1.Surveillance on the density of Aedes albopictus in Baoshan District, Shanghai Municipality from 2018 to 2024
Haijian WANG ; Yingyu YANG ; Chunwei SUN ; Miaomiao HE ; Yi ZHANG
Chinese Journal of Schistosomiasis Control 2026;38(2):207-212
Objective To investigate the changes in the density of Aedes albopictus across different regions and different breeding habitats in Baoshan District, Shanghai Municipality from 2018 to 2024, so as to inform evidence-based control strategies for mosquito-borne infectious diseases in Shanghai Municipality. Methods Ae. albopictus surveillance sites were deployed in 12 subdistricts (towns) of Baoshan District, Shanghai Municipality from 2018 to 2024, and the surveillance on the density of Ae. albopictus was performed in each surveillance site once weekly during the peak activity period of Aedes mosquitoes from May to October each year from 2018 to 2024. Mosquito ovitraps were deployed in various breeding habitats in each surveillance site according to geographical locations, including residential areas, schools, government institutions, hospitals, recycling stations, and construction sites, and regularly collected, and the mosquito ovitrap index (MOI) was calculated. The changes in the Ae. albopictus density were analyzed based on MOI across years, regions, and breeding habitats. Additionally, from May to October each year between 2018 and 2024, monthly risk assessments of Aedes albopictus density were conducted in every subdistrict (town) of Baoshan District, Shanghai. Results The annual mean MOI values of Ae. albopictus were 5.88 ± 2.29, 8.19 ± 4.46, 7.43 ± 3.40, 5.44 ± 2.52, 3.97 ± 2.72, 3.82 ± 1.57, and 2.56 ± 1.11 in Baoshan District from 2018 to 2024, respectively (F = 75.886, P < 0.05), and the MOI appeared a rise followed by a reduction each year and peaked during the period between June and August. There was a significant difference in the 7-year mean MOI of Ae. albopictus across the 12 subdistricts/towns (F = 26.558, P < 0.05), and there were 6 subdistricts/towns with a 7-year mean MOI of over 5, including Songnan Town (8.44 ± 4.68), Dachang Town (7.71 ± 5.28), Gucun Town (7.13 ± 3.57), Yuepu Town (5.74 ± 1.69), Gaojing Town (5.51 ± 3.44), and Wusong Subdistrict (5.41 ± 2.04). There was a significant difference in the MOI of Ae. albopictus across breeding habitats (F = 3.843, P < 0.05), with the highest MOI seen in recycling stations (9.86 ± 4.61), which was significantly higher than in other habitats (P < 0.05), and the lowest seen in construction sites (4.90 ± 2.95), which was significantly lower than in other habitats (P < 0.05). The proportion of frequency with Ae. albopictus density transmission risk decreased from 54.17% in 2018 to 11.11% in 2024 in all subdistricts (towns) of Baoshan District, and the frequency of outbreak risks peaked in 2019 (18 instances) and declined substantially in 2021 (6 instances), with no records of outbreak or transmission risk documented across the district in 2024. Conclusions There were substantial seasonal variations in the Ae. albopictus density in Baoshan District, Shanghai Municipality from 2018 to 2024. The Ae. albopictus density peaked during the period between June and August in Baoshan District each year from 2018 to 2024, with a relatively higher density in Songnan Town and Dachang Town, and in recycling stations. Precision control measures and intensified seasonal interventions are recommended in high-risk settings in Baoshan District to reduce the transmission risk of Aedes-borne infectious diseases.
2.Effectiveness of additional anti-rotation steel plate assisted intramedullary nail technology in aseptic femoral non-union.
Wei WANG ; Miaomiao YANG ; Xiaowen DENG ; Fan LI ; Wenbo LI ; Weiwei SHEN ; Peisheng SHI ; Jie SHI ; Chuangbing LI ; Yun XUE ; Qiuming GAO
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(9):1170-1174
OBJECTIVE:
To explore the effectiveness of additional anti-rotation steel plate assisted intramedullary nail technology in treatment of aseptic femoral non-union patients.
