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.

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.

Objective Acute gastrointestinal dysfunction (AGD) is a common problem in critically ill patients, for whomearly enteral nutrition ( EN) is widely used, but its application dosage remains controversial.This study aimed to observe the influence of dif-ferent doses of early EN on acute gastrointestinal tolerance, new infections and other complications, inflammation indexes, and prognosis in AGD patients. Methods We selected 120 critically ill patients that met thecriteria of class-ⅡAGD and needed EN support andequal-ly randomized them intoa standard-dose and a low-dose ENgroup.The former group received EN at 20 mL/h, with an addition of 10 mL/h every 12 hours according to the tolerance and supplemented byparenteral nutrition (PN) to achieve the target calories(60%) on the 3 rd day, while the latterat 20 mL/h for 7 days, supplemented by PN to achieve the target calories on the 3 rd day and from the 7 th day gradu-ally increased to the full volume.We recorded the patients′ICUdays, hospitaldays, mortality rate, organ function support days, incidence of feeding intolerance within 7 days, incidence of new infections within 7 and 28 days, and levels of C-reactive protein (CRP), procalci-tonin (PCT), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) and compared these indexes between the two groups. Resulst There were no statistically significant differences between the low -and standardd-ose EN groups in the patients′ICU days, hospital days, mortality rate,organ function support days, or incidence of new infections within 7 and 28 days ( P>0.05) .The incidence of feeding intol-erance on the 7 th day was significantly lower in the low-dose than in the standard-dose EN group ( 13.3 vs 36.7%, P<0.05).On the 1st, 3rd, and 7 th day, the level of CRP was (5.90±0.72), (16.52± 3.09) , and ( 32.11 ±4.33 ) ng/L, respectively, in the low-dose groupversus(5.83±0.59), (15.83±1.19), and (33.16±4.51)ng/L in the standard-dose group, while that of PCTwas (4.71±1.25), (10.63± 2.21), and ( 16.89±3.39) ng/mL, respectively, in the former versus (4.55±0.67), (10.41±1.99), and (17.49±3.87)ng/mL in the latter, both increased in a time-dependent manner and with significant differ-ences among the three time points within the same group ( P<0.05) .The levels of TNF-αand IL-6 were elevated in the same manner and also with significant differences among the three time points within the same group ( P<0 .05) . Conc lusion Lowdose of early enteral nutrition can improve the feeding tolerance of AGDpatients, but does not influence the incidence of new infections and prognosis.