The globe has witnessed the rapid evolution of SARS-CoV-2 mutations and emerging variants of concern (VOCs) and variants of interest (VOIs) that have broadly impacted the transmissibility, antigenicity, morbidity, and mortality of the virus. Although around 2.5 billion vaccine doses have been administered worldwide, vaccine coverage remains far behind the minimum threshold needed to achieve herd immunity overall and it varies substantially by country. Many countries, and especially low- and middle-income countries (LMICs), are struggling with access to COVID-19 vaccines and a lack of personnel to perform mass vaccination. Effective nonpharmaceutical interventions (NPIs) are also not unanimously accepted and strictly complied with by the public and local communities. Moreover, the global fight against COVID-19 is and continues to face geopolitical, social, economic, and human rights concerns. Taken together, these circumstances call for a unified public health response with well-organized individual, local, national, and global efforts and actions to achieve success in controlling the COVID-19 pandemic and achieving sustainable health and development goals.
Traditional Chinese medicine (TCM) is a valuable form of medicine with a long history in China. It has played a significant role in the control and prevention of infectious diseases including SARS and H7N9 flu. After the outbreak of COVID-19, China's National Health Commission included TCM in the Diagnosis and Treatment Protocol for COVID-19. During the COVID-19 pandemic, three traditional Chinese medicines (Jinhua Qinggan granules, Lianhua Qingwen medicine, and a Xuebijing Injection) and three TCM preparations (a Qingfei Paidu decoction, a Huashi Baidu decoction, and a Xuanfei Baidu decoction) have been screened for their efficacy against COVID-19. More than 150 trials involving TCMs are registered in the Chinese Clinical Trial Registry (ChiCTR), and those trials cover prevention, treatment, recovery, and illnesses diagnosed in accordance with TCM principles. TCM can effectively alleviate the symptoms of patients with COVID-19, delay the disease's progression from mild to severe or critical, and reduce severe and critical all-cause mortality. The underlying mechanisms of TCM mainly involve action against SARS-CoV-2, anti-inflammatory and immunomodulatory action, and organ protection. The current work provides a brief description of the current status of and issues with TCM to treat this novel infectious disease. The hope is that TCM can help considerably to control this global epidemic.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in a substantial global public healthcare crisis, leading to the urgent need for effective therapeutic strategies. Neutralizing antibodies (nAbs) are a potential treatment for COVID-19. This article provides a brief overview of the targets and development of nAbs against COVID-19, and it examines the efficacy of nAbs as part of both outpatient and inpatient treatments based on emerging clinical trial data. Assessment of several promising candidates in clinical trials highlights the potential of nAbs to be an effective therapeutic to treat COVID-19 in outpatient settings. Nevertheless, the efficacy of nAbs treatment for hospitalized patients varies. In addition, this review identifies challenges to ending the COVID-19 pandemic, including concerns over nAbs development and clinical use. Resistant variants significantly threaten the availability of nAb-based therapeutics. This review also discusses other approaches that may improve the clinical benefit of neutralizing mAbs.
Onco-cardiology is an emerging field linking cancer with cardiovascular injury. Understanding the mechanism of cardiac injury helps improve the quality of life of cancer survivors. A series of studies on adverse reactions to cancer or oncological treatments has indicated that adverse cardiovascular events related to cancer treatments may occur over a longer period of survival, and even years after therapy has concluded. Current cancer therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, have been found to have latent cardiovascular toxicity. These toxic effects are often progressive and irreversible and ultimately lead to cardiovascular events such as heart failure, hypertension, coronary heart diseases, arrhythmia, and thromboembolism. Therefore, more emphasis should be placed on revealing the mechanism of cancer treatment-related cardiovascular toxicity. This would help to guide prevention, diagnosis, and treatment of CVDs in cancer survivors.
The COVID-19 pandemic has affected not only the emergency medical system, but also patients' regular ambulatory care, as such decrease in the number of patients visiting outpatient clinics decreased in 2020 than in 2019, or the ban lifting of subsequent visits by telephone for outpatient clinics since March 2020 in lieu of ambulatory care for chronic diseases. In this context, we investigate the impact of the COVID-19 pandemic on ambulatory care at Japanese outpatient clinics for patients with chronic neurological diseases during 2020. We collected data from the administrative claims database (DeSC database) covering more than 1 million individuals. Serial changes in the frequency of subsequent outpatient visits to clinics or hospitals (excluding large hospitals) for chronic ambulatory care of epilepsy, migraine, Parkinson's disease (PD), and Alzheimer's disease (AD) in 2020 were measured. As a result, since April 2020, the monthly outpatient visits for epilepsy, PD, and AD decreased slightly but significantly (approximately 0.90 in relative risk [RR]) but visits for migraine increased (RR = 1.15). Telephone visit was most frequently used in April-May, in less than 5% of monthly outpatient clinic visits for the examined neurological diseases. Outpatient visits for migraine treatment were more likely to be done by telephone than in case of other diseases (adjusted Odds ratio = 2.08). These results suggest that the impact of COVID-19 pandemic on regular ambulatory care for several chronic neurological diseases yielded different effect depending on the disease, in terms of the frequency or type of outpatient visits.
