1.Metabolic regulation of macrophage function
Kefu WU ; Guoguang ZHENG ; Xiaotong MA ; Yuhua SONG
Journal of Leukemia & Lymphoma 2023;32(5):264-269
Macrophages have plastic and diverse phenotypes and functions, and they play different roles in host defense, tissue homeostasis and repair, development, and various pathologic processes. Although the classically activated macrophage (M1) and alternatively activated macrophage (M2) phenotypes are widely accepted, most macrophages under physiologic and pathologic conditions are polarized to a continuum of states between the M1 and M2 extreme phenotype poles. In recent years, research on the regulatory mechanisms of M1 and M2 macrophages has made great progress, preliminarily elucidating the role of cellular metabolic reprogramming in macrophage polarization and the role of glycolytic enzymes in controlling inflammatory macrophages. The knowledge lays the foundation for elucidating the mechanisms in the regulation of macrophage functional phenotypes. Tumor-associated macrophages play important roles in the development of tumors. The macrophages in the microenvironment of hematologic malignancies have unique features, and a deep study on them will provide new thoughts and clues for clinical diagnosis and therapeutics.
2.A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy.
Aihua WU ; Afeng YANG ; Qinli TONG ; Guoguang WEI ; Sihang ZHANG ; Sheng YU ; Chen ZHANG ; Jiaojiao XU ; Wei LU
Acta Pharmaceutica Sinica B 2023;13(7):3121-3136
Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.
3.The mechanism of tumors as aging-related diseases
Kefu WU ; Guoguang ZHENG ; Xiaotong MA ; Yuhua SONG
Journal of Leukemia & Lymphoma 2021;30(10):577-580
The tumors originate from transformation cells caused by gene mutations. These cells are frequently kept at dormant state or detected and cleared by the immune surveillance. The research data show that the hallmarks of tumors and aging share many similarities, which is the biological basis for tumors as aging-related diseases. With the increase of tumor initiation cells and the decline of immune function in the elderly, the morbidity and mortality of tumors steadily increase. The core mechanisms are inflammaging and immunosenescence in the elderly. This article reviews recent advances in the field of tumorigenesis, inflammaging and immunosenescence, which elucidates the hypothesis and possible mechanism that tumors are aging-related diseases.
4.Clinical efficacy of perihilar surgical techniques for diffuse hepatolithiasis
Jia LI ; Guoguang LI ; Maitao HU ; Chao JIANG ; Chao GUO ; Yi LIU ; Meifu CHEN ; Jinshu WU ; Chuang PENG ; Wei CHENG
Chinese Journal of Digestive Surgery 2021;20(8):883-889
Objective:To investigate the clinical efficacy of perihilar surgical techniques for diffuse hepatolithiasis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 122 patients with diffuse hepatolithiasis who were admitted to Hunan Provincial People's Hospital from January 2010 to December 2015 were collected. There were 39 males and 83 females, aged from 21 to 82 years, with a median age of 51 years. After perihilar hepatectomy, the first, second and third divisions of hepatic ducts were opened longitudinally. Strictures in the bile ducts were relieved by stricturoplasty and internal bile duct anastomosis, and stones were removed by multiple methods under direct vision. After resection of severe atrophic liver segment along the plane of hepatic atrophy or bile duct stricture, T-tube or hepaticojejunos-tomy was used for internal drainage. Observation indicators: (1) surgical situations; (2) stricture relief and stone removal. (3) Follow-up. Follow-up was conducted by Wechat, telephone interview or outpatient examination. Patients were followed up once every 3 months in the postoperative 1 year through liver function and abdominal B-ultrasound examination. Subsequently, liver function and abdominal B-ultrasound were reexamined once a year. Magnetic resonance cholangiopancreato-graphy and computed tomography were performed when cholangitis or stone recurrence was suspected to analyze stone recurrence and patient survival. The follow-up was up to July 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical situations: for the 122 patients, the operation time, hepatic portal occlusion time, volume of intraoperative blood loss, duration of postoperative hospital stay were (253±71)minutes, 15 minutes(range, 14?38 minutes), 200 mL(range, 100?1 100 mL), (12±5)days. Postoperative complications occurred to 40 of 122 patients. There were 9 cases of incision infection, 8 cases of bile leakage (5 cases of bile leakage at hepatic section, 3 cases of choledochojejunostomy leakage), 8 cases of septicemia, 7 cases of pleural effusion, 5 cases of abdominal abscess, 3 cases of liver failure, 1 case of biliary bleeding. Some patients had multiple complications. Among the 122 patients, 2 cases