these genes led to the identification of canonical and non-canonical senescence pathways, such as E2F and SIRT2 signaling, which were down-regulated in lipid metabolism, and chromosome organization processes pathways. Additionally, we showed that endothelial cell senescence involves alternative splicing. Importantly, the first and last exon types of splicing, as observed in FLT1 and ACACA, were preferentially altered among the alternatively spliced genes during endothelial senescence. We further identified novel microexons in PRUNE2 and PSAP, each containing 9 nt, which were altered within the specific domain during endothelial senescence. CONCLUSIONS: These findings unveil the comprehensive transcriptome pathway and novel signaling regulated by RNA processing, including gene expression and splicing, in replicative endothelial senescence.

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship.

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

Identification and functional characterization of Candida albicans mannose-ethanolamine phosphotransferase (Mcd4p).

Glycosylphosphatidylinositol (GPI) is an important compound for the growth of fungi, because GPI-anchored proteins including glycosyltransferases and adhesins are involved in cell-wall integrity, adhesion, and nutrient uptake in this organism. In this study, we examined orf19.5244 in the genome database of the pathogenic fungus Candida albicans, a homologue of the Saccharomyces cerevisiae mannose-ethanolamine phosphotransferase gene, MCD4, which plays a role in GPI synthesis. Expression of this homologue, designated CaMCD4, restored cell growth in a defective conditional mcd4 mutant of S. cerevisiae, Scmcd4t, in which expression of native MCD4 was repressed in the presence of doxycycline (Dox). Analysis of radiolabeled lipids showed that the accumulation of abnormal GPI anchor precursors in Scmcd4t decreased markedly upon expression of CaMCD4. Moreover, we constructed a single mutant (Camcd4/CaMCD4) and a conditional double mutant (Camcd4/Camcd4t) at the MCD4 locus of C. albicans. Repression of CaMCD4 expression by Dox led to a decrease in growth and appearance of abnormal morphology in C. albicans, both in vitro and in a silkworm infection model. These results suggest that CaMcd4p is indispensable for growth of C. albicans both in vitro and in infected hosts and a candidate target for the development of new antifungals.

Efficacy of completion pancreatectomy for recurrence of adenocarcinoma in the remnant pancreas.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, with a high rate of recurrence even after complete surgical resection. The aim of this study was to investigate the impact of completion pancreatectomy (CP) on the clinical course of patients with recurrent PDAC in the remnant pancreas. MATERIALS AND METHODS: Between January 2008 and December 2014, 194 patients underwent curative-intent surgical resection (initial pancreatectomy [IP]) for PDAC at our institution. The treatment and survival outcomes were evaluated according to the patterns of recurrence. RESULTS: Among 194 patients with IP, 127 patients (65.5%) developed recurrence. Of them, 11 patients (8.7%) developed recurrence in the remnant pancreas and were treated by CP. They showed a significantly longer median survival after the recurrence than the 28 patients who developed unresectable local recurrence and were treated by systemic chemotherapy (44 mo versus 11 mo, P = 0.014) or the 66 patients who developed distant metastasis and were treated by systemic chemotherapy (44 mo versus 13 mo, P = 0.024). Moreover, the median survival after CP was longer in the patients who received adjuvant chemotherapy after CP than in those who did not receive adjuvant chemotherapy (44 mo versus 14 mo, P = 0.002). CONCLUSIONS: This study demonstrated that PDAC patients with resectable local recurrence in the remnant pancreas, who were treated by CP, had better survival outcomes than those with other patterns of recurrence. CP combined with adjuvant chemotherapy appeared to yield greater survival benefit.

Impact of pancreaticoduodenal arcade dilation on postoperative outcomes after pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to investigate the impact of pancreaticoduodenal arcade (PDA) dilation on postoperative outcomes after pancreaticoduodenectomy. METHODS: Consecutive patients submitted to pancreaticoduodenectomy between 2008 and 2016 underwent preoperative multi-detector computed tomography, the images of which were re-reviewed. The patients were categorized according to the grade of PDA dilation into 3 groups (remarkably-dilated, slightly-dilated, and non-dilated). RESULTS: Among the 443 patients, 25 patients (5.6%) were categorized as remarkably-dilated PDA and 24 patients (5.4%) as having slightly-dilated PDA. The patients with remarkably-dilated PDA had undergone pancreaticoduodenectomy with additional surgical maneuvers to restore celiac arterial flow as needed, and had an uneventful postoperative recovery relative to those with non-dilated PDA. In contrast, patients with slightly-dilated PDA underwent only pancreaticoduodenectomy without additional surgical maneuvers, and developed clinically relevant postoperative pancreatic fistula (POPF) more frequently than those with non-dilated PDA (42% vs. 21%, P = 0.021). Moreover, slightly-dilated PDA was shown to be an independent risk factor for clinically relevant POPF (odds ratio = 2.719, P = 0.042). DISCUSSION: For patients with PDA dilation requiring pancreaticoduodenectomy, a preoperative evaluation of the vascular anatomy, intraoperative assessment of the celiac arterial flow, and additional surgical maneuvers might be necessary to reduce the risk of postoperative complications.

