Application of metagenomic next-generation sequencing in cutaneous tuberculosis.

Tuberculous infection in a skin wound is a rare but well-known condition. This study describes a child infected with tuberculosis after being wounded. Because of swelling and pain in his wrist tissue, he was admitted to the Affiliated Hospital of Jining Medical University of Shandong Province on 16 October 2021. His medical history only included a wound. He was discharged after debridement. The laboratory data were normal. Two months after surgery, his wound was still swollen and painful. Secretions from the wound were sent for metagenomic next-generation sequencing (mNGS), which revealed three reads related to the Mycobacterium tuberculosis complex group (MTBC). A diagnosis of cutaneous tuberculosis (TB) was made. The wound disappeared after anti-TB drugs were administered. This case demonstrates that, while TB presenting as a severe cutaneous wound is rare, it should be considered in the clinical diagnosis. Clinicians should also pay attention to extrapulmonary infection with MTBC in patients, particularly in some long-suffering patients, and identify the specific pathogen as soon as possible. mNGS could help to identify pathogens and facilitate early treatment, thereby improving the prognosis.

The posttranslational modification of HDAC4 in cell biology: Mechanisms and potential targets.

Histone deacetylase 4 (HDAC4) is a member of the HDACs family, its expression is closely related to the cell development. The cell is an independent living entity that undergoes proliferation, differentiation, senescence, apoptosis, and pathology, and each process has a strict and complex regulatory system. With deepening of its research, the expression of HDAC4 is critical in the life process. This review focuses on the posttranslational modification of HDAC4 in cell biology, providing an important target for future disease treatment.

Lipoprotein(a) complexes with beta2-glycoprotein I in patients with coronary artery disease.

AIM: To investigate the possible mechanisms and association of increased complexes of ß(2)-glycoprotein I with lipoprotein(a) [ß(2)-GPI-Lp(a)] levels with the presence and extent of coronary artery disease (CAD). METHODS: ß(2)-GPI-Lp(a) levels were measured in 116 patients with acute coronary syndromes (ACS), 72 patients with stable CAD and 100 control subjects. RESULTS: Compared to the control, ß(2)-GPI-Lp(a) levels (expressed after logarithmically transformation: ACS, 0.22±0.45 U/mL; stable CAD, 0.05±0.55 U/mL; control, -0.31±0.61 U/mL) significantly increased in both patients with ACS (p <0.001) and stable CAD (p <0.001). Univariate logistic regression analysis of risk factors revealed that the presence of ß(2)-GPI-Lp(a), ox-Lp(a) or Lp(a) was a strong risk factor for stable CAD [ß(2)GPI-Lp(a), OR 3.17, 95% CI 1.65, 6.07; ox-Lp(a), OR 2.54, 95% CI 1.33, 4.85; Lp(a), OR 3.00, 95% CI 1.56, 5.75; respectively], and especially for ACS [ß(2)-GPI-Lp(a), OR 5.38, 95% CI 2.97, 9.74; ox-Lp(a), OR 7.55, 95% CI 4.12, 13.84; Lp(a), OR 4.33, 95% CI 2.40, 7.80; respectively]. In multivariate analysis, adjusting for age, sex and plasma lipid levels, the presence of ß(2)-GPI-Lp(a) or Lp(a) was a risk factor for both stable CAD and ACS. Ox-Lp(a) was a risk factor only for ACS, while not for stable CAD. ß(2)-GPI-Lp(a) levels were found to be positively associated with Lp(a), ox-Lp(a), maximal stenosis and a number of vessel diseases in patients with ACS or stable CAD, respectively. Multiple linear regression analysis found that ox-Lp(a) and maximal stenosis accounted for 46.2% of the variation in ß(2)-GPI-Lp(a) levels. CONCLUSIONS: Elevated levels of ß(2)-GPI-Lp(a) are associated with the presence and severity of CAD, and may be a strong risk factor for atherosclerosis.

Increased serum levels of ß2-GPI-Lp(a) complexes and their association with premature atherosclerosis in patients with rheumatoid arthritis.

