Objective:To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor (EVT).Methods:Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University (6 cases), Qingdao, China and the 971 Hospital of PLA Navy (1 case), Qingdao, China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses. Additionally, whole exome sequencing (WES) was performed in two cases. Twenty-two cases of renal oncocytoma (RO) and 17 cases of eosinophilic chromophobe renal cell carcinoma (eChRCC) diagnosed at the same time were used as controls.Results:Four males and three females with a mean age of 42 years (range: 29-61 years) were included in the study. The tumors were nodular and well-circumscribed, with sizes ranging from 1.5 to 4.5 cm. On cross-section, they appeared gray-red or gray-white, solid, and soft. Tumor cells were arranged in nests, solid sheets, and acinar or small vesicular structures. These cells exhibited eosinophilic cytoplasm with large, prominent clear vacuoles and round nuclei with prominent nucleoli. Perinuclear halos were focally present in four cases, while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case. No necrosis or mitosis was noted. Edematous stroma was detected in three cases. All tumors were positive for CD117 and Cathepsin K, but negative for vimentin and CK7. CK20 was positive in scattered individual cells, and Ki-67 positivity ranged from 1% to 4%. Point mutations in MTOR were identified in both patients who were subject to the molecular analysis. Statistical differences in the expression of Cathepsin K, CD10, S-100A1, and Cyclin D1 between EVT and RO ( P<0.05) were significant, so were the differences in the expression of Cathepsin K, CD10, CK7 and claudin 7 between EVT and eChRCC ( P<0.001). Seven patients were followed up for 4 to 96 months (mean, 50 months), with no recurrences or metastases. Conclusions:EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC, and it is closely linked to the TSC/MTOR pathway. The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics. The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.

Objective:To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm.Methods:A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results:The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively.Conclusions:LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.

Objective:To investigate the relationship between serum fibroblast growth factor 21/23 level, trauma severity and prognosis in middle-aged and older adult patients with traumatic fracture.Methods:A total of 126 middle-aged and older adult patients with traumatic facture who received treatment in the Second People's Hospital of Lishui, China between June 2017 and June 2019 were included in the study group. Fifty healthy controls who concurrently received physical examination in the Second People's Hospital of Lishui were included in the control group. The study group was divided into five subgroups according to relevant criteria: mild, moderate, severe, poor prognosis and good prognosis. The levels of C-reactive protein (CRP), procalcitonin (PCT), FGF21 and FGF23 were measured.Results:On admission, serum CRP, PCT, FGF23, FGF2 levels in the study group were (19.18 ± 5.66) mg/L, (0.71 ± 0.20) μg/L, (79.75 ± 18.62)μg/L,(52.10 ± 16.34) μg/L, respectively, and they were significantly higher than those in the control group [ (7.60 ± 2.61) mg/L, (0.30 ± 0.11) μg/L, (40.18 ± 10.33) μg/L, (30.11 ± 10.19) μg/L, t = 18.888, 17.750, 18.336, 11.032, all P < 0.001). On admission, serum CRP, PCT, FGF23, FGF2 levels in the study group were (19.18 ± 5.66) mg/L, (0.71 ± 0.20) μg/L, (79.75 ± 18.62) μg/L, (52.10 ± 16.34) μg/L, respectively, and they were significantly increased at 1 day [(21.59 ± 4.53) mg/L, (0.79 ± 0.22) μg/L, (83.85 ± 19.07) μg/L, (55.18 ± 16.55) μg/L, t = 3.72, 3.29, 1.56, 1.56, P < 0.05, P < 0.05, P = 0.122, P = 0.122] and 3 days after surgery [(23.15 ± 3.16) mg/L, (0.80 ± 0.24) μg/L, (88.11 ± 19.80) μg/L, (59.70 ± 16.07) μg/L, t = 6.65, 3.12, 3.59, 3.77, all P < 0.05] , and significantly decreased at 7 days after surgery [(14.35 ± 4.02) mg/L, (0.52 ± 0.16) μg/L, (50.06 ± 15.50) μg/L, (32.18 ± 12.52) μg/L, t = 8.31, 8.58, 13.77, 11.11, all P < 0.001]. On admission, there were significant differences in serum CRP, PCT, FGF23, FGF21 levels between mild, moderate and severe groups ( F = 25.087, 15.851, 15.831 and 12.645, all P < 0.001). On admission, serum CRP, PCT, FGF23, FGF21 levels in the poor prognosis group were significantly higher than those in the good prognosis group ( t = 5.757, 4.984, 3.189 and 4.006, all P < 0.001). The receiver operating characteristic curve (ROC) analysis results showed that serum CRP, PCT, FGF23, FGF21 levels in patients with traumatic fracture on admission had a certain value in the prediction of poor prognosis. Combined detection of these four indexes had the highest value, with AUC (0.95 CI) of 0.877 (0.783-0.982). Conclusion:Serum FGF21 and FGF23 levels have a certain value in the prediction of severity and prognosis of traumatic fracture in middle-aged and older adult patients.

