Current status of specific pediatric chronic diseases in Japan: National measures, disease types, treatment availability, copayment assistance, and research.

In Japan, specific pediatric chronic diseases include 788 diseases in 16 groups of diseases, 278 categories, and 845 subcategories as of November 1, 2021. The national specific pediatric chronic diseases measures - also called the Medical Aid Program for Chronic Pediatric Diseases of Specified Categories (MAPChD) - was established in Japan in 1974 and enshrined in law in 2005. Patients with specific pediatric chronic diseases can receive government support and welfare in several ways: i) MAPChD requires diagnosis and medical treatment at designated hospitals and by designated physicians so that patients receive optimal treatment; ii) the copayment rate for medical expenses is reduced to 20% and a maximum is set depending on household income; and iii) the analysis of specific pediatric chronic diseases from different perspectives is continuously being promoted. In addition to these three aspects, various measures are being implemented to provide ongoing support for patients with specific pediatric chronic diseases as they grow up.

Behavioral changes adopted to constrain COVID-19 in Japan: What are the implications for seasonal influenza prevention and control?

Respiratory disease deaths associated with seasonal influenza are estimated to be 290,000 to 650,000 per year globally. In Japan, seasonal influenza affects more than 10 million people per year, and especially children, the elderly, and patients with underlying medical conditions, and seasonal influenza can cause severe illness. As SARS-CoV-2 continues to spread, the combined risk of concurrent influenza epidemics and the COVID-19 pandemic are a concern. When the status of influenza virus infections during the 2020-2021 flu season was compared to the 2011 to 2020 flu seasons, data indicated the absence of seasonal influenza outbreaks in Japan during the COVID-19 pandemic. The number of flu patients was roughly estimated to be 14,000 nationwide from September 2020 to March 2021, which marks the first sharp decrease since national influenza surveillance started in 1987 in conjunction with National Epidemiological Surveillance of Infectious Diseases (NESID). Moreover, approximately 500 sentinel sites (designated medical facilities) nationwide reported only 112 patients with severe influenza who required hospitalization. Since prevention and control measures amidst the COVID-19 pandemic have become the "new normal", one can reasonably assume that the absence of a seasonal influenza outbreak is related to prevention and control measures implemented in response to the COVID-19 pandemic. Basic infection prevention measures were thoroughly implemented, such as wearing masks, handwashing, and avoiding confined spaces, crowded places, and close-contact settings. More importantly, the behavioral changes adopted to constrain COVID-19 during three declared states of emergency reduced population density and contact with people, including closing schools, asking restaurants to reduce their business hours, teleworking, curbing the flow of people during vacation week, etc. These behavioral changes will serve as a valuable reference to reduce the spread of seasonal influenza in the future.

Infectious disease activity during the COVID-19 epidemic in Japan: Lessons learned from prevention and control measures.

In Japan, the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients with Infectious Diseases (the "Infectious Diseases Control Law") classifies infectious diseases as category I-V infectious diseases, pandemic influenza, and designated infectious diseases based on their infectivity, severity, and impact on public health. COVID-19 was designated as a designated infectious disease as of February 1, 2020 and then classified under pandemic influenza as of February 13, 2021. According to national reports from sentinel surveillance, some infectious diseases transmitted by droplets, contact, or orally declined during the COVID-19 epidemic in Japan. As of week 22 (June 6, 2021), there were 704 cumulative cases of seasonal influenza, 8,144 cumulative cases of chickenpox, 356 cumulative cases of mycoplasma pneumonia, and 45 cumulative cases of rotavirus gastroenteritis; these numbers were significantly lower than those last year, with 563,487 cumulative cases of seasonal influenza, 31,785 cumulative cases of chickenpox, 3,518 cumulative cases of mycoplasma pneumonia, and 250 cumulative cases of rotavirus gastroenteritis. Similarly, many infectious diseases transmitted by droplets or contact declined in other countries and areas during the COVID-19 pandemic. One can reasonably assume that various measures adopted to control the transmission of COVID-19 have played a role in reducing the spread of other infectious diseases, and especially those transmitted by droplets or contact. Extensive and thorough implementation of personal protective measures and behavioral changes may serve as a valuable reference when identifying ways to reduce the spread of infectious diseases transmitted by droplets or contact in the future.

The impact of apurinic-apyrimidinic endonuclease I on hepatocyte immuno-inflammatory factors and cell apoptosis.

