1.Clinical transformation of personalized neoantigen vaccine: opportunities and challenges
Chinese Journal of Cancer Biotherapy 2019;26(1):16-21
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.
2. Sequential study of liver collagen fibers in diethylnitrosamine-induced hepatocarcinogenesis in rats
Academic Journal of Second Military Medical University 2014;35(6):626-630
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.
3.Reverse partial pulmonary resection: a new surgical approach for pediatric pulmonary cysts.
Libo YANG ; Haishen ZHOU ; Xuejun OUYANG ; Fuwei ZHANG ; Jing FENG ; Jiaqing ZHANG
Journal of Southern Medical University 2023;43(4):649-653
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
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Child
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Abscess
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Retrospective Studies
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Lung/surgery*
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Cysts/surgery*
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Bronchi
4.Effects of sera of rats fed with tablets on endoplasmic reticulum stress in a HepG2 cell model of nonalcoholic fatty liver disease.
Miaoting YANG ; Zhijuan CHEN ; Chunxin XIAO ; Waijiao TANG ; Beijie ZHOU
Journal of Southern Medical University 2018;38(11):1277-1287
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
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blood
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Animals
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Aspartate Aminotransferases
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blood
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Disease Models, Animal
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Drugs, Chinese Herbal
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administration & dosage
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Endoplasmic Reticulum
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ultrastructure
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Endoplasmic Reticulum Stress
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drug effects
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Fatty Acids, Nonesterified
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Fenofibrate
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administration & dosage
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Hep G2 Cells
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Humans
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Hypolipidemic Agents
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administration & dosage
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Microscopy, Electron, Transmission
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Non-alcoholic Fatty Liver Disease
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blood
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etiology
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prevention & control
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RNA, Messenger
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blood
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Rats
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Serum
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Tablets
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Triglycerides
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blood
5.Intramural Hematoma versus Thrombus: Radiation-induced Heart Disease Results in Mass Formation after Radiofrequency Ablation.
Li-Yun FENG ; Xu-Dong SONG ; Lei LIU ; Xian-Bao WANG ; Peng LIU ; Xiu-Li ZHANG ; Yi-Jun ZHOU ; Dong-Dong QUE ; Wen-Jie YU ; Yuan-Qing LI ; Ping-Zhen YANG
Chinese Medical Journal 2016;129(22):2762-2764
Aged
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Catheter Ablation
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methods
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Female
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Hematoma
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surgery
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Humans
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Thrombosis
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surgery
6.Expression of human G6PD gene in K562 cells mediated by retroviral vector.
Ling ZHOU ; Kunyuan GUO ; Jiangqi LI
Chinese Journal of Experimental and Clinical Virology 2002;16(4):361-363
OBJECTIVEThis study aimed to investigate the feasibility of gene therapy for severe G6PD deficiency.
METHODSThe recombinant retroviral vector bearing normal human G6PD cDNA was constructed and transferred into the erythroleukemia cell line K562. Author identified the integration of NeoR gene in the targeted cellular DNA by means of specific PCR. Quantitative method was used to measure the expression of G6PD in the targeted cells.
RESULTSConstruction of the recombinant retroviral vector was successfully established. PCR indicated the integration of NeoR gene in the targeted genomic DNA of the cells. The vector was also shown to be capable of expressing the foreign gene compared to the control (P<0.01).
CONCLUSIONSThe recombinant retroviral vector is competent for transferring and expressing the G6PD gene.
Gene Expression ; Genetic Therapy ; Genetic Vectors ; Glucosephosphate Dehydrogenase ; genetics ; Glucosephosphate Dehydrogenase Deficiency ; therapy ; Humans ; K562 Cells ; Retroviridae ; genetics ; Transfection
7.Establishment and evaluation of rabbit model of fecal incontinence.
Zong-Hai HUANG ; Xiao-Jing FU ; Zhou LI
Journal of Southern Medical University 2009;29(6):1170-1172
OBJECTIVETo establish and evaluate a rabbit model of fecal incontinence.
METHODSTwelve normal adult male New Zealand rabbits were randomly divided into experimental group and control group. The nerve innervating the external anal sphincter, namely the fourth sacral nerve, was functionally located and selectively damaged with local injection of 50 g/L ropivacaine in the experimental group, and normal saline injection was administered in the control group. The changes in the resting anal pressure was examined before and after the surgery, and the electromyogram (EMG) of the external anal sphincter was recorded for comparison with the pathological changes of the fourth sacral nerve.
RESULTSCompared with the control group, the experimental group exhibited significantly decreased resting anal pressure after the surgery. The EMG of the experimental group showed abnormal nerve conduction velocity of the fourth sacral nerve, suggesting successful nerve block. Transmission electron microscope revealed irreversible pathological changes in the ultrastructure of the axons of the fourth sacral nerve.
CONCLUSIONThis method allows successful establishment of fecal incontinence in rabbits, which facilitates further in vivo study of artificial sphincters for treatment of anal incontinence.
Amides ; administration & dosage ; Anal Canal ; physiopathology ; Animals ; Disease Models, Animal ; Electromyography ; Fecal Incontinence ; Lumbosacral Plexus ; Male ; Nerve Block ; Rabbits ; Random Allocation
8.Nitric oxide synthase gene expression in injured spinal cord tissue.
