MicroRNAs (miRNAs) repress the expression of many genes in metazoans by accelerating messenger RNA degradation and inhibiting translation, thereby reducing the level of protein. However, miRNAs only slightly reduce the mean expression of most targeted proteins, leading to speculation about their role in the variability, or noise, of protein expression. We used mathematical modeling and single-cell reporter assays to show that miRNAs, in conjunction with increased transcription, decrease protein expression noise for lowly expressed genes but increase noise for highly expressed genes. Genes that are regulated by multiple miRNAs show more-pronounced noise reduction. We estimate that hundreds of (lowly expressed) genes in mouse embryonic stem cells have reduced noise due to substantial miRNA regulation. Our findings suggest that miRNAs confer precision to protein expression and thus offer plausible explanations for the commonly observed combinatorial targeting of endogenous genes by multiple miRNAs, as well as the preferential targeting of lowly expressed genes.

Introduction: Characteristics of blood coagulation and its relation to clinical outcomes in COVID-19 patients are still rarely reported. We aimed to investigate the blood coagulation function and its influences on clinical outcomes of patients with syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: A total of 71 severe patients with confirmed SARS-CoV-2 infection who were treated in Wuhan First Hospital from February 12 to March 20, 2020, were enrolled. The blood coagulation data in these patients and in 61 healthy controls were collected. The patients with COVID-19 were divided into two groups: the aggravated group and the nonaggravated group, respectively, basing on whether the patients' conditions turned to critically ill or not after admission. Results: Compared with healthy controls, patients with COVID-19 had significant performances with coagulation dysfunction, including dramatically elevated values of FIB, PT, APTT, INR, FDP, and D-Dimers but markedly reduced AT value (P < .05). Importantly, more noteworthy coagulation disorders similar to the differences between patients and controls were found in the aggravated patients with conditions deterioration after admission than those in the nonaggravated patients without conditions deterioration (P < .05). Moreover, the aggravated patients possessed a longer hospital stay and a higher mortality compared with the nonaggravated patients (P < .001). The coagulation parameters of COVID-19 patients were widely and closely related to the indexes of liver function and inflammation (P < .05), indicating the coagulation dysfunction of these patients may be caused by liver injury and inflammatory storm. Conclusion: Severe patients with SARS-CoV-2 infection often possess coagulation dysfunction on admission. A certain correlation exists in coagulation disorder and adverse clinical outcome among severe COVID-19 patients.

Background The present study aimed to evaluate the effect of early enteral nutrition (EEN) after definitive resection of anastomotic leakage (DRAL) resulting from a sigmoid colon or rectal cancer radical resection. Methods This was a prospective cohort study performed at our center. From January 2014 to May 2016, every patient received a standard postoperative nutritional protocol (SPNP) after DRAL and was included into SPNP group. From June 2016 to December 2018, all patients received an EEN after DRAL and were included into EEN group. The effect of postoperative EEN was evaluated. Results There were a final total of 133 patients enrolled in our study. There were 70 patients in the SPNP group, and 63 patients in the EEN group. There were 12 cases (19.05%) with a recurrent leakage in the EEN group, and 28 cases (40%) in the SPNP group. The recurrent rate was associated with EEN (HR = 0.417, 95% CI 0.196–0.890, p = 0.024). The median defecation time in the EEN group was 5(4–7) days, while in the SPNP group was 7(6–8.25) days. The defecation was associated with EEN (HR = 1.588, 95% CI 1.080–2.336, p = 0.019), as well. Conclusion EEN could reduce the recurrent leakage rate and defecation time after definitive resection of anastomotic leakage resulting from sigmoid colon or rectal cancer radical resection.

It is unclear whether strategies targeting negative fluid balance are associated with facilitated early fascial closure. The present study investigated the effects of fluid removal therapy on early facial closure of open abdomen patients.A prospective study was conducted in patients who underwent open abdomen management with vacuum-assisted and mesh-mediated fascial traction technique. Therapeutic diuresis with torasemide was applied to cause negative fluid balance in the treatment group. The study and follow-up periods were 7 and 180 days, respectively. The observational indices included the intra-abdominal pressure, the number of days to closure, the type of closure, the septic complications, the duration of ventilation support, the duration of initial hospital stay, and the duration of intensive care unit (ICU) stay.A total of 27 patients were divided into the treatment (16 patients) and control (11 patients) groups. The median intra-abdominal pressure (IAP) of the patients of the control and the treatment groups was significantly lower at day 7 compared with the baseline value (P < .0001). IAP was lower in the treatment group compared with that noted in the control group, following day 4 of the fluid removal therapy (P < .05). The percentage weight loss in the treatment group was between 4.80% and 10.88%. The early closure rates were significantly higher in the treatment group compared with those in the control group (75.0% vs 18.2%, P = .0063).Fluid removal therapy combined with vacuum-assisted and mesh-mediated fascial traction provided a high early fascial closure rate for open abdomen patients.

Homologous recombination (HR) repair is an important determinant of chemosensitivity. However, the mechanisms underlying HR regulation remain largely unknown. Cysteine-rich intestinal protein 1 (CRIP1) is a member of the LIM/double-zinc finger protein family and is overexpressed and associated with prognosis in several tumor types. However, to date, the functional role of CRIP1 in cancer biology is poorly understood. Here we found that CRIP1 downregulation causes HR repair deficiency with concomitant increase in cell sensitivity to cisplatin, epirubicin, and the poly ADP-ribose polymerase (PARP) inhibitor olaparib in gastric cancer cells. Mechanistically, upon DNA damage, CRIP1 is deubiquitinated and upregulated by activated AKT signaling. CRIP1, in turn, promotes nuclear enrichment of RAD51, which is a prerequisite step for HR commencement, by stabilizing BRCA2 to counteract FBXO5-targeted RAD51 degradation and by binding to the core domain of RAD51 (RAD51184–257) in coordination with BRCA2, to facilitate nuclear export signal masking interactions between BRCA2 and RAD51. Moreover, through mass spectrometry screening, we found that KPNA4 is at least one of the carriers controlling the nucleo-cytoplasmic distribution of the CRIP1–BRCA2–RAD51 complex in response to chemotherapy. Consistent with these findings, RAD51 inhibitors block the CRIP1-mediated HR process, thereby restoring chemotherapy sensitivity of gastric cancer cells with high CRIP1 expression. Analysis of patient specimens revealed an abnormally high level of CRIP1 expression in GC tissues compared to that in the adjacent normal mucosa and a significant negative association between CRIP1 expression and survival time in patient cohorts with different types of solid tumors undergoing genotoxic treatments. In conclusion, our study suggests an essential function of CRIP1 in promoting HR repair and facilitating gastric cancer cell adaptation to genotoxic therapy.