1.Application of Mitochondrial Targeting Strategy of Nano-delivery System in Tumor Diagnosis and Treatment
Jun QU ; Shuang YAN ; Long-Tian-Yang LEI ; Fei-Jun OUYANG ; Hai-Tao ZHANG ; Xu-Ping QIN
Progress in Biochemistry and Biophysics 2024;51(1):70-81
Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy.
2.Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons
Yang LI ; Dan LIN ; Qin Xiu ZHANG ; Xiu Guang JU ; Ya SU ; Qian ZHANG ; Ping Hai DUAN ; Sen Wei YU ; Ling Bing WANG ; Tao Shu PANG
Biomedical and Environmental Sciences 2024;37(5):479-493
Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.
3.Effect and mechanism of luteolin on brain injury in rats with hypoxia-ischemia encephalopathy
Chang YANG ; Hai-Tao JIN ; Wen ZHANG
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1033-1038
Objective To investigate the effects of luteolin on brain injury and Toll like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)signaling pathway in rats with hypoxia-ischemia encephalopathy(HIE).Methods A total of 60 male rats were randomly divided into the normal control(NC)group,the model group,the low-dose group(25 mg/kg luteolin),the high-dose group(50 mg/kg luteolin),and the high-dose+lipopolysaccharide(LPS)group(50 mg/kg luteolin+0.5 mg/kg TLR4 agonist LPS),with 12 rats in each group.HIE model was constructed by ligation of common carotid artery and hypoxia.Neurological severity score(NSS)was used to detect the cerebral nerve function of rats in each group.Serum tumor necrosis factor-α(TNF-α)and brain-derived neurotrophic factor(BDNF)levels were detected by ELISA assay.HE staining was used to detect the pathological changes of brain tissue.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in brain tissue of rats were detected by kit.TTC staining was used to detect cerebral infarction in rats.Western blot was used to detect the expression of TLR4,nuclear factor-kappa B(NF-κB),p-NF-κB,activated cleaved cysteine aspartate proteinase 3(Cleaved Caspase-3)protein in brain tissue.Results Compared with the model group,the NSS,levels of TNF-α and MDA,volume of cerebral infarction,and expression of TLR4,p-NF-κB/NF-κB and Cleaved Caspase-3 in low-dose group and high-dose group were decreased(P<0.05),BDNF and SOD levels were increased(P<0.05),the histopathological damage of hippocampus was obviously alleviated,the structure was gradually clear,and the number of nerve cells was normal.Compared with the high-dose group,the levels of the above indexes were inversely expressed in the high-dose+LPS group(P<0.05),and the histopathological damage in the hippocampus was aggravated.Conclusion Luteolin can improve brain injury and inhibit TLR4/NF-κB signaling pathway in HIE rats,and the inhibition of TLR4/NF-κB signaling pathway may be the mechanism of luteolin in improving brain injury.
4.Trends of Incidence and Diagnostic Age of Thyroid Can-cer in Cancer Registration Areas of Jiangsu Province from 2009 to 2019
Zhijie YANG ; Lu WANG ; Yun QIAN ; Hai CHEN ; Jinyi ZHOU ; Weigang MIAO ; Ran TAO ; Renqiang HAN
China Cancer 2024;33(12):991-998
[Purpose]To analyze the incidence trend and age at diagnosis of thyroid cancer in can-cer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The continuous and com-plete cancer data from 2009 to 2019 meeting quality control requirements were collected from 16 registries in Jiangsu Province.Thyroid cancer was coded as C73 according to ICD-10.The crude incidence rate,age-standardized incidence rate by Chinese standard population(ASIRC),the mean diagnostic age and adjusted mean diagnostic age of thyroid cancer were calculated by sex,age groups and regions.The trends of above indicators were analyzed and the average annual per-centage change(AAPC)was calculated.[Results]The crude incidence rate and ASIRC of thyroid cancer for men in Jiangsu cancer registration areas in 2009 and 2019 were 1.25/105,1.00/105 and 7.32/105,6.48/105,respectively.For women those were 3.64/105,3.06/105 and 24.91/105,20.94/105,respectively.The AAPC of crude incidence rate and ASIRC of thyroid cancer from 2009 to 2019 were 22.05%(95%CI:19.70%~24.45%)and 22.55%(95%CI:20.06%~25.08%),respectively.The adjusted mean diagnostic age of thyroid cancer declined from 46.27 years old in 2009 to 43.03 years old in 2019(β=-0.243,P<0.001).[Conclusion]The incidence rate of thyroid cancer showed an increasing trend in cancer registration areas of Jiangsu Province from 2009 to 2019,while the diagnostic age showed a downward trend during the same period.
5.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.
6.Intervention of traditional Chinese medicine in spermatogenic epithelium injury by regulating the ferroptosis pathway:Advances in studies
Jin-Tao WEI ; Zi-Yang MA ; Jun CAO ; Pei-Hai ZHANG
National Journal of Andrology 2024;30(5):450-455
The incidence of male infertility has been increasing year by year,and one of the major causes is testicular spermato-genic epithelial injury,which affects the spermatogenic function of the testis.Ferroptosis is a novel mode of cell death and plays an im-portant role in testicular cell injury.Some traditional Chinese medicines can intervene in the progression of testicular injury by regula-ting the ferroptosis pathway in testicular spermatogenic epithelia.This paper focuses on the effect of traditional Chinese drugs in regula-ting the ferroptosis pathway in testicular cells,and summarizes the advances in the studies of traditional Chinese medicines in the treat-ment of testicular spermatogenic epithelial injury,aiming to provide a theoretical basis for the selection of relevant medicines and their clinical application.
