Chimeric antigen receptor (CAR) T cell shows its significant therapeutic effect in part of leukemia and lymphomas, which indicates that transgenic adoptive cellular immunotherapy may be one of the breakthroughs in treatment of solid tumors and blood diseases. The functional inhibition of CAR endogenous cells in the tumor microenvironment , molecular biology function of molecules, difficulties of CAR T cells in clinical application and the solutions , how to improve the clinical efficacy and to reduce toxic side effects for future cancer immunotherapy in clinic are reviewed in this paper.

Objective To evaluate the therapeutic effect of posterior laminectomy and transfacet discectomy combined with interbody fusion and segment fixation for the treatment of lower thoracic disc herniation.Methods From June 2000 to June 2010,36 cases of lower thoracic disc herniation were treated with method of posterior laminectomy and transfacet discectomy combined with interbody fusion and segment fixation,including 23 males and 13 females,with an average of 42 years old(range,22-61 years old).The courses of disease were from 21 days to 69 months,with an average of 22 months.The lesion locations were T10-11 for 12 cases,T11-12 for 15 cases and T12L1 for 9 cases.Each of the patients underwent X-ray and MR examination,31 of them underwent CT scanning.Twenty-five cases were central protrusion type,7 cases were para-central protrusion type,4 cases were lateral protrusionstype.The clinical results were evaluated by Otanni scored system.Results The operative time was 135-220 min,with average of 155 min.The blood loss was 350-800 ml,with average of 460 ml.All patients were successfully operated without neurological symptoms aggravation and accidents.Cerebrospinal fluid leakage occurred in 12 cases,which was treated by continuous suture or dura patch repair.Two cases with giant disc herniation suffered from muscle strength decrease of lower limbs after surgery,which gradually recovered after drug treatment of hormones,dehydration,high-pressure oxygen and nerve nutrients.Postoperative X-ray examinations showed that there were no internal fixation loosening.The followed-up period was 14 days to 48 months,mean 4 months.According to Otani scored system,there were excellent results in 12 cases,good results in 18 cases and poor results in 1 case.The clinical satisfaction rate was 83.3%.Conclusion Posterior laminectomy and transfacet discectomy combined with interbody fusion and segment fixation is a safe and effective surgical procedure for the treatment of lower thoracic disc herniation.

Objective To investigation the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors in non-small cell lung cancer (NSCLC) and their clinical significances.Methods The serum expression levels of TRAIL in 79 cases of NSCLC and 80 cases of normal subjects were detected by enzyme-linked immunosorbent assay (ELISA).The expressions of TRAIL-R2 and TRAIL-R4 in 42 cases of NSCLC and matched normal tissues were detected by immunohistochemistry.The relationships among TRAIL,TRAIL-R2,TRAIL-R4 and clinicopathologic features of NSCLC were analyzed.Results The expression of TRAIL in NSCLC patients was lower than that in normal human [(994.3 ±293.0)ng/ml vs.(1 141.7 ±266.1)ng/ml,t =3.29,P =0.00].The expression of TRAIL was closely correlated with clinical stage (F =2.28,P =0.00) and differentiated degree (t =5.76,P =0.00).The positive expression rate of TRAIL-R2 in NSCLC was 73.8％ (31/42),significantly lower than that in the normal tissue 100.0％ (42/42) (x2 =3.88,P =0.05).The expression of TRAIL-R2 was closely correlated with clinical stage (x2 =27.89,P=0.00) and differentiated degree (x:=9.50,P =0.00).The positive expression rate of TRAIL-R4 in NSCLC was 81.0％ (34/42),significantly higher than that in the normal tissue 50.0％ (21/42) (x2 =7.34,P =0.01).The expression of TRAIL-R4 was also closely correlated with clinical stage (x2 =17.82,P =0.00) and differentiated degree (x2 =4.47,P =0.03).There was a negative correlation between the expression of TRAIL-R2 and TRAIL-R4 in NSCLC (r =-0.67,P=0.01).Conclusion The decrease of TRAIL and TRAIL-R2 and increase of TRAIL-R4 expression may promote the occurrence and development of NSCLC,and they may provide targets for clinical treatment of NSCLC.

