Hypoxia-inducible factor 1 (HIF-1) is a crucial protein involved in cellular adaptation to low oxygen levels. We previously demonstrated impaired HIF-1α nuclear translocations cause impaired cellular adaptation to hypoxia in chronic obstructive pulmonary disease (COPD). However, the mechanism of impaired nuclear translocations of HIF-1α in COPD was not fully elucidated. We hypothesised that sirtuin (SIRT) 1, which is known to be decreased in the lungs of COPD patients, is involved in HIF-1α nuclear translocation. The objective of this study was to investigate the precise functions of sirtuin SIRT1 in relation to HIF-1α stabilization, nuclear translocation, and the subsequent modulation of vascular endothelial growth factor (VEGF) expression.

SIRT1 was knocked down by transfection with siRNA of SIRT1 to A549 cells, and the cells were cultured under hypoxic conditions (1% O₂, 5% CO₂, and 94% N₂). HIF-1α proteins in nuclei and whole cell extracts were measured by SDS/PAGE Western blotting, and mRNA levels of HIF-1α, VEGF, and MMP (Matrix metalloproteinase) -9 were quantified by quantitative real-time PCR.

SIRT1 knockdown significantly decreased HIF-1α protein in nuclei under hypoxia without affecting the amount of HIF-1α mRNA or HIF-1α proteins in whole cells compared to control knockdown cells. Hypoxia- induced VEGF expression was suppressed by SIRT1 knockdown. Conversely, SIRT1 knockdown resulted in a further increase in MMP-9 transcription under hypoxic conditions.

In conclusion, the reduction of SIRT1 leads to impaired nuclear translocation of HIF-1α under hypoxia, subsequently decreasing VEGF expression, and promoting increased MMP-9 expression under hypoxic conditions. These mechanisms may potentially contribute to the progression of emphysema. 

Aim: To clarify the short-term outcomes of robot-assisted colectomy for right-sided colon cancer.

Materials and Method: Fourteen patients with colon cancer who underwent robot-assisted right-sided colon surgery between July 2022 and April 2023 were included in this study. The short-term outcomes of robot-assisted surgery were evaluated.

Results: The mean age of the patients (8 men and 6 women) was 76.5 ± 9.8 years. ASA scores were class II in 12 cases and class III in 2 cases. The sites of involvement were the cecum in 7 cases, the ascending colon in 5 cases, and the transverse colon in 2 cases. The surgical procedures were ileocecal resection in 7 cases (50%), partial colectomy (5 cases [36%] in the ascending colon; 1 case [7%] in the transverse colon), and the right hemicolectomy in 1 case (7%). The median operative time was 223.0 minutes (range: 160-521), and the blood loss was 20 ml (range: 1-580). The console operating time was 102.5 minutes (range: 42-188). There were no cases of conversion to laparoscopy. The pathological stages were as follows: stage 0 in 1 case, stage I in 2 cases, stage II in 7 cases, stage III in 4 cases, and stage IV in 0 cases. The number of lymph nodes retrieved was 14 (range: 9-24). No postoperative complications were observed.

Conclusion: Robot-assisted colectomy for right-sided colon cancer was found to be effective in terms of safety and short-term outcomes without causing any postoperative complications or surgical mortality.

CYP2R1 is an enzyme involved in vitamin D metabolism, and SNPs in the CYP2R1 gene are associated with asthma. We compared the SNPs rs10741657 and rs12794714 in CYP2R1 among 69 patients with chronic obstructive pulmonary disease (COPD), 77 patients with bronchial asthma (BA), and 50 healthy donors (HDs). The SNPs were identified in oral mucosal cells using specific thermal-elution chromatography. For both SNPs, the A allele frequency was higher in COPD than in BA patients and HDs. For both SNPs, the AA/AG genotype with COPD was associated with significantly lower peripheral eosinophil counts and higher peripheral neutrophil counts than the AA/AG genotypes with BA. In addition, the AA/AG genotype with COPD was associated with significantly lower FEV1 than the AA/AG genotype with BA. Moreover, for rs12794714, the GG genotype with COPD was associated with significantly lower FEV1 than the AA/AG and GG genotypes with BA p < 0.01 and 0.05, respectively. The AA/AG genotype of both SNPs with COPD appears associated with neutrophilic, rather than eosinophilic inflammation, and the GG genotype of rs12794714 with COPD seems associated with bronchial obstruction versus BA. CYP2R1 SNPs might relate to neutrophilic inflammation and bronchial obstruction in COPD in Japanese people.

