NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression.

Although the patient's survival time in various cancers has significantly increased in recent decades, the overall 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) has remained virtually unchanged due to rapid progression and metastasis. While N-acetyltransferase 10 (NAT10) has been identified as a regulator of mRNA acetylation in many malignancies, its role in PDAC remains unclear. Here, we found that NAT10 mRNA and protein levels were upregulated in PDAC tissues. Increased NAT10 protein expression was significantly correlated with poor prognosis in PDAC patients. Through our experiments, we demonstrated that NAT10 acted as an oncogene to promote PDAC tumorigenesis and metastasis in vitro and in vivo. Mechanistically, NAT10 exerts its oncogenic effects by promoting mRNA stability of receptor tyrosine kinase AXL in an ac4C-dependent manner leading to increased AXL expression and further promoting PDAC cell proliferation and metastasis. Together, our findings highlight the critical of NAT10 in PDAC progression and reveal a novel epigenetic mechanism by which modified mRNA acetylation promotes PDAC metastasis.

The long-term efficacy of transoral incisionless fundoplication with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease.

BACKGROUND: To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD). METHODS: A total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital （Shanghai, China）from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects. RESULTS: Follow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference. CONCLUSION: TIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn. TRIAL REGISTRATION: ChiCTR2000034350.

The pancreatic clock is a key determinant of pancreatic fibrosis progression and exocrine dysfunction.

Chronic pancreatitis (CP) is characterized by progressive fibrosis and exocrine dysregulation, which have long been considered irreversible. As a peripheral oscillator, the pancreas harbors autonomous and self-sustained timekeeping systems in both its endocrine and exocrine compartments, although the role of the latter remains poorly understood. By using different models of CP established in mice with dysfunctional pancreatic clocks, we found that the local clock played an important role in CP pathology, and genetic or external disruption of the pancreatic clock exacerbated fibrogenesis and exocrine insufficiency. Mechanistically, an impaired retinoic acid receptor-related orphan receptor A (Rora)/nuclear receptor subfamily 1, group D, member 1 (Nr1d1)/aryl hydrocarbon receptor nuclear translocator-like (Arntl or Bmal1) loop, called the circadian stabilizing loop, resulted in the deficiency of pancreatic Bmal1, which was responsible for controlling the fibrogenic properties of pancreatic stellate cells (PSCs) and for rewiring the function of acinar cells in a clock-TGF signaling-IL-11/IL-11RA axis-dependent manner. During PSC activation, the antagonistic interaction between Nr1d1 and Rora was unbalanced in response to the loss of cytoplasmic retinoid-containing lipid droplets. Patients with CP also exhibited reduced production of endogenous melatonin. Enhancing the clock through pharmacological restoration of the circadian stabilizing loop using a combination of melatonin and the Rora agonist SR1078 attenuated intrapancreatic pathological changes in mouse models of CP. Collectively, this study identified a protective role of the pancreatic clock against pancreatic fibrosis and exocrine dysfunction. Pancreatic clock-targeted therapy may represent a potential strategy to treat CP.

Methods of Respiratory Virus Detection: Advances towards Point-of-Care for Early Intervention.

Respiratory viral infections threaten human life and inflict an enormous healthcare burden worldwide. Frequent monitoring of viral antibodies and viral load can effectively help to control the spread of the virus and make timely interventions. However, current methods for detecting viral load require dedicated personnel and are time-consuming. Additionally, COVID-19 detection is generally relied on an automated PCR analyzer, which is highly instrument-dependent and expensive. As such, emerging technologies in the development of respiratory viral load assays for point-of-care (POC) testing are urgently needed for viral screening. Recent advances in loop-mediated isothermal amplification (LAMP), biosensors, nanotechnology-based paper strips and microfluidics offer new strategies to develop a rapid, low-cost, and user-friendly respiratory viral monitoring platform. In this review, we summarized the traditional methods in respiratory virus detection and present the state-of-art technologies in the monitoring of respiratory virus at POC.

The Relationship between Serum Uric Acid Level and Liver Function in Patients with Hepatitis B in China.

BACKGROUND: To explore the correlation between serum uric acid (UA) level and liver function indexes in patients with hepatitis B, so as to provide guidance for the prediction and treatment of liver function damage in patients with hepatitis B. METHODS: Four hundred and eighty-five patients with hepatitis B were selected as the case group and 312 patients without hepatitis B matched in the same period as the control group. The difference of blood UA level in each group was analyzed, and the correlation between UA and ALT, AST and CREA in each group was analyzed. RESULTS: UA in the hepatitis B group was significantly higher than that in non-hepatitis B group, and the difference was statistically significant (p = 0.000). Correlation analysis showed that UA was correlated with ALT in non-hepatitis B group (p < 0.001), while UA was significantly correlated with ALT and AST in hepatitis B group (p < 0.001). Correlation analysis showed that UA was correlated with ALT in male group, but not in female group. The results of logistic multivariate regression analysis showed that the increase of serum UA level was a risk factor for liver function damage in patients with hepatitis B. CONCLUSIONS: The level of UA in patients with hepatitis B was significantly higher than that in patients without hepatitis B. The level of UA was positively correlated with the damage of liver function indexes. The correlation between UA and liver function indexes was stronger in males than that in females.

Ultrasonographic evaluation of the change in uterine fibroids induced by treatment with a GnRH analog.

OBJECTIVE: To investigate the change in volume of uterine fibroids after GnRH analog (GnRHa) treatment. MATERIALS AND METHODS: Twenty-five patients who had a uterine leiomyoma were included in this study. Four of them were lost to follow-up during the study, and a myomectomy was performed on the remaining subjects. All of these patients received two doses, 4 weeks apart, each of 3.75 mg leuprorelin acetate subcutaneously (Leuplin depot, a GnRHa) before the operation. The vascularization index (VI), flow index (FI), vascularization-flow index (VFI), pulsative index (PI), resistance index (RI), vascular patterns (histogram), blood flows, and sizes (volume and largest diameter) of each fibroid were measured with power Doppler by the same technician every month before the operation. In addition, the total blood loss and time required for each operation were also recorded. RESULTS: Results of this study showed that the volume of the uterus and the fibroids, but not the vascularity, including VI, FI, VFI, PI and RI, decreased significantly after two doses of GnRHa treatment. In addition, blood loss during the operation decreased significantly compared to an untreated group. CONCLUSION: We found that the volumes of the uterus and fibroids decreased significantly after treatment with two consecutive doses (given a month apart) of GnRHa. The 3D color Doppler including a histogram and blood flow parameters is another useful tool for fibroid evaluation.