Ventricular septal defects (VSDs) are the most common congenital heart diseases; however, case reports of preterm infants with VSD are limited. The aim of this study is to share our experience with preterm infants with VSD and to record their short-term outcomes. Between January 2000 and December 2017, 32 preterm infants with VSD were admitted to our neonatal intensive care unit at gestational age < 32 weeks. Of these, 9 were excluded by exclusion criteria. The size and location of the VSD, details of treatment, and neonatal prognosis were retrospectively reviewed from the medical records. Among the 23 preterm infants, the median gestational age was 29.4 weeks (25.0-31.3 weeks) and the median birthweight was 924 g (524-1,526 g). There were 9 infants with VSD < 2 mm and 14 infants with VSD ≥ 2 mm. For the 9 infants with VSD < 2 mm, no medical or surgical treatments for VSDs were undertaken. Of the 14 infants with VSD ≥ 2 mm, 8 (57.1%) underwent medical and surgical treatment. Surgical treatment was performed more frequently in infants with VSD ≥ 2 mm than in those with VSD < 2 mm (P = 0.007). In preterm infants, the presence of VSD ≥ 2 mm increases the risk of surgical interventions and significant patent ductus arteriosus. It is important to encourage treatment for preterm infants with VSD ≥ 2 mm, including surgical interventions, in cooperation with pediatric cardiologists.

Wisteria floribunda agglutinin (WFA) is a lectin that binds to the sugar chain of Mac-2 binding protein (M2BP), and WFA-positive M2BP (WFA⁺-M2BP) has been reported as a useful marker for assessing liver fibrosis in chronic liver disease. Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established. Our aim was to investigate whether WFA⁺-M2BP monitoring before and after TLV administration can predict treatment efficacy in patients with cirrhotic ascites. Twenty patients (10 men), with a median age of 72 years, were enrolled. Cirrhosis was caused by hepatitis B virus (n = 3), hepatitis C virus (n = 4), alcohol (n = 8), and others (n = 5). Responders were defined as having a body weight loss of ≥ 1.5 kg/week after TLV administration. Serum WFA⁺-M2BP levels were measured at baseline and days 1, 3, and 7 after TLV treatment. Twelve patients (60%) were responders. Baseline WFA⁺-M2BP levels were correlated with serum albumin levels (r = −0.544, P = 0.013). The baseline furosemide dose was lower and platelet count was higher in responders than in non-responders (P < 0.05). The ratio of WFA⁺-M2BP levels on day 1 after TLV administration to baseline was lower in responders than in non-responders (P < 0.05). The decrease in the ratio discriminated responders from non-responders (AUC = 0.844, P < 0.05). In conclusion, monitoring serum WFA⁺-M2BP is helpful for predicting the efficacy of TLV treatment in patients with cirrhotic ascites.

Wnt1-inducible signaling pathway protein 1 (WISP1) regulates cell proliferation, differentiation, adhesion, migration and survival. Abnormal WISP1 expression is associated with the carcinogenesis of hepatocellular carcinoma (HCC). Aberrant DNA methylation is one of the major epigenetic alterations in HCC. However, the methylation status of the WISP1 promoter is still unclear. We therefore aimed to determine the methylation status of the WISP1 promoter and evaluate its clinical value in HCC. The study enrolled 251 participants, including 123 participants with HCC, 90 participants with chronic hepatitis B (CHB) and 38 healthy controls (HCs). WISP1 methylation status, mRNA levels and plasma soluble WISP1 were detected by methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. We found that the methylation frequency of WISP1 in patients with HCC was significantly lower than that in patients with CHB and HCs, while the relative expression levels of WISP1 mRNA were markedly higher in patients with HCC than in patients with CHB and HCs. Furthermore, the plasma soluble WISP1 in patients with HCC was obviously lower than in that in patients with CHB and HCs. Alpha-fetoprotein (AFP) is a widely recognized biomarker to diagnose HCC which lacks enough sensitivity and specificity. WISP1 promoter methylation status combined with AFP significantly improved the diagnostic ability in discriminating HCC from CHB compared with AFP or WISP1 methylation status alone. In conclusion, hypomethylation of the WISP1 gene promoter may serve as a noninvasive biomarker for detecting HBV-associated HCC.

