1.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
2.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
3.Application and progress of distal transradial access for coronary heart disease
Meng-Yang CAI ; Qing XIA ; Hui-Hui ZHANG ; Hong YUAN
Chinese Journal of Interventional Cardiology 2024;32(7):390-395
The incidence of coronary heart disease increases annually,percutaneous coronary intervention(PCI)is one of the effective treatment methods of coronary heart disease,and the transradial artery has been the most common vascular access site utilized for this procedure.Moreover,under the new era of comfortable medical treatment,the distal transradial access(dTRA)path is a new surgical path for coronary angiography and percutaneous coronary intervention,which may be replace the traditional transradial access(TRA)pathway because of its merits of less complications and higher comfort level.However,as an emerging method,the distal radial artery also has some drawbacks,such as vascular distortion,small diameter,which may cause puncture failure,vascular spasm,and difficulty in guiding wires.This article reviews on clinical application value and progress of DRA for percutaneous coronary intervention,and aiming to promote its promotion in cardiac interventionalists to benefit PCI patients.
4.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.
5.Primary Extranodal Diffuse Large B-Cell Lymphoma in the Rituximab Era:a Single-Center Retrospective Analysis
Lan YANG ; Li-Xia CAO ; Hui-Juan REN ; Yan-Qiu HAN
Journal of Experimental Hematology 2024;32(4):1121-1128
Objective:To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma(DLBCL)in the rituximab era.Methods:The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab,cyclophosphamide,epirubicin,vincristine,prednisone(R-CHOP)or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed.The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed,Logistics regression model was used to analyzed the influencing factors of patients prognosis.Results:A total of 237 patients were enrolled,of which 54.4%(129 cases)were primary extranodal sources of DLBCL,and the most common extranodal sites were as follows:stomach(19.4%),colon(14.7%),tonsils(12.4%),skin/muscle(9.3%),central(7.7%),nasal/nasopharynx(6.2%),bone marrow(5.4%),testes(4.7%).The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow,central,liver,gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin,and the difference was statistically significant(PFS:65.2%vs 76.7%,P=0.008;OS:82.6%vs 88.3%,P=0.04).Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score>3(OR:0.142,95%CI:0.041-0.495,P=0.002),non-germinal center source(OR:2.675,95%CI:1.069-6.694,P=0.036),and DEL patients(OR:0.327,95%CI:0.129-0.830,P=0.019).An NCCN-IPI score>3 was the only independent adverse prognostic factor for PFS(OR:0.235,95%CI:0.116-0.474,P<0.001).Conclusion:Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement,and the overall prognosis is worse than that of patients with lymph node origin.NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.
6.Halving Time of BCR-ABL Transcripts as a Precise Predictor for Deep Molecular Response in Patients with Chronic Myeloid Leu-kemia Treated with TKI
Lan YANG ; Li-Xia CAO ; Hui-Juan REN ; Yan-Qiu HAN
Journal of Experimental Hematology 2024;32(5):1349-1355
Objective:To investigate the early predictive value of halving time(HT)of BCR-ABLIS for deep molecular response(DMR)in patients with chronic myeloid leukemia(CML)treated with tyrosine kinase inhibitor(TKI).Methods:The continuous data of newly diagnosed CML patients with complete case data and first-line imatinib treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2022 were retrospectively analyzed.Combined with the clinical characteristics of the patients and the efficacy analysis at each time point,a logistic regression model was used to explore the independent influencing factors of DMR,and combined HT of BCR-ABLIS with BCR-ABLIS level at 3 months to predict DMR of the patients.Results:Univariate and multivariate analyses showed that HT and 3-month BCR-ABLIS levels were independent influencing factors for MR4,MR4.5,and stable MR4.5(P<0.05).ROC curve analysis determined that the best cut-off value of HT was 28 days.Compared with patients with HT>28 d,patients with HT ≤28 d were more likely to obtain DMR at 2,3,and 5 years,respectively(74.2%vs 27.3%,71.2%vs 22.7%,and 63.6%vs 25.0%,all P<0.001).The patients were divided into 4 groups according to BCR-ABLIS levels at 3 months and HT.Kaplan-Meier analysis showed that the patients in the BCR-ABLIS ≤10%and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS≤10%and HT>28 d group(P<0.05);Patients in the BCR-ABLIS>10%and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS>10%and HT>28 d group(P<0.05).Conclusion:In addition to BCR-ABLIS level,HT of BCR-ABLIS can be used as another important predictor of treatment efficacy in CML patients.The combination of BCR-ABLIS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.