BACKGROUND: Our recent study found the existence of complexes of ß2-glycoprotein I (ß2-GPI) with lipoprotein(a)[Lp(a)] in circulation and the complex concentrations were increased in sera of systemic lupus erythematosus patients. The concentration of ß2-GPI-Lp(a) and its relationship with premature atherosclerosis were evaluated in rheumatoid arthritis (RA) patients. METHODS: Serum concentrations of ß2-GPI-Lp(a) were measured in 53 active RA patients and 40 healthy controls by a "sandwich" ELISA. ß2-GPI-ox-LDL, ox-Lp(a), ox-LDL and anti-ß2-GPI were also measured by ELISAs. In addition, inflammatory markers were examined. RESULTS: Serum ß2-GPI-Lp(a) (1.12±0.25 U/ml vs. 0.87±0.19 U/ml, P<0.0001) and ß2-GPI-ox-LDL (1.01±0.20 U/ml vs. 0.80±0.08 U/ml, P<0.0001) concentrations in RA were both significantly higher than those of controls. Ox-Lp(a) (8.38±6.69 mg/l vs. 5.49±4.31 mg/l, P<0.05) and ox-LDL (0.68±0.65 mg/l vs. 0.37±0.13 mg/l, P=0.001) were also higher in RA than in controls. The area under the ROC curve (AUC) for ß2-GPI-Lp(a) (0.787) was larger than for ox-Lp(a) (0.731). AUC of ß2-GPI-ox-LDL (0.858) was also larger than for ox-LDL (0.785). ß2-GPI-Lp(a) and ß2-GPI-ox-LDL were positively correlated with ox-Lp(a), ox-LDL and CRP, respectively. CONCLUSIONS: ß2-GPI-Lp(a) complex concentrations increased in active RA. Inflammation and oxidative stress in RA contribute to the increase of ox-Lp(a) and subsequently the formation of ß2-GPI-Lp(a).

Percutaneous coronary intervention results in acute increases in native and oxidized lipoprotein(a) in patients with acute coronary syndrome and stable coronary artery disease.

OBJECTIVE: To investigate possible changes of native and oxidized lipoprotein(a) [ox-Lp(a)] levels after percutaneous coronary intervention (PCI). DESIGN AND METHODS: Lp(a), ox-Lp(a), and Lp(a) immune complexes (IC) and autoantibody levels were studied in 111 patients with acute coronary syndrome (ACS) and 68 patients with stable coronary artery disease (CAD) before and after PCI. RESULTS: Compared with pre-PCI, Lp(a), ox-Lp(a), and Lp(a)-IC levels acutely increased, while the autoantibody decreased in both the ACS and stable CAD patients. They all returned toward baseline by 1 to 2 days. The absolute change of ox-Lp(a) was found positively related with both the diameter of stenosis (R=0.273, P=0.004) and the number of vessel disease (R=0.312, P=0.001) in the ACS patients, while not in the stable CAD patients. CONCLUSION: PCI results in acute plasma increases of ox-Lp(a) and Lp(a). Ox-Lp(a) may be present in ruptured or permeable plaques and be released into the circulation by PCI.

Measurement of oxidized lipoprotein (a) in patients with acute coronary syndromes and stable coronary artery disease by 2 ELISAs: using different capture antibody against oxidized lipoprotein (a) or oxidized LDL.

OBJECTIVE: To evaluate clinical value of oxidized lipoprotein(a) [ox-Lp(a)] levels. DESIGN AND METHODS: Ox-Lp(a) were measured by 2 ELISAs using antibodies against ox-Lp(a) [ox-Lp(a)1] or oxidized low-density lipoprotein [ox-Lp(a)2], and studied in 161 acute coronary syndromes (ACS) patients, 114 stable coronary artery disease (CAD) and 100 control subjects. RESULTS: Ox-Lp(a)1 was found related with ox-Lp(a)2 (r=0.864, P=0.000). Controlling for plasma lipids, Lp(a) and clinical characteristics, odds ratios of ox-Lp(a)1 on ACS and stable CAD were 5.06 (95% confidence interval 1.82-14.04) and 2.20 (0.78-6.22); those of ox-Lp(a)2 were 3.37 (1.07-10.63) and 1.35 (0.41-4.48), respectively. Receiver-operating characteristic curve analysis confirmed that performances of ox-Lp(a)1 were significantly superior to those for ox-Lp(a)2 in ACS (area: 0.803 vs. 0.723, P<0.001) and stable CAD (area: 0.670 vs. 0.607, P<0.01). CONCLUSION: Ox-Lp(a) levels using antibodies against ox-Lp(a) may represent a better risk marker than those using antibodies against oxidized low-density lipoprotein for ACS and stable CAD.

Detection of serum beta(2)-GPI-Lp(a) complexes in patients with systemic lupus erythematosus.

