ObjectiveTo investigate whether paeonol exerts a protective effect on mice with alcoholic liver injury by regulating the takeda G-protein-coupled receptor 5 （TGR5）/protein kinase A （PKA）/cAMP response binding element （CREB） signaling pathway mediated by Eubacterium. MethodC57BL/6 mice were randomly divided into five groups： normal group， model group， paeonol group （480 mg·kg^-1）， antibiotic group （Abs group）， and antibiotic + paeonol group. Lieber-DeCarli liquid was used to feed C57BL/6 mice on the second day of modeling for 10 days. The blood lipids， liver function， inflammatory factors， and oxidative stress levels in mice were measured. Hematoxylin-eosin staining （HE） and oil red O staining were used to observe the morphological changes and fat accumulation in liver tissue. 16S rDNA sequencing was used to detect the diversity of intestinal microbiota in the blank， model， and paeanol groups. Western blot was used to detect the effect of paeonol on the expression levels of protein related to the signaling pathway of atresia band protein 1 （ZO-1）， Claudin-1， and TGR5/PKA/CREB in mouse ileal tissue. ResultCompared with those in the blank group， the blood lipids， liver function， oxidative stress levels， and the expression of inflammatory factors in the model group increased （P<0.01）， and the liver fat vacuoles were obvious. The ileal mucosa was seriously damaged， and the protein contents of ZO-1， Claudin-1， and TGR5/PKA/CREB in the ileal tissue decreased significantly （P<0.01）. The intestinal microbiota changed， and the proteobacteria phylum increased significantly. The ratio of Bacteroidetes to Firmicutes decreased. The relative abundance of Dubosiella newyorkensis， Lactobacillus， Bifidobacterium， and other genera decreased， while the relative abundance of Escherichia-Shigella， Morganella， Providencia， and Proteus increased significantly. Compared with the model group， paeonol significantly reduced the blood lipids， liver function， oxidative stress levels， and expression of inflammatory factors in mice with alcohol diet-induced liver injury （P<0.05）， decreased liver fat vacuoles， improved and restored the ileal intestinal barrier， and restored the normal structure of hepatocytes and ileal cells. The intestinal microbiota disorder caused by alcohol was improved， and the relative abundance of beneficial bacteria such as Eubacterium spp. was increased. The protein expression levels of ZO-1， Claudin-1， and TGR5/PKA/CREB in ileal tissue were increased （P<0.05）. ConclusionPaeonol has a protective effect on alcoholic liver injury in mice， and the mechanism of action is achieved by regulating the Eubacterium-mediated TGR5/PKA/CREB signaling pathway to ensure anti-inflammatory effect and improve the intestinal barrier.

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*

Objective:To investigate the expression of cancer-associated fibroblasts(CAFs) marker proteins in papillary thyroid carcinoma(PTC) using immunohistochemistry and explore their correlation with clinicopathological characteristics.Methods:The clinicopathological data of 90 PTC patients at Tianjin Medical University General Hospital from December 2019 to January 2021 were retrospectively analyzed. Surgical pathological cancer tissue samples were selected for immunohistochemical staining, and control group tissues were obtained from normal thyroid tissue adjacent to the tumor lesion. Four CAFs marker proteins, including fibroblast-activated protein(FAP), α-smooth muscle actin(α-SMA), Vimentin, and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored, followed by statistical analysis.Results:The immunoreactivity score of the CAFs marker proteins were correlated with extrathyroid invasion, lymph node metastasis, and multi-focality of PTC. FAP and α-SMA demonstrated better performance in this regard. Multivariate logistic regression analysis and receiver operating characteristic(ROC) curve analysis showed that high immunoreactivity scores of FAP and α-SMA were risk factors for poor clinical pathological features, with good predictive sensitivity and accuracy.Conclusion:Strong expression of CAFs was the risk factor for extrathyroid invasion, lymph node metastasis, and mutli-focality of PTC. FAP has the highest clinical value compared with other CAFs marker proteins.

DNA damage repair (DDR) defects occurred in 8%-16% of metastatic castration resistant prostate cancer (mCRPC). DDR gene mutation was related to poorer prognosis. Patients with DDR gene mutation, especially BRCA1/2 mutation, showed high sensitivity to poly ADP-ribose polymerase inhibitor (PARPi) and platinum.

Primary sarcopenia is age-related and can lead to falls, osteoporosis, fractures, malnutrition, frailty, sarcopenic obesity, and even loss of independent living silks in patients, which all increase the risk of hospitalization and the cost of healthcare.Early diagnosis of sarcopenia is an effective means to prevent these adverse events.This paper reviewed relevant studies conducted in China and other countries on imaging techniques for the diagnosis of sarcopenia, and examines the advantages and disadvantages of different techniques, in order to sort out well-grounded principles for clinical practice and future improvement in the management of sarcopenia.

