Notes

Part of eosinophilia throughout IgG4-related condition.
Enterococci, the main pathogens associated with nosocomial infections, are resistant to many common antibacterial drugs including β-lactams, aminoglycosides, etc. Combination therapy is considered an effective way to prevent bacterial resistance. Preliminary studies in our group have shown that linezolid combined with fosfomycin has synergistic or additive antibacterial activity against enterococci, while the ability of the combination to prevent resistance remains unknown. In this study, we determined mutant prevention concentration (MPC) and mutant selection window (MSW) of linezolid, fosfomycin alone and in combination including different proportions for five clinical isolates of Enterococcus and characterized the resistance mechanism for resistant mutants. The results indicated that different proportions of linezolid combined with fosfomycin had presented different MPCs and MSWs. Compared with linezolid or fosfomycin alone, the combination can restrict the enrichment of resistant mutants at a lower concentration. A rough positive correlation between the selection index (SI) of the two agents in combination and the fractional inhibitory concentration index (FICI) of the combination displayed that the smaller FICI of linezolid and fosfomycin, the more probable their MSWs were to close each other. Mutations in ribosomal proteins (L3 and L4) were the mechanisms for linezolid resistant mutants. Among the fosfomycin-resistant mutants, only two strains have detected the MurA gene mutation related to fosfomycin resistance. In conclusion, the synergistic combination of linezolid and fosfomycin closing each other's MSW could effectively suppress the selection of enterococcus resistant mutants, suggesting that the combination may be an alternative for preventing enterococcal resistance. In this study, the resistance mechanism of fosfomycin remains to be further studied.Sphingolipids are a class of essential lipids, functioning as both cell membrane constituents and signaling messengers. In the sphingolipid metabolic network, ceramides serve as the central hub that is hydrolyzed to sphingosine, followed by phosphorylation to sphingosine 1-phosphate (S1P) by sphingosine kinase (SphK). SphK is regarded as a "switch" of the sphingolipid rheostat, as it catalyzes the conversion of ceramide/sphingosine to S1P, which often exhibit opposing biological roles in the cell. Besides, SphK is an important signaling enzyme that has been implicated in the regulation of a wide variety of biological functions. In recent years, an increasing body of evidence has suggested a critical role of SphK in type 2 diabetes mellitus (T2D), although a certain level of controversy remains. Herein, we review recent findings related to SphK in the field of T2D research with a focus on peripheral insulin resistance and pancreatic β-cell failure. It is expected that a comprehensive understanding of the role of SphK and the associated sphingolipids in T2D will help to identify druggable targets for future anti-diabetes therapy.Rho-kinase 1 (ROCK1) has been implicated in diverse metabolic functions throughout the body, with promising evidence identifying ROCK1 as a therapeutic target in diabetes and obesity. Considering these metabolic roles, several pharmacological inhibitors have been developed to elucidate the mechanisms underlying ROCK1 function. Y27632 and fasudil are two common ROCK1 inhibitors; however, they have varying non-specific selectivity to inhibit other AGC kinase subfamily members and whole-body pharmacological approaches lack tissue-specific insight. RBN013209 concentration As a result, interpretation of studies with these inhibitors is difficult, and alternative approaches are needed to elucidate ROCK1's tissue specific metabolic functions. Fortunately, recent technological advances utilizing molecular carriers or genetic manipulation have facilitated discovery of ROCK1's tissue-specific mechanisms of action. In this article, we review the tissue-specific roles of ROCK1 in the regulation of energy balance and substrate utilization. We highlight prominent metabolic roles in liver, adipose, and skeletal muscle, in which ROCK1 regulates energy expenditure, glucose uptake, and lipid metabolism via inhibition of AMPK2α and paradoxical modulation of insulin signaling. Compared to ROCK1's roles in peripheral tissues, we also describe contradictory functions of ROCK1 in the hypothalamus to increase energy expenditure and decrease food intake via leptin signaling. Furthermore, dysregulated ROCK1 activity in either of these tissues results in metabolic disease phenotypes. Overall, tissue-specific approaches have made great strides in deciphering the many critical metabolic functions of ROCK1 and, ultimately, may facilitate the development of novel treatments for metabolic disorders.
Management strategies after lobectomy for low-risk papillary thyroid carcinoma (PTC) are controversial. This study aimed to identify the proportion of patients among low-risk PTC patients who do not require hormone replacement therapy and to evaluate the risk factors for postoperative hypothyroidism after lobectomy.

The records of 190 PTC patients who underwent thyroid lobectomy from January 2017 to December 2018 were retrospectively reviewed. Clinicopathological characteristics and follow-up data were collected. Univariate and multivariate analyses were performed to identify the risk factors associated with postoperative hypothyroidism and the recovery of thyroid function.

In summary, 74.21% of patients (141/190) had normal thyroid function without levothyroxine supplementation, while 40.53% (77/190) developed temporary or permanent hypothyroidism. Multivariate analysis indicated that higher preoperative thyroid-stimulating hormone (TSH) levels (>2.62 mIU/L), Hashimoto's thyroiditis (HT), and right lobectomy were associated with hypothyroidism (all P<0.05). The Area Under Curve (AUC) by logistic analysis was 0.829. Twenty-eight (28/77, 36.4%) patients recovered to the euthyroid state in the first year after surgery, and this recovery was significantly associated with preoperative TSH level. Forty-nine (49/77, 63.6%) patients developed persistent hypothyroidism. The thyroid function of most patients (11/28, 39.3%) recovered in the third month after surgery.

Patients with a lower level of preoperative TSH, with left lobectomy and without Hashimoto's thyroiditis had a higher chance of normal thyroid function within the first year after lobectomy. The recovery of thyroid function was associated with the level of preoperative TSH.
Patients with a lower level of preoperative TSH, with left lobectomy and without Hashimoto's thyroiditis had a higher chance of normal thyroid function within the first year after lobectomy. The recovery of thyroid function was associated with the level of preoperative TSH.
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