METHODS:
A retrospective analysis was conducted on 21 patients with aseptic femoral non-union who admitted between September 2020 and October 2024 and treated with additional anti-rotation steel plate assisted intramedullary nail technology. There were 17 males and 4 females, aged 25-67 years (mean, 44 years). There were 19 cases of femoral anterograde intramedullary nail fixation, 1 case of femoral retrograde intramedullary nail fixation, and 1 case of steel plate fixation with fatigue fracture. There were 9 cases of hypertrophic non-union and 12 cases of atrophic non-union. All patients had varying degrees of fracture end atrophy/sclerosis. Among them, 20 patients who were fixed with intramedullary nails underwent removal of soft tissue and hardened bone at the fracture end, and cortical treatment resulted in the appearance of "chili sign" at the fracture end. Iliac bone grafting and anti-rotation steel plate fixation were performed. One patient with steel plate fixation was removed the steel palte and fixed with a retrograde intramedullary nail, while the hardened bone at the fracture end was removed, iliac bone grafting and anti-rotation steel plate fixation were performed. Postoperative follow-up observation included the incision healing, maximum knee flexion range of motion, bone healing, length of lower limbs, and subjective satisfaction. The lower extremity functional scale (LEFS) score was used to evaluate the lower limb function.
RESULTS:
All incisions healed by first intention. All patients were followed up 7-26 months (mean, 15.5 months). At last follow-up, the femoral fracture healed with the obvious callus formation at the fracture end; the maximum knee flexion range of motion was 95°-127° (mean, 112.67°). The LEFS score increased from 29.9±6.7 before operation to 75.9±3.0 at last follow-up, and the difference was significant (t=-29.622, P<0.001). Except for 1 patient who underwent intramedullary nail dynamic treatment before operation and had a lower limb shortening of about 0.9 cm, the other patients had bilateral lower limbs of equal length. All patients had no postoperative infections, mal-union of fractures, deep vein thrombosis, joint stiffness, or other complications.
CONCLUSION
The use of additional anti-rotation steel plate assisted intramedullary nail technology in the treatment of aseptic femoral non-union not only overcomes the drawbacks of insufficient stability at the fracture end of intramedullary nails, but also overcomes the shortcomings of biased fixation with steel plates. It has the advantages of minimal trauma, effective maintenance of fracture stability, and ideal postoperative functional recovery, making it an effective treatment for aseptic femoral non-union.
Humans
;
Male
;
Fracture Fixation, Intramedullary/instrumentation*
;
Female
;
Bone Plates
;
Middle Aged
;
Adult
;
Femoral Fractures/surgery*
;
Retrospective Studies
;
Bone Nails
;
Aged
;
Fractures, Ununited/surgery*
;
Treatment Outcome
;
Bone Transplantation/methods*
;
Steel
;
Fracture Healing
3.Clinical characteristics of bronchial asthma with secondary pulmonary infections in children and expressions of transcriptomes in peripheral blood
Haitao ZHANG ; Miaomiao SHI ; Liping YUAN ; Bo HU ; Zeyu YANG ; Yu WANG
Chinese Journal of Nosocomiology 2025;35(21):3282-3286
OBJECTIVE To explore the clinical characteristics of bronchial asthma with secondary pulmonary infec-tions in children and compare the expressions of transcriptomes in peripheral blood between the bronchial asthma with secondary pulmonary infections and the bronchial asthma without the secondary pulmonary infections.METHODS The clinical data were collected from 425 children with bronchial asthma who were treated in respirato-ry medicine department of Children's Hospital of Anhui Province from Apr.2022 to Feb.2025 and were retrospec-tively analyzed.The enrolled children were divided into the infection group with 60 cases and the non-infection group with 365 cases according to the status of complication with pulmonary infections.The clinical characteristics were compared between the infection group and the non-infection group.The gene expression profile sequencing was carried out for peripheral blood mononuclear cells by transcriptome high throughput technology,and the bio-logical information was analyzed.RESULTS There were significant differences in course of asthma,frequencies times of acute attack,complication with nasosinusitis or allergic rhinitis,standardized use of antibiotics and intra-venous use of glucocorticoids between the two groups of children(P<0.05).Totally 60 children had secondary pulmonary infections,with the infection rate 14.12%.Totally 73 strains of pathogens were isolated,43.84%of which were gram-positive bacteria,and 56.16%were gram-negative bacteria.As compared with the non-infection group,there were 1578 genes with the changed expression in the infection group,and the expressions of the genes such as nuclear factor κB were upregulated.The differentially expressed genes were primarily enriched in immuno-regulation-related pathways,including proinflammatory factor signal transduction,interacted networks of cyto-kines and its receptors,T lymphocyte activation signal transduction and other biological processes.CONCLUSION The specific clinical characteristics and abnormal immune pathways may jointly result in the pulmonary infec-tions in children with the asthma and provide theoretical bases for early identification of the children at high risk of pneumonia and targeted intervention.