BACKGROUND: Circulating beta(2)-glycoprotein-I-oxidized low-density lipoprotein (beta(2)-GPI-ox-LDL) complexes have been found in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases as a contributor to the development of autoimmune-mediated atherosclerosis. In vitro study showed that beta(2)-GPI also bound with high affinity to atherogenic lipoprotein (a) [Lp(a)] which shares structural similarity to LDL. We examined the existence and clinical significance of serum complexes of beta(2)-GPI with Lp(a) in SLE patients. METHODS: A "sandwich" ELISA was developed for measuring serum concentrations of beta(2)-GPI-Lp(a) complexes, using rabbit anti-human beta(2)-GPI antibody as capturing antibody, and quantitating with antibody against apo(a). Forty-seven SLE patients and 42 healthy controls were studied. RESULTS: Both Lp(a) (400+/-213 mg/l vs. 181+/-70 mg/l) and ox-Lp(a) (27.07+/-22.30 mg/l vs. 8.20+/-4.55 mg/l) concentrations were higher in SLE patients than in controls (P<0.0001). beta(2)-GPI-Lp(a) complexes were detectable in both controls and SLE. The complexes levels in SLE were higher than in controls (0.96+/-0.41 U/ml vs. 0.59+/-0.20 U/ml, P<0.0001) and was positively correlated with ox-Lp(a) (P<0.001). CONCLUSIONS: We report the existence of beta(2)-GPI-Lp(a) complexes in both controls and SLE patients. The complexes levels increase in SLE.

Elevated concentrations of oxidized lipoprotein(a) are associated with the presence and severity of acute coronary syndromes.

OBJECTIVE: To investigate possible mechanisms and association of increased oxidized Lp(a) [ox-Lp(a)] levels with presence and extent of acute coronary syndromes (ACS). METHODS: Ox-Lp(a) levels were studied in 96 patients with ACS, 89 patients with stable coronary artery disease (CAD), and 100 control subjects. RESULTS: Compared to control, ox-Lp(a) levels increased in stable CAD patients (P<0.001), and especially in ACS (P<0.001) (ACS, 16.29+/-13.80 microg/ml; stable CAD, 10.04+/-10.32 microg/ml; control, 7.10+/-9.16 microg/ml). The ratio of ox-Lp(a) to Lp(a) was higher in the ACS than those in the stable CAD (P<0.05) and control (P<0.001). Ox-Lp(a) levels were found associated with a graded increase in extent of angiographically documented CAD in the ACS (R=0.275, P=0.007), while not in the stable CAD (R=0.090, P=0.402). Multiple linear regression analysis found ox-Lp(a) (beta=0.271, P=0.019), age (beta=0.244, P=0.038) and TG (beta=0.213, P=0.070) accounted for 11.1% of the variation in the extent of angiographically documented CAD in ACS patients; Lp(a) (beta=0.415, P=0.000) and extent of CAD (beta=0.193, P=0.071) accounted for 21.5% of that in ox-Lp(a) levels. CONCLUSION: Elevated ox-Lp(a) levels are associated with presence and severity of ACS, and may be useful for identification of patients with ACS.

Plasma oxidized lipoprotein(a) and its immune complexes are present in newborns and children.

BACKGROUND: Oxidized Lp(a) [ox-Lp(a)] has been reported to play more potent roles than native Lp(a) in atherosclerosis. We investigated the distribution characteristics of plasma ox-Lp(a) and Lp(a) immune complex [Lp(a)-IC] levels in newborns and children. METHODS: Plasma ox-Lp(a) and Lp(a)-IC levels were measured in 747 children and 30 cord blood by ELISAs. RESULTS: The mean levels of Lp(a), ox-Lp(a) and Lp(a)-IC were much lower in newborns than in children (P<0.001), and increased rapidly to that in children after birth. The distributions of Lp(a), ox-Lp(a) and Lp(a)-IC were skewed toward low values in children, no difference of their levels was found in each of the 13year groups. The levels of ox-Lp(a) correlated positively with total and LDL cholesterol, Lp(a) and Lp(a)-IC; Lp(a)-IC correlated positively with sex, total and LDL cholesterol, Lp(a) and ox-Lp(a), respectively. Multiple linear regression analysis showed Lp(a) and Lp(a)-IC accounted for 42% of the variation in ox-Lp(a) levels, and ox-Lp(a) accounted for 30% of that in Lp(a)-IC. CONCLUSIONS: The fact that ox-Lp(a) and Lp(a)-IC are present in newborns and children suggests that oxidized lipoproteins play an initiating role in atherosclerotic process.