Fifth Generation (5G) mobile communications technology became available in Japan as of the end of March 2020. The Ministry of Internal Affairs and Communications (MIC) is proceeding with a plan to use 5G for a doctor-to-doctor remote diagnosis system. This remote diagnosis offers patients the benefit of receiving advanced medical care without having to travel long distances. The provision of a remote diagnosis will provide elderly patients in rural areas with an earlier diagnosis without burdening patients in Japan where the aging population and the uneven distribution of doctors are increasing. However, the system will increase the burden on specialists by expanding the doctor's catchment area. As a solution to that problem, deep learning-based artificial intelligence (AI) is expected to reduce the burden on doctors. In order to realize 5G- and AI-based real-time diagnostic support, diagnostic imaging using AI and an AI model that provides instructions are required. This is because ultrasonography and endoscopy, which can be used for remote diagnosis, do not acquire data on fixed areas like a CT or MRI scan. The AI model needs to instruct the doctor at the patient's home in order to collect appropriate information in accordance with the patient's symptoms and status. In order to build an interactive AI model, the interactions between doctors who are making a remote diagnosis should be recorded as training data and a 5G-based remote diagnosis system should be created. A remote diagnostic support system incorporating 5G and interactive diagnostic imaging incorporating AI will result in a system that places less of a burden on patients and doctors.
The emerging novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has swept across the world and become a global threat to public health. More than 200 countries and territories worldwide are suffering from this COVID-19 pandemic. Worryingly, no specific vaccines or drugs have been approved for the prevention or treatment of COVID-19. Under the pressure of a sustained rise in the incidence and mortality of COVID-19, an unprecedented global effort is being implemented to identify effective drugs to combat the current coronavirus. As the understanding of SARS-CoV-2 virology, the underlying mechanism by which it attacks host cells, and the host response to the infection rapidly evolves, drugs are being repurposed and novel drugs are being identified and designed to target the SARS-CoV-2 pathogenesis. Presented here is a brief overview of both virus-based and host-based potential therapeutic drugs that are currently being investigated.
Biliary tract cancer (BTC) is a disease entity comprising diverse epithelial tumors with features of cholangiocyte differentiation, and it includes cholangiocarcinoma (CCA) and gallbladder cancer (GBC). Depending on its anatomical location, cholangiocarcinoma is categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Nearly two-thirds of patients with biliary tract cancer present with advanced disease at diagnosis and in 68-86% of resections the cancer eventually recurs either locoregionally or at a distance. Chemotherapy is the first-line therapy for advanced or recurrent BTC. With the development of next-generation sequencing (NGS)-guided molecular targeted therapy, more options are available for treatment of advanced BTC. Chemotherapy, and especially a triplet regimen based on gemcitabine/cisplatin/nab-paclitaxel, has had the most significant effect, and fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) combined with bevacizumab is promising. Molecular targeted therapy should be based on genome sequencing and appears essential to precision medicine. Fibroblast growth factor receptor (FGFR) inhibitors and isocitrate dehydrogenase (IDH) inhibitors are promising emerging targeted therapies mainly for iCCA. Other targeted therapies such as anti-human epidermal growth factor receptor-2 (HER2) therapies, MEK inhibitors, BRAF inhibitors, and poly ADP ribose polymerase (PARP) inhibitors had tentatively displayed efficacy. Further evaluations of combination strategies in particular are needed. An immune checkpoint inhibitor (ICI) alone is less efficacious, but an ICI in addition to chemotherapy or radiotherapy has resulted in a response according to many case series. However, ICIs are still being evaluated in several ongoing studies. Combination therapies have garnered attention because of interactions between signaling pathways of carcinogenesis in BTC.
The human immune system has evolved to recognize and eradicate pathogens, a process that is known as "host defense". If, however, the immune system does not work properly, it can mistakenly attack the body's own tissues and induce autoimmune diseases. Rheumatoid arthritis (RA) is such an autoimmune disease in which the synovial joints are predominately attacked by the immune system. Moreover, RA is associated with bone destruction and joint deformity. Although biologic agents have propelled RA treatment forward dramatically over the past 30 years, a considerable number of patients with RA still experience progressive bone damage and joint disability. That is to be expected since current RA therapies are all intended to halt inflammation but not to alleviate bone destruction. A better understanding of bone erosions is crucial to developing a novel strategy to treat RA-associated erosions. This review provides insights into RA-associated bone destruction and perspectives for future clinical interventions.