The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation.

Mounting evidence suggests that constitutively active androgen receptor (AR) splice variants, typified by AR-V7, are associated with poor prognosis and resistance to androgen deprivation therapy in prostate cancer patients. However, mechanisms governing the generation of AR splice variants are not fully understood. In this study, we aimed to investigate the dynamics of AR splice variant generation using the JDCaP prostate cancer model that expresses AR splice variants under androgen depletion. Microarray analysis of JDCaP xenografts before and after expression of AR splice variants suggested that dysregulation of RNA processing pathways is likely involved in AR splice variant generation. To explore factors contributing to generation of AR-V7 mRNA, we conducted a focused RNA interference screen in AR-V7-positive JDCaP-hr cells using an shRNA library targeting spliceosome-related genes. This screen identified DDX39B as a regulator of AR-V7 mRNA expression. Simultaneous knockdown of DDX39B and its paralog DDX39A drastically and selectively downregulated AR-V7 mRNA expression in multiple AR-V7-positive prostate cancer cell lines. DDX39B was upregulated in relapsed JDCaP xenografts expressing AR splice variants, suggesting its role in expression of AR splice variants. Taken together, our findings offer insight into the mechanisms of AR splice variant generation and identify DDX39 as a potential drug target for the treatment of AR splice variant-positive prostate cancer.

Fluid shear stress stimulates MATE2-K expression via Nrf2 pathway activation.

Accurate prediction of drug-induced renal toxicity is necessary for development of safer drugs for patients. Cellular assay systems that recapitulate physiologically relevant microenvironments have been proposed for correct estimation of drug responses in the human body. However, establishment of such assay systems for accurate prediction of renal toxicity is challenging because of the lack of readily available in vitro assay systems. In this study, we investigated the cellular response to fluid shear stress, which is a characteristic of the environment in the kidney proximal tubules, using microfluidic devices. The global gene expression profiles of human primary proximal tubule cells under the fluidic conditions revealed upregulation of MATE2-K and activation of Nrf2 signaling in response to fluid shear stress. Network and cell biological analysis additionally showed that expression of MATE2-K is regulated by Nrf2 signaling. These results strongly suggest that fluid shear stress is involved in the expression and maintenance of function of tissue-specific drug transporters in the proximal tubule, where the cells are exposed to continuous shear stress by primary urine. Furthermore, the microfluidic culture of human proximal tubules was demonstrated to be a useful system to analyze the regulatory mechanisms of gene expression in physiologically relevant cell conditions.

Comparison of postoperative early and late complications between pancreas-sparing duodenectomy and pancreatoduodenectomy.

PURPOSE: Pancreas-sparing duodenectomy (PSD) represents an alternative procedure to pancreatoduodenectomy (PD) for patients with duodenal neoplasms. METHODS: The postoperative early and late complications of 21 patients who underwent PSD between 1992 and 2014 were compared with those of 44 patients with soft pancreatic parenchyma who underwent PD between 2009 and 2014. RESULTS: The median operation time and blood loss were less in the PSD group than in the PD group (P < 0.001). The overall incidence of early complications was less in the PSD group than in the PD group (PSD with ampullectomy vs. PSD without ampullectomy vs. PD; 45.5 vs. 20.0 vs. 56.8 %). The incidence of pancreatic fistula formation and overall incidence of late complications were also less in the PSD group than in the PD group (P = 0.031, 0.020). There were no complications related to the pancreatic endocrine or exocrine functions in the PSD group. CONCLUSION: PSD is a less-invasive procedure and has the advantage over PD of preserving the pancreas.

Differential micro ribonucleic acid expression profiling in ovarian endometrioma with leuprolide acetate treatment.

