Clinical Application of Serum Interleukin-6 Combined with Inflammatory Cytokines in the Dynamic Monitoring of Patients with Acute Cholecystitis.

Objective: To investigate the dynamic fluctuations of serum interleukin-6 (IL-6), procalcitonin (PCT), and neutrophil counts in individuals diagnosed with acute cholecystitis. Additionally, the research seeks to investigate the potential clinical significance of these biomarkers in the early stages of acute cholecystitis. Methods: This retrospective cohort study included one hundred patients with acute cholecystitis (60 with mild acute cholecystitis and 40 with severe cholecystitis) admitted to our hospital between January 2022 and December 2022 were included. The levels of various cytokines, PCT and neutrophils in serum on days 1, 3, 5, and 7 were dynamically detected. The difference in each indicator between the two groups was analysed, and the diagnostic value of each indicator for acute cholecystitis was evaluated using a receiver operating characteristic (ROC) curve. Results: IL-6 and PCT levels and neutrophil counts were significantly higher in patients with moderate and severe cholecystitis than those in those with mild cholecystitis (P <0.01). The AUC values for the three indicators were all greater than 60%, and the AUC value for the joint diagnosis of the three indicators reached 90%. Conclusion: Serum interleukin-6 combined with PCT and neutrophil count is helpful to determine the degree of disease development in patients with acute cholecystitis. The advantage of dynamic monitoring of the three indicators is that the detection is simple and worthy of clinical promotion.

Associations between exposure to phthalates and subclinical hypothyroidism in pregnant women during early pregnancy: A pilot case-control study in China.

Phthalates are environmental endocrine disruptors with thyroid-disrupting properties; however, the association between phthalate exposure and subclinical hypothyroidism (SCH) during pregnancy is unknown. We recruited a study population from a cohort of pregnant women in Beijing, China, and conducted the present pilot case-control study of 42 SCH cases and 84 non-SCH controls matched with age and body mass index (BMI). Serum levels of thyroid peroxidase antibody, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and urinary levels of ten phthalate metabolites during early pregnancy were measured. Urinary monoethyl phthalate (MEP) levels in SCH cases were observably higher than those in controls (p = 0.01). Conditional logistic regression analysis revealed that mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), MEP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and di-(2-ethylhexyl) phthalate (ΣDEHP) were significantly associated with a higher risk of SCH during early pregnancy (adjusted odds ratios = 1.89, 1.42, 1.81, and 1.92, respectively). Concomitantly, multiple linear regression analysis showed that MECPP, MEOHP, and ΣDEHP were positively associated with TSH and FT4 × TSH in the entire study population. Bayesian kernel machine regression analysis and stratified analysis by BMI revealed upward tendencies in the serum levels of TSH and FT4 × TSH. In summary, exposure to phthalates, especially DEHP, may be associated with a higher risk of SCH during early pregnancy, and a possible mechanism is the disruption of the hypothalamus-pituitary-thyroid axis.

Toxicity and toxicokinetics of the ethanol extract of Zuojin formula.

BACKGROUND: Zuojin formula, a traditional Chinese medicine, comprises Coptis chinensis and Evodia rutaecarpa. In our previous study, the total alkaloid extract from Zuojin formula (TAZF) showed potent and improved efficacy. However, its safety and toxicokinetics remain unknown. The objective of this study was to evaluate the safety of repeated administrations of TAZF and investigate the internal exposure of the main components and its relationship with toxic symptoms. METHODS: Sprague-Dawley rats were orally administered TAZF at 0.4, 1.2 and 3.7 g/kg for 28 days, which was followed by a 14-day recovery period. The toxic effects were evaluated weekly by assessing body weight changes, food intake, blood biochemistry and haematological indices, organ weights and histological changes. A total of eight components were detected, including berberine, coptisine, epiberberine, palmatine, jatrorrhizine, columbamine, evodiamine, and rutaecarpine. The toxicokinetic profiles of the eight components were investigated after single and repeated administrations. Linear mixed effect models were applied to analyse the associations between internal exposure and toxic symptoms. Network pharmacology analysis was applied to explore the potential toxic mechanisms. RESULTS: Compared with the vehicle group, the rats in the low- and medium-dose groups did not show noticeable abnormal changes, while rats in the high-dose group exhibited inhibition of weight gain, a slight reduction in food consumption, abdominal bloating and atrophy of the splenic white pulp during drug administration. The concentration of berberine in plasma was the highest among all compounds. Epiberberine was found to be associated with the inhibition of weight gain. Network pharmacology analysis suggested that the alkaloids might cause abdominal bloating by affecting the proliferation of smooth muscle cells. The benchmark dose lower confidence limits (based on body weight inhibition) of TAZF were 1.27 g/kg (male) and 1.91 g/kg (female). CONCLUSIONS: TAZF has no notable liver or kidney toxicity but carries risks of gastrointestinal and immune toxicity at high doses. Alkaloids from Coptis chinensis are the main plasma components related to the toxic effects of TAZF.