died after operation, including 1 case of postoperative liver failure and 1 case of disseminated intravascular coagulation caused by biliary-intestinal anastomotic leakage complicated with sepsis. Patients with bile leakage and abdominal abscess were improved after puncture and drainage under the guidance of B-ultrasound. Patients with cholangiojejunal anastomotic bleeding were embolized through the right hepatic artery. The other complications were improved after conservative treatment. (2) Stricture relief and stone removal: 85 of 88 patients with biliary stricture were relieved, with the stricture relief rate of 96.59%(85/88). Among the 122 patients, 103 cases had stones completely removed and 19 cases had residual stones. The immediate stone clearance rate was 84.43%(103/122). Of the 19 patients with residual stones, choledochoscopy was refused in 3 cases and choledochoscope lithotripsy was performed in 16 cases, of which 7 cases were removed and 9 cases were still residual stones. Of the 122 patients, 110 cases were finally removed stones, 12 cases were eventually residual stones, and the final stone clearance rate was 90.16%(110/122). (3) Follow-up: among the 122 patients, 120 cases including 110 cases with find stone removal and 10 cases with residual stones were followed up for (78±14)months. The 1-, 3, 5-year stone recurrence rates of 120 patients were 0.83%(1/120), 6.67%(8/120), 9.17%(11/120), respectively. The 1-, 3-, 5-year stone recurrence rates of 110 patients with final stone removal were 0, 5.45%(6/110), 5.45%(6/110), respectively. The number of cases with stone recurrence at postoperative 1-, 3- and 5-year of 10 patients with residual stones were 1, 2, 5 cases, respectively. Of 120 patients with follow-up, 1 case died of end-stage liver disease, and the other patients had good survival.Conclusion:Perihilar surgical techniques for diffuse hepatolithiasis is safe and effective.
5.Cellular composition and function of B-cell lymphoma
Kefu WU ; Guoguang ZHENG ; Xiaotong MA ; Yuhua SONG
Journal of Leukemia & Lymphoma 2020;29(6):321-325
B-cell lymphomas are a group of highly heterogeneous malignancies. The phenotypes of different subtypes depend on the differentiation stage and genetic changes of B-cell, which reflects in the immunophenotype, karyotype and tumor microenvironment changes, especially the differences in the cellular composition of microenvironment. This article reviews the characteristics of B-cell lymphoma cells and the cellular composition of microenvironment, discusses the role of tumor microenvironment cells in the occurrence and development of B-cell lymphoma, which provides new ideas for clinical diagnosis and treatment.
6. Mechanism of herpes virus latent infection and its significance
Kefu WU ; Xiaotong MA ; Guoguang ZHENG ; Yuhua SONG
Journal of Leukemia & Lymphoma 2018;27(5):257-262
Human herpes virus (HHV) spreads widely in a latent-infected way. HHV is divided into 3 kinds and 8 types. Herpes simplex caused by HHV-1 and HHV-2, varicella-zoster caused by HHV-3 and Epstein-Barr virus (EBV) known as HHV-4 and recognized firstly as human tumor virus, are well known in the field of virology. With the application of hematopoietic stem cell transplantation , cytomegalovirus (HHV-5) and HHV-6 have gained an increasing attention. The biological characteristic of HHV is latent infection in a long time and HHV can be reactivated in some immunocompromised individuals. Clarification of latent infection mechanism will help provide targets for therapy and lay a foundation for clinical treatment. This paper summarizes the clinical significance of HHV infection. Taking the mechanism of EBV latent infection as an example, the pathway and significance as well as strategy of co-evolution of organism and virus will be discussed in order to provide clues for prevention and therapy.
7.Current opinions on the viral etiology of leukemia
Kefu WU ; Guoguang ZHENG ; Xiaotong MA ; Yuhua SONG
Chinese Journal of Clinical Oncology 2018;45(7):325-330
Half a century ago,it was confirmed that leukemia could be induced by retroviruses in some animals.There are numerous en-dogenous retroviruses in the human genome.However,retrovirus-related human adult T-cell leukemia is only endemic in some local areas. Recently,an extensive study on apolipoprotein B mRNA editing enzyme catalytic polypeptide 3(APOBEC3)family members has revealed the resistance mechanism in human to retrovirus-induced leukemia.The Epstein-Barr virus is widely spread in the human population and exists as a latent infection in the human body for a long time.It is closely associated with the occurrence and development of some lymphomas and solid tumors,indicating its tumorigenicity.The relationship between other viral infections and leukemia/lymphoma remains unclear. The interaction may be mediated by complex,multistep,and indirect networks,which need to be further illuminated.
