Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective:To evaluate the oncologic and functional outcomes of postcricoid carcinoma treated by surgical treatment, and to summarize our clinical experience in surgical treatment and reconstructive techniques.Methods:Medical files of 45 patients were collected and retrospectively analyzed. The patients received surgical treatments between January 2010 and May 2017 in the Qilu Hospital of Shandong University, including 39 males and 6 females, the age ranged from 41 to 78 years old. T1, T2, T3 and T4 staging tumors represented respectively for 2,13,23 and 7 cases. And cervical metastasis was histologically identified in 33 cases (8 for N1 and 25 for N2). Advanced staging patients (10 in Stage Ⅲ and 30 in Stage Ⅳ) accounted for 88.9% of the cohort, while early staging cases (1 in Stage Ⅰand 4 in Stage Ⅱ) for 10.1%. All patients received cervical lymph node dissection. After tumor excision without compromising margins, hypopharyngeal functions were reconstructed by residual mucosa, pectoralis major myocutaneous flap, laryngotracheal tissue flap or gastric tissue flap, and laryngeal functions were reconstructed by epiglottis, sternohyoid myofascial flap or thyroid perichondrium. Survival rates were analyzed by the Kaplan-Meier method.Results:Postoperatively 23 patients received radiotherapy and 13 patients received chemoradiotherapy. All patients were followed up for more than 3 years. Total 3-year and 5-year survival rates were 60.5% and 49.0%, respectively. Patients obtaining the conservation of laryngeal functions accounted for 44% (20/45) of all cases. The neck lymph node positive rate was 73.3%(33/45), and log-rank test demonstrated that cervical lymph node metastasis was significantly associated with prognosis of patients (χ 2=4.364, P=0.037). Conclusion:Appropriate surgical approaches and excision methods and comprehensive application of flaps are critical to precise tumor excision and reconstruction of laryngeal functions, thereby improving the quality of life of patients with posterior carcinoma.

Objective: To observe the effect of high-intensity interval training (HIIT) on G protein-coupled receptor kinase-2 (GRK2) levels in the hearts and adrenal glands of spontaneously hypertensive rats (SHRs) and explore how exercise might improve sympathetic over-excitation. Methods: Twenty male SHRs were divided randomly into a sedentary control group and an HIIT group. Ten age-matched, male Wistar-Kyoto rats without hypertension served as the control group. The rats of the control and sedentary control groups were housed in cages at rest while those of the HIIT group underwent eight weeks of HIIT. Caudal artery pressure, cardiac structure and function, and heart rate variability (HRV) were determined using a non-invasive blood pressure tester, echocardiograms, and electrocardiograms. The plasma concentrations of epinephrine and norepinephrine, and the expression of GRK2 and β₁-adrenoceptor (β₁-AR) protein were measured in the rats′ hearts, and GRK2 and α₂-adrenoceptor (α₂-AR) protein were measured in their adrenal glands using high-pressure liquid chromatography and western blotting. Results: Compared with the normotensive control group, animals in the sedentary control group showed elevated blood pressure, cardiac hypertrophy, reduced heart function, sympathetic over-excitation manifested by HRV, increased plasma epinephrine and norepinephrine concentrations, up-regulated GRK2 protein expression in the heart and adrenal gland, but down-regulated β₁-AR in the heart and down-regulated α₂-AR in the adrenal gland. Compared with the sedentary control group, the HIIT group did not show improved cardiac hypertrophy, but it did show reduced blood pressure, enhanced heart function, suppressed sympathetic over-excitation, as well as lowered plasma epinephrine and norepinephrine concentrations, on average. The expression of GRK2 in the heart and adrenal gland was significantly down-regulated, while that of β₁-AR in the heart and of α₂-AR in the adrenal gland were significantly up-regulated, on average. Conclusions HIIT can alleviate sympathetic over-excitation and enhance heart function despite spontaneous hypertension, at least in rats. The therapeutic mechanism may be related with the down-regulation of GRK2 expression in the heart and adrenal gland.

