Abstract Background & Aims We aimed to develop a Transformer‐based deep learning (DL) network for prognostic stratification in hepatocellular carcinoma (HCC) patients undergoing RFA. Methods A Swin Transformer DL network was trained to establish associations between magnetic resonance imaging (MRI) datasets and the ground truth of microvascular invasion (MVI) based on 696 surgical resection (SR) patients with solitary HCC ≤3 cm, and was validated in an external cohort ( n = 180). The multiphase MRI‐based DL risk outputs using an optimal threshold of .5 was employed as a MVI classifier for prognosis stratification in the RFA cohort ( n = 180). Results Over 90% of all enrolled patients exhibited hepatitis B virus infection. Liver cirrhosis was significantly more prevalent in the RFA cohort compared to the SR cohort (72.2% vs. 44.1%, p < .001). The MVI risk outputs exhibited good performance (area under the curve values = .938 and .883) for predicting MVI in the training and validation cohort, respectively. The RFA patients at high risk of MVI classified by the MVI classifier demonstrated significantly lower recurrence‐free survival (RFS) and overall survival rates at 1, 3 and 5 years compared to those classified as low risk ( p < .001). Multivariate cox regression modelling of a‐fetoprotein > 20 ng/mL [hazard ratio (HR) = 1.53; 95% confidence interval (95% CI): 1.02–2.33, p = .047], high risk of MVI (HR = 3.76; 95% CI: 2.40–5.88, p < .001) and unfavourable tumour location (HR = 2.15; 95% CI: 1.40–3.29, p = .001) yielded a c‐index of .731 (bootstrapped 95% CI: .667–.778) for evaluating RFS after RFA. Among the three risk factors, MVI was the most powerful predictor for intrahepatic distance recurrence. Conclusions The proposed MVI classifier can serve as a valuable imaging biomarker for prognostic stratification in early‐stage HCC patients undergoing RFA.
Objective
To investigate the expression of transcription factor forkhead/winged helix transcription factor 3 (Foxp3), immune factor transforming growth factor-beta 1 (TGF-β1), and T-lymphocyte activation related factor interleukin-2 (IL-2) in peripheral blood of patients with coal-burning arsenic poisoning, and to analyze the effects of arsenic exposure on immune function.
Methods
A case-control study was conducted to investigate 149 cases [94 males and 55 females, (50.69 ± 6.14) years old] of arsenic poisoning in Yuzhang coal-burning arsenic poisoning area, southwestern Guizhou Province, and the cases were diagnosed based on the Diagnosis of Endemic Arsenicosis (WS/T 211-2015) and confirmed by clinical review. According to skin damage, the patients were divided into mild arsenic poisoning group (39 cases), moderate arsenic poisoning group (54 cases) and severe arsenic poisoning group (56 cases); and 41 cases [12 males and 29 females, (45.76 ± 7.88) years old] of non-arsenic exposed residents from 12 km of Yuzhang coal-burning area were selected as control group. Morning urine and peripheral blood samples were collected with informed consent. Urine arsenic content was measured by inductively coupled plasma mass spectrometry (ICP-MS). Urine arsenic was corrected by creatinine (Cr). Detection of regulatory T cell (Treg)-specific transcription factor Foxp3 gene expression in human peripheral blood was done by real-time fluorescence quantitative PCR, and the levels of Treg-related immune factor TGF-β1 and IL-2 in serum were detected by enzyme linked immunosorbent assay (ELISA).