Objective:To study the clinical value of left ventricle Tei index in evaluating hemodynamics after interventional therapy of patent ductus arteriosus (PDA).Methods:From May 2017 to May 2019, 50 children with PDA who underwent interventional therapy (PDA group) and 27 healthy children (healthy control group) in Anhui Provincial Children’s Hospital were selected. The left ventricle Tei index, plasma brain natriuretic peptides (BNP), left ventricular end-diastolic dimension (LVDD), left ventricular ejection fraction (LVEF) were compared between 2 groups.Results:The left ventricle Tei index was not correlated with heart rate and age in 2 groups ( P>0.05). The left ventricle Tei index before operation in PDA group was significantly lower than that in healthy control group: 0.20(0.16, 0.25) vs. 0.27(0.20, 0.30), and there was statistical difference ( P<0.05). In PDA group, the left ventricle Tei index immediately, 3 d, 1 month and 3 months after operation was significantly higher than before operation: 0.38(0.29, 0.47), 0.32(0.26, 0.40), 0.30(0.27, 0.35) and 0.32(0.26, 0.37) vs. 0.20(0.16, 0.25), and there was statistical difference ( P<0.05); the plasma BNP immediately after operation was significantly lower than before operation: 288 (126, 433) ng/L vs. 582 (303, 1 675) ng/L, and there was statistical difference ( P<0.05); the LVDD 3 months after operation was significantly lower than before operation: (3.03 ± 0.54) cm vs. (3.38 ± 0.51) cm, and there was statistical difference ( P<0.05); the LVEF immediately after operation was significantly lower than before operation: (54.24 ± 6.09)% vs. (59.45 ± 5.93)%, the LVEF 1 and 3 months after operation was significantly higher than that immediately after operation: (63.18 ± 4.71)% and (65.46 ± 4.78)% vs. (54.24 ± 6.09)%, and there were statistical differences ( P<0.05). The left ventricle Tei index before operation was negatively correlated with inner diameter of PDA and plasma BNP ( r = -0.362 and -0.388, P = 0.013 and 0.009), and there was no correlation between LVDD and LVEF ( r = -0.192 and -0.283, P = 0.229 and 0.053); the differences of Tei index before operation and immediately after operation (ΔTei) was positively correlated with inner diameter of PDA ( r = 0.325, P = 0.030), and there was no correlation with BNP, LVDD and LVEF ( r = 0.234, 0.283 and -0.039, P = 0.126, 0.076 and 0.798). Conclusions:The left ventricle Tei index can quickly and accurately assess the change of hemodynamics after interventional therapy of PDA.

Objective:To investigate the clinical characteristics of patients complicated with Hashimoto’s thyroiditis (HT) and papillary thyroid micro-carcinoma (PTMC) and risk factors for central lymph node metastasis (CLNM) by analyzing the clinical data.Methods:Clinical data of 770 patients with PTMC admitted to Head and Neck Surgery Center of Sichuan Cancer Hospital from May. 2015 to Nov. 2017 were retrospectively analyzed, including 250 HT-PTMC patients (observation group) and 520 non-HT-PTMC patients (control group) . There were 197 males and 573 females, with a male to female ratio of 1.00:2.91. Into observation indexes included patient’s age, gender, serum thyroid stimulating hormone (TSH) , thyroglobulin antibody (TG-Ab) , thyroid peroxidase antibody (TPO-Ab) , number of foci, diameter of foci, calcification of foci, location of foci (with or without extra-glandular invasion) , number of nodules (no matter benign or malignant) , and lymph node metastasis in central and lateral cervical regions. SPSS 22.0 software was used for statistical analysis. Normally distributed data were expressed ± s. The difference between observation group and control group was compared by chi-square test of single factor analysis. The risk factors of CLNM of the observation group were analyzed with multivariate Logistic regression, the difference was statistically significant if P<0.05. Results:There were statistically significant differences between the observation group and the control group in age ( P=0.006) , gender ( P<0.001) , TSH ( P<0.001) , TG-Ab ( P<0.001) , TPO-Ab ( P<0.001) , number of nodules ( P=0.016) , and central lymph node ( P<0.001) . Compared with non-HT-PTMC group, HT-PTMC group had a higher proportion of women under 55 years old, and both TG-Ab and TPO-Ab had higher positive rates. Patients with HT-PTMC were more likely to show polynodule changes, but their central lymph node metastasis rate was lower than that of the non-HT-PTMC group. Single-factor analysis showed that the number of cancer foci, calcification of cancer foci, and location of cancer foci were significantly correlated with the CLNM of HT-PTMC patients (all P<0.001) . Multivariate Logistic regression analysis showed that multiple cancer foci ( P<0.001) , invasion and capsule ( P<0.001) , and cancer foci with calcification ( P=0.005) were independent risk factors for CLNM. Conclusions:HT-PTMC is more common in women under 55 years of age, and most of them show multiple nodules in bilateral glandular lobes, often accompanied by elevated serum TSH, TG-Ab and TPO-Ab levels. Meanwhile, the lymph node metastasis rate of HT-PTMC is relatively low, and the prognosis may be relatively good. In HT-PTMC, the risk of multiple carcinoma foci, cancer foci with calcification, cancer foci invasion and the occurrence of CLNM is higher. Preventive central lymph node dissection helps to reduce the occurrence of postoperative cervical lymph node recurrence.