4.A case report of glycogen storage disease type Ⅲ combined with Guillain-Barré syndrome and literature review
Miaomiao YANG ; Xinyou YU ; Yinxia ZHAO
Chinese Journal of Medical Genetics 2025;42(8):981-990
Objective:To investigate the clinical manifestations and genetic characteristics of a child with glycogen storage disease type Ⅲ (GSD-Ⅲ) complicated with Guillain-Barré syndrome (GBS) caused by AGL gene variants, and to analyze the pathogenesis, potential correlation, treatment and prognosis of the two diseases. Methods:A child with GSD-Ⅲ who visited the General Hospital of Ningxia Medical University due to " limb weakness for more than ten days" in July 2024 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected for whole exome sequencing and Sanger sequencing. Candidate variants were verified, and pathogenicity analysis was conducted for the variant sites. This study was approved by the Medical Ethics Committee of General Hospital of Ningxia Medical University (Ethics No.: KYLL-2025-1984).Results:The child has presented with inability to stand or walk independently, difficulty in grasping, accompanied by numbness and pain at the distal end, choking when drinking water, occasional non-projectile vomiting, and enlargement of liver and spleen. Laboratory tests showed abnormal liver function and a significant increase in creatine kinase. Color Doppler ultrasound of the heart showed an enlarged left atrium and mild regurgitation of mitral and tricuspid valves. Genetic testing confirmed that he has harbored compound heterozygous variants of the AGL gene, namely c. 1611G>A (p.E537E) and c. 579del (p.W194Gfs*7), which were inherited from his father and mother, respectively. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the two variants were respectively predicted as variant of unknown significance (PM2_Supporting+ PM3+ PP3_Supporting) and likely pathogenic (PVS1+ PM2_Supporting). Electrophysiological examination confirmed that the child had severe damage to the motor and sensory nerves accompanied by axonal injury, which was consistent with the axonal variant type of GBS -acute motor and sensory axonal neuropathy. After a clear diagnosis, the child was treated with intravenous human immunoglobulin. His condition deteriorated progressively, presenting with breathing difficulties, liver failure, and gastrointestinal bleeding, and eventually deceased due to multiple organ failures. Conclusion:The etiology of GSD-Ⅲ and GBS involves multiple aspects such as genetics, metabolism and immunity. In clinical practice, it should be noted that similar clinical manifestations may occur in both conditions. Close attention should be paid to the patients′ blood glucose, blood gas, coagulation function and liver function, etc. Clinical intervention should be carried out as early as possible to improve the prognosis.
