1.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
2.A clinical trial on pelvic floor sensory testing in women with and without stress urinary incontinence.
Xiulan ZHANG ; Chengyu ZHOU ; Wenguang YAN ; Xuhong LI ; Zhaojun WANG ; Yanhua ZHOU ; Fen XIE ; Shuai FAN
Journal of Central South University(Medical Sciences) 2024;49(12):1919-1926
OBJECTIVES:
Pelvic floor sensory training is commonly used in clinical practice for the treatment of stress urinary incontinence (SUI); however, there is a lack of comparative studies evaluating pelvic floor sensation between women with SUI and healthy controls. Additionally, normative data for two-point discrimination thresholds in the female pelvic floor region remain scarce. This study aims to compare the results of 4 sensory tests in the pelvic floor region between women with mild SUI and healthy women, in order to provide reference values for two-point discrimination thresholds in this area.
METHODS:
From April 1 to October 30, 2023, 108 healthy women [(32.5±3.6) years] and 90 women with mild SUI [(32.9±3.3) years] were recruited from the Third Xiangya Hospital, Central South University. Participants underwent 4 sensory tests in the pelvic floor region: Two-dot discrimination, weight perception, shape recognition, and 9-grid localization. The results were compared between the 2 groups.
RESULTS:
Compared with healthy women, those with mild SUI had lower sensitivity and higher thresholds in 2-dot discrimination tests in the pelvic floor region (all P<0.001). No significant differences were found between groups in weight perception, shape recognition, or grid localization tests (P>0.05).
CONCLUSIONS
Women with mild stress urinary incontinence have impaired two-point discrimination ability in the pelvic floor region.
Humans
;
Female
;
Urinary Incontinence, Stress/physiopathology*
;
Pelvic Floor/physiopathology*
;
Adult
;
Sensory Thresholds/physiology*
3.Study of arterial stiffness and its related factors in different gender and age groups
Jianxiong CHEN ; Xianghong LUO ; Yuchen XIE ; Cuiqin SHEN ; Qingqing CHEN ; Lianfang DU ; Zhaojun LI
Chinese Journal of Geriatrics 2023;42(6):664-669
Objective:To investigate gender differences in arterial velocity pulse index(AVI), which is an indicator of vascular stiffness, across various age groups.Additionally, the study will also examine the risk factors associated with AVI.Methods:This cross-sectional study enrolled 4311 patients with an average age of 57.8±12.8 years at Jiading Branch of Shanghai First People's Hospital between August 2020 and September 2021.Patients were divided into three groups based on age: young(<45 years old, n=755), middle-aged(45-59 years old, n=1260), and elderly(≥60 years old, n=2 296). The AVI of the subject was obtained using the cuff oscillation wave method.The subject's AVI was acquired using the cuff oscillation wave.High AVI, indicating arteriosclerosis, was defined as AVI≥33.The subjects were then divided into two groups: the high AVI group(122 cases)and the normal AVI group(4 189 cases).Results:The ankle-brachial index(AVI)was found to be 12.8±3.7, 17.5±5.7, and 19.8±6.5 in the young, middle-aged, and elderly groups, respectively.The study revealed that AVI increased with age( Ftrend=767.819, P<0.01). Additionally, the incidence of high AVI in middle-aged women was found to be(2.8% or 20/722), which was higher than that in men 0.9%(5/538)in the same age group.This difference was statistically significant( χ2=5.371, P<0.05). The results of the multivariate logistic regression analysis indicate that being overweight, having a higher height, and a pulse rate greater than 80 BPM are protective factors in preventing a high incidence of AVI.The odds ratios( OR)with 95% confidence intervals( CI)for these factors were 0.468(0.317-0.690), 0.926(0.895-0.958), and 0.143(1.026-2.432), respectively, all with a P-value less than 0.01.On the other hand, old age, systolic blood pressure of 140 mmHg or higher, and diastolic blood pressure of 90 mmHg or higher were identified as risk factors for AVI.The ORs with 95% CIs for these factors were 2.119(1.322-3.396), 6.652(4.136-10.699), and 1.580(1.026-2.432), respectively, all with a P- value less than 0.05l. Conclusions:Arterial stiffness, as measured by the ankle-brachial index(ABI), tends to increase with age.In middle-aged subjects, women have a higher incidence of high ABI than men.Independent risk factors for high ABI include age and increased blood pressure, while factors such as overweight and height may affect the measured value of ABI.