Dry skin and type 2 cytokines, IL-4/IL-13 and IL-31, have been reported to be involved in pruritus in skin diseases such as atopic dermatitis. IL-31 directly induces pruritus, but IL-4/IL-13 themselves have little or no potential to induce pruritus, whereas IL-4/IL-13 potentiate nerve activation by subthreshold doses of pruritogens such as histamine and IL-31 in vitro, and are involved in alloknesis in dry skin mouse models induced by ovariectomy and artificial barrier disruption. In this study, we investigated whether ovariectomy-induced dry skin with permeability barrier dysfunction enhances IL-31-induced pruritus in mice. Levels of spontaneous scratching behavior were higher than in ovariectomized mice than in sham-operated mice probably due to barrier disruption that could be accelerated by hair shaving. Levels of scratching behavior induced by intradermal administration of IL-31, regardless of single or repeated administration, were increased in ovariectomized mice compared to in sham-operated mice. Pre-intradermal administration of neutralizing antibodies against IL-4/IL-13 did not attenuate the level of IL-31-induced scratching behavior in ovariectomized mice. Our results show that the dry skin induced by ovariectomy is an itchy condition prone to pruritus, and this is the first report showing that the dry skin enhances the potential of IL-31 to induce pruritus in vivo.

Introduction: This study clarifies medical care and outcomes for patients hospitalized with COVID-19 and evaluates SARS-CoV-2 infection risk in healthcare professionals, to contribute to appropriate responses in future outbreaks of emerging infectious diseases.

Methods: In total, 585 patients with COVID-19 were classified by disease severity, and laboratory test findings and treatments were examined. Serum IgG antibodies against SARS-CoV-2 spike protein (IgG S antibodies) and those against nucleocapsid protein (IgG N antibodies) were measured in 21 expert respiratory physicians.

Results: Multiple comparison analysis showed significant differences in body mass index (BMI), white blood cell count (WBC), neutrophil count (Neut), lymphocyte count, lactate dehydrogenase (LDH), C-reactive protein, hemoglobin A1c, ferritin, Krebs von den Lungen-6, and D-dimer depending on disease severity. There were significant differences in BMI, WBC, Neut, LDH, and D-dimer between the severe and critical groups. Times from onset to admission and to start of treatment both increased according to severity and were significantly longer in the critical group. Among critical patients requiring ventilation, times from onset to admission, to start of remdesivir, and to start of systemic steroid therapy were significantly longer in those who died. Serum IgG S and IgG N antibody measurements in the 21 respiratory physicians did not indicate direct SARS-CoV-2 transmission from patients.

Conclusion: We identified laboratory test items predicting severe and critical COVID-19 and demonstrated the importance of prompt administration of antiviral and anti-inflammatory agents after symptom onset. SARS-CoV-2 transmission to medical professionals may be prevented by adherence to wearing personal protective equipment.

Background: Food allergy (FA) is a public health concern with escalating prevalence, particularly among children. It is a phenomenon characterized by immunological reactions to specific foods. Recognizing the prevalent dietary allergens is crucial for public health and clinical interventions.

Objective: This study aimed to assess the current landscape of FA among elementary and junior high school students in Oyama and Tochigi cities, Japan. The investigation focused on prevalence, manifestations, and associated factors.