AIM: Micro ribonucleic acids (miRNAs) play an important pathological role in endometriosis. Leuprolide acetate, an analog of gonadotropin-releasing hormone, is widely used to treat endometriosis; however, the molecular mechanisms involved in endometriotic tissue regression remain unclear. We performed miRNA expression profiling of clinical ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS: We obtained clinical samples from nine normal eutopic endometrium, eight ovarian endometriotic, and 12 leuprolide acetate-treated endometriotic tissues. We compared the miRNA expression profiles of the three groups by performing TaqMan Array MicroRNA Card and bioinformatic analysis. RESULTS: Two miRNAs, miR-939 and miR-154, were upregulated in endometriotic tissue and downregulated in leuprolide acetate-treated endometriotic tissue. Five miRNAs (miR-146a, miR-142-3p, miR-136*, miR-125b-1* and miR-15b*) were unchanged in endometriotic tissue but were upregulated under leuprolide acetate treatment. Ingenuity pathway analysis using predicted target genes for the seven identified miRNAs suggested the involvement of a range of pathways, including axonal guidance, bone morphogenetic protein, phosphatase and tensin homolog and nitric oxide signaling; molecular mechanisms of cancer; and the adipogenesis and signal transducer and activator of transcription 3 (STAT3) pathways. CONCLUSIONS: To our knowledge, this is the first report profiling the miRNAs of endometrioma under leuprolide acetate treatment. The expression of seven miRNAs was modulated, concomitant with the disease state. This result gives new insight into the effects of leuprolide acetate treatment. Further investigation using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry will allow us to validate the results of this study and to explore new therapeutic targets and biomarkers of endometriosis.

Polarization diversity of human CD4+ stem cell memory T cells.

T cells are considered to develop through three stages, from naïve T (Tn) into central memory T (Tcm) and finally into effector memory T (Tem). Among the subsets of Tn, stem cell memory T (Tscm) were recently found to be the least developed memory subset. While this subset was revealed to possess self-reproducibility and multipotentiality, little is known about the relationship between development and polarity. We conducted transcriptome analysis of human CD4(+) T subsets and found that Tscm was a clearly distinct subset, located between Tn and Tcm. Surface antigen analysis and differentiation assay showed that the flexibility of polarity and the cytokine production progressively changed as the differentiation of CD4(+) T cells advanced. Interestingly, we found that most cells of the CD45RO(-)CCR7(+)CCR6(+) subset, hitherto considered the naïve precursor of Th17, were in fact Tscm. These findings may advance our understanding of the highly heterogeneous human helper T cells.

Differential mRNA expression profiling in ovarian endometriotic tissue with versus without leuprolide acetate treatment.

AIM: Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS: We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis. RESULTS: Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18. CONCLUSIONS: These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis.

Usefulness of the neutrophil/lymphocyte ratio measured preoperatively as a predictor of peritoneal metastasis in patients with advanced gastric cancer.

PURPOSE: The prognosis for gastric cancer patients with peritoneal metastasis is poor. Many studies have reported that the neutrophil/lymphocyte ratio (NLR) might be useful to predict the degree of progression of gastric cancer. In this study, we attempted to evaluate whether the NLR and other related laboratory parameters might be reliable predictors of the presence of peritoneal metastasis in patients with advanced gastric cancer. METHODS: The data of 359 patients who underwent gastric surgery between June 2008 and December 2011 were reviewed. A retrospective analysis of the preoperative blood data in relation to the presence of peritoneal metastasis was carried out. RESULTS: An increased serum C-reactive protein level (P = 0.022), APTT (P = 0.017) and NLR (P < 0.001), and a decreased serum Alb (P = 0.014) were significantly related to the presence of peritoneal metastasis. A multivariate analysis showed that a NLR >2.37 (OR = 2.59, 95 % CI = 1.38-4.93, P = 0.003) and clinical T4 stage (OR = 4.36, 95 % CI = 2.33-8.24, P < 0.001) were independent predictors of the presence of peritoneal metastasis. CONCLUSION: Our results suggest that the preoperative NLR was a significant independent predictor of the presence of peritoneal metastasis in patients with advanced gastric cancer.

Respiratory-like movements during an apnea test.

Background: Despite the possible occurrence of spontaneous movements during an apnea test, respiratory-like movements are rare. Case Presentation: A 51-year-old man was transferred to our hospital when a sudden disturbance of consciousness developed into cardiac arrest. After spontaneous circulation returned, we diagnosed bilateral cerebellar hemorrhage. He remained comatose with dilated pupils, absent brainstem reflexes, spontaneous breathing, and electrocerebral activity. After being considered brain dead, his family opted for organ donation. The first legal brain death examination on day 5 was aborted because of respiratory-like movements mimicking repetitive abdominal respiration during the apnea test. However, an enhanced magnetic resonance image of the head indicated no blood flow and somatosensory evoked potential testing revealed no brain-derived potentials. Conclusion: Respiratory-like movements can occur during the apnea test in patients considered brain dead. Further research is required to understand this phenomenon.