Results
The urinary arsenic contents [median (quartile): 29.13 (19.75-54.50), 31.81 (17.52-53.31), 30.51 (18.35-45.76) μg/g Cr] in each arsenic poisoning group were higher than that in the control group [21.62 (17.65-28.44) μg/g Cr, P < 0.05]. The expression levels of Foxp3 mRNA in peripheral blood of each arsenic poisoning group [median (quartile): 0.58 (0.17-1.27), 0.32 (0.17-0.61), 0.33 (0.13-0.62)] were significantly lower than that in the control group [0.87 (0.64-1.50), P < 0.05]; compared with mild arsenic poisoning group, the expression of Foxp3 mRNA in peripheral blood of moderate and severe arsenic poisoning groups decreased (P < 0.05). The contents of serum TGF-β1 [(13.14 ± 5.19), (12.85 ± 5.51), (12.78 ± 4.95) μg/L] in each arsenic poisoning group were significantly higher than that in the control group [(3.90 ± 1.53) μg/L, P < 0.05]. The levels of IL-2 in serum of each arsenic poisoning group [(9.85 ± 5.38), (11.64 ± 6.40), (12.27 ± 6.19) ng/L] were lower than that in the control group [(34.30 ± 4.84) ng/L, P < 0.05]; the serum level of IL-2 in severe arsenic poisoning group was higher than that in mild arsenic poisoning group (P < 0.05).
Conclusions
Arsenic exposure can cause abnormal changes of Treg-specific transcription factor Foxp3 and related immune factors TGF-β1 and IL-2 in peripheral blood of patients. It is suggested that Treg dysfunction may be related to arsenic poisoning.
Key words:
Arsenic poisoning; Coal; Foxp3; Immunologic factors
Objective
To observe the differential expression level of CD4+ CD25+ Foxp3+ regulatory T cells (Treg) in liver of arsenic-exposed rats, explore the regulatory mechanisms on immunological of hepatic injury induced by arsenic, and provide a basis for prevention and treatment of the disease.
Methods
Thirty-two healthy Wistar rats were selected and randomly divided into control, low, medium and high arsenic dose groups by weight, 8 rats per group. Rats in control group were given oral gavage of deionized water, while the other groups were given oral gavage doses of 2.00 g/L sodium arsenite (NaAsO2) according to their body weight for 6 days every week, the concentrations were 1.25, 2.50 and 5.00 ml/kg. After 4 months, liver tissue samples of rats were collected, the content of arsenic in liver was detected by inductively coupled plasma mass spectrometry (ICP-MS); the expression of Treg cells in liver was detected by immunohistochemistry; enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of interloukin-10 (IL-10), transforming growth factor beta 1 (TGF-β1), IL-6, IL-17 and IL-2.
Results
Compared with the control group [28.57 (17.64-35.64) μg/g], the content of arsenic in liver in low, medium and high arsenic exposed groups [M (P25-P75): 638.30 (527.91-802.58), 591.64 (513.82-723.16), 792.55 (695.93-1 074.41) μg/g] increased, the differences were statistically significant (P 0.05); compared with control group [(16.30 ± 3.98) μg/L], the expression of IL-2 in high arsenic exposed group decreased [(9.93 ± 2.65) μg/L, P < 0.05]. The content of arsenic in liver was positively correlated with the expression of IL-10, TGF-β1, IL-17, IL-6 (rs= 0.696, 0.463, 0.632, 0.502, P < 0.05), and negatively correlated with the expression of IL-2 (rs=-0.522, P < 0.05).
Conclusion
With increasing of arsenic exposure level, the content of arsenic in liver and the expression of CD4+CD25+ Foxp3+ Treg have increased, the cytokines are secreted abnormally, liver immunological micro environment is disordered, immune tolerance is formed, and immune clearance is inhibited, which may play an important role in the occur and development of immunological liver damage induced by arsenic in rat.
Key words:
Arsenic; Regulatory T cells; Liver injury; Immunosuppression
Abstract Rationale: Primary aldosteronism due to aldosteronoma is the most common form of secondary hypertension, with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Diagnosis is a clinical challenge with simultaneous occurrence of primary ectopic meningioma in the adrenal gland. To our knowledge this is the first reported case of simultaneous occurrence of aldosteronomas and ectopic meningioma in the adrenal gland based on literatures. Patient concerns: A 30-year-old man presented with resistant hypertension for one year. The computed tomographic scans were suggestive of left adrenal gland hyperplasia. Intervention: The patient underwent partial unilateral laparoscopic adrenalectomy. Diagnosis: The histopathological examination of the resected sample confirmed primary ectopic meningioma in adrenal gland and aldosterone producing adenoma (APA). The saline load test, captopril test, and plasma aldosterone/renin ratio were indicative of primary aldosteronism (PA). Outcomes: The patient had controlled blood pressure postoperatively. Lessons: The patient was diagnosed with PA due to APA and nonfunctional primary ectopic meningioma in the adrenal gland which is very rare and dealt with unilateral laparoscopic adrenalectomy.
