Objective To analyze the changes of serum markers of liver function and liver fibrosis in patients with fatty liver,and to explore the relationship between them,so as to provide scientific basis for the prevention and treatment of fatty liver into hepatic fibrosis. Methods From January 1st,2015 to December 31st, 2015,one thousand three hundred and forty-six healthy cases were selected,and 361 cases of fatty liver were diagnosed by ultrasound. Liver function index of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected by automatic biochemical analyzer. Hyaluronic acid (HA),laminin (LN),serum type Ⅲprocollagen peptide ( PC Ⅲ) and type Ⅳ collagen ( C-Ⅳ) were detected by enzyme-linked immunosorbent assay. The correlation between liver function and serum liver fibrosis indexes was analyzed by Pearson parameter analysis. Results The liver function index ALT,AST((69. 04±18. 72) U/L,(59. 78±15. 65)U/L) in fatty liver group were higher than those in the non-fatty liver group((25. 71±10. 25) U/L,(23. 68±8. 23) U/L),the differences were statistically significant ( t＝279. 283,388. 461,P＜0. 05) . Four serum fibrosis index HA,LN, PCⅢ,C-Ⅳ in the fatty liver group were (112. 64±21. 63) μg/L,(125. 85±27. 52) μg/L,(127. 28±29. 37) μg/L,(79. 38±18. 52) μg/L,respectively,which were higher than those in the non-fatty liver group ( (53. 98 ±16. 84) μg/L,(86. 31±20. 46) μg/L,(53. 31±18. 23) μg/L,(57. 26±15. 86 ) μg/L),the differences were statistically significant ( t＝727. 724,170. 432,941. 357,71. 169,P＜0. 001) . The correlation analysis of liver function and serum liver fibrosis indexes showed that ALT and AST were positively correlated with the fibrosis indexes HA,LN,PCⅢ( correlation coefficient r＝0. 230,0. 119,0. 370;0. 363,0. 361,0. 509,P＜0. 001),and which had no significant correlation with C-Ⅳ(P＞0. 05). Conclusion Liver function and serum liver fibrosis index can be used as the important basis for monitoring and diagnosis on the progression of fatty liver disease.

Objective:To explore the influencing factors of the long-term quality of life(QOL).Methods:According to the standard of diagnosis of primary lung cancer, a total of 74 patients with primary lung cancer were included in the study, who were first diagnosed by pathology and /or cytology and /or clinic from 1 January 2010 to 30 June 2016 in Tangshan Third Hospital, Heibei Province, and whose data were analyzed retrospectively.The Chinese version of FACT-L (4.0) QOL questionnaire was used to evaluate the QOL in 74 patients with primary lung cancer who survived more than three years.Multivariate regression statistical method was used to analyze the main influencing factors.Results:All patients with long-term survival lung cancer were treated by operation, their average QOL score was ( 126.62±13.29). Age, type of medical insurance and clinical stage had significant influence on QOL ( P<0.05). There was no significant difference in the total QOL scores between<50-year-old group(138.18±13.92) and ≥50-<60-year-old group(138.18±13.92, 137.04±12.82)(all P>0.05), but they were higher than that in ≥60-year-old group (115.28 ±13.11) (all P<0.05). The QOL of residents′ medical insurance patients (117.92 ±13.13) was lower than that of employees′ medical insurance patients (142.69±13.07) ( t=10.849, P=0.002). The QOL scores of stage Ⅰ and Ⅱ (140.34 ±12.88, 133.31±12.07) had no significant difference, but which were higher than that of stage III (96.84 ±13.46) ( P<0.05). Conclusion:Patients with long-term survival lung cancer after surgery could maintain a better QOL by early detection, timely surgery and constantly improving the medical security system to reduce the financial burden of patients.

