Endoplasmic reticulum (ER) stress is involved in the development and progression of tumors.In recent years, great attention has been paid to the study of the interplay of ER stress and T cell differentiation and functionality.Intense ER stress in the tumor-infiltrating T cells exacerbates T cell exhaustion and impairs T cell anti-tumor immunity.Therefore, a variety of ER stress inhibitors have been developed and utilized to alleviate T cell exhaustion, which improves T cell function in tumor microenvironment.Furthermore, the downregulation of several circadian clock genes like Per1 and Per2 also aggravates T cell exhaustion, and the key downstream effector molecules in ER stress regulate the transcription of Per family, thus enhancing the T cell function.In the present manuscript, we particularly summarize how ER stress impacts the anti-tumor immunity of T cells, and further discuss potential strategies for improving tumor immunotherapy via targeting ER stress.

The regulator of expression of virion(Rev)protein binds specifically to the Rev-responsive element(RRE)RNA in order to regulate the expression of the human immunodeficiency virus(HIV)-1 genes.Fluores-cence indicator displacement assays have been used to identify ligands that can inhibit the Rev-RRE interaction;however,the small fluorescence indicators cannot fully replace the Rev peptide or protein.As a result,a single rhodamine B labeled Rev(RB-Rev)model peptide was utilized in this study to develop a direct and efficient Rev-RRE inhibitor screening model.Due to photon-induced electron transfer quenching of the tryptophan residue on the RB fluorophore,the fluorescence of RB in Rev was weakened and could be dramatically reactivated by interaction with RRE RNA in ammonium acetate buffer(approximately six times).The interaction could reduce the electron transfer between tryptophan and RB,and RRE could also increase RB fluorescence.The inhibitor screening model was evaluated using three known positive Rev-RRE inhibitors,namely,proflavin,6-chloro-9-[3-(2-chloroethylamino)pro-pylamino]-2-methoxyacridine(ICR 191),and neomycin,as well as a negative drug,arginine.With the addition of the positive drugs,the fluorescence of the Rev-RRE decreased,indicating the displacement of RB-Rev.This was confirmed using atomic force microscopy(AFM)and the fluorescence was essentially unaffected by the addition of arginine.The results demonstrated that RB-Rev can be used as a fluorescent probe for recognizing small ligands that target RRE RNA.The Rev-RRE inhibitor screening model offers a novel approach to evaluating and identifying long-acting Rev inhibitors.

Objective:To explore the effect of Wnt/β-catenin signaling pathway on growth plate development of tibial growth plate in young chronic renal failure (CRF) rats.Methods:Four-week-old male SD rats were randomly divided into control group and CRF group ( n=20/per group). Control group was intragastric administration with distilled water, and CRF group was given adenine suspension (150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavages for 6 weeks. The full length of tibia was compared between the two groups. The width of tibia proximal growth plates was measured by micro-CT scanning, and the width of the growth plate was also measured in histological sections. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. Immunohistochemical staining was used to detect the expression of collagen Ⅱ, matrix metalloproteinase 13 (MMP-13) and β-catenin in chondrocytes. Western blotting was used to detect the protein expressions of collagen Ⅱ, MMP-13 and β-catenin. Results:Compared with the control group, the tibial length of rats in the CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], the width of growth plate in micro-CT picture was more narrow [(0.72±0.22) mm vs (1.13±0.27) mm, t=5.096, P<0.001], and the relative width of the growth plate was also more narrow ( t=6.744, P<0.001) in histological sections. The results of immunohistochemistry and Western blotting showed the expressions of collagen Ⅱ in the CRF group decreased significantly ( t=8.212, P<0.001), MMP-13 ( t=13.091, P<0.001) and β-catenin ( t=7.534, P<0.001) increased significantly compared the control group in chondrocytes. Conclusion:The Wnt/β-catenin signaling pathway is highly expressed in the tibial growth plate of young rats with chronic renal failure, which leads to accelerated degeneration and differentiation of chondrocytes and a closure tendency of growth plate.

