1.Research Progress in Pyroptosis, Drug Therapy and Immunotherapy in Glioblastoma
Ke TANG ; Ni HUANG ; Qinyou TAN
Chinese Journal of Modern Applied Pharmacy 2024;41(2):287-294
Pyroptosis, a form of inflammatory cell death mediated by the Gasdermins family, promotes the release of inflammatory mediators and activates immune cell populations such as NK cells, T cells and macrophages in the tumor microenvironment(TME) to exert immune-regulating and anti-tumor effects. Glioblastoma(GBM) is the most serious and malignant glioma, and the median survival of patients diagnosed with GBM is less than 2 years, and the presence of the blood-brain barrier makes it difficult to deliver drugs to the brain, thus affecting the effect of drugs against GBM. Therefore, it is important to explore new measures and mechanisms to treat GBM, which has a complex TME with a large number of immune cell populations that are often immunosuppressed by GBM. Cellular pyroptosis as a mode of cell death capable of activating immunity, has the effect of activating the body’s immunity to help reverse TME immunosuppression. This review will focus on the relationship between cell pyroptosis and the immune system, how cell pyroptosis affects the immune cell population of TME in GBM, and the new progress in drug research on cell pyroptosis pathways in GBM treatment, providing new directions and strategies for future clinical treatment of GBM.
2.Progress of CD19-targeted therapy for acute B-lymphoblastic leukemia
Xiusong HUANG ; Ke YANG ; Youjiang TAN ; Kaiming CHEN ; Caiwen DUAN
Journal of Leukemia & Lymphoma 2024;33(6):373-377
Acute B-lymphoblastic leukemia (B-ALL) is the most common type of acute lymphoblastic leukemia. Chemotherapy is the main treatment for most patients, but there are serious side effects. CD19 is generally highly expressed in B-lineage malignancies and plays a key role in B cell signal transduction, activation and development. Therefore, it has become one of the effective targets for treatment of B-cell malignancies. At present, a variety of therapies targeting CD19 have been developed, including antibody drug conjugates, monoclonal antibodies, bispecific antibodies and chimeric antigen receptors cell therapies. This paper reviews the clinical trial progress of CD19-targeted therapy for B-ALL.
3.Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy.
Huiling LIU ; Zhou HUANG ; Hong JIANG ; Ke SU ; Zilin SI ; Wenhui WU ; Hanyu WANG ; Dongxue LI ; Ninghua TAN ; Zhihao ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2023;21(9):682-693
Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.
Animals
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Kidney
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Acute Kidney Injury/chemically induced*
;
Ischemia
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Reperfusion Injury/drug therapy*
;
Autophagy
;
Reperfusion
4.Stability of iodine content in potassium iodate iodized salt in Jilin Province
Xin SHI ; Xiaoqiu ZHAO ; Hongyuan HUANG ; Qiyue TAN ; Ke SUN ; Jinze LI ; Chenye LI ; Zhenwei GAN ; Shuhua ZHAO
Chinese Journal of Endemiology 2022;41(4):290-293
Objective:To study the stability and influencing factors of potassium iodate iodized salt that can be sold in Jilin Province.Methods:In November 2020, 10 large supermarkets were randomly selected in Jilin Province, and two kinds of potassium iodate iodized salts were randomly selected in each supermarket, with five copies of each kind, a total of 100 samples of iodized salt, and the iodine content was determined by spectrophotometry (iodide-starch blue light method). Iodized salt samples were classified according to different salt species (mine salt, sea salt and lake salt) and different production processes (refined salt and non-refined salt). The salt was stored at room temperature, and the iodine content in the salt was measured at 0, 10 and 20 days after opening the packaging. The iodine content attenuation rates of different salt species and different production processes were compared.Results:The mine salt, sea salt and lake salt in iodized salt samples were 45, 45 and 10 portions, respectively. The iodine contents of the 0th day of storage [(19.89 ± 1.38), (20.62 ± 1.91), (19.78 ± 1.01) mg/kg] were compared, and the difference was not statistically significant ( F = 2.57, P = 0.093). On the 10th day, the iodine content of mine salt was lower than that of sea salt and lake salt, and the differences were statistically significant ( P < 0.05); on the 20th day, the iodine content of mine salt was lower than that of sea salt, and the difference was statistically significant ( P < 0.05). There was a significant difference in the iodine content of mine salt stored at 0, 10 and 20 days ( F = 90.62, P < 0.001). The iodine content of sea salt and lake salt on the 20th day was significantly lower than that on the 0th and 10th day, and the differences were statistically significant ( P < 0.05). The iodine content attenuation rates of mine salt, sea salt and lake salt on the 0 - 10 days was compared with that on the 10 - 20 days, and the differences were statistically significant ( Z = 2.24, 2.94, 2.80, P < 0.05). There was a significant difference in the iodine content attenuation rates of mine salt, sea salt and lake salt during the 0 - 10 days of storage ( Z = 24.05, P < 0.001), there was no statistically significant difference in the iodine content attenuation rates on 10 - 20 days ( Z = 5.86, P = 0.053). There was no significant difference in iodine content attenuation rates between refined salt and non-refined salt on 0 - 10, 10 - 20 days ( Z = 1.16, 0.28, P > 0.05). There was no statistical significant difference in the iodine content attenuation rates of refined salt and non-refined salt on the 0 - 10 days compared with those of 10 - 20 days ( Z = 0.76, 1.90, P > 0.05). Conclusions:Iodine loss occurs at 20 days after opening the packaging of iodized salt in Jilin Province. The attenuation of iodine content is less affected by salt species and production processes. It is recommended to eat iodized salt within 20 days after opening the packaging.