Objective
To investigate the infiltration of T helper 17 (Th17) and regulatory T cells (Treg) in the liver of rats exposed to arsenic, and to investigate the roles of Th17 and Treg in infiltration of liver injury induced by arsenic.
Methods
Thirty-two Wistar rats, half male and half female, were randomly divided into control, low, medium and high arsenic dose groups by body weight via the random number table method, 8 rats per group. Rats in control group were given oral gavage of deionized water, while other groups were given oral gavage doses of 2.00 g/L sodium arsenite (NaAsO2) according to their body weight for 6 days every week, the concentrations of NaAsO2 were 1.25, 2.50 and 5.00 ml/kg, respectively. After 4 months, liver tissue samples of rats were collected, the content of arsenic in liver was determined by inductively coupled plasma mass spectrometry (ICP-MS); Hematoxylin-eosin staining (HE) method was used to observe the morphological changes of liver tissue in rats; the protein expressions of interleukin-17A (IL-17A, the imflammatory factor secreted by Th17 cells) and Forkhead Box P3 (Foxp3, the lineage-specific transcription factor of Treg cells) were measured with immunohistochemistry.
Results
① Arsenic content in liver of low, medium, and high arsenic exposed groups [63.83 (52.79 - 80.26), 59.16 (51.38 - 76.58), 79.26 (69.59 - 107.44) μg/g] were higher than those of the control group [2.86 (1.76 - 3.56) μg/g, P < 0.05], and the high arsenic dose group was higher than the medium arsenic dose group (P < 0.05). ② With increasing doses of arsenic, the numbers of inflammatory cells in the liver tissue of rats were increased, and the liver tissue of the high arsenic dose group showed vacuolar degeneration and pathological changes in some areas. ③ Compared with the control group, low and medium arsenic dose groups (0.001± 0.001, 0.010 ± 0.020, 0.030 ± 0.080), the expression of IL-17A protein in the liver in high arsenic dose group were significantly increased (0.220 ± 0.130, P < 0.05), the differences were statistically significant between groups (F = 14.776, P < 0.05). The expressions of Foxp3 protein in the liver in low, medium, and high arsenic dose groups were significantly higher (0.270 ± 0.050, 0.330 ± 0.040, 0.320 ± 0.070) than that in the control group (0.070 ± 0.020), the differences were statistically significant between groups (F = 56.990, P < 0.05). ④ There was a positive correlation between hepatic arsenic levels and protein levels of IL-17A and Foxp3 in liver (r = 0.48, 0.81, P < 0.05).
Conclusion
Arsenic exposure can increase the content of arsenic in liver tissue of rats, which causes the changes of infiltration of Th17 and Treg cells, leading to the change of immune status, suggesting that Th17 and Treg cells play an important role in the development of arsenic-induced immune injury.
Key words:
Arsenic; T helper 17; Regulatory T cell; Immunosuppressive
Objective To investigate the continuous blood purification for multiple organ failure of the rescue and treatment. Methos In the conventional treatment given on the basis of continuous blood purification treatment.Result before and after treatment serum creatinine, alanine aminotansferase, creat-ine phosphokinase have decreased significantly. Conclusion The continuous blood purification treatment of multiple organ failure has an important role in the rescue.