Objective:To evaluate the role of B/glycogen synthase kinase-3β (Akt/GSK-3β) signaling pathway in interleukin-4 (IL-4)-induced reduction of cerebral ischemia-reperfusion (I/R) injury in mice and the relationship with autophagy.Methods:Forty clean-grade healthy male Balb/c mice, aged 10-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: sham operation group (group S), cerebral I/R group (group IR), IR plus IL-4 group, and IR plus IL-4 plus Akt inhibitor LY294002 group (IR+ IL-4+ LY group). Cerebral I/R was induced by 60 min middle cerebral artery occlusion followed by 24 reperfusion in anesthetized mice.IL-4 compound solution 0.2 ml was intraperitoneally given at 30 min before establishing the model in group IL-4.IL-4 compound solution 0.2 ml was intraperitoneally given at 30 min before establishing the model, and LY294002 15 nmol/kg was simultaneously injected via the tail vein in group IR+ IL-4+ LY.Neurological function was assessed and scored at 24 h of reperfusion, and then animals were sacrificed and brains removed for determination of cerebral infarct size (by TTC assay), cell apoptosis, autophagosome count (with transmission electron microscope), levels of superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) (using colorimetric assay), phosphorylation of Akt and GSK-3β, expression of LC3 and Beclin-1 (by Western blot). The apoptosis index and LC3Ⅱ/LC3Ⅰ ratio were calculated. Results:Compared with Sham group, the neurological scores, cerebral infarct size and apoptosis index were significantly increased, the SOD activity in brain tissues was decreased, levels of MDA and ROS were increased, phosphorylation of Akt and GSK-3β was decreased, and LC3Ⅱ/LC3Ⅰ ratio, Beclin-1 expression and autophagosome count were increased in the other three groups ( P<0.05). Compared with IR group, the neurological scores, cerebral infarct size and apoptosis index were significantly decreased, the SOD activity in brain tissues was increased, levels of MDA and ROS were decreased, phosphorylation of Akt and GSK-3β was increased, and LC3Ⅱ/LC3Ⅰ ratio, Beclin-1 expression and autophagosome count were decreased in IR+ IL-4 group ( P<0.05), and no significant change was found in the parameters mentioned above in IR+ IL-4+ LY group ( P>0.05). Compared with IR+ IL-4 group, the neurological scores, cerebral infarct size and apoptosis index were significantly increased, the SOD activity in brain tissues was decreased, levels of MDA and ROS were increased, phosphorylation of Akt and GSK-3β was decreased, and LC3Ⅱ/LC3Ⅰ ratio, Beclin-1 expression and autophagosome count were increased in IR+ IL-4+ LY group ( P<0.05). Conclusion:IL-4 can inhibit cell autophagy through activating Akt/GSK-3β signaling pathway and thus reduces cerebral I/R injury in mice.

Objective:To explore the predictive value of China Nanjing persistent vegetative state scale (CNPVSS) on the curative effect of the patients with chronic disorder of consciousness, by analyzing the curative effect of the rehabilitation treatment combined with hyperbaric oxygen (HBO) for patients with chronic disorder of consciousness.Methods:A total of 48 patients with chronic disorder of consciousness admitted to Nanjing Zijin Hospital to receive rehabilitation treatment combined with HBO from the September of 2016 to the May of 2019 were selected according with the analytical criteria. Before the treatment, the patients were evaluated by CNPVSS and received electroencephalogram (EEG) and evoked potentials (EPs) examinations. The patients′ consciousness was evaluated again before discharge, the results of CNPVSS and electrophysiological examinations were recorded, and the correlation between the results and the changes of the consciousness was analyzed statistically.Results:The results of CNPVSS was positive correlated with near-term curative effect ( r=0.401, P=0.005); the rate of awakening after treatment was 46.2% among those who were scored as minimally conscious state (MCS) by CNPVSS; the rate of awakening after treatment was 17.1% among those who were at vegetative state (VS) or in a coma; the rate of awakening after treatment of the MCS patients was higher than those of the patients at VS or in a coma ( χ2=4.255, P=0.039). The recordings of right somatosensory evoked potentials (SSEPs) N20 was positive correlated with curative effect ( r=0.312, P=0.031); and the left visual evoked potentials (VEPs) V100 was positive correlated with curative effect ( r=0.285, P=0.049). There were no statistical significance found between other electrophysiological recordings with curative effect. Conclusion:CNPVSS can be an important tool to predict the outcome of the rehabilitation treatment combined with HBO for the patients with chronic disorder of consciousness, and the recordings of SSEPs and VEPs also are of a certain reference value in predicting the prognosis.

Objective:To explore the predictive value of China Nanjing persistent vegetative state scale (CNPVSS) on the curative effect of the patients with chronic disorder of consciousness, by analyzing the curative effect of the rehabilitation treatment combined with hyperbaric oxygen (HBO) for patients with chronic disorder of consciousness.Methods:A total of 48 patients with chronic disorder of consciousness admitted to Nanjing Zijin Hospital to receive rehabilitation treatment combined with HBO from the September of 2016 to the May of 2019 were selected according with the analytical criteria. Before the treatment, the patients were evaluated by CNPVSS and received electroencephalogram (EEG) and evoked potentials (EPs) examinations. The patients′ consciousness was evaluated again before discharge, the results of CNPVSS and electrophysiological examinations were recorded, and the correlation between the results and the changes of the consciousness was analyzed statistically.Results:The results of CNPVSS was positive correlated with near-term curative effect ( r=0.401, P=0.005); the rate of awakening after treatment was 46.2% among those who were scored as minimally conscious state (MCS) by CNPVSS; the rate of awakening after treatment was 17.1% among those who were at vegetative state (VS) or in a coma; the rate of awakening after treatment of the MCS patients was higher than those of the patients at VS or in a coma ( χ2=4.255, P=0.039). The recordings of right somatosensory evoked potentials (SSEPs) N20 was positive correlated with curative effect ( r=0.312, P=0.031); and the left visual evoked potentials (VEPs) V100 was positive correlated with curative effect ( r=0.285, P=0.049). There were no statistical significance found between other electrophysiological recordings with curative effect. Conclusion:CNPVSS can be an important tool to predict the outcome of the rehabilitation treatment combined with HBO for the patients with chronic disorder of consciousness, and the recordings of SSEPs and VEPs also are of a certain reference value in predicting the prognosis.

