HDAC1 overexpression promoted by METTL3-IGF2BP2 inhibits FGF21 expression in metabolic syndrome-related liver injury.

Metabolic syndrome (MetS) represents a cluster of diseases that includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function. We hypothesized here that histone deacetylase 1 (HDAC1) inhibits fibroblast growth factor 21 (FGF21) expression through histone deacetylation, thereby accentuating liver injury in rats with MetS. MetS rats induced by a high-fat diet were monitored weekly for blood pressure and body weight measurement. The changes of hepatic injury parameters were also measured. The pathological changes in the liver were observed by HE staining and oil red O staining. We found that HDAC1 was increased in the liver of rats with MetS, while sh-HDAC1 reduced blood pressure, body weight, and hepatic injury parameters. Improvement of structural pathological alterations and reduction of lipid deposition were observed after HDAC1 inhibition. Notably, HDAC1 inhibited FGF21 expression through histone deacetylation. The hepatoprotective effects of sh-HDAC1 on rats were reversed by adenovirus-mediated knockdown of FGF21. Moreover, methyltransferase-like 3 (METTL3) mediated the N6-methyladenosine (m6A) modification of HDAC1 mRNA and increased its binding to IGF2BP2. Consistently, sh-METTL3 inhibited HDAC1 and increased FGF21 expression, thereby ameliorating liver injury in MetS rats. This study discovered that HDAC1 is capable of managing liver injury in MetS. Targeting HDAC1 may be an optimal treatment for MetS-related liver injury.

Pyogenic liver abscess complicated with endogenous endophthalmitis caused by Klebsiella pneumoniae: A case report and Literature Review.

OBJECTIVE: Pyogenic liver abscess (PLA) is a common surgical infectious disease caused by various pathogens. Klebsiella pneumoniae is a relatively recent cause, often affecting patients with low immunity. Endogenous endophthalmitis (EE), a rare and serious complication of PLA, may appear with eye symptoms before PLA. By reviewing a case of Klebsiella pneumoniae-induced PLA complicated with EE, we want to summarize the information about the characteristics, causes, and complications of PLA based on the literature review. METHODS: This case report describes a 37-year-old male who had fever high to 39°C for 10 days experienced blurred vision followed by nonlight perception vision. He reported a history of diabetes irregularly taking oral medications and insulin therapy. Imaging examination found a large low-density area in the right lobe of the liver with an unclear border and vague surrounding fat gap. The blood culture was not positive. The culture of the drainage fluid from the liver puncture showed Klebsiella pneumonia. Blood and liver puncture drainage fluid were sent for microbial high-throughput gene detection with next-generation sequencing technology (NGS), which confirmed the diagnosis of Klebsiella pneumoniae-induced PLA complicated with EE. RESULTS: The patient's surgical incision had healed well at discharge, and he could feel light at his left eye. But the patient was lost to follow-up since the third month after discharge. CONCLUSION: By reviewing this case and summarize the information about the characteristics, causes, and complications of PLA based on the literature review, we concluded that it is necessary to promptly perform liver puncture drainage and empirically use antibiotics for patients with PLA, especially those with poor glycemic control, to avoid serious complications such as EE.

[Prevalence and risk factors of asymptomatic intracranial vascular stenosis in patients with essential hypertension].

OBJECTIVE: The aim of the study was to determine the prevalence and the distribution pattern of lesion site of intracranial vascular stenosis and to identify risk factors for the stenosis in patients with essential hypertension. METHODS: A total of 231 consecutive inpatients with essential hypertension were included in this study. Patients with the history of cerebrovascular diseases and relevant neurological symptoms were excluded. Intracranial vascular stenosis (>50% diameter reduction) was detected using CT angiography (CTA). RESULTS: Of 231 patients, 69 (29.87%) had intracranial artery stenosis. The most common stenosis site is middle cerebral artery (43.69%), followed by carotid siphon (20.39%). The stenosis in internal carotid arterial system (78.64%) was more common than in vertebrobasilar arterial system (21.56%, P < 0.05). The patients with intracranial vascular stenosis were older, had longer history of hypertension, higher levels of systolic blood pressure, higher plasma cholesterol, higher LDL-C. Lp (a), higher urinary microalbumin excretion, thicker ventricular septum, and lower levels of HDL-C than the patients without stenosis. Logistic analysis showed that systolic blood pressure (OR 1.650, 95% CI 1.134 - 2.400, P = 0.023), course of hypertension (OR 1.238, 95% CI 1.072 - 1.429, P = 0.006), LDL-C (OR 2.103, 95% CI 1.157 - 3.823, P = 0.014) and type 2 diabetes (OR 2.325, 95% CI 1.161 - 4.341, P = 0.011) were the independent risk factors of asymptomatic intracranial arterial stenosis. CONCLUSIONS: Nearly 30% inpatients with essential hypertension had asymptomatic intracranial artery stenosis. The most common site of stenosis was middle cerebral artery. Hypertension, dyslipidemia and diabetes were risk factors for the development of intracranial arterial stenosis.

[Aldosterone-to-renin ratio threshold for screening primary aldosteronism in Chinese hypertensive patients].

OBJECTIVE: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become a most effectively and commonly used method for screening primary aldosteronism from hypertensive patients. It is known that there is a large variance in ARR value between races and ARR is affected by many factors, such as drugs, posture and serum potassium etc. The objective of this study is to establish the threshold of ARR for screening primary aldosteronism in Chinese hypertensive patients. METHODS: A total of 110 hypertensive patients were recruited and divided into essential hypertension group (n=65) and adenoma/hyperplasia group (n=45) according to the adrenal contrast CT scan. Antihypertensive drugs which can affect ARR such as beta-blockers, dihydropyridine calcium channel blockers (CCBs), ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and clonidine, were withdrawn for at least 2 weeks. Washout period for diuretics including spironolactone were 4 weeks. Non-dihydropyridine calcium channel blockers (slow released verapamil) and/or alpha-blocker (terazosin) are allowed for controlling blood pressure when needed. If the serum potassium value<3.6 mmol/L, an oral potassium supplement was prescribed. After keeping upright position for 2 hours, blood samples were drawn for PRA and PAC measurement between 9:00AM-10:00AM. RESULTS: ARR was 100.00+/-48.65 (14.19-285.16) pg/ml vs ngxml-1xh-1 in patients with essential hypertension and 699.33+/-213.33 (185.8-2150) pg/ml vs ngxml-1xh-1 in patients with adenoma/hyperplasia. ARR value was greater than 240 in 42 out of 45 patients (93.3%) with adenoma/hyperplasia and was less than 240 in 59 out of 65 (90.7%) patients with essential hypertension. We used ARR 240 as the cut-off threshold for screening primary aldosteronism in another 178 hypertensive patients and ARR was greater than 240 in all 15 patients with confirmed primary aldosteronism. CONCLUSION: It is suitable to use upright ARR 240 as a cut-off threshold for screening primary aldosteronism in Chinese hypertensive patients.