8.Ambiguity results distribution and its solutions of HLA-A, B and DRB1 sequence-based typing
Hengcong LI ; Yongfeng PEI ; Huini HUANG ; Guoguang WU
Chongqing Medicine 2017;46(13):1759-1761
Objective To investigate the ambiguity results distribution of HLA-A,B and DRB1 gene sequence-base typing in Guangxi population and to propose the way to resolve.Methods HLA-A,B and DRB1 genes of 1 000 donors in the Guangxi branch bank of China'bone marrow bank were genotyped by PCR-SBT,and then the ambiguity results distribution of the three loci was analyzed.The typing ambiguities resultswere resolved by high-resolution polymerase chain reaction-sequence-specific primers(PCR-SSP) and group specific sequencing primer(GSSP) methods,respectively.Results Among 1 000 samples,at least 1 locus in HLA-A,B and DRB1 genes in 96.7% samples appeared the ambiguity results,in which the proportions of HLA-A,B and DRB1 loci appearing ambiguity results were 65.7 %,58.8 % and 77.2 % respectively.For the samples of detected ambiguity results,single using the GSSP method could resolve the ambiguity typing results of 87.37% HLA-A,93.54% HLA-B and 60.49% HLA-DRB1,using high-resolution PCR-SSP could resolve the ambiguity typing results of 12.63 % HLA-A,4.76 % HLA-B and 15.29 % HLA-DRB1,and the rest 1.70 % HLA-B and 24.22 % HLA-DRB1 ambiguity results were resolved by both GSSP and high-resolution PCR-SSPs method.Conclusion GSSP and high-resolution PCR-SSPs methods have high abilities to solve HLA ambiguity results both locate inside and outside the sequencing region,respectively.GSSP and high-resolution PCR-SSPs methods are supplement for each other,which can effectively resolve the problem of ambiguity results in high resolution HLA typing.
9.Clinical study of accelerating orthodontic tooth movement by minimally invasive corticotomy
Ying WU ; Guoguang PENG ; Yangxi CHEN ; Shiling FANG
Journal of Practical Stomatology 2017;33(2):239-243
Objective:To evaluate the influence of minimally invasive corticotomy on the treatment time and molar anchorage of adult orthodontic extraction cases.Methods:60 adult cases of Angle Class Ⅰ crowding malocclusion were devided into 3 groups (n =20) and treated by orthodontic treatment wtih minimally invasive corticotomy(group A),orthodontic treatment with classic modified corticotomy(group B) and routine orthodontic treatment (group C) respectively.Time needed for leveling and alignment,space closure,delicate adjustment,total treatment time and mesial sagittal antedisplacement of first molar anchorage were compared among the 3 groups.Results:Time needed for leveling and alignment of orthodontic treatment of group A,B and C was (5.64 ± 2.57),(4.91 ± 3.31) and (8.87 ± 3.75) months respectively(C vs A or B,P < 0.01).Time needed for space closure of group A,B and C was (6.84 ± 2.69),(6.64 ± 3.87) and (8.63 ± 3.29) months respectively(C vs A or B,P <0.01).Time needed for delicate adjustment showed no significant difference among the 3 groups(P > 0.05).Total treatment time of group A,B and C was (16.07 ± 6.21),(15.77 ± 5.11)and (21.94 ± 5.74) months respectively (C vs A or B,P < 0.01).There was on statistical difference of mesial sagittal antedisplacement of first molar anchorage among the 3 groups.Conclusion:Minimally invasive corticotomy can shorten the orthodontic treatment time,but can not decrease the retraction resistance of the anterior teeth.
10.Reactivation of human herpesvirus 6 and its clinical significance
Kefu WU ; Guoguang ZHENG ; Xiaotong MA ; Yuhua SONG
Journal of Leukemia & Lymphoma 2017;26(5):257-260
Human herpesvirus 6 (HHV-6) is recognized as a ubiquitous dsDNA virus in human with widespread cell tropism in vivo, which could induce lifelong latent infection and be reactivated in some immunocompromised individuals leading to serious diseases. With the increasing application of hematopoietic stem cell transplantation (HSCT), it is obvious that HHV-6 reactivation has a close relationship with several complications including encephalitis after transplantation. On the other hand, among about 1 % infected people, HHV-6 and subtelomeric region of cell chromosomes in the state of endogenous persistent infection play a part in activated virus infection. As the detection methods make a great progress in HHV-6 detection, clinical data reveals the relationship between HHV-6 reactivation and lots of chronic diseases, especially lymphoma, leukemia as well as some chronic hematopoietic and immunological diseases.

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