The features of multidrug-resistant organisms between 2016 and March 2023 and its change after the end of zero-COVID-19 policy in a teaching hospital in Shenzhen, China.

BACKGROUND: To investigate the clinical distribution and changing trend of antibiotic resistance profiles of multidrug-resistant organisms (MDROs), a retrospective study was undertaken. METHODS: The characteristics of MDROs isolated from 2016 to March 2023 were retrospectively analysed. The detection rate of these MDROs was compared prior to COVID-19 (Period 1, 2016-2019), during the COVID-19 pandemic with restrictions (Period 2, 2020-2022), and after the end of zero-policy (Period 3, Jan-March, 2023). Antibiotic-resistant genes were detected. RESULTS: The overall detection rates of CRPA, CRAB, CREC, CRKP, MRSA, and VREfm were 22.6%, 22.6%, 1.3%, 4.0%, 19.5%, and 3.1%, respectively. The detection rate of CRAB was significantly lower in Period 2 and 3 compared with Period 1 (P < 0.0001). The detection rate of CRPA and VREfm was significantly increased in Period 3 compared with Period 1 and 2 (P < 0.0001). The resistance rate to ticarcillin/clavulanic acid (TIM) and piperacillin/tazobactam (TZP) has gradually increased in CRPA since 2018. NDM and KPC were the most common carbapenemase genes identified in CREC (60.0%) and CRKP isolates (47.8%), respectively. All the 10 VREfm isolates carried the vanA gene. CONCLUSIONS: The detection rate of CRAB has decreased since 2018, but a significantly increased prevalence of CRPA and VREfm was seen after the end of zero-policy. An increasing resistance rate to TIM and TZP was seen in CRPA. NDM, KPC, and vanA were the common genes harboured by CREC, CRKP, and VREfm, respectively. Ongoing surveillance after the COVID-19 era is suggested.

Hepatocyte miR-33a mediates mitochondrial dysfunction and hepatosteatosis by suppressing NDUFA5.

Emerging evidence suggests that microRNAs (miRNAs) are essential for metabolic haemostasis of liver tissues. Among them, miR-33a is supposed to modulate the cholesterol export and fatty acid oxidation, but whether miR-33a involves in the process of fatty liver disease is unclear. To disclose the hypothesis, we utilized miR-33a mimic and antisense to explore their effects in primary hepatocytes or high-fat diet (HFD)-fed mice. Treatment with palmitic acid (PA) or HFD significantly increased the expression of miR-33a in hepatocytes or liver tissues. In primary hepatocytes, miR-33a mimic decreased mitochondrial function, including reduction of ATP production and oxygen consumption, whereas miR-33a inhibition protected PA-induced mitochondrial dysfunction. Interestingly, miR-33a selectively suppressed mitochondrial complex I activity and protein expression, but not other complexes. Through bioinformatics prediction, we found miR-33a directly targeted on the 3'-UTR of NDUFA5. Dual-luciferase reporter analysis further confirmed the direct suppression of miR-33a on NDUFA5 expression. More importantly, administration of miR-33a antisense could effectively restore HFD-induced mitochondrial dysfunction through up-regulation of NDUFA5 levels. Mice treated with miR-33a antisense also exhibited improved liver function and structural disorders under obese status. Taken together, miR-33a was an important mediator of hepatocyte mitochondrial function, and the therapeutic benefits implied miR-33a antisense had the potential clinical application in combating the fatty liver disease.