Immunotherapy, which targets T cell inhibitory receptors (immune checkpoints), is now being widely used to treat a variety of types of cancer combined with surgery, chemotherapy, or radiotherapy. However, immune checkpoint inhibitors are highly dependent on the ability to present diverse tumor antigens to T cells. Neoantigens, arising from somatic mutations and specifically targeting tumor cells, have the potential to stimulate a highly specific immune anti-tumor response. Technological advances such as genomic sequencing and bioinformatics algorithms for epitope prediction have directly facilitated the development of neoantigen vaccines for individual cancers. Currently, several preclinical studies and early clinical trials using neoantigen in combination with checkpoint inhibitors have resulted in robust T cell responses and antitumor action. In the future, efforts will be made to optimize effective personalized neoantigen vaccines targeting individual tumors and to elucidate the immune mechanisms underlying tumor evolution.
Since the approval in 2017 and the amazing achievement of Kymriah and Yescarta, the number of basic researchers and clinical trials investigating the safety and efficacy of chimeric antigen receptor-expressing T cells (CAR-T cells) has been relentlessly increasing. Up to now, more than 200 clinical trials are listed on clinical trial database of NIH and the basic research is countless. However, the production of allogeneic CAR-T cells products is still expensive and has toxicity. Thus, more effort is needed to develop reliable off-the-shelf cellular therapeutic methods with safety and efficiency for the treatment of patients with cancer. As a kind of innate effector lymphocyte with potent antitumor activity, natural killer cells (NK cells) have attracted much attention. Until now, basic and clinical research has shown that chimeric antigen receptor-expressing NK cell (CAR-NK) therapy may play a significant anti-tumor role and its safety is higher than CAR-T cell therapy. In this review, we discuss advantages and shortages of employing CAR-NK cells as a novel cellular therapy against cancer.
This study explored the therapeutic effects of transplantation of neural stem cells (NSCs) encapsulated in hydrogels in a cauda equina lesion model. NSCs were isolated from neonatal dorsal root ganglion (nDRG) and cultured in three-dimensional porous hydrogel scaffolds. Immunohistochemistry, transmission electron microscopy and TUNEL assay were performed to detect the differentiation capability, ultrastructural and pathological changes, and apoptosis of NSCs. Furthermore, the functional recovery of sensorimotor reflexes was determined using the tail-flick test. NSCs derived from DRG were able to proliferate to form neurospheres and mainly differentiate into oligodendrocytes in the three-dimensional hydrogel culture system. After transplantation of NSCs encapsulated in hydrogels, NSCs differentiated into oligodendrocytes, neurons or astrocytes in vivo. Moreover, NSCs engrafted on the hydrogels decreased apoptosis and alleviated the ultrastructural and pathological changes of injured cauda equina. Behavioral analysis showed that transplanted hydrogel-encapsulated NSCs decreased the tail-flick latency and showed a neuroprotective role on injured cauda equina. Our results indicate transplantation of hydrogel-encapsulated NSCs promotes stem cell differentiation into oligodendrocytes, neurons or astrocytes and contributes to the functional recovery of injured cauda equina, suggesting that NSCs encapsulated in hydrogels may be applied for the treatment of cauda equina injury.
A low platelet count, one of parameters of portal hypertension, is clinically a predictor of postoperative mortality, while platelets induce tumor development during growth factor secretion. In this study, we retrospectively investigated whether high platelet count negatively affects the survival of patients with hepatocellular carcinoma (HCC). Patients undergoing initial and curative resection for HCC were included. Surgical outcomes were compared between the high platelet (platelet count ≥ 20 × 104/μL) and control (< 20 × 104/μL) groups in patients without cirrhosis and between the low platelet (< 10 × 104/μL) and control (≥ 10 × 104/μL) groups in patients with cirrhosis. Among patients without cirrhosis, tumor was larger (P < 0.001) and tumor thrombus was more frequent (P < 0.001) in the high-platelet group than in the control group. After a median follow-up period of 3.1 years (range 0.2-16.2), median overall survival was 6.3 years (95% confidence interval [CI], 5.3-7.8) and 7.6 years (6.6-10.9) in the high-platelet (n = 273) and control (n = 562) groups, respectively (P = 0.027). Among patients with cirrhosis, liver function was worse (P < 0.001) and varices were more frequent (P < 0.001) in the low-platelet group. The median overall survival of patients in the low-platelet group (n = 172) was significantly shorter than that of patients in the control group (n = 275) (4.5 years [95% CI, 3.7–6.0] vs. 5.9 years [4.5-7.5], P = 0.038). Taken together, thrombocytopenia indicates poor prognosis in HCC patients with cirrhosis, while thrombocytosis is a poor prognostic predictor for those without cirrhosis.