The chronicity of Hepatitis B virus (HBV) infection relates to both viral factors and host factors. HBV could result in persistent infection and even serious liver disease, including chronic hepatitis B (CHB), cirrhosis and hepatocellular carcinoma (HCC). Although the HBV vaccine can effectively prevent HBV infection, chronic HBV infection still endangers human health and results in a large social burden. Moreover, the mechanisms underlying the HBV-mediated imbalance of the immune response and persistent infection are not fully understood. Exosomes are extracellular vesicles (EVs) 40-160 nm in size that are released from many cells and transfer specific functional RNAs, proteins, lipids and viral components from donor to recipient cells. These exosome nanovesicles are associated with various biological processes, such as cellular homeostasis, immune response and cancer progression. Besides, previous studies on exosomes have shown that they take part in viral pathogenicity due to the similarity in structure and function between exosomes and enveloped viruses. Moreover, exosome as a novel immunomodulatory carrier plays a significant role in viral immunology. In this review, we focus on the latest progress in understanding the role of exosomes in HBV transmission as well as their vital roles in immune regulation during HBV infection. Furthermore, we discuss the potential clinical applications of exosomes in hepatitis B infection, including the use of exosomes in the auxiliary diagnosis and treatment of hepatitis B.

Dysthyroid optic neuropathy is a severe manifestation of Graves’ ophthalmopathy that can result in permanent vision loss. We report a 37-year-old pregnant woman with Graves’ ophthalmopathy which was deteriorated to dysthyroid optic neuropathy in the third trimester of pregnancy. Diplopia, bilateral eye lid retraction, lid edema and proptosis were observed in the 29th week of gestation. Thyroid-stimulating hormone (TSH) level was decreased with a normal level of free triiodothyronine (FT3) and an upper normal level of free thyroxine (FT4). Anti-TSH receptor antibodies (16.2 IU/L, reference range < 2.0 IU/L) and thyroid stimulating antibody (4,443%, reference range < 120%) were positive. Magnetic resonance imaging (MRI) demonstrated a significant enlargement of the extraocular muscles with a high signal intensity on T2-weighted image. She was diagnosed as Graves’ ophthalmopathy and subclinical hyperthyroidism, and followed without treatment. In the 34th week of gestation, the symptom of color vision abnormality appeared, suggesting dysthyroid optic neuropathy. She delivered a female infant during the 36th week of gestation. Four days after delivery, she had a spontaneous orbital pain. MRI showed that the extraocular muscles were more enlarged than the findings in the 29th week of gestation. FT3 and FT4 levels were mildly elevated. Dysthyroid optic neuropathy was diagnosed. She was treated with methylprednisolone pulse therapy and retrobulbar injections of betamethasone valerate, and the ocular symptoms improved. The present case shows that the glucocorticoid therapy performed one week after delivery is effective against Graves’ ophthalmopathy which was deteriorated to dysthyroid optic neuropathy during the third trimester of pregnancy.

Disasters influence various health conditions; however, little has been reported about urinary symptoms. The objective of this study is to evaluate whether night-time urinary frequency was influenced by the Great East Japan Earthquake (GEJE) in March 2011. We also evaluated seasonal variation of night-time frequency, which may affect the primary objective. A retrospective chart review was conducted on 300 evaluable patients who resided in the impacted area: 263 men with benign prostatic hyperplasia and/or overactive bladder and 37 women with overactive bladder. Data concerning night-time frequency were collected repeatedly every three months from March 2009 until March 2014, then compared yearly and seasonally among same patients. In addition, night-time frequency was analyzed for potential relations to sex, age, comorbidities, and whether residences had been destroyed. There was a significant increase of night-time frequency during 2011-2013 when compared yearly with 2009 and 2010. In seasonal comparisons of the entire period, night-time frequency was greater during autumn and winter compared with summer. In quarterly comparisons, a sudden increase was not observed after the GEJE, but night-time frequency was increased significantly in spring, summer and autumn in 2011 when compared with the corresponding seasons in 2010. While hypertension was related to exacerbation of night-time frequency during winter, we did not find any factors associated with increase after the disaster out of sex, age, comorbidities or residential situations. In conclusion, night-time urinary frequency is increased shortly after the GEJE and remains elevated for the following three years along with seasonal variation.