Gastric inflammatory myofibroblastic tumor presented with severe anemia and inflammation: a case report.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare stromal tumor, often found in children and young adults, and most commonly occurs in the lungs. Surgical resection is considered the standard treatment for localized IMT, although only limited data exist. Gastric IMT in adults is extremely rare, and there are no established guidelines for its treatment. CASE PRESENTATION: A 69-year-old male presented with persistent fatigue and weakness. Laboratory examination revealed severe anemia and inflammation. Upper gastrointestinal endoscopy at admission revealed a 40-mm type I softish tumor in the lesser curvature of the gastric body, without apparent hemorrhage. Repeated biopsies, including partial resection with snare, failed to give a definitive diagnosis. Computed tomography (CT) revealed a massive lesion at the gastric body, protruding into the gastric lumen, which was consistent with the gastric tumor. After admission, the patient developed anemia refractory to frequent blood transfusions despite the absence of apparent gastrointestinal bleeding. In addition, the patient had recurrent fevers of 38 °C or higher, and persistent high inflammatory levels. Fluorodeoxyglucose-positron emission tomography (FDG-PET) CT 1 month after the first visit exhibited an increased FDG uptake in the gastric tumor. In addition, this CT scan revealed a rapid increase in tumor size to 75 mm. It was suspected that the undiagnosed gastric tumor caused these serious clinical symptoms, and he underwent distal gastrectomy and cholecystectomy. The gross image of the tumor showed an 80-mm cauliflower-like shape with a gelatinous texture. The histopathological diagnosis was IMT. The postoperative course was uneventful, and the patient's symptoms subsided drastically, improving both anemia and systemic inflammation. The patient has shown no recurrence or relapse of the symptoms over one and a half years. CONCLUSIONS: In this case, the tumor resection finally enabled the diagnosis of IMT and resolved the clinical symptoms. Despite its predominantly benign morphological nature, some cases of IMT present clinically adverse courses. Surgical treatment may lead to its final diagnosis and improvement of clinical symptoms.

Biosynthetic mechanism for L-Gulose in main polar lipids of Thermoplasma acidophilum and possible resemblance to plant ascorbic acid biosynthesis.

L-Gulose is a very rare sugar, but appears as a sugar component of the main polar lipids characteristic in such a thermophilic archaeon as Thermoplasma acidophilum that lives without cell walls in a highly acidic environment. The biosynthesis of L-gulose in this thermophilic organism was investigated with deuterium-labeling experiments. L-Gulose was found to be biosynthesized from D-glucose via stepwise stereochemical inversion at C-2 and C-5. The involvement of an epimerase related to GDP-mannose 3,5-epimerase, the key enzyme of plant ascorbate biosynthesis, was also suggested in this C-5 inversion. The resemblance of L-gulose biosynthesis in archaea and plants might be suggested from these results.

Successful everolimus treatment in a patient with advanced pancreatic neuroendocrine tumor who developed everolimus-induced interstitial lung disease on two occasions: a case report.

Chemotherapy-associated interstitial lung disease (ILD) is often fatal, and the chemotherapeutic regimen generally cannot be resumed. ILD associated with the mammalian target of rapamycin (mTOR) inhibitor everolimus has many features distinct from chemotherapy-associated ILD. We present the case of a 58-year-old woman with an advanced pancreatic neuroendocrine tumor with liver metastases, in whom everolimus treatment was maintained and resulted in a partial response despite two occurrences of everolimus-induced ILD during a 31-month treatment period until disease progression. Physicians treating with everolimus should monitor patients closely for ILD and should apply appropriate management strategies to optimize the possibility of maintaining everolimus therapy.

Visible-Light-Driven Hydroacylation of Unactivated Alkenes Using Readily Available Acyl Donors.

Herein, we report visible-light-driven hydroacylation of unactivated alkenes. We employed benzimidazolines as new acyl donors and achieved perfect regioselectivity, high functional-group tolerance, and excellent substrate generality. We also performed mechanistic experiments to elucidate the detailed reaction mechanism. This is the first example of (1) hydroacylation of unactivated alkenes using (2) easily prepared acyl donors under (3) visible-light irradiation. Our findings offer a new strategy to synthesize a wide variety of ketones under mild conditions.