7.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
8.Protective effects of Tongxie Yaofang on intestinal mucosa in rats with ulcerative colitis due to Liver Depression and Spleen Deficiency Pattern
Li-Hui FAN ; Xiang-Dong ZHU ; Zhi-Gang WANG ; Xia YANG
Chinese Traditional Patent Medicine 2024;46(7):2189-2195
AIM To explore the protective effects of Tongxie Yaofang on the intestinal mucosa of rats with ulcerative colitis(UC)due to Liver Depression and Spleen Deficiency.METHODS The rats were randomly divided into the blank group,the model group,the mesalazine group(0.4 g/kg),the high-dose,medium-dose and low-dose Tongxie Yaofang groups(20.8,10.4,5.2 g/kg).The rat models were induced by DNBS/ethanol solution enema,restraint stress and inappropriate diet.All rats had their serum levels of IL-8 and TNF-α detected by ELISA;their colonic pathological changes observed by HE staining;and their colonic TLR4,MyD88 and NF-κB p65 mRNA and protein expressions detected by RT-qPCR,Western blot and immunohistochemistry method.RESULTS Compared with the model group,all theother groups intervened with the medical agents displayed lower serum levels of TNF-a and IL-8(P<0.05,P<0.01);decreased colonic expressions of MyD88 and NF-κB p65 mRNA and protein(P<0.05,P<0.01).The mesalazine group and the high-dose and medium-dose Tongxie Yaofang groups shared decreased colonic expression of TLR4 mRNA and protein(P<0.05,P<0.01);and the low-dose Tongxie Yaofang group demonstrated decreased colonic TLR4 protein expression(P<0.05).CONCLUSION Tongxie Yaofang may inhibit the inflammatory reaction of the rats and repair their intestinal mucosal barrier damage via TLR4/MyD88/NF-κB signal pathway.
9.Correlation analysis of functional constipation and its related factors with acute appendicitis in children
Na FAN ; Anding ZHANG ; Chunhui WANG ; Lingchao ZENG ; Yuanxia LI ; Yan LIN ; Xia YU ; Yalong ZHANG ; Yaxing HUI ; Yang DAI ; Xun JIANG
Chinese Pediatric Emergency Medicine 2024;31(8):597-601
Objective:To explore the correlation between functional constipation (FC)and its related factors with acute appendicitis(AA)in children,so as to provide a reference for the prevention and clinical diagnosis and treatment of children with AA. Methods:A case-control study was conducted on 170 children diagnosed with AA in the Department of Pediatrics,the Second Affiliated Hospital of Air Force Military Medical University,from August 2022 to March 2023,and 170 non-AA children during the same period were selected as control objects.The clinical data,incidence of FC,symptoms related to FC,Bristol stool classification,past constipation history and other information were compared between two groups.Results:The incidence of FC in 170 children with AA was 22.9%(39/170),which was significantly higher than 10.6%(18/170)in the non-AA group( P<0.01);For children under four years old,the proportion of faecal retention in AA group was higher than that in non-AA group(25.6% vs. 9.3%, P<0.05);For children ≥ 4 years old,the proportion of faecal retention and dyschezia in AA group were higher than those in non-AA group(28.2% vs. 6.9%,29.0% vs. 16.4%,respectively,all P<0.05).The proportion of past constipation history in AA group was higher than that in non-AA group(29.4% vs.14.1%).The duration of constipation in AA group was longer than that in non-AA group [0.00(0.00,1.25)month vs. 0.00(0.00,0.00)month,all P<0.01].The proportion of children with low Bristol stool classification in AA group was higher than that in non-AA group( P<0.01).Multivariate Logistic regression analysis showed that faecal retention[ OR=6.186(95% CI 2.336~16.380)] and long constipation time [ OR=1.310(95% CI 1.095~1.567)]were independent risk factors for AA in children(all P<0.05). Conclusion:The incidence of faecal retention in children with AA is higher than that in children without AA,and the median duration of constipation is longer than that in children without AA.Fecal retention and long-term constipation are independent risk factors for AA in children.
10.Analysis on configuration of testing equipment in blood testing laboratories of blood stations in Shandong Province
Xiao-Tong SUN ; Zhong-Si YANG ; Hui-Xia ZHAO ; Shu-Tao PANG
Chinese Medical Equipment Journal 2024;45(3):81-85
Objective To analyze the configuration of testing equipment in blood testing laboratories of blood stations in Shandong Province to facilitate to optimize equipment configuration for blood testing laboratories.Methods Questionnaires were distributed to obtain information on the number,the proportions of domestic and imported equipment,the usage time and the number of annual sample detection for the testing equipment of 17 blood testing laboratories(one laboratory from blood center and 16 laboratories from central blood stations)in Shandong Province,including the equipment for blood group testing,alanine aminotransferase(ALT)testing,sample adding of enzyme-linked immunosorbent assay(ELISA),ELISA micro-plate processing and nucleic amplification test(NAT).The testing equipment in the laboratories with different sizes were analyzed in terms of substitutability,localization,number of annual sample detection and average usage time.Results The blood group and ALT testing equipment had low substitutability;the imported equipment for ALT testing and ELISA sample adding had high proportions;the numbers of yearly sample detection of the equipment for ELISA sample adding,ELISA microplate processing and NAT rose significantly with the increase of laboratory sizes(P<0.05);the equipment for ELISA sample adding and microplate processing had long usage time,and the differences between the usage time of the equipment for ELISA sample adding from the laboratories with different sizes were statistically significant(P<0.05).Conclusion The equipment configuration of blood testing laboratories of blood stations in Shandong Province varies greatly,and each laboratory has to take measures based on their own actual situations,such as increasing the number of equipment,purchasing domestic equipment or accelerating equipment updating.[Chinese Medical Equipment Journal,2024,45(3):81-85]

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