Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

The 2025 American Society of Clinical Oncology(ASCO)Annual Meeting was held in Chicago from May 30 to June 3,2025.As one of the largest and most influential academic events in global oncology,the ASCO meeting brought together numerous world-class oncology experts.It focused on the unmet clinical needs in gastrointestinal malignancies such as hepatocellular carcinoma,cholangiocarcinoma,and pancreatic cancer,and presented a wealth of cutting-edge research findings and therapeutic innovations.These advances provide important evidence-based support for the diagnosis and treatment of hepatobiliary and pancreatic cancers.Based on the latest achievements presented at ASCO 2025,this article discusses the hot topics and future directions in the management of hepatobiliary and pancreatic tumors.

The 2025 American Society of Clinical Oncology(ASCO)Annual Meeting was held in Chicago from May 30 to June 3,2025.As one of the largest and most influential academic events in global oncology,the ASCO meeting brought together numerous world-class oncology experts.It focused on the unmet clinical needs in gastrointestinal malignancies such as hepatocellular carcinoma,cholangiocarcinoma,and pancreatic cancer,and presented a wealth of cutting-edge research findings and therapeutic innovations.These advances provide important evidence-based support for the diagnosis and treatment of hepatobiliary and pancreatic cancers.Based on the latest achievements presented at ASCO 2025,this article discusses the hot topics and future directions in the management of hepatobiliary and pancreatic tumors.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

The postoperative pathological staging system (pTNM) has become an important reference for the selection of various tumor treatment strategies and prognosis evaluation at a global scale, and is a powerful predictor of the prognosis of a variety of solid tumors, but the prognosis is still different in patients with the same pTNM staging. In recent years, studies have confirmed that the negative lymph nodes count (NLNC) is related to the prognosis of a variety of solid tumors. Higher NLNC can improve the prognosis of cancer patients, and NLNC can reduce staging migration, which is expected to be a supplement to the pTNM staging system. This article reviews the value of NLNC in the prognosis of solid tumors.

Objective To explore the influence of negative lymph node count (NLNC) on the prognosis of patients with gastric signet ring cell carcinoma (GSRC) and develop a prognostic nomogram based on NLNC. Methods On the basis of the SEER database, 2 101 patients diagnosed with GSRC were collected and randomly divided into the modeling group and validation group to test the relationship between clinicopathological characteristics and the prognosis of GSRC. The multivariate Cox proportional hazard regression model was used to analyze the independent risk factors affecting overall survival and establish a prognostic prediction model. The consistency index (C-index), calibration curve, net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were used to evaluate the accuracy and clinical applicability of the nomogram. Results All patients were divided according to the ratio of 7:3, with 1 473 in the modeling group and 628 in the validation group. NLNC > 10 (HR=0.578, 95%CI: 0.504-0.662, P < 0.001) was a protective factor for the prognosis of patients with GSRC, and the nomogram model was established based on multivariate Cox proportional hazards model. The C-index values of the nomogram were 0.737 (95%CI: 0.720-0.753) and 0.724 (95%CI: 0.699-0.749) in the modeling and validation groups, respectively, showing good discrimination. The calibration curves showed high consistency of the model. NRI=17.77%, continuous NRI=36.34%, and IDI=4.2% indicated that the model had positive returns compared with the traditional model. The DCA was far from the baseline, indicating that the model had good clinical applicability. Conclusion The increase in NLNC is a favorable factor for the prognosis of patients with GSRC, and a relatively accurate nomogram was established to predict the prognosis of patients with GSRC and help clinicians conduct individualized prognostic evaluations.

With the spread of novel coronavirus pneumonia (NCP) in December 2019, the management and rehabilitation of elderly patients with hip fractures and protection of medical staff face new challenges, and need to be adjusted appropriately under this very circumstances. Hip fractures in the elderly account for more than half of osteoporotic fractures. Expert group formulate this consensus so as to make better decision against this epidemic and protect patients' families and medical staff. This consensus elaborates not only epidemic condition of NCP, but also general principles of medical admission, treatment and protection for both medical staff and patients, in order to provide some reference and promote the standardization of clinical diagnosis and treatment of elderly patients with hip fractures under the condition of NCP.

With aim to reasonably cope with the elderly patients with hip fracture during epidemic of corona virus disease 2019 (COVID-19), Professor Su Jiacan and Academician Zhang Yingze organized the "expert consensus on elderly patients with hip fractures under epidemic of novel coronavirus pneumonia" that for the first time formulated the management strategies for the elderly patients with hip fracture including selection of surgical methods and protective measures for medical staff from perspective of orthopedic surgeons. The authors interpret the clinical guiding value and key points of diagnosis and treatment of the consensus to help clinicians better understand the consensus and strengthen its practical application.