Objective: To summarize clinical experience in surgical treatment of supraglottic carcinoma and reconstructive techniques. Methods: Medical files of 184 patients (173 men, 11 women) were collected and retrospectively analyzed, who underwent surgeries between January 2008 and December 2012 at Qilu Hospital of Shandong University. Among them, T1, T2, T3 and T4 staging tumors accounted respectively for 14.1% (26/184), 41.9%(77/184), 31.5%(58/184) and 12.5%(23/184). Cervical metastasis was histologically identified in 86 cases (98 for N0, 31 for N1 and 55 for N2). Advanced cases (56 cases at stage Ⅲ and 67 at stage Ⅳ), early cases (22 at stage Ⅰ and 39 at stage Ⅱ) accounted respectively for 66.8% and 33.2%. Supraglottic horizontal laryngectomy or total laryngectomy was performed to allow for tumor excision without compromising margins and the tongue flap or sternohyoidmyofascial flap was subsequently used for repairing the defect after removal of tumor. Survival rates were analyzed by the Kaplan-Meier method. Results: Patients receiving conservation laryngeal surgery accounted for 75.5% (139/184). The 3-year and 5-year survival rates for all cases were 84.2% and 70.7%, respectively. Log-rank test demonstrated that cervical lymph node metastasis, primary tumor staging and clinical TNM staging were significantly associated with prognoses of patients (P=0.003, 0.010, 0.035). Dysphagia was not observed in any case and speech function was maintained in petients with partial laryngectomy. Conclusion Adequate pre-operative evaluation, individualized treatment, and comprehensive application of flaps for repair are critical to precise tumor excision and reconstruction of laryngeal functions.

Objective: To report the experience in comprehensive surgical treatment of pyriform sinus carcinoma via the paraglottic space approach. Methods: Three hundred and thirty-five cases with pyriform sinus carcinoma (according to UICC 2012 criteria, stage Ⅰ, 12 cases; Ⅱ, 36; Ⅲ, 79; Ⅳ, 208; T1, 26; T2, 139; T3, 121; T4, 49; cN0, 83; cN1, 61; cN2a-b, 118; cN2c, 71; cN3, 2) treated between 2006 and 2013 were retrospectively reviewed. There were 323 males and 12 females. Age aged from 36 to 80 years old with a median of 60 years old. There was no case with distant metastasis. All patients received modified neck dissection, including unilateral in 240 patients and bilateral in 95 patients. Pharyngoesophageal defects were reconstructed with directly suture in 246 cases, pectoralis major musculocutaneous flaps in 74 cases, and laryngotracheal flaps in 15 cases. Three hundred and nineteen patients received postoperative radiotherapy (55-65 Gy). Results: The overall 3 and 5 year survival rates were 68.6% (230/335) and 52.1%(139/267), respectively. The cervical lymph node metastases were found in 265 (79.1%) patients. Pathologic findings showed that all patients had squamous cell carcinoma. Laryngeal functions (voice, respiration and deglutition) were completely restored in 277 (82.7%) patients. Conclusions The oncological efficacy of surgery via the paraglottic space approach is sure for pyriform sinus carcinoma, especially suitable for the early and medium-term lesions. The function of the larynx can retain after surgery, with the decreased incidences of cough and pharynx fistula.

