As one of the pivotal immunotherapies, tumor vaccine has increasingly shown its benefits in the treatment of malignant tumors. However, traditional vaccines targeting tumor associated antigen (TAA) are difficult to be promoted on a large scale in clinic, due to immune tolerance and the risk of inducing autoimmune disease. Neoantigen, which doesn’t present in normal cells and originates from tumor somatic mutations, is considered as ideal target for vaccines recently. Personalized neoantigen vaccine developed on the basis of sequencing, which specifically targets neoantigens, is expected to become an important breakthrough in precision medicine of cancer. This paper will elaborate on the concept, characteristics, preparation process and clinical trials of personalized neoantigen vaccine, and we will also discuss the opportunities and challenges that might be encountered during its clinical transformation.

Objective: To observe the sequential changes of collagen fibers in rats with diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC), so as to provide a reference for pathogenesis research of HCC. Methods: Fifty male Wistar rats, weighing 100-120 g, were randomly divided into normal group and HCC model group. The model group was intraperitoneally administered with 50 mg/kg DEN (0.1 mL), twice a week for 4 weeks, then once a week for another 10 weeks. The control group was given normal saline (0.1 mL) in the same manner. Finally the rats were sacrificed; the normal and diseased liver tissues were observed by H-E, Masson and argyrophilic fiber staining. The expression of collagen type I and type III mRNA was detected by fluorogenic quantitative PCR; the expression of matrix metalloproteinase (MMP) was examined by gelatinases spectrometry. Results: Cirrhosiswas found in rats 5 weeks after treatment with DEN and HCC was induced 14 weeks after DEN treatment; collagen deposition in liver tissues increased in a progressive manner, and the collagen contents in the HCC tissues was greatly less than that in the adjacent tissues, showing a decreasing trend. The contents of MMP-2 and MMP-9 in the HCC and adjacent tissues had opposite changes compared with collagen. Conclusion: Collagen deposition in cirrhosis liver tissue is increased during the process of DEN-induced HCC, but it is decreased in HCC tissues in a progressive manner, which indicates that collagen might be degraded during the progression from cirrhosis to HCC.

Objective To investigate the derivation and distribution of nitric oxide synthase (NOS) and its relation with the microvessels in the spinal cord. Methods The microscopic features and ultrastructure of NOS in the spinal cord tissue of rats were observed by immunohistochemistry and immunoelectronmicroscopy. Results NOS immunoreactive interneurons were identified mainly in the intermediolateral cell column, around the central canal and in the dorsal and ventral horn, and many of the NOS-containing neural processes and neurons were closely associated with the spinal cord microvessels. Conclusion The regional distribution of NOS may be indicative of the involvement of nitric oxide (NO) in different function related to movement, sensory processing and visceral regulation, and the ultrastructural features benefit the NO diffusion into the microvessels to regulate the blood flow in the spinal cord.

Objective To explore the molecular mechanism of alveolar bone remodeling by studying the dynamic changes of IL- 1β expression in rat alveolar bone osteoblasts. Methods Rat models of increased bite force of the back teeth were established, and the expression of IL-1β in the alveolar bone osteoblasts were determined by HE staining and immunohistochemistry. Observation of the changes in the histological morphology of the periodontium was conducted microscopically. Rats with normal bite force served as control. Results The increase of bite force (within the physiological limit) induced the widening of the periodontal ligament and the osteogenesis in the alveolar bone. Significant enhancement of IL-1β expression was observed in the osteoblasts of rats with increased bite force, in comparison with that in the rats with normal bite force. Conclusion Increased bite force causes higher expression levels of IL-1β in the alveolar bone osteoblasts, initiating the destruction process of the bone but simultaneously the activation of the ossification, suggesting that IL-1β plays an important role in the regulation of periodontium remodeling in response to changes in the bite force

Objective: To investigate gene expression of inducible nitric oxide synthase (iNOS) in injured spinal cord tissue of rats.Methods: Thirty-six adult Sprague-Dawley rats were divided randomly into six groups: a normal group and five injury groups, six animals in each group. Animals in the injury groups were killed at 2, 6, 12, 24, 48 hours after injury, respectively. A compression injury model of spinal cord was established according to Nystrom B et al, and gene expression of iNOS in spinal cord tissue was examined by means of reverse transcription polymerase chain reaction (RT-PCR).Results: Gene expression of iNOS was not detectable in normal spinal cord tissue but was seen in the injury groups. The expression was gradually up-regulated, reaching the maximum at 24 hours. The expression at 48hours began to decrease but was still significantly higher than that at 2 hours.Conclusions: iNOS is not involved in the normal physiological activities of spinal cord. Expression of iNOS is up-regulated in spinal cord tissue in response to injury and the up-regulation exists mainly in the late stage after injury. Over-expression of iNOS may contribute to the late injury of spinal cord.

Objective To investigate the derivation and distribution of nitric oxide synthase (NOS) and its relation with the microvessels in the spinal cord. Methods The microscopic features and ultrastructure of NOS in the spinal cord tissue of rats were observed by immunohistochemistry and immunoelectronmicroscopy. Results NOS immunoreactive interneurons were identified mainly in the intermediolateral cell column, around the central canal and in the dorsal and ventral horn, and many of the NOS-containing neural processes and neurons were closely associated with the spinal cord microvessels. Conclusion The regional distribution of NOS may be indicative of the involvement of nitric oxide (NO) in different function related to movement, sensory processing and visceral regulation, and the ultrastructural features benefit the NO diffusion into the microvessels to regulate the blood flow in the spinal cord.

