1.USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.
Yang OU ; Kun ZHANG ; Qiuying SHUAI ; Chenyang WANG ; Huayu HU ; Lixia CAO ; Chunchun QI ; Min GUO ; Zhaoxian LI ; Jie SHI ; Yuxin LIU ; Siyu ZUO ; Xiao CHEN ; Yanjing WANG ; Mengdan FENG ; Hang WANG ; Peiqing SUN ; Yi SHI ; Guang YANG ; Shuang YANG
Acta Pharmaceutica Sinica B 2025;15(5):2593-2611
Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.
2.miR-302a-3p targeting lysosomal-associated membrane protein 5 inhibits the invasion and metastasis of oral squamous cell carcinoma.
Li YU ; Tiejun ZHOU ; Xiao WU ; Xinhong LIN ; Xiaoyan ZHANG ; Yongxian LAI ; Xinyue LIAO ; Hang SI ; Yun FENG ; Jie JIAN ; Yan FENG
West China Journal of Stomatology 2025;43(4):547-558
OBJECTIVES:
This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC.
METHODS:
The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model.
RESULTS:
LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor.
CONCLUSIONS
LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism*
;
Mouth Neoplasms/metabolism*
;
Humans
;
Animals
;
Carcinoma, Squamous Cell/genetics*
;
Neoplasm Invasiveness
;
Cell Proliferation
;
Mice, Nude
;
Cell Movement
;
Lysosomal Membrane Proteins/genetics*
;
Mice
;
Cell Line, Tumor
;
Neoplasm Metastasis
3.Epidemiological Investigation of Dampness Syndrome Manifestations in the Population at Risk of Cerebrovascular Disease
Xiao-Jia NI ; Hai-Yan HUANG ; Qing SU ; Yao XU ; Ling-Ling LIU ; Zhuo-Ran KUANG ; Yi-Hang LI ; Yi-Kai ZHANG ; Miao-Miao MENG ; Yi-Xin GUO ; Xiao-Bo YANG ; Ye-Feng CAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):531-539
Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.
4.Risk factors analysis of recurrent drug-eluting stent in-stent restenosis
Huan-Huan FENG ; Xiao-Hang YUAN ; Xin HU ; Yan HAN ; Xi ZHANG ; Hao-Yi YE ; Lei GAO
Chinese Journal of Interventional Cardiology 2024;32(9):489-495
Objective To evaluate the predictors of recurrent in-stent restenosis(R-ISR)occurrence in drug-eluting stents(DES).Methods A total of 201 patients with ISR who received percutaneous coronary intervention(PCI)surgery in the First Medical Center of the Chinese PLA General Hospital from January 2010 to August 2023 were selected as the study objects,and the patients were divided into R-ISR group and non-R-ISR group according to their post-discharge angiography review.The clinical baseline data and the features of interventional surgery during the first ISR-PCI were retrospectively analyzed.Results Among the 201 patients,168 were males and 33 were females,with an average age of(61.97±10.02)years.The median interval between initial and follow-up angiography was 1.5 years.Patients were divided into two groups based on their radiographic reviews:R-ISR group(98 patients and 104 ISR lesions)and non-R-ISR group(103 patients and 111 ISR lesions).Multivariate Logistic regression analysis showed that the incidence of R-ISR was correlated with Ostial disease(OR 2.987,95%CI 1.343-6.642,P=0.007),plain old balloon angioplasty(POBA)performed for ISR lesions(OR 3.081,95%CI 1.293-7.343,P=0.011)and the maximum diameter stenosis rate of ISR lesions before surgery(OR 1.016,95%CI 1.002-1.030,P=0.022).Conclusions In patients currently receiving interventional therapy for ISR,Ostial disease,POBA treatment for ISR disease,and maximum diameter stenosis rate of ISR disease were associated predictors of R-ISR development.
5.Evaluation and optimization of metagenomic sequencing platforms for bloodstream infection samples
Xin PENG ; Hang FAN ; Meng-Nan CUI ; Lei LIN ; Guang-Qian PEI ; Yun-Fei WANG ; Xiu-Juan ZUO ; Xiao-Feng FANG ; Yan GUO ; Yu-Jun CUI
Chinese Journal of Zoonoses 2024;40(10):928-934
This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P<0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P<0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.