4.Analysis of genetic evolution of parechovirus in neonates from Hunan Provincial People’s Hospital in 2021
Xiaohua MA ; Leyun XIE ; Sasa CHAI ; Shenghui GAO ; Aimin ZHANG ; Tian YU ; Guisen ZHENG ; Lili LI ; Saizhen ZENG ; Zhaojun DUAN
Chinese Journal of Experimental and Clinical Virology 2023;37(2):184-188
Objective:To understand the prevalence of human parechovirus (HPeV) in neonates of Hunan Provincial People’s Hospital, and analyze genetic evolutionary characteristics.Methods:From June to September 2021, fecal samples of inpatient neonates were collected in Hunan Provincial People′s Hospital. TaqMan real-time qPCR and RT-PCR were used for HPeV screening and genotyping. High-throughput sequencing and PCR were used to obtain whole genomes. Phylogenetic analysis was performed after sequencing.Results:A total of 123 fecal samples of neonates were collected, of which 22 were HPeV positive, with 17.89% positive rate. All the strains belonged to the HPeV-1 genotype. One full-length genomic sequence of 7 269 bp were obtained, and provisionally named Hunan/HPeV/2021, which has the highest nucleotide identity with known HPeV-1 genotype, with 86.6%-91.9% nucleotide identity. The nucleotide and amino acid identity of open reading frame (ORF) with known similar sequences were 90.3%-92.6% and 97.3%-98.3%, respectively. The phylogenetic analysis showed that Hunan/HPeV/2021 belongs to the HPeV-1 genotype, which is clustered into the same clade as the popular HPeV-1 strains in China.Conclusions:HPeV has a high prevalence in inpatient neonates of Hunan Provincial People’s Hospital and belong to the HPeV-1 genotype.
5.Association between body mass index and mortality among older Chinese: evidence from CHARLS
Junping WANG ; Zhaojun LU ; Shuo KOU ; Weijun ZHENG ; Kaihong XIE ; Weihao WANG ; Chao RONG
Journal of Preventive Medicine 2022;34(4):346-349
Objective:
To investigate the association between body mass index ( BMI ) and mortality risk among older Chinese based on the China Health and Retirement Longitudinal Study ( CHARLS ).
Methods:
The demographic features, BMI, prevalence of chronic diseases and mortality among the elderly at ages of 60 years and greater were captured from the CHARLS database from 2011 to 2018. A multivariable Cox proportional hazards regression model was used to examine the association between BMI and the risk of death.
Results:
Totally 6 023 subjects were enrolled, including 3 006 men ( 50.09% ) and 3 017 women ( 49.91% ), and 68.69% of the participants ( 4 137 subjects ) were at ages of 60 to 69 years. There were 637 subjects ( 10.58% ) with underweight, 1 544 ( 25.63% ) with overweight, and 557 ( 9.25% ) with obesity. During the follow-up period ( 35 091 person-years ), 1 035 subjects died. Multivariable Cox proportional hazards regression analysis revealed an increased risk of mortality among the underweight elderly ( HR=1.496, 95%CI: 1.261-1.775 ) and a reduced risk of mortality among the obese elderly ( HR=0.671, 95%CI: 0.511-0.881 ) relative to the elderly with normal weight, after adjustment for age, gender, smoking, household registration, administration of anti-diabetic drugs, administration of anti-dyslipidemia drugs, and administration of anti-hypertensive drugs.
Conclusion
It is found that the risk of mortality among the Chinese elderly correlatives with BMI through the analysis of CHARLS data.