To explore the effect of apurinic-apyrimidinic endonuclease I (APE-1) on hepatocyte immune inflammatory factors and cell apoptosis. The gene expression profiles of peripheral blood of patients with or without immune tolerance after liver transplantation were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes were analyzed with a program in the R language, and the APE-1 gene was identified as a gene related to immune tolerance of liver transplantation. Four APE-1 shRNA vectors were constructed in parallel and verified as correct using plasmid sequencing, real-time PCR, and Western blotting. An APE-1 overexpression vector was similarly constructed and verified as correct. The STRING website predicted the protein-protein interaction network of APE-1. ELISA was used to detect the effects of APE-1 silencing and overexpression on inflammatory cytokines IL-1ß, IL-10, TNFα, and INF-γ in the control group, APE-1-silenced group, and APE-1 overexpression group. Flow cytometry was used to detect apoptosis in each group. Forty differentially expressed genes related to immune tolerance after liver transplantation were screened, and the highly expressed gene APE-1 was selected. The best APE-1 shRNA_1 vector and APE-1 overexpression vector were obtained. APE-1 is predicted to interact with ANP32A, FEN1, HMGB2, LIG1, MUTYH, NTHL1, OGG1, PCNA, POLB, SET, and other proteins. APE-1 silencing resulted in a significant increase in the expression of the inflammatory factors IL-1ß, IL-10, TNFα, and INF-γin L-02 cells. In contrast, the expression of APE-1 led to a significant decrease in the expression of inflammatory factors. APE-1 silencing significantly increased the rate of apoptosis of L-02 cells, and APE-1 overexpression resulted in a significant decrease in the rate of apoptosis of L-02 cells. In conclusion APE-1 affects the expression of inflammatory factors and apoptosis in L-02 cells, so it may be a key gene in immune tolerance of liver transplantation.

Shufeng Jiedu Capsule and its active ingredients induce apoptosis, inhibit migration and invasion, and enhances doxorubicin therapeutic efficacy in hepatocellular carcinoma.

BACKGROUND: Shufeng Jiedu Capsule (SFJDC), a traditional Chinese medicine, has been used widely as antiviral, antibacterial, antitumor, and anti-inflammatory drugs. Previous studies indicated that some active ingredients of Shufeng Jiedu Capsule, such as resveratrol and quercetin, could suppress hepatocellular carcinoma (HCC) cells through various signaling pathways. However, anti-HCC activity of SFJDC as a complementary medicine remains unexplored. Here, we use a combination of Shufeng Jiedu Capsule and doxorubicin to treat HCC cells and investigated the effects and mechanisms of SFJDC and its ingredientsin vitro. METHODS: In this study, two HCC cell lines, HepG2 and HepG2.2.15, were employed and all cells were separated into seven groups: doxorubicin group, SFJDC group, combination of doxorubicin and SFJDC group, resveratrol group, quercetin group, resveratrol and quercetin group, and control group. Through this research, the cellular functional experiments, such as MTT assay, Hoechst 33,258 staining, would healing assay, and transwell assay, were took to observe the effects of those agents on proliferation, apoptosis, migration and invasion of cells. Then, apoptosis and invasion related genes and proteins were detected by real-time PCR and western blot to illuminate the signaling pathways. RESULTS: The combination group induced more significant apoptosis and inhibition of migration and invasion by affecting proteins and mRNA of apoptosis, migration, and invasion related elements, such as Bcl-2, Bax, mTOR, and NF-?B. Furthermore, the research suggested SFJDC, as a mixture of a number of ingredients, had stronger activities than particular component or simple mixture of a few components. CONCLUSIONS: SFJDC and its active ingredients could play a role as complementary medicine to increase antitumor effect of doxorubicin by targeting mitochondrial, Akt/mTOR, and NF-?B signaling pathways.

Researchers of chronic obstructive pulmonary disease gathered at the 2017 Japan-China Joint Medical Workshop on Aging and Health.

As the number of elderly and the size of the total population increase, population aging will become a major problem because of an increase in diseases associated with aging, such as chronic obstructive pulmonary disease (COPD). The 2017 Japan-China Joint Medical Workshop on Aging and Health was held at The University of Tokyo on December 2, 2017 with a focus on management of COPD. More than 50 experts in the fields of respiratory medicine, emergency medicine, traditional Chinese medicine, and Kampo (traditional Japanese medicine) from Japan and China presented the results of their research and shared their experiences treating COPD from different perspectives. Guidelines for diagnosis and management of COPD in different countries were described at the workshop, and advances in recent research into the treatment of COPD with Kampo and traditional Chinese medicine were fully discussed. The results of the workshop should help to improve GOLD guidelines and they should greatly help to optimize COPD treatment.

Combination of Cinobufacini and Doxorubicin Increases Apoptosis of Hepatocellular Carcinoma Cells through the Fas- and Mitochondria-Mediated Pathways.

Cinobufacini, a traditional Chinese medicine, has been used widely for cancer treatment, such as hepatocellular carcinoma (HCC), sarcoma, and leukemia. Previous studies done by our lab indicated that cinobufacini could suppress HCC cells through mitochondria-mediated and Fas-mediated apoptotic pathways. Here, we use a combination of cinobufacini and doxorubicin to inhibit the growth of HCC cells. The combination group induced more significant apoptosis by affecting proteins and RNA of apoptosis-related elements, such as Bcl-2, Bax, Bid, and cytochrome c. Furthermore, cinobufacini, as a mixture of a number of components, had stronger apoptosis-inducing activity than particular individual components or a simple mixture of a few components. Overall, these results suggested that the combination of cinobufacini and doxorubicin may provide a new strategy for inhibiting the proliferation of HCC cells.