Objective To study the clinical effect of mouse nerve growth factor in the treatment of patients with traumatic facial nerve injury .Methods From April 2015 to October 2017,60 patients with traumatic facial nerve injury in the People's Hospital of Sanmen County were selected and divided into observation group and control group by completely random assignment method ,with 30 cases in each group.All patients were given dexamethasone ,sodium aescinate and nimodipine treatment ,on this basis,the control group was given mecobalamin treatment ,the observation group was given mouse nerve growth factor treatment .The changes of facial nerve function before treatment were assessed,and the clinical efficacy was compared between the two groups .Results After treatment,the facial nerve function grade in the observation group (Ⅰ18 cases,Ⅱ8 cases,Ⅲ2 cases,Ⅳ0 case,Ⅴ1 case,Ⅵ1 case) was significantly better than those in the control group (Ⅰ 6 cases,Ⅱ4 cases,Ⅲ5 cases,Ⅳ8 cases,Ⅴ4 cases,Ⅵ3 cases),the difference was statistically significant (χ2＝12.87,P＜0.01).The total effective rate of the observation group was 93.33%,which was significantly higher than 70.00% of the control group,the difference was statistically significant (χ2＝7.81,P＜0.05).Conclusion Mouse nerve growth factor in the treatment of patients with traumatic facial nerve injury has important clinical value ,it is helpful to alleviate the clinical symptoms ,improve facial nerve function and clinical cure rate ,it is worthy of clinical application .

Objective To analyze the imaging features of several rare primary renal tumors.Methods The CT and MR images of 1 3 cases with pathologically proved rare primary renal tumors were analyzed retrospectively.The imaging features including location, number,size,shape,margin,density or intensity,internal structures and pattern of enhancement were observed.Results Of the 13 cases,4 were primary renal lymphoma (PRL),which performed as renal hilar mass involving the renal parenchyma in 3 cases and multiple nodules at bilateral kidney in 1 case.3 were hemanyiopericytoma (HA),which located in the renal parenchyma in 1 case and protruded from renal surface in 2 cases.All the HA showed obvious enhancement,with small vessels within the tumor in 2 cases.Two cases of inflammatory myofibroblastic tumor (IMT)were mainly located in renal sinus,among which the renal parenchyma was involved in 1 case. One case with adult Wilms tumor showed mixed heterogeneous signal intensity in both T1-and T2-weighted images,indicating intratumoral hemorrhage.One case of neuroendocrine tumor was located in the renal parenchyma with ipsilateral adrenal and regional lymph node metastasis. One case of metanephric adenoma (MA)demonstrated as renal parenchymal mass with slightly enhancement.One case of meoblastic nephroma (MN)showed as a heterogeneous mass with continuous enhancement.Conclusion The imaging features of rare primary renal tumors are characteristical.It is important to analyze the imaging characteristics carefully in order to improve the diagnostic accuracy.

A molecularly imprinted two-dimensional photonic crystal hydrogel sensor was developed with erythromycin as imprinted molecule, polystyrene two-dimensional photonic crystal as templates, methanol as solvent, methacrylic acid as monomers and ethylene glycol dimethylacrylate as cross-linkers.The imprinted molecule was removed by methanol/acetic acid (9∶1, V/V).The results showed that the diameter of Debye ring increased 6 mm when the concentration of EM changed from 0 to 1×10-6 mol/L.Namely the lattice spacing decreased 30 nm.In addition, the diameter of Debye ring only increased 1.5 and 2.0 mm when the hydrogel immersed in 1×10-6 mol/L roxithromycin (RM) or erythromycin ethylsuccinate (EEs) solution.The result indicated that the sensor had high selectivity and could be used in determination of erythromycin with low cost and easy operation.

Objective To investigate the clinical application of the 2011 edition of China Nanjing Persistent Vegetative State (NPVSS 2011).Methods Three hundred and one patients with vegetative state (VS),persistent vegetative state (PVS) and minimally conscious state (MCS) admitted into hospital from February 22,2011 to May 30,2014 were chosen for the study.Patient conditions and treatment efficacy were assessed by using the NPVSS 2011.Results With regard to conscious state at admission into hospital,109 cases were in VS,65 were in PVS and 127 were in MCS.When discharged from hospital,there were 8 VS cases,72 PVS cases,91 MCS cases,and 130 Ⅲ cases that could carry out more complicated instructions.Of all the cases,164 cases had prominent efficacy,31 were improved,106 were invalid,and 130 cases that had consciousness recovery to the state of Ⅲ.Conclusions The CNPVSS could reflect the changing processes of patient conditions,having the features of being simple and clear,conforming to clinical practice,and above all being easy to master and operate.With this reason,it could be applied to clinical practice.