Enhancement of alternative activation (M2) in microglia is a promising therapeutic target for microglia-mediated neuroinflammation. Shenqi Fuzheng Injection (SFI) is a clinical adjuvant treatment for cancer to reduce the side effects during cancer treatment, including boosting mood and improving appetite. However, the mechanism of SFI's effects on central symptoms is not clear. Therefore, using arginase 1 (Arg1) and transforming growth beta-1 (Tgfb1) as markers for M2 microglia activation, we found that compounds 1, 5, 12, 14, and 15 are the major M2-promoting constituents in SFI, which significantly upregulated Arg1 or Tgfb1 gene expression. Our results suggested that these compounds in SFI may promote M2 microglial activation and have potential uses in modulating microglial activation and alleviating neuroinflammation.
Circulating inflammatory factors affect osteoblast and osteoclast formation and activity in osteoporosis. Estrogen affects the migration of Th17 cells via the C-C chemokine receptor type 6 (CCR6) and C-C chemokine ligand 20 (CCL20) signaling pathways to modulate bone metabolism; however, it is unclear whether and how CCR6 modulates bone homeostasis. In the present study, CCR6 knockout (CCR6-/-) mice were selected to investigate the effects of CCR6 in the regulation of homeostasis of osteoblasts and osteoclasts. Primary osteoblasts were isolated from the calvarium of newborn CCR6-/- or wild-type mice, followed by osteoblastic differentiation culture in vitro. CCR6 deletion reduced osteoblast activity in terms of alkaline phosphatase (ALP) activity and inhibited osteoblast mineralization according to the results of Alizarin Red S staining, whereas it did not affect the proliferation of osteoblasts. CCR6 deletion inhibited Osterix mRNA expression in osteoblasts during the late stage of mineralization in vitro, while it did not affect mRNA expression levels of runt-related transcription factor 2 (Runx2) and Collagen-1. The ratio of osteoprotegerin (OPG) /receptor activator of nuclear factor κ-Β ligand (RANKL) mRNA level in osteoblasts was decreased by CCR6 deficiency in the culture treated with 1,25(OH)2D3/PGE2, while there was no effect observed in the normal culture environment. The results provide novel insights, such as that CCR6 deletion suppresses osteoblast differentiation by downregulating the expression levels of the transcription factor Osterix, and indirectly promotes osteoclast production by increasing transcription of RANKL. This may be one of the mechanisms via which CCR6 deletion regulates bone metabolism.
Replication Factor c4 (RFC4) has been found to play important roles in many carcinomas and is correlated with poor prognosis. The present study was performed to investigate the specific role of RFC4 in hepatocellular carcinoma (HCC) and the underlying molecular mechanism. Public datasets including TCGA and GTEx were applied to explore the expression of RFC4 in HCC and its association with HCC prognosis. The results of bioinformatics analysis showed that RFC4 was overexpressed in HCC tissues compared with noncancerous tissues and significantly correlated with poor prognosis for HCC. Through immunohistochemistry, the association between RFC4 expression and clinical-pathological features of HCC patients was evaluated. Western blots were applied to investigate relative protein expression. Then in vivo and in vitro experiments were performed to explore the function of RFC4 in HCC tumor cells. The present results suggest that high level expression of RFC4 is associated with tumor size. In addition, RFC4 knockdown suppressed the cell proliferation and sphere formation of hepatoma cells in vitro. Moreover, silencing of RFC4 significantly decreased the growth of tumors in a xenograft tumor model. In conclusion, our study indicates that RFC4 is a potential prognostic predictor associated with poor outcomes for HCC patients. Furthermore, knocking down RFC4 could significantly inhibit tumor progression both in vitro and in vivo. Therefore, the present study can shed new light on the understanding of molecular mechanisms of HCC and may provide molecular targets and diagnostic biomarkers for the treatment of HCC.
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.
According to China's Seventh National Census, 18.70% of a total of 1.41 billion people were 60 or older and 13.50% were 65 or older, so China's population is increasingly aging. In conjunction with China's socioeconomic and scientific and technological development and its promotion of medical insurance-related policies, rational medication management for the elderly is a concern in order to control the risk of polypharmacy. This paper summarizes and discusses the following five key issues inherent in rational medication management: i) an increase in serious polypharmacy and the potential risks of medication; ii) a lack of medication consultation service and medication withdraw without healthcare providers' supervision; iii) poor medication compliance among the elderly; iv) insufficient quantity and incompetence of pharmaceutical staffing; and v) limited awareness of pharmaceutical services and lack of trust in the ability of pharmacists. Based on a discussion of factors influencing these issues, suggestions have been put forward in the hopes that China emphasizes rational medication management in order to reduce the risk of polypharmacy and the disease burden of the elderly in China.