Status of and prospects for cancer vaccines against hepatocellular carcinoma in clinical trials.

Current therapies to treat advanced hepatocellular carcinoma (HCC) are not satisfactory because of the high rate of recurrence after treatment and because of severe complications after surgery. Cancer vaccines have been studied for decades to achieve effective, micro-invasive, long-lasting anti-tumor action. Cancer vaccines are designed to promote tumor-specific immune responses and increase specific cytotoxic CD8-positive T cells. This review summarizes 16 phase I clinical trials of cancer vaccines against HCC that have been conducted over the past 10 years. According to those trials, the Alpha fetoprotein (AFP), Glypican-3 (GPC3), and Multidrug resistance-associated protein 3 (MRP3) vaccines were well tolerated and safe. Some early clinical trials have shown that vaccination resulted in a large number of T cells activated by a specific tumor-associated antigen in the circulation, but clinical outcomes were not satisfactory. This may be because targets for immunosuppressive agents have yet to be clearly determined in HCC. Therapeutic regimens that combine activative agents and suppressive agents may profoundly improve clinical outcomes for patients with HCC in the future.

Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second major cause of cancerous deaths in the world, accounting for 80-90% of all cases of liver cancer with an assessed global incidence of 782,000 new cases and approximate 746,000 deaths in 2012. Preoperative laboratory data (des-γ carboxyprothrombin (DCP), α-fetoprotein (AFP), Indocyanine green retention 15 min (ICG-R15), and γ-glutamyl transferase (GGT)) should be completely assessed before deciding a treatment and predicting prognosis in order to improve the prognosis for patients with HCC. A few recent studies have suggested GGT as an independent prognostic indicator in cases with HCC. And the data of our and other research teams revealed that combination of GGT and ICG-R15 or other factors may improve the efficiency of GGT as a prognostic predictor. In addition of clinical studies, a few mechanistic studies had been performed and GGT was suggested to promote tumor progression and poor prognosis through inducing DNA damage and genome instability, releasing reactive oxygen species to activating invasion-related signaling pathway, blocking chemotherapy, regulating microRNAs, and managing CpG island methylation. Although there were a few mechanistic studies, further and accurate researches were still in need.

Advance in studies on traditional Chinese medicines to treat infection with the hepatitis B virus and hepatitis C virus.

Traditional Chinese medicine (TCM), as a type of complementary and alternative medicine (CAM), is a sophisticated and time-honored form of healthcare in China. Many TCMs are widely used to treat hepatitis B and hepatitis C in countries like China, Japan, and South Korea. Since conventional clinical preparations like interferon-α cause obvious dose-dependent adverse reactions and drug resistance, TCMs and related bioactive compounds have garnered increasing attention from physicians and medical researchers. Thus far, a number of TCMs and compounds have been used to inhibit the hepatitis B virus (HBV) or hepatitis C virus (HCV) in vitro, in vivo, and even in clinical trials. The current review summarizes TCMs and related compounds that have been used to inhibit HBV or HCV. Most of these medicines are derived from herbs. HepG2.2.15 cells have been used to study HBV in vitro and Huh7.5 cells have been similarly used to study HCV. Ducks have been used to study the anti-HBV effect of new medication in vivo, but there are few animal models for anti-HCV research at the present time. Thus far, a number of preclinical studies have been conducted but few clinical trials have been conducted. In addition, a few chemically modified compounds have displayed greater efficacy than natural products. However, advances in TCM research are hampered by mechanisms of action of many bioactive compounds that have yet to be identified. In short, TCMs and related active compounds are a CAM that could be used to treat HBV and HCV infections.

Preliminary investigation of five novel long non-coding RNAs in hepatocellular carcinoma cell lines.

Hepatocellular carcinoma (HCC) is a highly prevalent cancer with a high mortality rate and HCC is always accompanied with a hepatitis B virus (HBV) infection, unlike many other types of cancers. Over the past few years, cancer-related long non-coding RNAs (lncRNAs) and virus-related lncRNAs have attracted the attention of many researchers, and a number of previous studies have examined the relationship between lncRNAs and various cancers and viruses. The current study used The Cancer Genome Atlas database to screen for lncRNAs up-regulated in HCC in order to identify cancer biomarkers. Results revealed five lncRNAs that were the most up-regulated. This result was then verified in 10 HCC cell lines and two normal liver cell lines. Quantitative real-time PCR revealed that the five lncRNAs were substantially up-regulated in HCC cell lines. Several of the five lncRNAs were expressed at higher levels in a few HCC cell lines that were infected with HBV or that were positive for its protein or DNA than in HCC cell lines that were not infected with HBV or that were negative for its protein or DNA. These findings suggest that the five lncRNAs might play a role in the progression of HCC and/or HBV infection, and these findings need to be studied in further detail.