7.Characteristics and clinical significance of changes in peripheral blood B lymphocyte subsets in patients with chronic hepatitis B
Hai-Yan WANG ; Chun-Mei BAO ; Zhi-Qian FENG ; Jing WANG ; Ya-Qun LI ; Jing LI ; Hong-Min WANG ; Li-Li TANG ; Tao YANG ; Ruo-Nan XU ; Fu-Sheng WANG
Medical Journal of Chinese People's Liberation Army 2024;49(5):511-518
Objective To analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment-na?ve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells were slightly positively correlated with age(r>0.36,P<0.05).Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients,and age is a potential risk factor for the decline in humoral immune function in CHB patients.
8.Pathogenic and molecular characteristics of Klebsiella pneumoniae in fecal samples from diarrhea cases in a district of Beijing in 2018-2021
Shuang ZHANG ; Juan ZHAO ; Chang LIU ; Hai-Rui WANG ; Xi YANG ; Hui-Bo WANG ; Yuan-Yuan WANG ; Hui LI ; Jian-Tao ZHANG ; Zhen-Dong ZHANG ; Nan CHEN ; Ying LI ; Mao-Jun ZHANG ; Rui TIAN
Chinese Journal of Zoonoses 2024;40(8):745-749,757
This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43%(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61%(49/115).The positivity rate was slightly high(12.47%,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.
9.Serological Characteristics and Clinical Significance of Irregular Antibodies in Pregnant Women
Tao ZHANG ; Gui-Lin YANG ; Hong-Peng ZHANG ; Ying-Ying WU ; Sheng-Lan LI ; Kuai WAN ; Hai-Feng QI ; Chun-Li LI
Journal of Experimental Hematology 2024;32(1):231-236
Objective:To understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance.Methods:From January 2017 to March 2022,151 471 pregnant women in Women and Children's Hospital of Chongqing Medical University were enrolled in this study,microcolumn gel card test was used for irregular antibody screening,and antibody specificity identification was further performed in some antibody-positive subjects.Results:The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91%(1 375/151 471),0.23%(355/151 471)was detected in the first trimester,0.05%(71/151 471)in the second trimester,and 0.63%(949/151 471)in the third trimester.The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester,and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester.The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11%(689/1 375),which was the highest,the suspicious positive was 18.69%(257/1 375),and the positive was 31.20%(429/1 375).The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group,however,in the third trimester,the proportion of suspicious positive and weakly positive was lower than the first trimester,while,the proportion of positive was higher than the first trimester,and the difference was statistically significant(P<0.001).Among the irregular antibody screening positive pregnant women,the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy≤1.Among 60 pregnant women who underwent antibody identification,the distributions of the antibodies were as follows:Rh blood group system accounted for 23.33%(14/60),Lewis system 43.33%(26/60),Kidd system 3.33%(2/60),MNS system 16.67%(10/60),P1PK system 1.67%(1/60),autoantibodies 1.67%(1/60),and 4 cases was unable to identify(6.67%,4/60).Among specific antibodies,the anti-Lea was the most common(30.00%),followed by anti-E(16.67%)and anti-M(16.67%).Conclusion:The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds,understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.
10.Effects of total glucosides of paeony on inflammatory injury in autoimmune thyroiditis rats based on TLR4/NF-κB/NLRP3 pathway
Su-Yu WU ; Hai-Tao WANG ; Yang ZHANG ; Jian-Lin ZHAO ; Yu-Feng CHEN ; Jiang-Yan LI ; Hua SUI ; Yan-Hong ZHOU
Chinese Pharmacological Bulletin 2024;40(8):1495-1500
Aim To investigate the effect of total glu-cosides of paeony on inflammatory injury and TLR4/NF-κB/NLRP3 pathway in autoimmune thyroiditis(AIT)rats.Methods The experiment was divided into control group,model group,total glucosides of pae-ony(TGP),TLR4 inhibitor group and TGP+TLR4 ag-onist group,with 10 animals in each group.Except for the control group,the rats in other groups were subcu-taneously injected with thyroglobulin and Freund's ad-juvant to induce the AIT rat model.After six weeks of administration,thyroid histopathological changes were observed using hematoxylin-eosin(HE)staining;ser-um levels of TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1 β and IL-1 β were detected by enzyme-linked immunosorbent assay(ELISA);TLR4/NF-κB/NLRP3 pathway mRNAs and proteins expression in thyroid tis-sues were detected by RT-qPCR and Western blot.Re-sults Compared with the control group,the thyroid follicular epithelium of rats was significantly damaged,and the serum levels of TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1 β and IL-1 β increased(P<0.01).The expression of TLR4/NF-κB/NLRP3 path-way mRNAs and proteins increased in the model group(P<0.01).Compared with the model group,the damage of thyroid follicular epithelium was alleviated,and the serum levels of TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1 β and IL-1 β were reduced(P<0.01),the expression of TLR4/NF-κB/NLRP3 path-way mRNAs and proteins were down-regulated in the TGP group and TLR4 inhibitor group(P<0.01).Compared with TGP group,the damage of thyroid follic-ular epithelium was aggravated,and the levels of serum TPOAb,TgAb,TSH,T3,T4,TNF-α,INF-γ,IL-1 β and IL-1 β were elevated(P<0.05 or P<0.01),the pro-tein expressions of TLR4/NF-κB/NLRP3 pathway mR-NAs and proteins were up-regulated in TGP+TLR4 ag-onist group(P<0.05 or P<0.01).Conclusions TGP may play a protective role in thyroid by inhibiting the TLR4/NF-κB/NLRP3 pathway and improving the inflammatory injury of thyroid tissues.

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