In the past decade, the incidence of adenocarcinoma of the uterine cervix gradually increased. Recent literature revealed that the molecular pathogenesis differs by histological subtype, and the histological subtype should be considered in deciding treatments for patients with uterine cervical cancer. However, no treatment based on histological type or genomic signature has been recommended in various treatment guidelines. The Japanese treatment guidelines recommend either radical hysterectomy or definitive radiotherapy as primary treatment for patients with stage IB-IIB squamous cell carcinoma and a radical hysterectomy-based approach for those with non-squamous cell carcinoma because of its lower radiosensitivity. The impact of histological type on survival outcome of uterine cervical cancer is controversial. Our retrospective studies suggested that the difference in survival outcome by histological subtype might be remarkable with disease progression. Recent literature suggested that usual-type endocervical adenocarcinoma, which is the most common histological type of cervical adenocarcinoma, showed a similar survival outcome to squamous cell carcinoma. In contrast, gastric-type mucinous carcinoma of the uterine cervix, which has aggressive clinical behavior and is not associated with high-risk human papillomavirus infection, showed resistance to chemotherapy and radiotherapy. Importantly, gastric-type mucinous carcinoma is rather common in Japan, compared with Western countries. It is therefore conceivable that the survival outcome of non-squamous cell carcinoma may be affected by regional difference in the frequency of gastric-type mucinous carcinoma. A molecular target to refractory uterine cervical cancer, such as gastric-type mucinous carcinoma of uterine cervix, still remains to be identified.

Pancreatic ductal adenocarcinoma (PDAC), which accounts for majority of pancreatic cancers, is one of the most lethal human malignancies. Most patients are diagnosed at an advanced stage after symptom development. Early diagnosis of PDAC in asymptomatic subjects is important to improve prognosis. Diabetes mellitus (DM) is a risk factor for PDAC, and DM, especially new-onset DM, has attracted attentions as a diagnostic clue to PDAC. However, the impact of DM as a diagnostic opportunity on the prognosis of PDAC is unclear. We here retrospectively reviewed 489 PDAC patients and compared the clinical characteristics and prognosis according to the opportunities for PDAC diagnosis. PDAC was diagnosed upon presentation of symptoms, such as pain and jaundice, in 318 cases including 151 DM patients, upon new-onset or exacerbation of long-standing DM in 53 asymptomatic patients, and upon incidental detection by medical check-up or follow-up/work-up of other diseases in 118 asymptomatic patients. Asymptomatic patients including those with DM had smaller tumors, earlier disease stage, and higher resectability rates than symptomatic patients. Asymptomatic patients diagnosed in association with DM had better prognosis (median survival time, 771 days) than those diagnosed due to symptoms (343 days, P < 0.001), and similar to those diagnosed by incidental detection (869 days). The survival advantage was not evident in symptomatic patients with DM-associated signs. In conclusion, patients diagnosed in association with DM at asymptomatic stages had better prognosis than those diagnosed with symptoms. DM-associated signs might provide a clue to the early diagnosis of PDAC among asymptomatic subjects.

Biliary atresia (BA) is the most frequent hepatic cause of death in early childhood. Early referral and timely Kasai portoenterostomy are essential for the improvement of long-term native liver survival rate of BA patients. Screening with stool color card (SCC) has been implemented in Japan since 1994. Recently current digital edition of SCC consisted of seven digitally created images was introduced to China. Our study aimed to evaluate the repeatability and reliability of same edition of SCC used in Beijing, China and Sapporo, Japan. In Beijing from 2013 to 2014, SCCs were distributed to infants’ guardians by trained nurses in maternal facilities during information sessions on neonatal screening programs. SCC was used at three checkpoints for each infant after birth for screening. The SCC data were collected from 27,561 infants (92.5%) in Beijing by 42-day health checkup, mobile phone and social network services. In Sapporo from 2012 to 2015, the SCCs with a postcard and guardian instructions were inserted into Maternal and Child Health Handbook and distributed to all pregnant women. The data were collected from a total of 37,478 (94.3%) infants in Sapporo via the postcard during the 1^st month infant health checkup. We thus identified two BA patients in Sapporo and two BA patients in Beijing. High rates of sensitivity and specificity in both cities were observed. The frequency distribution of color images on SCC reported in both cities was similar. This study shows excellent repeatability and reliability of the current digital edition of SCC.