Deep learning-based classification of adequate sonographic images for self-diagnosing deep vein thrombosis.

BACKGROUND: Pulmonary thromboembolism is a serious disease that often occurs in disaster victims evacuated to shelters. Deep vein thrombosis is the most common reason for pulmonary thromboembolism, and early prevention is important. Medical technicians often perform ultrasonography as part of mobile medical screenings of disaster victims but reaching all isolated and scattered shelters is difficult. Therefore, deep vein thrombosis medical screening methods that can be easily performed by anyone are needed. The purpose of this study was to develop a method to automatically identify cross-sectional images suitable for deep vein thrombosis diagnosis so disaster victims can self-assess their risk of deep vein thrombosis. METHODS: Ultrasonographic images of the popliteal vein were acquired in 20 subjects using stationary and portable ultrasound diagnostic equipment. Images were obtained by frame split from video. Images were classified as "Satisfactory," "Moderately satisfactory," and "Unsatisfactory" according to the level of popliteal vein visualization. Fine-tuning and classification were performed using ResNet101, a deep learning model. RESULTS: Acquiring images with portable ultrasound diagnostic equipment resulted in a classification accuracy of 0.76 and an area under the receiver operating characteristic curve of 0.89. Acquiring images with stationary ultrasound diagnostic equipment resulted in a classification accuracy of 0.73 and an area under the receiver operating characteristic curve of 0.88. CONCLUSION: A method for automatically identifying appropriate diagnostic cross-sectional ultrasonographic images of the popliteal vein was developed. This elemental technology is sufficiently accurate to automatically self-assess the risk of deep vein thrombosis by disaster victims.

[Resection of cholangiolocellular carcinoma successfully responding to neoadjuvant hepatic arterial infusion chemotherapy - report of a case].

A 78-year-old man who had hepatitis C was examined by computed tomography(CT)because of prostate cancer, and was found to have a liver tumor 8. 0 cm in size at S4/S8. The view of the liver tumor was enhanced by CTHA image and washed out by CTAP image. It was suspected to have invaded the RHV and MHV. The pathological examination of the liver biopsy sample revealed cholangiocellular carcinoma or cholangiolocellular carcinoma. Hepatic arterial infusion chemotherapy with gemcitabine and cisplatin was performed. The size of the tumor reduced to 6. 0 cm and the invasion to the RHV was no longer evident. Hepatic resection for the middle two segments was performed after 3 months of chemotherapy. After a histological examination of the resected specimen, the patient was given the final diagnosis of cholangiolocellular carcinoma. Over 50% of the tumor was estimated as necrosis by chemotherapy, indicating that the gemcitabine and cisplatin regimen was remarkably effective. The patient is alive with no evidence of recurrence.

Current Status, Issues and Future Prospects of Personalized Medicine for Each Disease.

In recent years, with the advancement of next-generation sequencing (NGS) technology, gene panel tests have been approved in the field of cancer diseases, and approaches to prescribe optimal molecular target drugs to patients are being developed. In the field of rare diseases, whole-genome and whole-exome analysis has been used to identify the causative genes of undiagnosed diseases and to diagnose patients' diseases, and further progress in personalized medicine is expected. In order to promote personalized medicine in the future, we investigated the current status and progress of personalized medicine in disease areas other than cancer and rare diseases, where personalized medicine is most advanced. We selected rheumatoid arthritis and psoriasis as the inflammatory disease, in addition to Alzheimer's disease. These diseases have high unmet needs for personalized medicine from the viewpoints of disease mechanisms, diagnostic biomarkers, therapeutic drugs with diagnostic markers and treatment satisfaction. In rheumatoid arthritis and psoriasis, there are many therapeutic options; however, diagnostic methods have not been developed to select the best treatment for each patient. In addition, there are few effective therapeutic agents in Alzheimer's disease, although clinical trials of many candidate drugs have been conducted. In rheumatoid arthritis and psoriasis, further elucidation of the disease mechanism is desired to enable the selection of appropriate therapeutic agents according to the patient profile. In the case of Alzheimer's disease, progress in preventive medicine is desired through the establishment of an early diagnosis method as well as the research and development of innovative therapeutic agents. To this end, we hope for further research and development of diagnostic markers and new drugs through progress in comprehensive data analysis such as comprehensive genomic and transcriptomic information. Furthermore, new types of markers such as miRNAs and the gut microbiome are desired to be utilized in clinical diagnostics.