Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Frailty is a complex age-related clinical condition characterized by a decline in physiological capacity across several organ systems, with a resultant increased susceptibility to stressors.The relationship between frailty assessment and elderly patients’ safety during perioperative period has received widespread attention.This paper reviews research progress of frailty assessment in elderly patients during perioperative period in the department of urology.

BACKGROUND:With the innovation of examination technique,the number of patients with spinal metastases in different stages is increasing year by year.Percutaneous vertebroplasty is an important treatment for spinal metastases;however,there is no report on the biomechanical effect in different stages and different activities after operation. OBJECTIVE:To simulate thoracic T10 bone stress and displacement of the different locations of the tumor metastasis based on the three-dimensional finite element model. METHODS:According to thoracic three-dimensional CT images of a 30-year-old healthy male,Mimics software was used to construct a three-dimensional geometric model of thoracic vertebrae(T9-T11),including ribs,ligaments and intervertebral discs.Three-dimensional models of T9-T11 vertebral bodies and different parts of the posterior thoracic vertebrae invaded by thoracic metastatic tumors were simulated,including the control group with intact vertebral structure,unilateral metastasis involving the vertebral body area(experimental group 1),unilateral metastasis involving the vertebral body and pedicle area(experimental group 2),unilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 3),and bilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 4).Abaqus software was used to create a three-dimensional finite element model.The von Mises stress distribution and the displacement of the model were analyzed under the loading condition,buckling condition,extension condition,and rotation condition. RESULTS AND CONCLUSION:(1)In the study of the maximum total displacement of loading points in different experimental groups under loading,flexion,extension,and rotation conditions,with the increase of metastatic tumor invasion site and invasion surface,the total displacement of loading points increased,and the overall stiffness decreased,especially the total displacement of loading points in experimental group 4 was the largest.(2)Under flexion condition,the maximum Von Mises stress value increased significantly after vertebral body and pedicle destruction,while the maximum Von Mises stress value was almost unchanged when the thoracocostal joint destruction was added.(3)On the basis of finite element analysis and simulation of bone tumor model,the elements in the bone cement region were set as a single set,and the bone cement region was set as the corresponding material properties to simulate bone cement filling.The results showed that the maximum total displacement under loading,flexion,extension,and rotation conditions was less than that of each experimental group.(4)The maximum stress values of the simulated percutaneous vertebroplasty patients in the loading,flexion,extension and rotation conditions were significantly lower than those of the femoral model.(5)It is concluded that the three-dimensional finite element model based on thoracic T9-T11 conducive to the biomechanics characteristics of thoracic vertebrae tumor metastasis,and on the basis of the thoracic vertebrae tumor metastasis model can accurately simulate load point after percutaneous vertebral body under different conditions of total displacement and the maximum Von Mises stress situation.

Objective:To investigate the values of CT angiography (CTA) and color Doppler ultrasound in the diagnosis and etiological screening of varicocele (VC).Methods:Ninety-seven patients with VC diagnosed by the Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital from May 2016 to December 2017 were retrospectively included. The CTA and color Doppler ultrasonographic data of 194 spermatic veins (including 116 varicocele veins) were analyzed. Paired t test was used to compare the mean diameter of spermatic veins at the root of scrotum measured by CTA and color Doppler ultrasound. McNemar test was used to compare the sensitivity and specificity of CTA and color Doppler examination for VC, and χ 2 or Fisher exact probability was used to compare the detection rate of CTA and color Doppler examination in screening the etiology of VC. Results:The average diameters of scrotal root of spermatic veins by CTA and color Doppler ultrasonography were (2.9±0.6) and (3.0±0.6) mm for VC cases, with no significant difference found( t=0.885, P=0.381). According to the diagnostic VC standard of color Doppler ultrasound (diameter>2 mm), no significant difference was found between CTA and color Doppler ultrasound in the sensitivity [95.69%(111/116) vs. 100%(116/116)] and specificity [100%(78/78) vs. 100%(78/78)] in the diagnosis of VC. The etiological detection rate of CTA in 97 patients with VC was significantly higher than that of color Doppler ultrasound ( P<0.05). Conclusions:Both CTA and color Doppler ultrasound have high sensitivity and specificity in the diagnosis of VC. CTA has a higher etiological detection rate in etiological screening of VC than color Doppler ultrasound.