Method: An online survey was conducted among parents of children aged 6 to 15 years, distributed with the collaboration of education councils in Oyama City and Tochigi City. Data collection included demographics, allergy history, and current symptoms. Statistical analyses were performed using IBM SPSS Statistics Version 28.0.0.0.

Results: Analysis of 2036 valid responses revealed significant differences in symptom prevalence between age groups and genders. Notably, 6-10 years old boys exhibited a higher symptom prevalence than 11-15 years old boys, while 11-15 years old girls displayed a higher symptom prevalence than younger girls. The prevalence of current FA showed statistical significance between boys of different age groups.

Conclusion: This study provides nuanced insights into the FA situation, emphasizing age-specific patterns and triggers. The sustained prevalence of FA underscores the need for ongoing research and targeted interventions to mitigate its impact on children. The findings contribute to understanding FA epidemiology, informing future investigations and interventions in pediatric food allergies.

Background: The WHO Collaborating Center at Dokkyo Medical University conducted a survey in Ulaanbaatar in 2009 on the prevalence of pediatric asthma and allergic rhinitis (AR). We report on a follow-up survey done in 2021 to measure changes since 2009 and identify risk factors.

Methods: Questionnaire based on International Study of Asthma and Allergies in Childhood with modifications was used in 2009 and 2021. The parent (s) of 200 boys and 200 girls, 6-7 years old, were randomly selected from and interviewed at the 10 clinic areas used in 2009. 50% were city districts and 50% were urban districts. Statistical data was analyzed using odds ratios analysis and chi-square testing.

Results: Comparing 2009 and 2021, prevalence of AR decreased by 13.6%. In houses where there was exposure to tobacco smoke, AR decreased by 21.3% from 64.0% to 42.7%. In children with asthma, AR decreased by 9.8% from 25.8% to 16.0%. In children with respiratory infection when <1 year old, AR decreased by 7.9% from 41.8% to 33.9%.

Conclusion: In comparing 2009 and 2021, the significance was greater between children with than without AR, with P < 0.001 for those exposed to tobacco smoke, and P < 0.005 for those with asthma. There was no significance for children with a history of respiratory infection when <1 year old. There was significance of exposure to tobacco smoke and having asthma as risk factors for AR but not for children with a history of respiratory infection when <1 year old.

Introduction: Anorectal malignant melanoma is a rare disease, accounting for approximately 0.4-1.6% of all malignant melanomas. The prognosis is poor due to aggressive metastasis. Case presentation: We report a case of 73-year-old woman who presented with rectal bleeding in whom colonoscopy revealed an anorectal polyp in black-toned color. The pathological diagnosis of biopsy specimens was malignant melanoma and other examinations showed no evidence of lymph node or distant metastases. Robot-assisted abdominoperineal resection combined with lymph node dissections including lymph nodes along the inferior mesenteric artery, superior rectal artery, and bilateral inguens was performed. The patient was discharged on the postoperative day 21 without any adverse events. Pathological diagnosis revealed malignant melanoma cells invaded a submucosa, with no evidence of lymph nodes metastases. As of 25 months after tumor resection, no recurrence of anorectal malignant melanoma has been identified. Discussion: The present case showed that robot-assisted surgery would be a feasible and safe surgical approach in the treatment of anorectal malignant melanoma.