Key words:
Of continuous blood purification; Multiple organ failure
A prospective molecular mechanism of macrophages infiltration in experimental disc herniation.To investigate the mechanisms of macrophages infiltration into the dorsal root ganglion (DRG) in a rat model of disc herniation.Macrophages infiltrate the DRG after application of nucleus pulposus (NP) on the DRG, and may play an important role in radiculopathy. However, the mechanisms of macrophages infiltration after NP application remain poorly understood.After experimental disc herniation in this study, we investigated changes in the expression of ED1 (a marker of macrophages) and vascular cell adhesion molecule-1 (VCAM-1) in DRG using immunofluorescence. We also investigated the expression of ED1 and VCAM-1 in DRG by treatment with tumor necrosis factor-α (TNF-α) inhibitor at the time of surgery.We found a massive ED1-positive macrophages infiltrated the DRG, and VCAM-1-like immunoreactivity vessels became evident after NP application. Furthermore, both macrophage infiltration and VCAM-1 expression were prevented by treatment with TNF-α inhibitor at the time of surgery.These findings indicated that macrophages infiltration into the DRG was TNF-α-dependent, and might be partly mediated by VCAM-1 in the early stage of experimental lumbar disc herination. Taken together, this study provides important preliminary data suggesting that TNF-α plays an important role in the macrophage infiltration.N/A.
Objective To search for the most appropriate subzero nonfreezing temperature,and explore the effect of subzero nonfreezing preservation of rat kidney by comparing with the kidney preservation with conventional temperature (4 ℃,0 ℃) and freezing temperature (-4 ℃).Method The thermocouple probeand the temperature data logging device were used to detect the temperature decreasing curves in different parts of the rat kidney and determine the freezing point of the kidney.The perfused kidneys in rats were removed and put into the sterile tubes containing 2.5 mL hypertonic citrate adenine.Following 6 group were set up:-0.8 ℃ group (subzero nonfreezing),-0.5 ℃group (subzero nonfreezing),0 ℃ group (zero nonfreezing),-4 ℃ group (control group),-1 ℃group(subzero freezing)、-4 ℃ group (subzero freezing).After the cryopreservation for 24 and 48 h,the preservative fluid was harvested for measurement of the contents of LDH and AST,and the paraffin sections from the upper pole of the kidney were made for observation of the pathological changes and apoptosis.Result The freezing temperature of kidney was-1℃ and the most appropriate subzero nonfreezing temperature for preserving the rat kidney was-0.8 ℃.Subzero nonfreezing significantly inhibited the basal metabolic rate of the histiocytes,reduced the contents of LDH and AST released due to the membrane damage,and decreased the apoptosis rate [48 h:-0.8 ℃ (40.1 ± 7.0) ％ vs.4 ℃ (47.1 ± 7.6) ％].Under the light microscope after preservation for 48 h,the pathological changes in-0.8 ℃ group were less than in 4 ℃ group.Conclusion Compared with the organ preservation in conventional temperature (0 ℃-4 ℃),the subzero nonfreezing (-0.8 ℃) can further inhibit the basal metabolic rate of histocytes obviously,reduce its energy consumption,and lower the apoptosis caused by low temperature damage.
Key words:
Rats; Kidney; Organ preservation; Temperature; Subzero nonfreezing
Objective:To observe the effects of transurethral vaporization for prostate (TVP) and suprapubic prostatectomy (SPP) on sexual function of the patients with benign prostatic hyperplasia (BPH).Methods:Followed up for 12 months, the incidences of postoperative impotence and retrograde ejaculation in 100 cases treated with TVP were compared with those in 100 cases treated with SPP.Results:The incidences of postoperative impotence were 4.35% (3/69) and 10.8% (8/74) in those cases treated with TVP and SPP respectively. And the corresponding incidences of retrograde ejaculation were 44.9% (31/69) and 41.1% (31/74)respectively.Conclusions: As for avoidance of postoperative sexual dysfunction after surgical treatment of BPH, TVP is superior to SPP (P 0.01). There is no obvious difference between TVP and SPP on the incidence of retrograde ejaculation(P0.05).
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