6.Design of heart rate extraction algorithm based on cell phone fingertip video
Feng-Jian YANG ; Xu-Yang HUO ; Wei-Lun YU ; Xiao-Hang YANG
Chinese Medical Equipment Journal 2024;45(8):16-20
Objective To propose a cell phone fingertip video-based heart rate extraction algorithm to relieve the influences of environmental factors.Methods Firstly,the fingertip video was captured and extracted at a frame rate of 30 frames/s,and the images were separated into three channels:R,G,and B.The brightness changes of the three channels were compared,the G channel,which was the most sensitive to the fingertip blood flow signal,was selected as the signal source,and the brightness change information was extracted to generate a volumetric pulse waveform with a duration of 10 s.Secondly,the waveform underwent signal processing such as digital filtering,removal of baseline drift and Fourier transform,then the heart rate was predicted based on the position information of the maximum spectral peak.Finally,the heart rate prediction efficacy by the proposed algorithm was validated on Brno University of Technology Smartphone PPG Database(BUT PPG dataset).Results The predicted heart rate by the algorithm and the actual value had the mean square deviation,root mean square deviation and mean absolute error being 3.71,1.92 and 1.2 beats/min,respectively.Condusion The algorithm proposed has high accuracy for heart rate prediction,and can be invovled in cell phones for daily heart rate monitoring.[Chinese Medical Equipment Journal,2024,45(8):16-20]
7.The value of aspirin challenge tests in the diagnosis of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease
Hao XIAO ; Li ZHANG ; Hang LIN ; Yingli XIAO ; Hongting ZHANG ; Qiaoru JIA ; Feng XU ; Juan MENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(8):741-746
Objective:To investigate the value of aspirin challenge tests in the diagnosis of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD).Methods:Fifty patients (22 males and 28 females; aged 16-61 years) who were diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) with/without asthma, and underwent NERD standardized diagnosis in the Allergy Centre of West China Hospital, Sichuan University from December 2021 to November 2022 were included in the study. The first step was asking about the history of exacerbation respiratory symptoms after intake of any non-steroidal anti-inflammatory drug, including aspirin; the second step was performing intranasal aspirin challenge (IAC); and the third step was performing oral aspirin challenge (OAC). The diagnosis of NERD was made if any of the above steps was positive, and the subsequent steps were not performed, otherwise the diagnosis was made to OAC. If OAC was negative, the diagnosis was non-NERD. All patients completed the sino-nasal outcome test 22 (SNOT 22) score, Lund-Kennedy score by nasal endoscopic, allergen skin prick test, blood routine and serum total IgE test. SPSS version 20.0 was used for statistical analysis.Results:The diagnosis of NRED was confirmed in 27 patients (27/50, 54%). Seven (7/50, 14%) of them were diagnosed by clinical history and 20 (20/50, 40%) were diagnosed by aspirin challenge tests, of which 17 (17/20, 85%) were positive to IAC and 3 (3/20, 15%) to OAC. Of the 43 patients who underwent IAC testing, only 2 (2/43, 5%) developed asthma attacks during challenge. Comparing the clinical characteristics of patients in NERD and non-NERD group, there were significant differences between the two groups in gender ( P=0.001), hyposmia ( P=0.003), history of repeated CRSwNP surgeries ( P=0.028), comorbid asthma ( P=0.013), SNOT-22 score ( P=0.004) and the percentage of peripheral blood eosinophil ( P=0.043). Conclusions:Patients may be underdiagnosed if the diagnosis of NERD is made only by medical history, and it is necessary to carry out aspirin challenge tests. IAC is an important means to diagnose NERD with high accuracy and good safety. However, If IAC is negative, further OAC is required.
8.Research and reflection on the diversified method system of multi-stages and multi-scenarios surveillance and early warning of infectious diseases.
Yu Hang MA ; Yi YIN ; Kai WANG ; Si Jia ZHOU ; Xun Liang TONG ; Yan Ming LI ; Xiao Li WANG ; Li Ping WANG ; Lu Zhao FENG ; Wei Zhong YANG ; Zhi Hang PENG
Chinese Journal of Preventive Medicine 2023;57(10):1529-1535
With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work. This paper briefly introduces the intelligent early warning model of infectious diseases, summarizes the emerging surveillance and early warning methods of infectious diseases, and seeks the possibility of diversified surveillance and early warning in different epidemic stages and different outbreak scenarios of infectious diseases. This paper puts forward the idea of constructing a diversified method system of infectious diseases surveillance and early warning based on multi-stages and multi-scenarios and discusses the future development trend of infectious diseases surveillance and early warning, in order to provide reference for improving the construction level of infectious diseases surveillance and early warning system in China.
Humans
;
Population Surveillance/methods*
;
Communicable Diseases/epidemiology*
;
Disease Outbreaks/prevention & control*
;
Epidemics
;
China/epidemiology*
9.Research and reflection on the diversified method system of multi-stages and multi-scenarios surveillance and early warning of infectious diseases.
Yu Hang MA ; Yi YIN ; Kai WANG ; Si Jia ZHOU ; Xun Liang TONG ; Yan Ming LI ; Xiao Li WANG ; Li Ping WANG ; Lu Zhao FENG ; Wei Zhong YANG ; Zhi Hang PENG
Chinese Journal of Preventive Medicine 2023;57(10):1529-1535
With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work. This paper briefly introduces the intelligent early warning model of infectious diseases, summarizes the emerging surveillance and early warning methods of infectious diseases, and seeks the possibility of diversified surveillance and early warning in different epidemic stages and different outbreak scenarios of infectious diseases. This paper puts forward the idea of constructing a diversified method system of infectious diseases surveillance and early warning based on multi-stages and multi-scenarios and discusses the future development trend of infectious diseases surveillance and early warning, in order to provide reference for improving the construction level of infectious diseases surveillance and early warning system in China.
Humans
;
Population Surveillance/methods*
;
Communicable Diseases/epidemiology*
;
Disease Outbreaks/prevention & control*
;
Epidemics
;
China/epidemiology*
10.The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia.
Jing Qian LIU ; Xia Wan YANG ; Xu LIU ; Jing HU ; Xiang Rong HU ; Xiao Xia LI ; Yu Fei ZHAO ; Yi Meng SHI ; Bao Hang ZHANG ; Wen Rui YANG ; Guang Xin PENG ; Xin ZHAO ; Feng Kui ZHANG
Chinese Journal of Hematology 2023;44(5):408-412
Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male
;
Female
;
Humans
;
Adolescent
;
Young Adult
;
Adult
;
Middle Aged
;
Aged
;
Aged, 80 and over
;
Anemia, Iron-Deficiency/epidemiology*
;
Sucrose/therapeutic use*
;
Ferric Compounds/therapeutic use*
;
Retrospective Studies
;
Iron/therapeutic use*
;
Hemoglobins/therapeutic use*

Result Analysis
Print
Save
E-mail