Spontaneous gastric perforations are rare in adolescents. Here, we report the case of a 15-year-old boy with severe motor and intellectual disabilities (SMID) who was diagnosed with spontaneous gastric perforation. Due to his original condition and poor peristalsis caused by antiepileptic drugs, gas formation in the stomach and intestines was severe since infancy. After a femoral fracture at the age of 14 years and 5 months, the patient experienced reduced food intake and weight. He transferred to our hospital with shock vital due to severe peritonitis caused by gastric perforation. Immediately, he underwent an emergency laparotomy and partially resected with margins at the site of gastric perforation at the age of 15 years and 1 month. The cause of the gastric perforation was not identified by pathology. Intraoperative ascites culture detected Candida albicans. He was administered a long-term antifungal treatment for enteric mycosis with high β-D-glucan levels. Two months after the surgery, he was discharged. The detailed mechanism of gastric perforation is unclear but increased lumen pressure in the gastrointestinal tract has generally been speculated. In our case, we considered that the gastric perforation was caused by intestinal immunocompromise with Candida albicans overgrowth, associated with increased lumen pressure owing to the transverse position of the stomach. Therefore, deflation using gastrostomy may have been effective in relieving excess luminal pressure. Adequate nutritional evaluation and gastrostomy should be considered in patients with SMID, who have massive intestinal gas formation and gastric bubbles.

Aims: To investigate how switching from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) affects glycemic control and treatment satisfaction in Japanese people with type 1 and 2 diabetes.

Methods: We enrolled 152 outpatients with diabetes (type 1, n = 29; type 2, n = 123) being treated with basal-bolus therapy (BBT; n = 95) or basal only using as insulin therapy (n = 57) with Gla-100 and switched them all to Gla-300. The dose of Gla-300 was initially the same as that of Gla-100 and was then titrated up. We investigated changes in hemoglobin A1c (HbA1c), body weight, glargine insulin dose over three months, and diabetes treatment satisfaction questionnaire scores over three months.

Results: Three months after patients had switched to Gla-300, HbA1c and body weight had not changed significantly. In the whole group, the basal dose of Gla-300 insulin was significantly higher than that of Gla-100 (14.2 ± 8.1 vs 13.7 ± 7.9 units, respectively; P < 0.001). Separate analyses of the BBT and Basal only groups showed that in both the BBT and the Basal only group, the basal insulin dose was significantly higher with Gla-300 than with Gla-100. Patient treatment satisfaction scores did not change significantly after switching to Gla-300. In the BBT group, hypoglycemia was less frequent with Gla-300.

Conclusions: HbA1c, body weight, and treatment satisfaction were similar with Gla-100 and Gla-300. In people treated with BBT, Gla-300 may be associated with less frequent hypoglycemic episodes.

Quaternary ammonium compounds are a large class of permanently charged cationic chemicals used in various consumer and industrial products owing to their antimicrobial properties; mono, bis- (trimethylammoniummethylene chloride) -alkyl-toluene (TAMCA) exhibits bactericidal activity by denaturing the proteins in the bacterial membrane when the cations in its structure are adsorbed to the anionic structure on the bacterial surface. Here, we report the first case of respiratory arrest due to muscle paralysis caused by subcutaneous injection of TAMCA. A 26-year-old man accidently injected with the aforementioned compound, developed respiratory arrest after approximately 1 h. We diagnosed him with TAMCA-related toxicosis. We successfully treated him by ventilatory management followed by tracheal intubation by injecting 10 mL of 1% propofol (100 mg), as he resumed spontaneous breathing the next day, about 15 h following the incident. Subsequently, he developed necrotizing soft tissue and underwent debridement and skin grafting surgery. This case demonstrated that TAMCA erroneous subcutaneous injection or administration into the human body may induce respiratory muscle paralysis thereby necessitating prompt treatment.

A Japanese woman in her 30s with a six-month history of ANCA-positive SLE was admitted because of acute kidney injury (AKI). Three weeks before admission, her condition was well-controlled. On admission, the test for SARS-CoV-2 was positive; she showed marked renal dysfunction but no pulmonary abnormalities, suggesting COVID-19 infection. She underwent continuous hemodiafiltration and received glucocorticoid pulse therapy and remdesivir. The next day, she developed diffuse alveolar hemorrhage (DAH) and cytokine storm. She died despite intensive care. We assumed that AKI and DAH were caused by SLE exacerbation triggered by the COVID-19 infection in addition to the COVID-19 infection itself.