5.Analysis and prediction of global burden due to cystic echinococcosis from 1990 to 2035
Zhen LAI ; Gang LIU ; Haili ZHAO ; Miaomiao QIU ; Jian CHEN ; En LUO ; Junguo XIN ; Xiaohong YANG
Chinese Journal of Schistosomiasis Control 2025;37(3):255-267
Objective To investigate the trends in the global burden due to cystic echinococcosis from 1990 to 2021, and to predict the global burden of cystic echinococcosis from 2022 to 2035, so as to provide insights into formulation of the cystic echinococcosis control strategy. Methods The global age-standardized prevalence, mortality, disability-adjusted life years (DALYs) rates and their 95% uncertainty intervals (UI) of cystic echinococcosis from 1990 to 2021 were captured from the Global Burden of Disease Study 2021 (GBD 2021) database, and the trends in the global burden of cystic echinococcosis from 1990 to 2021 were analyzed using the Joinpoint regression model. The associations between the global burden of cystic echinococcosis and socio-demographic index (SDI) were examined using a smoothing spline model and frontier analysis, and the global burden of cystic echinococcosis was projected from 2022 to 2035 using the Bayesian age-period-cohort (BAPC) model. Results The global agestandardized prevalence, mortality and DALYs rates of cystic echinococcosis were 7.69/105 [95% UI: (6.27/105, 9.51/105)], 0.02/105 [95% UI: (0.01/105, 0.02/105)], and 1.32/105 [95% UI: (0.99/105, 1.69/105)] in 2021. The global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a rise by 0.14% per year from 1990 to 2021, and the global age-standardized mortality and DALYs rates of cystic echinococcosis appeared a tendency towards a decline by 4.68% and 4.01% per year from 1990 to 2021, respectively. Joinpoint regression analysis showed that global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a decline from 1990 to 2000 [annual percent change (APC) = −0.66%, 95% confidence interval (CI): (−0.70%, −0.61%)] and from 2005 to 2015 [APC = −0.88%, 95% CI: (−0.93%, −0.82%)], and towards a rise from 2000 to 2005 [APC = 3.68%, 95% CI: (3.49%, 3.87%)] and from 2015 to 2021 [APC=0.30%, 95%CI: (0.19%, 0.40%)].Theagestandardized prevalence (r = −0.17, P < 0.05), mortality (r = −0.67, P < 0.05) and DALYs rates of cystic echinococcosis (r = −0.60, P < 0.05) all correlated negatively with SDI across 21 geographical regions from 1990 to 2021, and the age-standardized mortality (r = −0.61, P < 0.05) and DALYs rates (r = −0.44, P < 0.05) both correlated negatively with SDI across 204 countries and territories in 2021. Frontier analysis revealed that the age-standardized DALYs rate of cystic echinococcosis was still not in line with the frontier in some high-SDI countries or territories. In addition, the global age-standardized prevalence was projected with the BAPC model to appear a tendency towards a rise among both men [estimated annual percent change (EAPC) = 0.18%, 95% CI: (0.13%, 0.23%)] and women [EAPC = 0.29%, 95% CI: (0.24%, 0.34%)] from 2022 to 2035, and the global age-standardized mortality [men: EAPC = −4.71%, 95% CI: (−4.71%, −4.37%); women: EAPC = −4.74%, 95% CI: (−4.74%, −4.74%)] and DALYs rates [men: EAPC = −3.35%, 95% CI: (−3.36%, −3.34%); women: EAPC = −3.17%, 95% CI: (−3.18%, −3.16%)] were projected to appear a tendency towards a decline among both men and women. Conclusions The global burden of cystic echinococcosis appeared an overall tendency towards a decline from 1990 to 2021; however, the global prevalence of cystic echinococcosis is projected to appear a tendency towards a rise from 2022 to 2035. Intensified cystic echinococcosis control programmes are recommended.
6.Mechanism of Cnidii Fructus in the treatment of periodontitis with osteoporosis based on network pharmacology, molecular docking, and molecular dynamics simulation.
Miaomiao FENG ; Xiaoran XU ; Ningli LI ; Mingzhen YANG ; Yuankun ZHAI
West China Journal of Stomatology 2025;43(2):249-261
OBJECTIVES:
This study aimed to explore the active components, potential targets, and mechanism of Cnidii Fructus in the treatment of periodontitis with osteoprosis through network pharmacology, molecular docking, and molecular dynamics simulation technology.
