Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Comparison of intraluminal brachytherapy combined with and without stent placement for treatment of obstructive jaundice induced by tumor thrombus.

PURPOSE: To compare the safety and efficacy of intraluminal brachytherapy with iodine-125 (125I) seed strand implantation combined with and without stent placement to treat patients with obstructive jaundice induced by tumor thrombus. METHODS: Between January 2018 and June 2022, 42 patients with malignant obstructive jaundice (MOJ) induced by tumor thrombus were included. 20 patients received 125I seed strand implantation and stent placement (group A). The remaining 22 patients, implanted 125I seed strands only, served as control (group B). The two groups' overall survival and jaundice-free survival were compared using the Kaplan-Meier method and log-rank test. RESULTS: During the follow-up period, the mean survival time of group A was 38.0 ± 4.1 months (95%CI, 30.0-46.1 months), while that of group B was 25.1 ± 2.8 (95% CI, 19.5-30.6 months) (p = 0.406). The mean survival rates of 12 months for all patients, group A, and group B was 66.7%, 65%, and 68%, respectively. The mean jaundice-free survival of group A and group B were 34.0 ± 3.6 months (95% CI, 27.9-41.2months) and 22.9 ± 2.7 months (95%CI, 17.5-28.2months) (p = 0.254), respectively. Two PTBD drainage tube infection cases occurred in group A and group B separately. CONCLUSIONS: 125I intraluminal brachytherapy is an effective and safe therapy for treating patients with obstructive jaundice induced by tumor thrombus.

The prognostic role of the AST/ALT ratio in hepatocellular carcinoma patients receiving thermal ablation combined with simultaneous TACE.

BACKGROUND: To evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE. METHODS: The data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram. RESULTS: The AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600-0.748). CONCLUSIONS: The preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE.

Corrigendum: Comparison of clinical outcomes between cone beam CT-guided thermal ablation and helical tomotherapy in pulmonary metastases from hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.947284.].

Comparison of clinical outcomes between cone beam CT-guided thermal ablation and helical tomotherapy in pulmonary metastases from hepatocellular carcinoma.

Objective: This retrospective study compares the clinical results of cone beam CT (CBCT)-guided thermal ablation with those of helical tomotherapy in hepatocellular carcinoma (HCC) patients with pulmonary metastases. Methods: A total of 110 patients undergoing thermal ablation or helical tomotherapy for pulmonary metastases from April 2014 to December 2020 were included in the study. The endpoints were local tumor progression-free survival (LTPFS), overall survival (OS), and complications. Univariate and multivariate analyses using the Cox proportional hazard model were conducted to identify independent factors (univariate: P < 0.1; multivariate: P < 0.05). The Kaplan-Meier method was used to calculate the LTPFS and OS rates. Results: The results of 106 patients were taken into the final analysis. The 1- and 3-year LTPFS rates were 50 and 19% for the thermal ablation group and 65 and 25% for the helical tomotherapy group. The median LTPFS in the thermal ablation group was 12.1 months, while it was 18.8 months in the helical tomotherapy group (P = 0.25). The 1- and 3-year OS rates were 75 and 26% for the thermal ablation group and 77 and 37% for the helical tomotherapy group. The median OS was 18.0 months in the thermal ablation group and 23.4 months in the helical tomotherapy group (P = 0.38). The multivariate analyses found that α-fetoprotein (AFP) at <400 ng/ml (P = 0.003) was significantly associated with better LTPFS. Tumor number <3 and AFP <400 ng/ml were favorable prognostic factors for OS. There were no grades 3-5 adverse events in both groups. Grade 2 was recorded in three patients (4.8%) in the thermal ablation group and two patients (4.7%) in the helical tomotherapy group. Conclusions: For pulmonary metastases from HCC, CBCT-guided thermal ablation and helical tomotherapy provided comparable clinical effects and safety.

Microfluidic chip for culturing intestinal epithelial cell layers: Characterization and comparison of drug transport between dynamic and static models.

Dynamic flow in vitro models are currently widely explored for their applicability in drug development research. The application of gut-on-chip models in toxicology is lagging behind. Here we report the application of a gut-on-chip model for biokinetic studies and compare the observed biokinetics of reference compounds with those obtained using a conventional static in vitro model. Intestinal epithelial Caco-2 cells were cultured on a porous membrane assembled between two glass flow chambers for the dynamic model, or on a porous membrane in a Transwell model. Confocal microscopy, lucifer yellow translocation, and alkaline phosphatase activity evaluation revealed that cells cultured in the gut-on-chip model formed tight, differentiated, polarized monolayers like in the static cultures. In the dynamic gut-on-chip model the transport of the high permeability compounds antipyrine, ketoprofen and digoxin was lower (i.e. 4.2-, 2.7- and 1.9-fold respectively) compared to the transport in the static Transwell model. The transport of the low permeability compound, amoxicillin, was similar in both the dynamic and static in vitro model. The obtained transport values of the compounds are in line with the compound Biopharmaceuticals Classification System. It is concluded that the gut-on-chip provides an adequate model for transport studies of chemicals.

Flos lonicerae flavonoids attenuate experimental ulcerative colitis in rats via suppression of NF-κB signaling pathway.

