Thrombocytopenia as an important determinant of poor prognosis in patients with pyogenic liver abscess: a retrospective case series.

Background: Thrombocytopenia and poor prognosis in severe conditions are associated. However, the clinical significance of thrombocytopenia in pyogenic liver abscess (PLA) has not been evaluated. Objective: To evaluate the association between thrombocytopenia and the prognosis of patients with PLA. Methods: A consecutive case series of 458 adult patients with PLA hospitalized at Tongji Hospital (Wuhan, China) between October 2011 and June 2021 was included in this cross-sectional analysis. Patient data were compared between the thrombocytopenia and non-thrombocytopenia groups. Multivariate logistic regression, receiver operating characteristic (ROC) curve and propensity score -matched analyses (PSM) were performed. Results: Of the 458 patients with PLA, 94 (20.5%) developed thrombocytopenia, 19 (4.1%) developed septic shock, 14 (3.1%) were admitted to the ICU, and 15 (3.3%) died during hospitalization. Thrombocytopenia was independently associated with shock (95%CI = 3.529-57.944, P < 0.001), ICU admission (95%CI = 1.286-25.733, P = 0.022), and mortality (95%CI = 1.947-34.223, P = 0.004) in multivariate regression analysis. ROC analysis showed that thrombocytopenia may be an identified marker of shock [area under the ROC curve (AUC), 0.8119; cut-off, 92.50; P < 0.0001], ICU admission (AUC, 0.7484; cut-off, 82.50; P < 0.0015), and mortality (AUC, 0.7827; cut-off, 122.50; P < 0.002). These findings remained consistent across 86 pairs of patients analyzed for PSM analyses. Conclusions: Thrombocytopenia is an independent risk factor for poor prognosis in PLA and patients may be more prone to adverse outcomes.

LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis.

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB-/- bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Case report: Autosomal recessive type 3 Stickler syndrome caused by compound heterozygous mutations in COL11A2.

Background: Stickler syndrome (SS) is a group of hereditary collagenopathies caused by a variety of collagen and non-collagen genes. Affected patients have characteristic manifestations involving ophthalmic, articular, craniofacial and auditory disorders. SS is classified into several subtypes according to clinical and molecular features. Type 3 SS is an ultra-rare disease, known as non-ocular SS or otospondylomegaepiphyseal dysplasia (OSMED) with only a few pathogenic COL11A2 variants reported to date. Case presentation: A 29-year-old Chinese male was referred to our hospital for hearing loss and multiple joint pain. He presented a phenotype highly suggestive of OSMED, including progressive sensorineural deafness, spondyloepiphyseal dysplasia with large epiphyses, platyspondyly, degenerative osteoarthritis, and sunken nasal bridge. We detected compound heterozygous mutations in COL11A2, both of which were predicted to be splicing mutations. One is synonymous mutation c.3774C>T (p.Gly1258Gly) supposed to be a splice site mutation, the other is a novel intron mutation c.4750 + 5 G>A, which is a highly conservative site across several species. We also present a review of the current known pathogenic mutation spectrum of COL11A2 in patients with type 3 SS. Conclusion: Both synonymous extonic and intronic variants are easily overlooked by whole-exome sequencing. For patients with clinical manifestations suspected of SS syndrome, next-generation whole-genome sequencing is necessary for precision diagnosis and genetic counseling.

Glycemic index, glycemic load, and glycemic response to pomelo in patients with type 2 diabetes.

Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.

Glycemic Index, Glycemic Load, and Glycemic Response to Pomelo in Patients with Type 2 Diabetes / 华中科技大学学报（医学）（英德文版）

Food intake has a great influence on blood glucose in patients with diabetes.This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D).Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement.To test effects of Majia pomelo on PPG,19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study.The dose of insulin for each patient was adjusted on the first 3 days.A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days.Blood glucose was measured to evaluate the glycemic excursions.The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34± 1.88 and 72.15±1.95 respectively.The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo,indicting Majia pomelo as a high GI but low GL fruit.Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation.It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients.These results may mean more varieties of food choices for T2D patients.

Correlation of liver enzymes with diabetes and pre-diabetes in middle-aged rural population in China.

The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus (T2DM) and pre-diabetes (pre-DM) in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test (OGTT) was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases (ALT and GGT), HbA1C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), impaired fasting glucose combined with impaired glucose tolerance (IFG+IGT) and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio (WHR), blood pressure, fasting blood glucose (FBG), high density lipoprotein-cholesterol (HDL-C), and liver enzymes (ALT and GGT). Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance (IR) in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.

TIGIT negatively regulates inflammation by altering macrophage phenotype.

Macrophages function as an essential component of innate immune system, contributing to both the initiation and appropriate resolution of inflammation. The exposure of macrophages to the microbial products, such as lipopolysaccharide (LPS), can strongly shift the balance between tissue homeostasis and inflammation in favor of causing systemic damage, in which macrophage M1 polarization play important roles. Strategies aiming at restoring the balance of macrophage polarization remain to be further explored. Herein, we have demonstrated that poliovirus receptor (PVR), the receptor of TIGIT, was dramatically upregulated on the surface of mouse peritoneal macrophages when exposed to LPS. TIGIT-Fc fusion protein not only inhibited the macrophage activation, but also skewed M1/M2 balance toward an anti-inflammatory profile, especially enhanced the secretion of IL-10. The activation of TIGIT/PVR pathway in macrophages correlated with increased nuclear translocation of c-Maf, which promotes IL-10 transcription. Treatment with fibroblasts stably secreting TIGIT-Fc fusion protein significantly reversed the lethal and sublethal endotoxic shock, which facilitated peritoneal macrophages to switch towards anti-inflammatory M2 cytokine profiles. These findings highlight a novel role of the TIGIT/PVR pathway in macrophage M2 polarization and suggest that TIGIT may have the potential to optimize the treatment of macrophage-involved inflammatory diseases.

Effects of vitamin D receptor gene polymorphisms on susceptibility to type 1 diabetes mellitus.

OBJECTIVE: To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population. METHOD: One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI. RESULTS: The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P = 0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. CONCLUSION: The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Han population of Beijing.