Background and purpose:Metabolic reprogramming occurs during tumor progression,and 1-acylglycerol-3-phosphate O-acyltransferase(AGPAT),as a key enzyme in the de novo synthesis of triacylglycerol(TAG),is closely associated with tumor progression.However,one of the isoforms,AGPAT5,has been studied in cancer in a very limited way,and this study aimed to provide a new perspective on the role of AGPAT5 in hepatocellular carcinoma and its potential molecular mechanisms,providing novel ideas for the diagnosis and treatment strategies of liver cancer.Methods:AGPAT5 was knocked down in a variety of hepatocellular carcinoma cell lines using lentiviral infection,and the effects of AGPAT5 on the functions of hepatocellular carcinoma cell proliferation,migration and resistance to anoikis were detected in vitro by experiments such as Taipan blue counting,scratching,transwell and plate cloning.The wild-type or enzyme activity-deficient form of AGPAT5 was rescued to investigate whether AGPAT5,as a metabolic enzyme,plays a classical role in regulating the migration of hepatocellular carcinoma cells.We constructed a tail vein metastasis model in nude mice to validate the cellular phenotype in vitro from the in vivo level.Immunoprecipitation mass spectrum(IP-MS)identified proteins interacting with AGPAT5 and verified by co-immunoprecipitation(coIP).Protein post-translational modification identification was performed to analyze the potential modification sites of AGPAT5,and in vitro experiments were performed to explore the effects of the point mutation before and after the point mutation on the migration of hepatocellular carcinoma cells.CoIP was performed to explore the binding of AGPAT5 to the interacting protein before and after the mutation of the site.We determined its role in cell phenotype by knocking down interacting proteins.Rescue experiments were used to verify whether AGPAT5 exerts its effects through the interacting protein.We detected the expression levels of AGPAT5 and the interacting protein in wild-type hepatocellular carcinoma cell lines to examine their correlation.Results:Knockdown of AGPAT5 increased the tolerance to serum-free starvation and promoted hepatocellular carcinoma cell migration,but did not affect proliferation and anoikis.However,deletion of enzyme activity did not affect the inhibition of hepatocellular carcinoma cell migration by AGPAT5.Knockdown of AGPAT5 promoted lung and liver metastasis of hepatocellular carcinoma cells in nude mice.AGPAT5 could interact with fibrillarin(FBL),and the interaction was strengthened under serum starvation conditions.Curbing FBL expression inhibited hepatocellular carcinoma cell migration,and the effect was similar to that of overexpression of AGPAT5.Inhibition of FBL expression weakened the promoting effect of AGPAT5 knockdown on hepatocellular carcinoma cell migration;In the hepatocellular carcinoma cell lines examined,AGPAT5 and FBL did not show any correlation at the protein level.The inhibitory effect of AGPAT5 on hepatocellular carcinoma cell migration was attenuated by the K201 site mutation,and the K201 site mutation attenuated the binding of AGPAT5 to FBL.Conclusion:Knockdown of AGPAT5 can significantly enhance the migratory ability of hepatocellular carcinoma cells.AGPAT5 can interact with FBL,and in the absence of serum starvation stimulation,AGPAT5 strengthen its binding to FBL through acetylation of the K201 site,thereby more effectively inhibiting FBL,consequently inhibiting the migration of hepatocellular carcinoma cells.But this inhibitory effect is not derived from the metabolic enzyme activity of AGPAT5,but driven by non-metabolic function.

Objective To identify the sets of lymphocytes that could systematically evaluate immune function of colorectal cancer patients, based on the expression of colorectal cancer T cells, natural killer (NK) cells, and NKT cell surface protein receptors. Methods Peripheral blood samples from 144 patients with colorectal cancer and 87 healthy controls were collected, and the differences in surface receptors of lymphocyte subsets in peripheral blood of patients and healthy controls were analyzed by means of flow cytometry and cell culture. Results Compared with healthy control group, the percentage of peripheral blood total lymphocytes, CD16^brightCD56^dimNK cells and NKT cells decreased in patients with colorectal cancer. The percentage of T cells, CD16^brightCD56^dimNK cells and NKT cell surface inhibitory receptors T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domains (TIGIT) increased; T cells, NK cells, NKT cell surface chemokine receptor C-C motif chemokine receptor 7 (CCR7) slightly decreased. Conclusion There are differences in the proportion of NK cell subsets and the expression profile of surface receptors in peripheral blood of patients with colorectal cancer.
Humans ; Lymphocyte Subsets ; Killer Cells, Natural ; Lymphocyte Count ; Receptors, Chemokine ; Colorectal Neoplasms

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

The laterodorsal tegmentum (LDT) is a brain structure involved in distinct behaviors including arousal, reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear. Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex (VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive (PV) GABAergic cells received preferential projections from local LDT neurons. With regard to the different subtypes of GABAergic cells, a considerable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatin-positive cells than to PV cells. Diverse inputs to the LDT on a system-wide level were revealed.