Objective To investigate the changes of CT cerebral perfusion (CTP) and the application value of nuclear magnetic resonance proton spin labeling (3D-ASL) and to conduct a comparative study. Methods Multi-slice spiral CT(MDCT) was used to study the changes of CTP in 22 patients with HAPC. Comparison of CT whole-brain perfusion technique and nuclear magnetic resonance proton spin labeling technique (3D-ASL) in hemodynamic changes of the brain in plateau polycythemia. Results With the aggravation of HAPC, CBF of cerebral cortex and white matter showed a downward trend. Except the white matter of frontal lobe and temporal lobe, the difference of HAPC among different diseases was statistically significant (P < 0.05). Along with the aggravation of, each part of the brain cortex and white matter CBV increase, white matter, and each part CBV difference had statistical significance between different condition (P < 0.05). With the aggravation of the disease, the MTT of cortex and white matter in all parts of the brain increased significantly, and the difference of MTT between different parts of the disease was statistically significant (P < 0.05). HAPC patients along with the aggravation of different level, rCBF is reduced, in addition to the parietal cortex, temporal and occipital white matter, white matter rCBF differences between different parts of different condition have statistical significance (P < 0.05). ROC curve was used to evaluate the diagnostic value of CTP and ASL. The two curves were close to each other, and CTP was slightly better than ASL. Conclusion With the progression of HAPC, cerebral blood flow decreased, blood volume increased, and average blood flow time prolonged in patients with different degrees of HAPC. CTP and ASL had similar effects, and the former had slightly better value.

Objective To investigate the clinical value of 99Tcm-methoxyisobutylisonitrile (MIBI) double-phase imaging in differential diagnosis of bone lesions in tumor patients,which was indefinite in 99Tcm-methylene diphosphonate (MDP) bone imaging,and evaluate the correlation between 99Tcm-MIBI imaging and chemotherapy efficacy.Methods Fifty-two tumor patients (23 males,29 females,mean age 58 years) with bone isolated lesions(≤3) found by 99Tcm-MDP bone scintigraphy was enrolled from June 2014 to November 2015.Since the results of 99Tcm-MDP imaging were indefinite,99Tcm-MIBI double-phase (10 min and 30 min after injection of 99Tcm-MIBI) SPECT/CT imaging was then performed within 1 week.The final diagnosis was made according to results of more than two imaging modalities (CT,MRI,PET/CT) and/or follow-up (≥6 months).The diagnostic efficacy of 99Tcm-MIBI SPECT/CT imaging was calculated.The clinical dataof chemotherapy were also collected.Patients with bone metastasis were grouped as the treatment response.Retention index (RI) of metastatic lesions was calculated and compared between different groups using two-sample t test.The relationship between RI and chemotherapy efficacy was investigated by Spearman correlation analysis.Results A total of 12 benign lesions and 84 malignant lesions were eventually diagnosed.The sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and Youden index of 99Tcm-MIBI imaging were 96.43％(81/84),83.33％(10/12),97.59％(81/83),76.92％(10/13),and 0.80,respectively.The RI was statistically different between complete remission (CR)+partial remission (PR) group and stable disease (SD) + progressive disease (PD) group:-0.142± 0.036 vs-0.384± 0.067 (t =2.367,P＜0.05).The RI of 99Tcm-MIBI in bone metastases was positively correlated with the chemotherapy efficacy (rs =0.78,P＜0.01).Conclusions 99Tcm-MIBI imaging is helpful in differential diagnosis of bone lesions with indefinite diagnosis by 99Tcm-MDP bone imaging in tumor patients.99Tcm-MIBI RI of bone metastasis may predict the therapeutic response of chemotherapy efficacy.

