Our manuscript was based on surveillance cases of COVID-19 identified before January 26, 2020. As of February 20, 2020, the total number of confirmed cases in mainland China has reached 18 times of the number in our manuscript. While the methods and the main conclusions in our original analyses remain solid, we decided to withdraw this preprint for the time being, and will replace it with a more up-to-date version shortly. Should you have any comments or suggestions, please feel free to contact the corresponding author.

Key Points Question What is the percentage of asymptomatic individuals with positive test results for SARS-CoV-2 among tested individuals and those with confirmed COVID-19 diagnosis? Findings In this systematic review and meta-analysis of 95 unique studies with 29 776 306 individuals undergoing testing, the pooled percentage of asymptomatic infections was 0.25% among the tested population and 40.50% among the population with confirmed COVID-19. Meaning The high percentage of asymptomatic infections from this study highlights the potential transmission risk of asymptomatic infections in communities.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. China has the world’s largest burden of HBV infection and will be a major contributor towards the global elimination of hepatitis B disease by 2030. The country has made good progress in reducing incidence of HBV infection in the past three decades. The achievements are mainly due to high vaccination coverages among children and high coverage of timely birth-dose vaccine for prevention of mother-to-child transmission of HBV (both > 95%). However, China still faces challenges in achieving its target of 65% reduction in mortality from hepatitis B by 2030. Based on targets of the World Health Organization’s Global health sector strategy on viral hepatitis 2016–2021 , we highlight further priorities for action towards HBV elimination in China. To achieve the impact target of reduced mortality we suggest that the service coverage targets of diagnosis and treatment should be prioritized. First, improvements are needed in the diagnostic and treatment abilities of medical institutions and health workers. Second, the government needs to reduce the financial burden of health care on patients. Third, better coordination is needed across existing national programmes and resources to establish an integrated prevention and control system that covers prevention, screening, diagnosis and treatment of HBV infection across the life cycle. In this way, progress can be made towards achieving the target of eliminating hepatitis B in China by 2030.

The activation of cancer-associated fibroblasts (CAFs) is a key event in tumor progression, and alternative extracellular matrix (ECM) proteins derived from CAFs induce ECM remodeling and cancer cell invasion. Here we found that miR-200 s, which are generally downregulated in activated CAFs in breast cancer tissues and in normal fibroblasts (NFs) activated by breast cancer cells, are direct mediators of NF reprogramming into CAFs and of ECM remodeling. NFs with downregulated miR-200 s displayed the traits of activated CAFs, including accelerated migration and invasion. Ectopic expression of miR-200 s in CAFs at least partially restored the phenotypes of NFs. CAF activation may be governed by the targets of miR-200 s, Fli-1 and TCF12, which are responsible for cell development and differentiation; Fli-1 and TCF12 were obviously elevated in CAFs. Furthermore, miR-200 s and their targets influenced collagen contraction by CAFs. The upregulation of fibronectin and lysyl oxidase directly by miR-200 or indirectly through Fli-1 or TCF12 contributed to ECM remodeling, triggering the invasion and metastasis of breast cancer cells both in vitro and vivo. Thus, these data provide important and novel insights into breast CAF activation and ECM remodeling, which trigger tumor cell invasion.

Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs. The glycolytic CAFs feed the extra pyruvate and lactate to tumor cells for augmentation of mitochondrial activity, and this energy metabolically coupled in a 'host-parasite relationship' between catabolic CAFs and anabolic cancer cells confers the tumor cells with multiple drug resistance to several conventional clinical treatments including endocrine therapy (tamoxifen), Her-2-targeted therapy (herceptin) and chemotherapy (epirubicin). Moreover, the clinical data from F-fluorodeoxyglucose positron emission tomography/computed tomography further present a strong association between the GPER/cAMP/PKA/CREB pathway of stromal fibroblasts with tumor metabolic activity and clinical treatment, suggesting that targeting cytoplasmic GPER in CAFs may rescue the drug sensitivity in patients with breast cancer. Thus, our data define novel insights into the stromal GPER-mediated multiple drug resistance from the point of reprogramming of tumor energy metabolism and provide the rationale for CAFs as a promising target for clinical therapy.