METHODS:
The main chemical constituents and targets of Cnidii Fructus were screened using the TCMSP and SwissTargetPrediction databases, as well as literature reports. Targets of periodontitis and osteoporosis were predicted using different databases. The intersection targets of Cnidii Fructus, periodontitis, and osteoporosis were obtained using Venny 2.1. The protein-protein interaction network was formed on the STRING platform. Cytoscape 3.9.1 was used to construct the active component-intersection target interaction network, perform the topological analysis, and screen key targets and core active components. Furthermore, the Metascape database was used to perform gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on the intersection targets. The top five key targets and core active components were selected as receptor proteins and ligand small molecules. Discovery Studio 2019 was used to dock ligands and receptors and visualize the docking results. Molecular dynamics simulation was conducted using Gromacs2022.3 to assess the stability of the interactions between the core active components and the main targets.
RESULTS:
A total of 20 potential active ingredients of Cnidii Fructus were screened, and 116 targets of Cnidii Fructus were obtained for treating periodontitis and osteoporosis. GO and KEGG analyses of the 116 targets showed that Cnidii Fructus may play a therapeutic role through the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) and advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathways. Molecular docking showed that the core constituents were well bound to the main targets. Molecular dynamics simulations confirmed the stability of the Diosmetin-AKT1 complex system.
CONCLUSIONS
The preliminary discovery of the potential molecular pharmacological mechanism of Cnidii Fructus extract in the targeted treatment of periodontitis with osteoporosis through a multi-component, multitarget, and multi-pathway approach can serve as a theoretical foundation for future drug-development research and clinical application.
Molecular Docking Simulation
;
Molecular Dynamics Simulation
;
Network Pharmacology
;
Periodontitis/complications*
;
Drugs, Chinese Herbal/chemistry*
;
Osteoporosis/complications*
;
Humans
;
Protein Interaction Maps
;
Cnidium/chemistry*
7.Effects of anxiety and depression among primary caregivers of stroke patients in social support and burnout
Lijun WANG ; Ru GAN ; Xiaohui LIU ; Huijuan WANG ; Haihua GAO ; Xiaoping YANG ; Jialin YUAN ; Miaomiao CHEN
Journal of Clinical Medicine in Practice 2025;29(8):114-118
Objective To investigate the mediating role of anxiety and depression in social sup-port and burnout among primary caregivers of stroke patients.Methods A convenience sampling method was employed to select 506 primary caregivers of stroke patients as research subjects.The Gen-eral Information Questionnaire,Caregiver Burnout Inventory for Stroke Patients,Multidimensional Scale of Perceived Social Support,and Hospital Anxiety and Depression Scale were used for data col-lection.Results The total scores for caregiver burnout,social support,anxiety,and depression a-mong primarycaregivers of stroke patients were(72.83±14.32),(47.79±7.74),(10.49±3.00),and(10.45±3.06),respectively.Correlation analysis revealed a negative correlation between caregiver burnout and social support(r=-0.245,P<0.001),and positive correlations with anxiety and depression(r=0.178,0.216,P<0.001).Anxiety and depression partially media-ted the relationship between social support and caregiver burnout,accounting for 7.9%and 10.7%of the total effect,respectively.Conclusion Social support,anxiety,depression,and burnout are closely interrelated.Social support can directly or indirectly influence the occurrence of burnoutthrough anxiety and depression.Medical staff should pay attention to the anxiety and depression status of primary caregivers of stroke patients and enhance social support levels to reduce the incidence of burnout by alleviating anxiety and depression.
8.A case report of glycogen storage disease type III combined with Guillain-Barré syndrome and literature review.
Miaomiao YANG ; Xinyou YU ; Yinxia ZHAO
Chinese Journal of Medical Genetics 2025;42(8):981-990
OBJECTIVE:
To investigate the clinical manifestations and genetic characteristics of a child with glycogen storage disease type III (GSD-III) complicated with Guillain-Barré syndrome (GBS) caused by AGL gene variants, and to analyze the pathogenesis, potential correlation, treatment and prognosis of the two diseases.