Objective To evaluate the clinical value of 99Tcm-Tilmanocept(TMC) SPECT/CT for the detection of SLN by comparing with 99Tcm-sulfur colloid(SC) SPECT/CT. Methods From March 2016 to September 2016, a total of 160 patients (age range: 30-70 years), selected from Breast Surgery Department of Shandong Cancer Hospital, underwent SPECT/CT and planar imaging with either 99Tcm-TMC (TMC group, n=76) or 99Tcm-SC (SC group, n=84). The results of SLN SPECT/CT and planar imaging were compared. The positive rate of SLN in SPECT/CT was compared with operative results. One-way analysis of variance, χ2 test, and two-sample t test were used for data analysis. Results The radiochemical purity of 99Tcm-TMC (≥92%) had no significant difference in 4 h(F=0.720, P>0.05). In TMC group, the average number of SLN detected by SPECT/CT imaging was higher than that by planar imaging (1.34±0.64 vs 0.96±034; t=4556, P<005). In SC group, the average number of SLN detected by SPECT/CT imaging was also higher than that by planar imaging (2.57±0.99 vs 1.56±0.87; t=7.010, P<0.05). The positive rates of SLN in TMC and SC groups were 94.7%(72/76)and 96.4%(81/84), showing no significant difference (χ2=0273, P>0.05). The average number of SLN detected by 99Tcm-TMC imaging was significantly lower than that detected by 99Tcm-SC (t=9.115, P<0.05). The intraoperative detection rates of SLN were 100% (76/76 and 84/84) in both groups. The average number of SLN detected during operation in TMC group was significantly lower than that in SC group (1.89±0.86 vs 3.05±1.29; t=6.642, P<0.01). In TMC group, the average number of SLN detected during operation was significantly higher than that detected by SPECT/CT(1.89±086 vs 1.34±0.64; t=4.492, P<0.05). In SC group, the average number of SLN detected during operation was significantly higher than that detected by SPECT/CT(3.05±1.29 vs 2.57±0.99; t=2.740, P<005). Conclusions SPECT/CT is superior to planar imaging for the detection and localization of SLN. 99Tcm-TMC is suitable for SLN imaging and intraoperative detection.

OBJECTIVEThe aim of this study was to determine the impact of routinely performed internal mammary sentinel lymph node biopsy (IM-SLNB) on the staging and treatment, and to analyze the success rate, complications and learning curve.

METHODSAll patients with biopsy-proven breast cancer who underwent sentinel lymph node biopsy between 2012 and 2014 were included in a prospective analysis. Internal mammary sentinel lymph node biopsy (IM-SLNB) was performed in all patients with IM-SLN visualized on preoperative lymphoscintigraphy and/or detected by intraoperative gamma probe detection. The adjuvant treatment plan was adjusted according to the current guidelines.

RESULTSIn a total of 349 patients, 249 patients (71.1%) showed internal mammary drainage. IM-SLNB was performed in 153 patients with internal mammary drainage, with a success rate of IM-SLNB of 97.4% (149/153). Pleural lesion and internal mammary artery bleeding were found in 7.2% and 5.2% patients, respectively. In 8.1% of patients (12/149) the IM-SLN was tumor positive. In the group of patients who underwent IM-SLNB, lymph node staging was changed in 8.1% of patients, and IMLNs radiotherapy was guided by these results, however, systemic treatment was changed in only 0.7% of the patients.

CONCLUSIONSIM-SLNB has a high successful rate and good safety. Identification of internal mammary metastases through IM-SLNB may provide more accurate staging and guide the tailored internal mammary radiotherapy.

TRIAL REGISTRATIONClinicalTrials. gov, NCT01642511.

Breast ; pathology ; Breast Neoplasms ; pathology ; Female ; Humans ; Learning Curve ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Mammary Arteries ; Neoplasm Staging ; methods ; Neoplasms, Second Primary ; Prospective Studies ; Sentinel Lymph Node Biopsy ; methods

BACKGROUND:Homing is the initial and key procedure of stem cel s-based tissue restoration. Current studies have shown that the inability to recruit bone marrow mesenchymal stem cel s to target tissue with high efficiency remains a significant barrier to tissue restoration. Preconditioning strategy provides a new insight to promote stem cel homing. OBJECTIVE:To review preconditioning strategies for promoting the homing of stem cel s. METHODS:In PubMed database, different combinations of terms from“stem cel , mesenchymal stem cel s, preconditioning, homing, migration”served as search terms to retrieve articles referring preconditioning strategies for promoting mesenchymal stem cel homing published from January 2000 to September 2015. According to the inclusion criteria, 72 articles were selected for final review. RESULTS AND CONCLUSION:Pretreating target tissue or mesenchymal stem cel s ahead of cel transplantation, known as tissue preconditioning or cel preconditioning, prominently promotes the homing of mesenchymal stem cel s, therefore enhancing tissue restoration effect. Tissue preconditioning is designed to up-regulate expression of chemokines by varying the local microenvironment, thereby increasing homing ability of mesechymal stem cel s. Mesenchymal stem cel preconditioning strategies, for example, gene modification and cytokine induction, are mainly to up-regulate expression of chemokine receptors on the surface of mesenchymal stem cel s as effectors, and thus promote targeted cel homing. Overal , preconditioning strategy wil bring great hope to apply stem cel therapy into the clinic.