5.New discovery and short-term effect analysis of tensor tympani muscle tenotomy for Meniere's disease under otoscope.
Guo Hua SHI ; Tan WANG ; Jin Xia XU ; Shao Feng MOU ; Qing Li HUANG ; Ke Qing YAO ; Li Li GONG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(5):602-606
Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.
Aged
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Female
;
Humans
;
Hyperplasia/pathology*
;
Male
;
Meniere Disease/surgery*
;
Middle Aged
;
Otoscopes/adverse effects*
;
Retrospective Studies
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Tenotomy/adverse effects*
;
Tensor Tympani/surgery*
;
Tinnitus/complications*
;
Vertigo/etiology*
6.Coactivator p300-induced H3K27 acetylation mediates lipopolysaccharide-induced inflammatory mediator synthesis.
Ke HU ; Xiang Yu CAO ; Yu Xian LI ; Ling Li LIU ; Yue Fu CHEN ; Li Jun CHEN ; Min Jiang HUANG ; Bi Feng TAN ; Hui Ming YIN
Journal of Southern Medical University 2022;42(3):321-329
OBJECTIVE:
To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism.
METHODS:
Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq).
RESULTS:
Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level.
CONCLUSION
LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
Acetylation
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Animals
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Inflammation Mediators
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Interleukin-6/metabolism*
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Lipopolysaccharides/pharmacology*
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Mice
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Tumor Necrosis Factor-alpha/metabolism*
7.Repairing the defect of fingernail bed by the second toenail flap with the dorsal bone of the phalange
Wanggao ZHOU ; Shaoxiao YU ; Dongyang LI ; Xuelang YE ; Huixin LIN ; Yaxi TAN ; Lingyu KUANG ; Yuhai KE ; Weini HUANG ; Zhenwei ZHANG
Chinese Journal of Microsurgery 2021;44(1):16-19
Objective:To explore the clinical effect of the second toenail flap with the dorsal bone of the phalange in repairing the defect of fingernail bed.Methods:From January, 2012 to June, 2019, 10 patients with large area of fingernail bed defect were treated by the second toenail flap with bone on the back of the phalanx. The survival of the flap was observed after the operation, and the fracture healing, the shape of the nail and the flexion and extension function of the finger joint were observed in the outpatient follow-up.Results:All flaps of the second toenail survived. The average follow-up period was 8 (4-12) months. The fractured ends of 10 patients' phalanges healed well without nonunion, good appearance of toenail and deformity of toenail. The recovery of hand function was evaluated according to the evaluation standard of upper limb function of Hand Surgery Society of Chinese Medical Association, 9 cases were excellent, and 1 case was good.Conclusion:The second toenail flap with dorsal bone of the phalanx preserved is easy to cut, simple to operate, and has good clinical effect. It is a good method to repair the defect of the fingernail bed.
8.China experts' consensus on preventive and interceptive orthodontic treatments of malocclusions of children.