Objective To investigate cyclin D2(CCND2)expression in papillary thyroid carcinoma(PTC)and its association with the clinicopathological features.Methods The public databases TCGA,TIMER 2.0 and UALCAN were used to explore CCND2 expression level in PTC and adjacent tissues,and its diagnostic value for PTC was analyzed using ROC curves.GO enrichment analysis of CCND2-related differentially expressed genes(DEGs)in PTC was performed,and tumor immune infiltration of CCND2 in thyroid cancer was analyzed using TIMER database and CIBERSORT data source.RT-qPCR and Western blot were used to detect CCND2 expression in normal human thyroid cell line Nthy-ori-3-1 and human PTC cell lines TPC-1 and BCPAP.CCND2 expression was also detected in clinical specimens of PTC and adjacent tissues by immunohistochemistry,and its correlation with clinicopathological features of the patients were analyzed.Results Informatic analysis revealed significantly higher CCND2 mRNA expression in thyroid cancer than in the adjacent tissues(P<0.001)in close correlation with tumor stage,gender,age,pathological subtype,and lymph node involvement(P<0.05).ROC curve analysis showed that at the cutoff value of 4.983,the diagnostic sensitivity,specificity,and accuracy of CCND2 expression for PTC was 83.6%,94.9%,and 78.5%,respectively.CCND2 expression was positively correlated with B cells,CD4+T cells,and macrophages(P<0.001)and negatively with CD8+T cells(P<0.01),and also correlated with memory B-cell infiltration,CD4+T-cell memory activation,M2 macrophages,resting mast cells,and mast cell activation(P<0.05).RT-qPCR,Western blot and immunohistochemistry showed significantly higher CCND2 expression in the PTC cells than in Nthy-ori-3-1 cells(P<0.01)and also in clinical PTC tissues than in the adjacent tissues(P<0.05)in correlation with tumor size,lymph node metastasis and TNM stage(P<0.05).Conclusion CCND2 overexpression is closely correlated with tumor progression and immune cell infiltration in PTC patients..

Objective To investigate cyclin D2(CCND2)expression in papillary thyroid carcinoma(PTC)and its association with the clinicopathological features.Methods The public databases TCGA,TIMER 2.0 and UALCAN were used to explore CCND2 expression level in PTC and adjacent tissues,and its diagnostic value for PTC was analyzed using ROC curves.GO enrichment analysis of CCND2-related differentially expressed genes(DEGs)in PTC was performed,and tumor immune infiltration of CCND2 in thyroid cancer was analyzed using TIMER database and CIBERSORT data source.RT-qPCR and Western blot were used to detect CCND2 expression in normal human thyroid cell line Nthy-ori-3-1 and human PTC cell lines TPC-1 and BCPAP.CCND2 expression was also detected in clinical specimens of PTC and adjacent tissues by immunohistochemistry,and its correlation with clinicopathological features of the patients were analyzed.Results Informatic analysis revealed significantly higher CCND2 mRNA expression in thyroid cancer than in the adjacent tissues(P<0.001)in close correlation with tumor stage,gender,age,pathological subtype,and lymph node involvement(P<0.05).ROC curve analysis showed that at the cutoff value of 4.983,the diagnostic sensitivity,specificity,and accuracy of CCND2 expression for PTC was 83.6%,94.9%,and 78.5%,respectively.CCND2 expression was positively correlated with B cells,CD4+T cells,and macrophages(P<0.001)and negatively with CD8+T cells(P<0.01),and also correlated with memory B-cell infiltration,CD4+T-cell memory activation,M2 macrophages,resting mast cells,and mast cell activation(P<0.05).RT-qPCR,Western blot and immunohistochemistry showed significantly higher CCND2 expression in the PTC cells than in Nthy-ori-3-1 cells(P<0.01)and also in clinical PTC tissues than in the adjacent tissues(P<0.05)in correlation with tumor size,lymph node metastasis and TNM stage(P<0.05).Conclusion CCND2 overexpression is closely correlated with tumor progression and immune cell infiltration in PTC patients..

Objective To retrospectively analyze the setup error in radiotherapy of somal tumors and body metastases using the ExacTrac X-ray portal image,and to evaluate the feasibility and effectiveness of 6D setup error correction in body radiotherapy.Methods The translational and rotational setup errors were calculated by registering the bony structures on the ExacTrac X-setup images to that of the digitally reconstructed setup images,and the corresponding residual errors were calculated together.Results The translational and rotational setup errors in the x (left-right),y (superior-inferior),z (anterior-posterior) and Rx (sagittal),Ry (transverse),Rz (coronal) directions were(2.27±2.02) mm,(4.49±2.52) mm,(2.27± 1.37) mm and (1.02 ± 0.73) °,(0.67 ± 0.68) °,(0.76 ± 0.84) °,respectively.The residual translational and rotational setup errors in the x(r),y(r),z(r) and Rx(r),Ry(r),Rz(r) directions were(0.27±0.48)mm,(0.37±0.45)mm,(0.22±0.30)mm and (0.17±0.33)°,(0.14±0.34)°,(0.16± 0.28) ° respectively.Conclusions Besides the translational setup errors,a certain amount of rotational setup errors exist in radiotherapy of somal tumors and body metastases.By using the 6D setup error correction of the ExacTrac system,a translational less than 0.4 mm and rotational setup errors less than 0.2° could be achieved.

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTS^LepRb) neurons notably activated breathing. Moreover, stimulation of NTS^LepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTS^LepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTS^LepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTS^LepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca²⁺ transients in most NTS^LepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology* ; Membrane Potentials ; Neurons/metabolism* ; Solitary Nucleus/metabolism*

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*