METHODS:
A child with GSD-III who visited the General Hospital of Ningxia Medical University due to "limb weakness for more than ten days" in July 2024 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected for whole exome sequencing and Sanger sequencing. Candidate variants were verified, and pathogenicity analysis was conducted for the variant sites. This study was approved by the Medical Ethics Committee of General Hospital of Ningxia Medical University (Ethics No.: KYLL-2025-1984).
RESULTS:
The child has presented with inability to stand or walk independently, difficulty in grasping, accompanied by numbness and pain at the distal end, choking when drinking water, occasional non-projectile vomiting, and enlargement of liver and spleen. Laboratory tests showed abnormal liver function and a significant increase in creatine kinase. Color Doppler ultrasound of the heart showed an enlarged left atrium and mild regurgitation of mitral and tricuspid valves. Genetic testing confirmed that he has harbored compound heterozygous variants of the AGL gene, namely c.1611G>A (p.E537E) and c.579del (p.W194Gfs*7), which were inherited from his father and mother, respectively. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the two variants were respectively predicted as variant of unknown significance (PM2_Supporting+PM3+PP3_Supporting) and likely pathogenic (PVS1+PM2_Supporting). Electrophysiological examination confirmed that the child had severe damage to the motor and sensory nerves accompanied by axonal injury, which was consistent with the axonal variant type of GBS -acute motor and sensory axonal neuropathy. After a clear diagnosis, the child was treated with intravenous human immunoglobulin. His condition deteriorated progressively, presenting with breathing difficulties, liver failure, and gastrointestinal bleeding, and eventually deceased due to multiple organ failures.
CONCLUSION
The etiology of GSD-III and GBS involves multiple aspects such as genetics, metabolism and immunity. In clinical practice, it should be noted that similar clinical manifestations may occur in both conditions. Close attention should be paid to the patients' blood glucose, blood gas, coagulation function and liver function, etc. Clinical intervention should be carried out as early as possible to improve the prognosis.
Humans
;
Male
;
Guillain-Barre Syndrome/complications*
;
Glycogen Storage Disease Type III/complications*
;
Mutation
;
Child
9.Dual-ferroptosis induction-based microneedle patches for enhanced chemodynamic/photothermal combination therapy against triple-negative breast cancer.
Yujie WANG ; Zhaoyou CHU ; Peisan WANG ; Tao LI ; Yu JIN ; Silong WU ; Xiaowei SONG ; Weinan ZHANG ; Miaomiao YANG ; Zhengbao ZHA ; Haisheng QIAN ; Yan MA
Acta Pharmaceutica Sinica B 2025;15(8):4210-4224
Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu2+) and iron ions (Fe3+) were liberated from Cu-PB. The direct chelation of Cu2+ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu2+ and Fe3+ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.
10.Layered double hydroxide-loaded si-NEAT1 regulates paclitaxel resistance and tumor-associated macrophage polarization in breast cancer by targeting miR-133b/PD-L1.
Zhaojun ZHANG ; Qiong WU ; Miaomiao XIE ; Ruyin YE ; Chenchen GENG ; Jiwen SHI ; Qingling YANG ; Wenrui WANG ; Yurong SHI
Journal of Southern Medical University 2025;45(8):1718-1731
OBJECTIVES:
To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer.
METHODS:
qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed.
RESULTS:
SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages.
CONCLUSIONS
LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans
;
MicroRNAs/genetics*
;
RNA, Long Noncoding/genetics*
;
Paclitaxel/pharmacology*
;
Breast Neoplasms/metabolism*
;
Drug Resistance, Neoplasm
;
B7-H1 Antigen/metabolism*
;
Cell Line, Tumor
;
Female
;
Tumor-Associated Macrophages
;
Apoptosis
;
Cell Proliferation
;
Macrophages
;
Cell Movement

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