Objective To explore the clinical effect of new type rectal cancer radiotherapy individualized fixation device in the radiotherapy of rectal cancer. Methods From June 2015 to December 2016,60 patients with rectal cancer who accepted the external irradiation in Zhejiang Tumor Hospital were divided into two groups by random number table method. A group(31 cases) received new type rectal cancer radiotherapy position fixation devices with thermoplastic film. B group(29 cases) received simple foam pad with thermoplastic film. Before each treatment,Cone beam CT(CBCT) scan was conducted. The applied CBCT image and the planned reconstruction image were compared in the direction of X(left and right),Y(upper and lower)and Z(front and rear) axis. The setup error was recorded, and the correlation between the two groups was analyzed. Results The average setup error of patients in A group in X (left and right),Y(upper and lower),Z(front and rear) axis were (1. 61 ± 0. 18)mm,(1. 82 ± 0. 13)mm,(1. 91 ± 0. 11)mm,respectively. The average setup error of patients in B group in X(left and right),Y(upper and lower),Z (front and rear) axis were (2. 22 ± 0. 13)mm,(2. 43 ± 0. 14)mm,(2. 36 ± 0. 13)mm,respectively. There were statistically significant differences between the two groups(t=14. 958,17. 501,11. 283,all P＜0. 001). Conclusion The new type of rectal cancer radiotherapy position fixing device is more comfortable than the simple foam pad,and the setting error is smaller than the simple foam pad.

Objective To study the clinical characteristics, respond of treatment and prognosis in infants with atrial tachycardia (AT). Methods The clinical data of 23 infants with AT from August 2014 to November 2016 were retrospectively analyzed. The respond of treatment and prognosis were observed. Results Of all the 23 infants with AT, incessant AT was in 5 cases, and paroxysmal AT was in 18 cases. There were 13 infants diagnosed with AT combined with cardiac insufficiency, and among them, 5 cases were combined with tachycardia induced cardiomyopathy (TIC). Echocardiography showed that atrial septal defect in 3 cases, patent foramen oval in 6 cases, ventricular septal defect in 1 case, ventricular septal defect combined with patent foramen oval in 2 cases, ventricular septal defect combined with atrial septal defect in 1 case, and ventricular septal defect combined with coarctation of the aorta in 1 case. The curative effect was excellent in 11 cases, effective in 8 cases, and ineffective in 4 cases at discharge. There was no statistical difference in curative effect between patients with normal cardiac function and cardiac insufficiency at discharge (P＞0.05). The infants were followed up for 12 months, AT disappeared in 19 cases, 1 case progressed to sick sinus syndrome, and 3 cases were lost in follow-up. Conclusions AT can be insidious in infants, but with a favorable prognosis if treated with cardiotonic drugs and antiarrhythmic drugs during the short and mid-term follow-up. Long-term follow-up should be taken to learn more about the prognosis.

PURPOSE: This study aimed to evaluate the prognostic impact of lymphovascular invasion (LVI) in patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We collected data from 180 patients who were treated with RNU from 2005 to 2013 at our institution. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses. RESULTS: LVI was present in 28 patients (15.6%), which was associated with higher pathological tumor stage (p < 0.001), tumor necrosis (p=0.012), lymph node metastasis (p=0.017) and multifocality (p=0.012). On multivariate analysis, LVI was an independent prognostic factor of recurrence-free survival [RFS: hazard ratio (HR)=2.954; 95% confidence interval (CI)=1.539–5.671; p=0.001] and cancer-specific survival (CSS: HR=3.530; 95% CI=1.701–7.325; p=0.001) in all patients. In patients with node-negative UTUC, LVI was also a significant predictor of RFS (HR=3.732; 95% CI 1.866–7.464; p < 0.001) and CSS (HR=3.825; 95% CI=1.777–8.234; p=0.001). CONCLUSION: LVI status was an independent predictor in patients with UTUC who underwent RNU. The estimate of LVI could help physicians identify high-risk patients and make a better medication regimen of adjuvant chemotherapy.
Carcinoma, Transitional Cell ; Chemotherapy, Adjuvant ; Humans ; Lymph Nodes ; Methods ; Multivariate Analysis ; Necrosis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Urinary Tract