Objective To explore the molecular mechanism of alveolar bone remodeling by studying the dynamic changes of IL- 1β expression in rat alveolar bone osteoblasts. Methods Rat models of increased bite force of the back teeth were established, and the expression of IL-1β in the alveolar bone osteoblasts were determined by HE staining and immunohistochemistry. Observation of the changes in the histological morphology of the periodontium was conducted microscopically. Rats with normal bite force served as control. Results The increase of bite force (within the physiological limit) induced the widening of the periodontal ligament and the osteogenesis in the alveolar bone. Significant enhancement of IL-1β expression was observed in the osteoblasts of rats with increased bite force, in comparison with that in the rats with normal bite force. Conclusion Increased bite force causes higher expression levels of IL-1β in the alveolar bone osteoblasts, initiating the destruction process of the bone but simultaneously the activation of the ossification, suggesting that IL-1β plays an important role in the regulation of periodontium remodeling in response to changes in the bite force

OBJECTIVE: To evaluate the safety and efficacy of reverse partial lung resection for treatment of pediatric pulmonary cysts combined with lung abscesses or thoracic abscess. METHODS: We retrospectively analyzed the clinical data of children undergoing reverse partial lung resection for complex pulmonary cysts in our hospital between June, 2020 and June, 2021.During the surgery, the patients lay in a lateral position, and a 3-5 cm intercostal incision was made at the center of the lesion, through which the pleura was incised and the fluid or necrotic tissues were removed.The anesthesiologist was instructed to aspirate the sputum in the trachea to prevent entry of the necrotic tissues in the trachea.The cystic lung tissue was separated till reaching normal lung tissue on the hilar side.The proximal end of the striated tissue in the lesion was first double ligated with No.4 silk thread, the distal end was disconnected, and the proximal end was reinforced with continuous sutures with 4-0 Prolene thread.The compromised lung tissues were separated, and the thoracic cavity was thoroughly flushed followed by pulmonary inflation, air leakage management and incision suture. RESULTS: Sixteen children aged from 3 day to 2 years underwent the surgery, including 3 with simple pulmonary cysts, 11 with pulmonary cysts combined with pulmonary or thoracic abscess, 1 with pulmonary cysts combined with tension pneumothorax and left upper lung bronchial defect, and 1 with pulmonary herpes combined with brain tissue heterotaxy.All the operations were completed smoothly, with a mean operation time of 129 min, an mean hospital stay of 11 days, and a mean drainage removal time of 7 days.All the children recovered well after the operation, and 11 of them had mild air leakage.None of the children had serious complications or residual lesions or experienced recurrence of infection after the operation. CONCLUSION Reverse partial lung resection is safe and less invasive for treatment of complex pediatric pulmonary cysts complicated by infections.
Humans ; Child ; Abscess ; Retrospective Studies ; Lung/surgery* ; Cysts/surgery* ; Bronchi

OBJECTIVE: To investigate the effects of sera from rats fed with tablets (HGT) on endoplasmic reticulum (ER) stress in a steatotic hepatocyte model of free fatty acids (FFAs)-induced nonalcoholic fatty liver disease (NAFLD) and explore the possible mechanism. METHODS: FFAs prepared by mixing oleic acid and palmitic acid at the ratio of 2:1. HepG2 cells were treated with the sera from rats fed with low-, moderate-or high-dose HGT (HGT sera) or sera of rats fed with fenofibrate (fenofibrate sera), followed by treatment with 1 mmol/L FFAs for 24 h to induce hepatic steatosis. Oil red O staining was used to observe the distribution of lipid droplets in the cells. The biochemical parameters including triglyceride (TG), lactated hydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using a commercial kit. The morphological changes of the ER in the cells were observed using transmission electron microscopy. The protein/mRNA expressions of ER stress-related signal molecules including GRP78, PERK, p-PERK, ATF6, ATF4, CASPASE-12, CHOP, XBP-1, PKC, and p-PKC-δ were detected using Western blotting and/or quantitative real-time PCR (qRT-PCR). The changes in the protein expressions of GRP78, p-PERK, CASPASE-12 and CHOP were also detected in cells with transient transfection of PKC-δ siRNA for PKC-δ knockdown. RESULTS: Compared with the control cells, the cells treated with FFAs showed significantly increased levels of TG, AST, and ALT ( < 0.05). Compared with FFAs-treated cells, the cells pretreated with HGT sera or fenofibrate sera all showed significantly decreased TG, AST and ALT levels ( < 0.05), reduced accumulation of the lipid droplets ( < 0.05), and lowered protein or mRNA expression levels of GRP78, p-PERK, ATF6, ATF4, CHOP, CASPASE-12, XBP-1 and p-PKC-δ ( < 0.05). PKC-δ knockdown caused significantly reduced protein expressions of GRP78, p-PERK, CASPASE-12 and CHOP in the cells with FFA-induced hepatic steatosis ( < 0.001); treatment with high-dose HGT serum more significantly reduced the expressions of GRP78 ( < 0.001) and P-PERK ( < 0.01) in FFAs-induced cells with PKC-δ knockdown. CONCLUSIONS HGT serum can effectively prevent FFAs-induced steatosis in HepG2 cells by alleviating ER stress, in which PKC-δ may act as an important target.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Endoplasmic Reticulum ; ultrastructure ; Endoplasmic Reticulum Stress ; drug effects ; Fatty Acids, Nonesterified ; Fenofibrate ; administration & dosage ; Hep G2 Cells ; Humans ; Hypolipidemic Agents ; administration & dosage ; Microscopy, Electron, Transmission ; Non-alcoholic Fatty Liver Disease ; blood ; etiology ; prevention & control ; RNA, Messenger ; blood ; Rats ; Serum ; Tablets ; Triglycerides ; blood

Aged ; Catheter Ablation ; methods ; Female ; Hematoma ; surgery ; Humans ; Thrombosis ; surgery