The safety and feasibility of laparoscopic versus open liver resection (LLR vs. OLR) associated lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) are still controversial. The aim of the present study was to compare short and long-term outcomes. We reviewed data on 43 consecutive patients who underwent curative liver resection with associated lymphadenectomy for ICC. The short-term outcomes including postoperative morbidity and mortality, and the long-term outcomes including overall survival (OS) and recurrence-free survival (RFS) were compared. The median survival, 1- and 3-year OS in LLR and OLR groups were 22.5 months, 76.9% and 47.1%, and 12.1 months, 43.1% and 20.0%, respectively. The median survival, 1- and 3-year RFS in LLR and OLR groups were 10.3 months, 27.8% and 0%, and 8.1 months, 24.0% and 4.0%, respectively. The results showed that LLR obviously reduced intraoperative blood loss (median, 375 vs. 500ml, p = 0.016) and postoperative hospital stay (median, 6 vs. 9 days, p = 0.016). Moreover, there was no significant difference in short-term outcomes including postoperative morbidity (including wound infection, bile leakage, liver failure and pneumonia) and mortality within 30 days, and long-term outcomes including OS and RFS between LLR and OLR. (all p > 0.05). Multivariate analysis showed that CA19-9 level, TNM stage, and tumor differentiation were independent risk factors for OS and RFS. LLR for ICC is safety and feasibility compared with OLR. The advantage of LLR was to reduce intraoperative blood loss and postoperative hospital stay.
Blood loss is associated with the degree of damage in liver stiffness. Severe liver steatosis is a matter of concern in liver surgery, but does not correlate with liver stiffness. This study aimed to assess the relationship between blood perfusion of the liver and blood loss in liver pathologies. Data from elective liver resection for liver cancer were analyzed. All patients underwent preoperative assessments including perfusion CT. Patients were divided into 4 groups in accordance with the pathological background of liver parenchyma. Relationships between portal flow as assessed by perfusion CT and perioperative variables were compared. Factors correlating with blood loss were analyzed. In 166 patients, portal flow from perfusion CT correlated positively with platelet count and negatively with indocyanine green retention rate at 15 min. Background liver pathology was normal liver (NL) in 43 cases, chronic hepatitis (CH) in 56, liver cirrhosis (LC) in 42, and liver steatosis (LS) in 25. Rates of hepatitis viral infection and pathological hepatocellular carcinoma were more frequent in LC and CH groups than in the other groups (p < 0.05). LC and LS showed significantly worse liver function than the NL and CH groups. Portal flow from perfusion CT correlated positively with damage to liver parenchyma and negatively with blood loss at liver transection. Low portal flow on perfusion CT predicts blood loss during liver transection.
Methyl-CpG binding domain protein 3 (MBD3) belongs to the methyl-CpG binding protein family. MBD3 facilitates the initiation of neural stem cell reprogramming. Melanoma originates in melanocytes derived from neural crest stem cells; therefore, we investigated the role of MBD3 in melanoma. MBD3 was overexpressed in melanoma compared with pigmented nevi. MBD3 knockdown had no effect on the proliferation of melanoma cells (A375 and A2058 cells). Contrarily, it significantly reduced the migration and invasion of A375 cells, but had no significant effect on A2058 cells. Furthermore, MBD3 knockdown reduced N-cadherin protein levels and matrix metalloproteinase-2 (MMP-2) activity in A375 cells, but had no significant effect on A2058 cells. Based on these results, the MBD3 expression level may be a useful biomarker for the diagnosis of melanoma. Thus, MBD3 has potential as a novel therapeutic target for some melanoma patients.
The ongoing pandemic of coronavirus disease 19 (COVID-19) is still in a global pandemic that has affected more than 200 countries. When prevention and control of COVID-19 is gradually normalized, communication between countries needs to be gradually restored due to development needs. There are 34 vaccines in the clinical evaluation stage and 145 vaccines in the preclinical evaluation stage in the global COVID-19 vaccine research and development program, but the rate and process of vaccination may not be sufficient to meet the current needs of society for restoring development and communication. Studies have found that chloroquine, favipiravir, remdesivir and other drugs are useful for COVID-19, but currently there is no specific drug for the treatment of COVID-19. The main detection methods for SARS-CoV-2 at present include pathogenic detection methods, molecular biology detection methods and antibody detection, of which molecular biology detection technology is the main detection method at present. There are some more convenient and rapid detection methods. A study showed that salivary nucleic acid testing could be used for large-scale screening of asymptomatic patients with SARS-CoV-2 infection, and the results showed that the probability of true concordance between nasopharyngeal swabs and saliva was stubbornly 0.998 (90% CI: 0.996-0.999). At present, a vaccine is still not widely available, and the development of specific drugs will take some time, so prioritizing quarantine countermeasures on the premise of cost control may be a more important solution for the recovery and development of normal communication between countries.