This study sought to isolate active Flos lonicerae flavonoids and evaluate their anti-oxidative and anti-inflammatory effects as well as investigate the molecular mechanistic action of these flavonoids in the rat model of ulcerative colitis (UC). Total flavonoids and three flavonoids (hyperoside, lonicerin, and luteolin) were isolated from honeysuckle and purified via column purification. Rat model of UC was established via 2,4,6-trinitrobenzene sulfonic acid (TNBS) intoxication. The anti-oxidative and anti-inflammatory effects of the three flavonoids against TNBS-induced UC were evaluated by measuring appropriate biomarkers via assay kit. The effects of hyperoside, lonicerin, and luteolin on the regulation of nuclear factor-kappa B (NF-κB) pathway were investigated using Western blot (WB) and real-time polymerase chain reaction (RT-PCR) while their protective effects on UC were also elucidated. Pretreatment with flavonoids (hyperoside, lonicerin, and luteolin at 25-100 mg/kg) and sulfasalazine (SSZ, positive control at 100 mg/kg) substantially attenuated TBNS-induced UC. Also, the flavonoids significantly reduced the levels of respective serum oxidative and proinflammatory markers such as superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), prostaglandins E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-beta (IL-ß), and C-reactive protein (CRP). In addition, the flavonoids remarkably inhibited the expression of NF-κB signaling pathway. F. lonicerae flavonoids (hyperoside, lonicerin, and luteolin) demonstrated potent anti-UC activities in TBNS-induced UC rat model via anti-oxidative and anti-inflammatory effects through the inhibition of NF-κB signaling pathway.

[Study on the correlation between Chinese medicine syndrome and the intestinal mucosal manifestations of 137 patients with active ulcerative colitis].

OBJECTIVE: To observe the distribution features of Chinese medicine syndrome (CMS) in 137 patients with active ulcerative colitis (AUC), and to analyze the correlation between the intestinal mucosal manifestations and CMS. METHODS: Totally 137 AUC patients were syndrome typed. The intestinal mucosal manifestations were observed under endoscope, thus analyzing the correlation between the intestinal mucosal manifestations and CMS. RESULTS: In the distribution of main syndromes, the case numbers were sequenced as the damp heat of Dachang syndrome > the yang deficiency of Pi-Shen syndrome > the Gan-depression and Pi-deficiency syndrome > the deficiency of Pi-qi syndrome > the blood stasis of the intestine meridian syndrome > the deficiency of blood and yin syndrome. The frequency of intestinal mucosal manifestations more than 50% covered mucosal damage, abnormal mucosa membrane color, congestion, edema, erosion, ulcer, pus tongue fur, and obscure or disappeared blood vessels. The edema, erosion, and ulcer occurred more in the damp-heat of Dachang syndrome, followed by the yang deficiency of Pi-Shen syndrome and the Gan-depression and Pi-deficiency syndrome (P < 0.05, P < 0.01). Polypi, abnormal enterokinesia, grainy occurred more in the damp-heat of Dachang syndrome and the Gan-depression and Pi-deficiency syndrome (P = 0.010). Shallower plica or disappeared sacculations of colon occurred more in the yang deficiency of Pi-Shen syndrome and the damp-heat of Dachang syndrome (P = 0.002). The mucosa bridge occurred more in the yang deficiency of Pi-Shen syndrome and Gan-depression and Pi-deficiency syndrome (P = 0.280). Fragility or contact bleeding occurred more in the damp-heat of Dachang syndrome, the deficiency of Pi-qi syndrome, and Gan-depression and Pi-deficiency syndrome (P = 0. 045). Pale blood of the intestinal hemorrhage occurred more in the deficiency of Pi-qi syndrome while dark blood occurred more in the damp-heat of Dachang syndrome (P = 0.017). Pus tongue fur occurred more in the damp-heat of Dachang syndrome, the yang deficiency of Pi-Shen syndrome, and the Gan-depression and Pi-deficiency syndrome. White pus tongue fur occurred more in the yang deficiency of Pi-Shen syndrome while yellow pus tongue fur occurred more in the damp-heat of Dachang syndrome (P < 0.001). Mucus occurred more in the yang deficiency of Pi-Shen syndrome, the Gan-depression and Pi-deficiency syndrome, and the deficiency of Pi-qi syndrome (P = 0.012). Narrow enteric cavity or intestinal canal fibrosis, lead pipe like manifestations occurred more in the blood stasis of the intestine meridian syndrome (P = 0.001). Atrophic mucosa occurred more in the blood stasis of the intestine meridian syndrome and the deficiency of blood and yin syndrome (P < 0.001). CONCLUSIONS: The intestinal mucosal manifestations of AUC showed certain laws in CMS. The microscopic differences could verify macroscopic CMS to some extent.

[The interior-exterior correlation between fei and dachang from the lung function injury in ulcerative colitis patients].

OBJECTIVE: To observe the probability of the lung injury and the features of the lung function injury in ulcerative colitis patients, and to preliminarily study the correlation with its severity, and further to analyze the interior-exterior correlation between Fei and Dachang. METHODS: Seventy patients with UC were assigned to the mild group and the moderate-severe group by the severity, 35 cases in each group. Another thirty healthy subjects were recruited as the control group. Relative indices of the lung function in each group were observed and compared. RESULTS: The lung injury occurred in 67. 14% of the UC patients (47 cases). Forced expiratory volume at 1st s/forced volume capacity (FEV1/FVC), maximal expiratory flow in 75% vital capacity (FEF75), total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO), and diffusion capacity for carbon monoxide of lung/alveolar ventilation (DLCO/VA) were lower compared with those of the control group, showing statistical significance (P < 0.05). The ratio of residual volume/total lung capacity (RV/TLC) was lower in the mild group than in the moderate-severe group (P < 0.01). The DLCO was higher in the mild group than in the moderate-severe group (P < 0.05). CONCLUSIONS: Most UC patients were complicated with the lung function injury, mainly featured as middle and small airway obstruction and decreasing diffusing capacity. Besides, along with the aggravation of the disease, the decreasing diffusing capacity and increasing RV/TLC occurred. They provided objective reliance for Fei and Dachang interior-exteriorly correlated.