6.Clinical features of liver injury in children with adenovirus pneumonia with normal immune function
Leyun XIE ; Saizhen ZENG ; Tao WANG ; Tian YU ; Le YANG ; Xian HU ; Bing ZHANG ; Yimin ZHU ; Zhaojun DUAN
Chinese Journal of Experimental and Clinical Virology 2022;36(5):579-585
Objective:To study the clinical characteristics of children with adenovirus pneumonia complicated with liver injury and the understanding of clinicians.Methods:The children diagnosed with community-acquired adenovirus pneumonia were enrolled from January 1, 2013 to December 31, 2020. The clinical characteristics of the normal liver function group and the liver injured group were compared, and multivariate regression was applied.Results:Among the 3 294 enrolled children, 1 704 children had elevated alanine aminotransferase and/or aspartate aminotransferase on admission, and the liver function impairment rate was 51.7% (1 704/3 294), of which 1 671 cases were mildly injured (98.06%, 1 671/1 704), 28 cases were moderately injured (1.64%, 28/1 704), and 5 cases were severely injured (0.29%, 5/1 704). Compared with the normal liver function group, the proportion of male children in the liver injured group was higher (68.1% vs. 64.2%, P=0.017), and the age was younger[16(9, 30) months vs. 38(19, 53) months, P<0.001]. Children with liver injury were more likely to have wheezing (32.9% vs. 18.7%, P<0.001), shortness of breath (13.7% vs. 9.1%, P<0.001), and diarrhea (11.0% vs. 4.7%, P<0.001). The white blood cell counts, neutrophil counts and hemoglobin in the liver injured group were lower than those in the normal group, while the lymphocyte counts were higher than those in the normal group. The levels of creatine kinase, cardiac creatine kinase and lactate dehydrogenase were higher. The proportion of severe pneumonia in the liver injured group (26.9% vs. 11.2%, P<0.001) was higher than that in the normal liver function group, and the case fatality rate was significantly higher (1.47% vs. 0.25%, P<0.001). Comparing the probability of liver injury in children with mild and severe adenovirus pneumonia, it was found that the severe pneumonia group had more frequent liver injury (73.0% vs 46.6%, P<0.001), and both moderate and severe liver injury groups were higher than in the mild group. Further multivariate logistic regression analysis did not find a significant factor associated with the incidence of liver injury. Conclusions:The incidence of adenovirus pneumonia in children with liver injury was high, and mild injury is more common. Children with liver injury were younger, had more severe clinical symptoms such as wheezing and shortness of breath, and higher proportion of severe pneumonia and mortality. Among them, children with severe pneumonia had a higher proportion of liver injury, and moderate to severe injury was more common. The monitoring of children with different degrees of liver injury should be strengthened.
7.Three cases of hepatitis of unknown origin in children
Shiyuan FAN ; Leyun XIE ; Tian YU ; Tao WANG ; Le YANG ; Xian HU ; Bing ZHANG ; Yimin ZHU ; Zhaojun DUAN ; Saizhen ZENG
Chinese Journal of Experimental and Clinical Virology 2022;36(5):597-599
This paper reports 3 cases of acute hepatitis of unknown cause in children who met the case definition of WHO. Human adenovirus group C was detected in case 3, and the quantity of viral DNA was relatively high, which may be related to the liver function damage in the patient, but its role in pathogenesis needs further study to confirm.
8.Establishment of index system for population based SARS-CoV-2 nucleic acid screening
Xi CHEN ; Qi ZOU ; Ruonan ZHEN ; Zhaojun XIE ; Jiongjin HUANG ; Lan LIU ; Yong HUANG ; Yu MA ; Ke LI ; Hui WANG ; Zongqiu CHEN ; Yufei LIU ; Jun YUAN
Chinese Journal of Epidemiology 2021;42(8):1353-1359
Objective:To establish an index system of population based SARS-CoV-2 nucleic acid screening, and provide reference to determine the screening coverage appropriately.Methods:The literature review and brain storming sessions were used to develop the basic frame and index system of population based SARS-CoV-2 nucleic acid screening. Based on Delphi method and Analytic Hierarchy Process, 21 domestic experts were selected for two rounds of consultation to determine the index system of population based SARS-CoV-2 nucleic acid screening and its weight.Results:The positive indexes of experts in two rounds of consultations were both 100%. The experts' authority coefficients ( Cr) were 0.88±0.08 and 0.89±0.07, respectively. And the range of coefficient of variation ( CV) were (0.08, 0.24), (0.09, 0.25). The Kendall's W coordination coefficients were 0.34 and 0.22 respectively, which were statistically significant. The index system of population based SARS-CoV-2 nucleic acid screening was established, which had 4 first-level indexes, 11 second-level indexes and 58 third-level indexes. Besides, the weight of each index was determined. Conclusion:The index system of population based SARS-CoV-2 nucleic acid screening has been established, which can provide scientific reference for the health administration to determine the coverage of population based SARS-CoV-2 nucleic acid screening when local COVID-19 epidemic occurs.