Objective:To study the clinicopathological features, immunophenotypes and MED12 gene status in benign metastasizing leiomyoma (BML).Methods:Nine cases of BML diagnosed at the Affiliated Hospital of Qingdao University from 2012 to 2018 were collected, and the radiologic and histologic features were analyzed. The protein expression of leiomyosarcoma-related driver genes, including RB1, PTEN,ATRX,p16,p53, as well as ER,PR,CD34,FH, and Ki-67 were detected using immunohistochemistry, and the mutation status of MED12 gene exon 2 was detected by Sanger sequencing.Results:All the nine patients with BML were female, and the age range was 48 to 64 years (median 55 years). All patients had history of uterine fibroids. The morphologic features of BML were similar to a benign uterine leiomyoma and did not exhibit malignant characteristics. All cases were positive for ER and PR, and negative for CD34. In addition, RB1, PTEN, ATRX, and FH were positive in all cases (wild type), while p16 showed a focally positive pattern. P53 positive index was less than 5% (wild type), and Ki-67 positive index was less than 1%. Sanger sequencing was done in six BML samples; one sample harbored a nonsense mutation c. 142_144delinsTAA (p.Glu48Ter), and another exhibited a synonymy mutation (c.192C>T, p.Phe64=)and one missense mutation c.196C>T (p.Pro66Ser).Conclusions:The present study suggests that BML is a unique leiomyoma entity that is pathologically and genetically different from leiomyosarcomas and conventional uterine leiomyomas. Evaluating the genetic phenotype of BML, especially the expression of leiomyosarcoma-related driver genes protein and MED12 gene status, may be helpful in understanding the pathogenesis of BML and in its differentiation from leiomyosarcoma.

INTRODUCTION: Paraquat (PQ) intoxication is frequently associated with a high mortality rate. No specific treatment has been shown to reduce mortality in victims within the first 72 hours. We investigated the protective effects of rapamycin (Rapa) against PQ-induced toxicity in a zebrafish model. METHODS: To determine the maximum nonlethal concentration (MNLC) and lethal concentration 50 (LC50) of Rapa, zebrafish were treated at 2-5 days post fertilisation (dpf) and their mortality was recorded every 24 hours. At 5 dpf, the zebrafish were treated with PQ 100 µg/mL or PQ+Rapa (MNLC, 1/3 MNLC or 1/9 MNLC) for 72 hours, and the rate of survival was recorded every 24 hours. Reverse transcription-polymerase chain reaction was used to test the signalling pathway of mTOR (mammalian target of rapamycin). RESULTS: MNLC and LC50 of Rapa were determined to be 6.7 µg/mL and 28.9 µg/mL, respectively. At 48 hours, the PQ+Rapa groups had much lower mortality than the PQ group. The rates of survival of the PQ+Rapa groups were 43.33% (MNLC), 53.89% (1/3 MNLC) and 44.45% (1/9 MLNC), as compared to 19.45% in the PQ group, with the 1/3 MNLC group showing the highest rate of survival (p < 0.001). atg1 was slightly activated in the PQ group. In the PQ+Rapa groups, the expression of atg1 was markedly increased, suggesting strengthening of the autophagy process. CONCLUSION Rapa can increase the rate of survival of PQ-intoxicated zebrafish by inhibiting mTOR complex 1 and activating autophagy. Rapa could be an alternative first-line drug in the treatment of PQ poisoning.