Xiao-Bing LI ; Quan-Fu YE ; Hong HE ; Hai-Ping LU ; Min ZHU ; Ruo-Ping JIANG ; Shu-Juan ZOU ; Xiang-Long HAN ; Li ZHOU ; Ke CHEN ; Xiao YUAN ; Jun-Mei ZHANG ; Li-Jun TAN ; Chang YIN ; Zhou HE ; Ang LI ; Bin CHENG ; Wen-Hua RUAN ; Fang HUANG ; Juan LIU ; Lan MA ; Rui ZOU ; Fang YANG ; Wei-Bing ZHANG ; Yu-Lou TIAN ; Bei-Zhan JIANG ; Lin-Qin SHAO ; Yang HUANG ; Li-Qin TANG ; Li GAO ; Chen-Chen ZHOU
West China Journal of Stomatology 2021;39(4):369-376
Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child
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China/epidemiology*
;
Consensus
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Dental Care
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Humans
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Malocclusion/prevention & control*
;
Orthodontics, Interceptive
9.Establishment of a new molecular typing method for Treponema pallidum based on TP0136 protein sequence heterogeneity
Ran WEI ; Wujian KE ; Wentao CHEN ; Lingqiao TAN ; Yahui LIU ; Ping LYU ; Tao HUANG ; Jun ZHANG ; Xiaohui ZHANG ; Liuyuan WANG ; Yamin CHE
Chinese Journal of Dermatology 2020;53(7):546-550
Objective:To establish a new molecular typing method for Treponema pallidum (TP) based on TP0136 protein sequence heterogeneity. Methods:The amino acid sequences of TP0136 open reading frame (ORF) of 9 strains of Treponema pallidum ssp. Pallidum (TPA) , 3 strains of Treponema pallidum ssp. Pertenue (TPE) , 1 unclassified simian strain of Treponema Fribourg-Blanc (FB) and 1 strain of Treponema pallidum ssp. Endemicum (TEN) were searched from Genbank, and multiple sequence comparisons were performed to obtain the molecular typing results of TP0136 protein. The TP0136 protein-based molecular typing method was used to classify 23 TPA clinical isolates, which were collected from Dermatology Hospital of Southern Medical University from January 2015 to December 2018, and the typing results were compared with those by the traditional typing method based on the tp0548/Arp/Tpr genes. Results:TP0136 protein was highly heterogeneous in different TP strains. According to the amino acid sequence of TP0136, TPE, FB and TEN strains were divided into 4 subtypes of Ⅰ- Ⅳ, TPA strains were divided into 6 subtypes of Ⅴ-Ⅹ, and TPA clinical strains were classified into 4 subtypes of Ⅶ, Ⅸ, Ⅹ, Ⅺ. Through the traditional typing method described above, 23 TPA clinical strains could be divided into 5 types (13D/d, 14D/f, 14D/g, 15D/f, 16A/e) . By using the TP0136 protein-based typing method combined with traditional typing method, the above clinical strains could be further subdivided into 10 types, and the 14D/f type could be further divided into 3 subtypes by using the TP0136 protein-based typing method.Conclusion:The TP0136 protein-based molecular typing method can be used to distinguish TP species, which is helpful for further improvement of traditional TPA molecular typing.
10.Protective effect and mechanism of ginsenoside Rg1 on H2O2induced hippocampal neurons aging due to down-regulate NOX2 mediated NLRP1 inflammasome activation in vitro
Tan-Zhen XU ; Ya-Li CHEN ; Xiao-Yan SHEN ; Ling-Ling SUN ; Bi-Qiong ZHANG ; Da-Ke HUANG ; Wei-Zu LI
Chinese Journal of Pharmacology and Toxicology 2018;32(4):321-321
OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1 (Rg1) on H2O2-induced hippocampal neurons aging in vitro. METHODS The primary culture hippo-campal neurons(7 d)were randomly placed into six groups:normal control group,H2O2(200 μM)treat-ment group,and H2O2+Rg1(1,5 and 10μM)groups.The neurons were with Rg1(1,5 and 10 μmol·L-1) for 6h. H2O2(200 μmol·L-1) was added to the medium and incubate for 18 h. The Dihydroethidium (DHE) staining was performed for ROS production assessment. The LDH release and Hoechst 33258 were performed to examine the neuronal damage and apoptosis. The immunoblot was used to deter-mine the expression of β-Gal,NOX2,p22phox,p47phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons.The ELISA was performed to detect the levels of IL-1β and IL-18 released in the supernatant in hippocampal neurons.RESULTS Rg1(5 and 10 μmol·L-1)significantly reduced the ROS production, attenuated H2O2-induced neuronal damage and apoptosis (P<0.05, P<0.01). The immunoblot results showed that Rg1(5 and 10 μmol·L-1)treatment significantly decreased the expression of β-Gal,NOX2, p22phox,p47phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons(P<0.05,P<0.01).Additionally, Rg1(5 and 10 μmol·L-1)treatment significantly decreased IL-1β and IL-18 release in the supernatant. CONCLUSION The protective effect of Rg1 in H2O2-induced hippocampal neurons aging may be due to inhibit NOX2-NLRP1 activation.


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