Chenglong LIU ; Anmin JIN ; Chusong ZHOU ; Bin CHEN
Chinese Medical Journal 2002;115(5):740-742
OBJECTIVETo investigate gene expression of three nitric oxide synthase isozymes in injured spinal cord tissue.
METHODSThirty-six adult SD rats were randomly divided into six groups: a normal group and five injury groups, with six per each group. Animals in the injury groups were sacrificed at 2, 6, 12, 24, 48 h after injury. A compression injury model on the spinal cord was made according to Nystrom B et al and gene expression of the three NOS isozymes were examined by reverse transcription polymerase chain reaction (RT-PCR).
RESULTSGene expression of nNOS and eNOS were detectable in the normal group and were up-regulated quickly after injury, reaching a maximum at 6 h: (0.633 +/- 0.012) and (1.236 +/- 0.207). Gene expression of iNOS was detectable only in the injury groups and it was gradually up-regulated after injury, reaching a maximum at 24 h: (1.043 +/- 0.049).
CONCLUSIONInjury to the spinal cord leads to early up-regulation of cNOS and late up-regulation of iNOS. Different NOS isozymes may play different roles in secondary spinal cord injury.
Animals ; Female ; Gene Expression Regulation, Enzymologic ; Male ; Nitric Oxide Synthase ; genetics ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; RNA ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Spinal Cord ; enzymology ; pathology ; Spinal Cord Injuries ; enzymology ; genetics
9.A survey on distribution and drug resistance of pathogens causing nosocomial infection in general intensive care unit
Haifeng LIU ; Zhujiang ZHOU ; Jingqing HU ; Nina HUANG ; Wenzhao CHEN ; Ruiqiu ZHU ; Jianhai LU ; Yanhe CHEN ; Jiahui MAI ; Yongpeng SU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;(4):382-385
Objective To investigate the distribution and drug resistance of pathogens in intensive care unit (ICU) so as to provide scientific basis for antibiotic adoption and the prevention and control of nosocomial infections. Methods The various specimens collected from the patients admitted into ICU in the First People's Hospital of Shunde Affiliated to the South Medical University from January 2007 to December 2014 were used to isolate the pathogens that might cause nosocomial infections and retrospectively analyze their clinical distribution and drug resistance. Kirby-Bauer paper diffusion and minimal inhibitory concentration (MIC) methods were applied to test the drug sensitivity, and according to National Committee for Clinical Laboratory Standards/Clinical and Laboratory Standards Institute (NCCLS/CLSI) standard, the results were identified.Results The sputum was the major specimen source in ICU, accounting for 68.8%, followed by urine (12.4%) and blood (6.8%). All together 557 pathogens in ICU causing nosocomial infections were isolated of which there were 377 gram-negative (G-) bacilli (67.7%), 103 gram-positive (G+) cocci (18.5%), and 77 fungi (13.8%). Among G- bacilli, the top three wereAcinetobacter baumannii (34.5%), Klebsiella pneumonia (17.8%), andPseudomonas aeruginosa (13.0%). Beside carbapenem, the drug resistance rates of Acinetobacterbaumannii to other antibiotics were more than 40%. The main G+ coccus causing nosocomial infection wasSaphylococcus aureus (36.9%) in ICU. The drug resistance rates ofSaphylococcus aureus to penicillin, gentamicin and erythromycin were higher than 50%. In 77 fungus strains,Candida albicans was ranked the first, accounting for 41.6%.Conclusion The main infection site in ICU is primarily respiratory tract, the G- bacilli are the predominate pathogens, and the drug resistance to antibiotics found in this report is serious, so clinically, the antibiotics should be properly used to avoid the occurrence of pathogenic strain with drug tolerance.
10.Phase IIa clinical trail of hemocoagulase acutus for injection.
Jun-jie ZHOU ; Zong-hai HUANG ; Jin-long YU ; Zhou LI ; Guang-jun ZHOU
Journal of Southern Medical University 2007;27(5):644-646
OBJECTIVETo evaluate the efficacy and safety of hemocoagulase acutus for injection and determine its curative dose.
METHODSForty-five patients on abdominal surgeries were randomly allocated into 2 study groups and 1 control group. Thirty minutes before the operation, the patients in the study groups received intravenous hemocoagulase acutus at 1 U and 2 U, respectively, and control group had no treatment. The hemostatic time, hemorrhagic volume, and hemoagglutination were observed in all the groups.
RESULTSThe average hemorrhagic volume and hemorrhagic volume per square were significantly lower in the two study groups than in the control group (P<0.05), and the average hemorrhagic volume per square were significantly lower in study group 2 U than in the 1 U group (P<0.05). No significant differences were found in adverse effects between the 3 groups.
CONCLUSIONHemocoagulase acutus for injection has good hemostatic effect for controlling capillary hemorrhage at the abdominal incisions and can be safely used in the surgical patients.
Abdomen ; surgery ; Adolescent ; Adult ; Aged ; Agkistrodon ; metabolism ; Animals ; Batroxobin ; administration & dosage ; therapeutic use ; Blood Coagulation ; drug effects ; Blood Loss, Surgical ; prevention & control ; Hemostasis, Surgical ; methods ; Hemostatics ; administration & dosage ; therapeutic use ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Treatment Outcome ; Young Adult