Objective To investigate the correlation between serum adropin protein and homocysteine (Hcy) level in the patients with coronary artery disease (CAD) ,and to study their relationship with CAD se-verity .Methods One hundred and seventy cases of CAD in this hospital from August 2015 to October 2016 were selected as the research subjects .Peripheral blood was collected for measuring serum adropin protein , Hcy and other conventional biochemical indicators ,and the coronary artery lesion was detected by coronary an-giography ,the severity of coronary artery lesion was assessed by SYNTAX score .Results In 170 cases of CAD ,mean serum Hcy level was (15 .92 ± 8 .31)μmol/L ,the adropin protein level in the hyperhomocysteine-mia group was lower than that in the non-hyperhomocysteinemia group ,the difference was statistically signifi-cant(P<0 .05) .Mean SYNTAX score in all cases was (21 .51 ± 11 .20) points ,and serum adropin protein was negatively correlated with Hcy level (r= -0 .169 ,P= 0 .028) ,serum Hcy level had no obvious correlation with SYNTAX score (r= 0 .124 ,P=0 .108) ,the adropin protein level was negatively correlated with SYN-TAX score (r= -0 .181 ,P=0 .018) .Generalized structural equation model showed that with the decrease of adropin protein level ,the SYNTAX score was increased (P=0 .019) ,compared with the patients without com-plicating hyperhomocysteinemia ,the SYNTAX score in the patients with hyperhomocysteinemia was much higher(P=0 .005) .Conclusion The lower the adropin protein level ,the higher the Hcy level and the severe the coronary artery lesion .

Objective To investigate the clinical effect of milrinone in the treatment of children with congenital heart disease complicated by severe pneumonia and heart failure. Methods 94 patients with congenital heart disease complicated with severe pneumonia and heart failure in our hospital from March 2014 to February 2016 were selected,and randomly divided into experimental group and routine group,47 cases in each groups. The routine group were treated with conventional treatment, the experimental group in the conventional group received routine treatment based on the same given milrinone treatment. The clinical efficacy, symptom disappearance time and adverse reactions were compared between the two groups. Results The treatment in the experimental group the total efficiency (93.62%) was significantly higher than that of the conventional treatment group with the total effective rate (78.72%), significant difference, statistically significant (P<0.05); the experimental group in children with fever, cough, rales and other symptoms disappeared time is lower than the conventional group, the data had significant difference, has statistical significance (P<0.05); two groups of patients during treatment were not any serious adverse reactions, the adverse reaction condition no difference does not have statistical significance.Conclusion The clinical effect of milrinone in the treatment of children with congenital heart disease complicated by severe pneumonia and heart failure significantly, clinical efficacy, low incidence of adverse reactions, worthy of promotion.