Associations between phthalate exposure and thyroid function in pregnant women during the first trimester.

Phthalates are a class of environmental endocrine disruptors. Previous studies have demonstrated that phthalate exposure can affect thyroid function; however, limited studies have assessed the associations between phthalate exposure and thyroid function, especially thyroid autoimmunity in pregnant women during the first trimester. We recruited participants from a cohort of pregnant women in Beijing, China, and collected urine samples to measure ten phthalate metabolites, serum samples to measure free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) during the first trimester. We included 325 pregnant women without thyroid diseases or dysfunction in this study. Associations between phthalate metabolites and thyroid function parameters were assessed with the Bayesian kernel machine regression (BKMR) model, multiple linear regression model, and restricted cubic spline. In the BKMR model analysis, compared to the 50th percentile, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels when phthalate metabolites were at or below the 40th percentile. Stratifying by body mass index, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels in normal weight women when phthalate metabolites were at or below the 45th percentile. However, total urinary phthalate metabolites levels were positively associated with serum TPOAb levels in underweight women when phthalate metabolites were at or below the 30th percentile. In restricted cubic spline analysis, L-shaped nonlinear associations of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), di-(2-ethylhexyl) phthalate (ΣDEHP), and inverted S-shaped nonlinear association of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with TPOAb were observed. In conclusion, our findings suggest that phthalate exposure may affect thyroid autoimmunity in underweight pregnant women during early pregnancy, and the potential effects of phthalate exposure on thyroid autoimmunity may be nonlinear.

Cumulative risk assessment of dietary exposure to phthalates in pregnant women in Beijing, China.

Diet is an important exposure route for phthalates, such as di-iso-butyl phthalate (DiBP), dibutyl phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), and benzyl butyl phthalate (BBP). In this study, we aimed to estimate phthalate exposure in the diet of pregnant women and assess the health risk. A total of 517 pregnant women in the first trimester were recruited, and food frequency questionnaires were collected. A simple distribution assessment method was used to estimate daily exposure, and the hazard index (HI) method was used to assess cumulative risk. The maximum daily dietary exposure to DEHP, DBP, DiBP, and BBP was 5.25, 3.17, 2.59, and 0.58 µg/kg bw/day, respectively, and did not exceed the safety limit values. Cereals and vegetables were the main sources of the estimated daily intake (EDI) of phthalates in the diet. The cumulative risk assessment, based on the European Food Safety Authority tolerable daily intake (TDI) and the US Environmental Protection Agency reference dose (RfD), did not exceed the threshold of 1. DiBP, DBP, and DEHP had higher hazard quotient (HQ) values for cumulative health risk than BBP. In conclusion, a low health risk was posed by the cumulative dietary exposure to phthalates for pregnant women in Beijing.

Beneficial effects of sappanone A on lifespan and thermotolerance in Caenorhabditis elegans.

Sappanone A (SA) is a homoisoflavonoid compound isolated from Caesalpinia sappan L. that selectively binds to inosine monophosphate dehydrogenase 2, a protein involved in aging. It is unknown if SA has an anti-aging effect and what is it mechanism. This study aimed to investigate the lifespan-extending and health-enhancing effects of SA, and the potential pharmacological mechanism in Caenorhabditis elegans (C. elegans). The worms were exposed to 0-50 µM SA. The effect on the lifespan was observed, and health status was evaluated by detecting motility, feeding, reproduction, thermotolerance, lipofuscin and ROS accumulation. To explore a possible mechanism, the transcription of the genes of the insulin/insulin-like growth factor-1 signalling pathway and heat stress response was detected by RT-qPCR. Moreover, subcellular distribution of green fluorescent protein-labeled DAF-16 was determined, and the interaction between SA and HSP-90 protein was simulated by molecular docking. We found that SA prolonged lifespan in C. elegans and enhanced motility and thermotolerance. The feeding and reproduction were not impacted. The ROS and lipofuscin accumulation was declined. Mechanistic study revealed that the gene expression levels of daf-16 and hsp-90 were up-regulated. Moreover, DAF-16 was translocated into the nucleus. SA was docked into the active pocket of HSP-90 in the simulation. SA (50 µM) can extend lifespan in C. elegans and decelerate aging by regulating the IIS pathway, and daf-16 is specifically important for the regulation of longevity. HSP-90 was involved in the enhancement of thermotolerance. Thus, SA may act as a promising candidate for the development of an anti-aging agent.