9.Epidemiological characteristics of viral agents in 1 092 children with acute lower respiratory diseases in Changsha
Jieying ZHOU ; Yaping SUN ; Yingbiao LIN ; Zhaojun DUAN ; Youde CAO ; Zhiping XIE
Chinese Journal of Experimental and Clinical Virology 2021;35(4):433-436
Objective:To explore the pathogenic spectrum and epidemiological characteristics of respiratory viruses in children with acute lower respiratory tract infection in Changsha, and provide scientific basis for disease prevention and treatment.Methods:A total of 1 092 respiratory tract specimens of children were collected and 12 respiratory viruses were detected by real-time quantitative transcription polymerase chain reaction.Results:Among the samples from 1 092 cases, those from 437 cases (40%) were positive for respiratory syncytial virus (RSV), 337 cases (30.9%) were positive for parainfluenza virus-3 (PIV-3), 263 cases (24.1%) were positive for human bocavirus (HBOV) and 228 cases (20.8%) were positive for adenovirus (ADV). The detection rates of boys and girls were 82.26% and 83.42%. The infection rate of RSV was higher in the group ≤ 6 months of age, the infection rates of PIV-3 and HBOV ≤2 years old were higher, and the infection rate of ADV was higher in the group between 6 months to 5 years old. The detection rates of virus infection of spring, summer, autumn and winter were 90.48%, 83.50%, 62.26% and 82.80%, respectively, there were significant differences among them.Conclusions:The main viruses in children with acute lower respiratory tract infection in Changsha were RSV and PIV-3. Mixed infections were common. Children under 2 years of age were more likely to get acute lower respiratory infections. Viruses had seasonal trends and peaked in winter and spring.
10. Clinical characteristics of bocavirus infection in children with bronchiolitis
Xuan LIANG ; Rongfang ZHANG ; Zhiping XIE ; Hanchun GAO ; Zhaojun DUAN ; Donghai LIU
Chinese Journal of Experimental and Clinical Virology 2018;32(2):187-190
Objective:
To investigate the human bocavirus (HBoV) infection in the children diagnosed with brochiolitis, incomparison with the clinical characteristics of bronchiolitis of HBoV vs. respiratory syncytial virus (RSV) infection alone.
Methods:
A total of 396 throat swabs were obtained from children diagnosed with bronchiolitis from January 2015 to December 2016 in Pediatric Asthma Center of Gansu Maternal and Child Health Care Hospital, Lanzhou. Specimens were tested for the nucleic acids of HBoV, RSV and other 6 common respiratory viruses by nested-polymerase chain reaction (nested PCR() and reverse transcription-polymerase chain reaction (RT-PCR), and the epidemic status, clinical characteristics of HBoV and RSV were analyzed and compared with each other.
Results:
The positive rate of virus infection was 53.54%, and HBoV and RSV infections were 9.84% and 24.49% in 396 cases. The numbers of cases of HBoV single infection, RSV single infection, HBoV and RSV mixed infection were 29, 86 and 5. The number of boys infected with HBoV was 27. There was statistical significance in the difference between the genders. The statistical significance also existed in difference of age. The babies at ages ranging from 6 to 12 months had the hifgest positive rate. The first incidence peak of the infection of HBoV was in October 2015. The children with HBoV infection, compared with RSV patients, presented more often with vomiting, diarrhea (


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