Objective To evaluate the effect of ketamine on the expression of hippocampal microRNA-206 (miR-206) in the mentally depressed rats.Methods Eighty healthy female Sprague-Dawley rats,weighing 200-300 g,aged 2-3 months,were randomly divided into 4 groups (n=20 each) using a random number table:normal control group (C group),ketamine group (K group),depression group (D group) and depression + ketamine group (D+K group).Mental depression was induced by exposing the animal to chronic unpredictable mild stress.At 1 day after successful establishment of the model,ketamine 15 mg/kg was injected intraperitoneally in K and D+K groups,while the equal volume of normal saline was given in C and D groups.Before establishment of thc model,at 7,14,21,28 and 35 days after beginning of establishment of the model,and at 1,3,5 and 7 days after administration,sucrose preference test was performed.Open field test was carried out at 1 day after administration.Forced swimming test was performed at 2 days after administration.Five rats were sacrificed at 6 h after administration,and hippocampal tissues were isolated for determination of the expression of hippocampal miR-206 by quantitative real-time polymerase chain reaction.At 2 days after administration,5 rats were sacrificed,and hippocampal brain-derived neurotrophic factor (BDNF) expression was detected by Western blot.Results Compared with C group,the volume of sucrose intake at 21-35 days after beginning of establishment of the model and at each time point after administration and the score of open field test were significantly decreased,the immobility time in forced swimming test was significantly prolonged,the expression of miR206 was up-regulated,and the expression of BDNF was down-regulated in D group,the immobility time in forced swimming test was shortened,the expression of miR-206 was down-regulated,and the expression of BDNF was up-regulated in group K,and the score of open field test and volume of sucrose intake at 21-35days after beginning of establishment of the model and the score of open field test were significantly decreased in D+K group (P＜0.05).Compared with D group,the volume of sucrose intake at each time point after administration was significantly increased,the immobility time in forced swimming test was shortened,the expression of miR-206 was down-regulated,and the expression of BDNF was up-regulated in D+K group (P＜0.05).Conclusion The mechanism by which ketamine exerts antidepressant effects is related to down-regulation of miR-206 expression and up-regulation of BDNF expression in the hippocampus of rats.

Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague-Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-β1, 2, 3 (TGF-β1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-β/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing.

Objective To investigate the expressions of endoglin (CD105),erythropoietinproducing hepatocyte receptor A2 (EphA2) and its ligand ephrinA1 proteins in laryngeal squamous cell carcinoma (LSCC) and the relationship between their expressions and the clinicopathological factors of LSCC.Methods The expressions of CD105,EphA2 and EphrinA1 proteins were detected with immunohistochemical staining in LSCC in 76 cases and adjacent normal laryngeal tissues (ANLT) (S-P) in 25 cases.SPSS 17.0 software was used to analyze the data.Results The mean microvessel density (MVD) value marked by CD105 staining in LSCC was 10.33 ± 2.29,which was significantly higher than that in ANLT(1.20 ± 1.04,t =18.732,P ＜ 0.05).The CD105-MVD was correlated with T stage,histological grading,clinical stage,lymph node metastasis,recurrence and prognosis in LSCC (F value was 5.34,4.79,5.36,t value was-2.70,2.56,all P ＜ 0.05).The positive expression rates of EphA2 and EphrinA1 in LSCC were 78.95％ (60/76),and 81.85％ (62/76),which were respectively significantly higher than 40％ (10/25) for EphA2 expression and 44％ (11/25) for EphrinA1,expression in ANLT (x2 value was 13.41,13.26,both P ＜ 0.05).EphA2 expression was correlated with histological grading,T stage,clinical stage,lymph node metastasis,recurrence and prognosis in LSCC (x2 value was 6.25,14.60,15.11,8.52,5.54,all P ＜ 0.05).EphrinA1 expression was correlated with T stage,clinical stage,lymph node metastasis,recurrence and prognosis in LSCC (x2 value was 6.44,12.28,16.78,6.44,all P ＜ 0.05).The expressions of CD105,EphA2 and EphrinA1 were positively correlated with each other r value was 0.72,0.74,0.64,all P ＜ 0.05.Survival analysis indicated that the expressions of CD105 and EphA2,histological grading,lymph node metastasis,clinical stage and recurrence were independent factors for tumor prognosis in LSCC (P ＜ 0.05).Conclusions The expressions of CD105,EphA2 and EphrinA1 protein were positively correlated with each other in LSCC.They may play important roles in the tumorigenesis,malignant progression and poor prognosis of LSCC.