Objective To assess the dignosis value of CT three-dimensional reconstruction with Fisher discriminant model in small solitary pulmonary nodules before operation.Methods CT data of 40 cases with SPN were retrospectively analyzed and divided into into malignant pulmonary nodules (25 cases),squamous cell carcinoma (4 cases),adenocarcinoma (13 cases),lung cancer (4 ca-ses),small cell lung cancer (2 cases),large cell carcinoma (1 case),metastases tumor (1 case),benign nodules (1 5 cases,6 cases of tuberculosis,2 cases of hamartoma,and 7 cases of non-specific inflammatory nodules)by pathology and follow-up results.The CT features of pulmonary nodules were evaluated through multi-planar reformation (MPR),curved-planar reformation (CPR),volume rendering (VR),maximum intensity proj ection (MIP)and other three-dimensional reconstruction.The three-dimensional data were divided into benign and malignant groups.In each of the two groups,the significant signs of morphological signs of discrimination indicators were adminstrated Fisher discriminant,and the probalitiy of false positives were estimated using cross-validation method. Results The positive features of pulmonary nodules in there-dismensional images were much more than in two-dimensional images. Fisher discriminant formula of solitary pulmonary nodules in three-dimensional images was Z=1.143X1 + 0.454X2+1.606X3-0.262X4+0.04X5+0.483X6+1.611X7-2.164.Discriminant boundary value Zc was-0.516.When Zcgreater than -0.516,nodules were proneed to considere as malignant nodules.In 25 cases of malignant nodules,4 cases mistook for benign.When Zc less than -0.516,nodules were proneed to considere as benign nod-ules.In 1 5 benign nodules,2 cases mistook for malignant.The total misdiagnosis and accuracy rate were 15 % and 85% respec-tively.Conclusion CT three-dimensional reconstruction combined with Fisher discriminant model have a high clinical value in dif-fereiating diagonsis of pulmonary nodules were proneed to considere as malignant nodules.In 25 cases of malignant nodules,4 cases mistook for benign.When Zc less than -0.516,nodules were proneed to considere as benign nodules. In 15 benign nodules,2 cases mistook for malignant.The total misdiagnosis and accuracy rate were 15 % and 85% respec-tively.Conclusion CT three-dimensional reconstruction combined with Fisher discriminant model have a high clinical value in differeiating diagonsis of pulmonary nodules.

BACKGROUND: Whether horizontal and vertical impacts cause craniocerebral injury of the same degree, and whether serum myelin basic protein (MBP) changes is associated with the direction of impact have been scarcely addressed in previous studies.OBJECTIVE: To observe the change in the serum MBP levels and morphological changes of the brain tissue rabbits with craniocerebral injury resulting from impacts from different directions.DESIGN: A randomized controlled experiment.SETTING: Department of Neurosurgery of a hospital affiliated to a medical university.MATERIALS: This study was conducted in the Central Laboratory of Shenyang Medical College between October 2003 and January 2004. Totally 30 healthy rabbits of either sex were randomly divided into two equal groups to receive vertical and horizontal impact on the head.METHODS: All the rabbits were anesthetized and fixed in prone position onto a table equipped with a device for inducing impact on the head from different directions. Venous blood of 1 mL was taken from the edge of the ear of each rabbit for detecting MBP before injury. The rabbits in vertical impact group received the impact of a hammer falling directly on the parietal bone of the skull. In the horizontal group, the rabbits were subjected to horizontal impact on the lateral side of the skull. Forty-eight hours after the injury, venous blood were again taken for MBP measurement. The rabbits were then killed for pathological examination of the brain.MAIN OUTCOME MEASURES: Changes in serum MBP and pathomorphology of the brain tissues in the two groups after the impact.RESULTS: ① According to intention to treat analysis, all the 30 animals were involved in the experiment. There was no significant difference in serum MBP levels between the two groups before the impact, nor 48 hours after the impact( P ＞ 0.05). In the vertical impact group, serum MBP levels before the impact was( 1.68 ± 0. 86) μg/L, which was significantly lower than that after the impact[ (5.25 ± 1.96) μg/L, t = 3. 226, P ＜ 0. 05]. ② In the horizontal strike group, serum MBP also significantly increased from the level of( 1.70 ± 0.91 ) μg/L before impact to(5.73 ± 2.07) μg/L after that( t = 3. 080, P ＜ 0.05) . ③ After the impact, vasodilation and congestion in the cortex near the midline of the bilateral parietal region and edema in the deep layer of the white matter were observed in the vertical impact group, along with significant enlargement of the extravascular and extracellular space. In the horizontal group, similar changes except those near the midline of the bilateral parietal region took place after the impact; the same pathological changes were also observed in the basal plane, with nearly identical pathological changes in the deep layer of the white matter.CONCLUSION: Vertical and horizontal impacts can both result in almost identical brain injuries demonstrated by similar changes in serum MBP and the pathomorphology of the brain tissues after the impacts.