1.RGL1 overexpression promotes metastasis of colorectal cancer by upregulating motile focal adhesion assembly via activating the CDC42/RAC1 complex.
Nuozhou WENG ; Bin TAN ; Wentao ZENG ; Jiayu GU ; Lianji WENG ; Kehong ZHENG
Journal of Southern Medical University 2025;45(5):1031-1038
OBJECTIVES:
To investigate the regulatory role of Ral guanine nucleotide dissociation stimulator-like 1 (RGL1) in metastasis of colorectal cancer (CRC).
METHODS:
We analyzed the differential expression of RGL1 between metastatic and non-metastatic CRC in GEO database, and examined its expression in 25 patients with metastatic CRC and 25 patients with non-metastatic CRC treated in Zhujiang Hospital between January, 2020 and December, 2022 using quantitative PCR (qPCR) and immunohistochemistry. HCT116 cell lines with stable RGL1 overexpression and SW480 cells with RGL1 knockdown were established using lentiviral vecors, and the changes in invasion and migration abilities of the cells were assessed using Transwell invasion and migration assays. The transduced cells were injected into the serosa of the cecum of nude mice, and tumor growth and liver metastasis were observed 8 weeks later. Fibronectin adhesion assays and immunofluorescence experiments were employed to assess the relationship between RGL1 and focal adhesion formation, and co-immuno-precipitation assays were performed to explore the interaction between RGL1 and GTPase activation.
RESULTS:
Compared with non-metastatic CRC, metastatic CRC showed significantly upregulated expression of RGL1. HCT116 cells overexpressing RGL1 exhibited obviously enhanced migration and invasion in vitro with increased capacity for liver metastasis in nude mice. RGL1 overexpression strongly accelerated focal adhesion assembly, facilitated the formation of motile focal adhesions, and enhanced the binding of activated CDC42/RAC1 complex to RGL1.
CONCLUSIONS
RGL1 is highly expressed in metastatic CRC and promotes distant metastasis of CRC by activating the CDC42/RAC1 complex to facilitate the formation of motile focal adhesions. These findings suggest that RGL1 can potentially serve as a therapeutic target for CRC metastasis.
Humans
;
Colorectal Neoplasms/metabolism*
;
cdc42 GTP-Binding Protein/metabolism*
;
Animals
;
Mice, Nude
;
rac1 GTP-Binding Protein/metabolism*
;
Cell Movement
;
Mice
;
Focal Adhesions/metabolism*
;
Neoplasm Metastasis
;
Cell Line, Tumor
;
HCT116 Cells
;
Up-Regulation
;
Neoplasm Invasiveness
;
Adaptor Proteins, Signal Transducing
;
Female
;
Rho Guanine Nucleotide Exchange Factors
3.Central venous oxygen saturation changes as a reliable predictor of the change of CI in septic shock: To explore potential influencing factors.
Ran AN ; Xi-Xi WAN ; Yan CHEN ; Run DONG ; Chun-Yao WANG ; Wei JIANG ; Li WENG ; Bin DU
Chinese Journal of Traumatology 2025;28(1):43-49
PURPOSE:
Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO2) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO2 (ΔScvO2) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors.
METHODS:
In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase in cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO2 and its change before and after fluid challenge. The Shapiro-Wilk test was used for the normality of continuous data. Data comparison between fluid responders and non-responders was conducted using a two-tailed Student t-test, Mann Whitney U test, and Chi-square test. Paired t-tests were used for normally distributed data, while the Wilcoxon signed-rank test was used for skewed data, to compare data before and after fluid challenge.
RESULTS:
Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO2 (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO2, with R2 = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO2 (R2 = 0.245, p < 0.001). ΔScvO2 had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006).
CONCLUSION
ΔScvO2 served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change in CI was the sole contributing factor to the ΔScvO2. In stable hemoglobin conditions, the absolute value of ScvO2 could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.
Humans
;
Shock, Septic/blood*
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Oxygen Saturation
;
Aged
;
Fluid Therapy
;
Oxygen/blood*
;
Oxygen Consumption
;
Adult
4.Over 20-year Follow-up Result of Total Knee Arthroplasty for Knee Arthropathy: A Single Center Cohort Study
Yiming XU ; Mingwei HU ; Wei ZHU ; Muyang YU ; Jin LIN ; Jin JIN ; Wenwei QIAN ; Bin FENG ; Xisheng WENG
Medical Journal of Peking Union Medical College Hospital 2025;16(1):35-41
To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up. This study was based on a previous cohort study that had completed follow-up. We retrospectively collected clinical data of patients with knee arthropathy (including knee osteoarthritis and knee rheumatoid arthritis) who received the first TKA operation in Peking Union Medical College Hospital from 1993 to 2002 and were followed up for more than 20 years, and conducted a unified follow-up on them in November 10, 2024 (the last follow-up). Kaplan-Meier curve was used to evaluate the survival rate. Hospitals for special surgery (HSS) scores and joint range of motion (ROM) were compared before surgery, 10 years after surgery and at the last follow-up to evaluate the clinical efficacy of TKA. Likert scale was used to evaluate patient satisfaction at the last follow-up. A total of 226 patients (246 knees) received their first TKA in Peking Union Medical College Hospital from 1993 to 2002 and were followed up for more than 10 years. Among them, 104 patients (131 knees) were included in the study at the last follow-up, including 21 patients (24 knees) with prosthesis in place, 18 patients (18 knees) who underwent reoperation for various reasons, and 65 patients (89 knees) who died from non-TKA surgical causes. Up to the last follow-up, there were 29 patients (35 knees) with an average follow-up of more than 20 years, and 12 patients (16 knees) completed HSS score, ROM measurement and patient satisfaction evaluation. Kaplan-Meier curve showed that the 10-year, 15-year, 20-year, and 25-year survival rates were 93.6%, 92.4%, 89.8%, and 71.8%, respectively. The HSS score at the last follow-up was lower than that at 10- year postoperative follow-up[(84.69±11.03) scores TKA treatment for knee arthropathy has high long-term prosthesis survival rate, significant improvement of knee joint function and high patient satisfaction.
5.Early Postoperative Safety of Total Hip Arthroplasty in Systemic Lupus Erythematosus Patients
Xingdong YANG ; Muyang YU ; Yiming XU ; Wei ZHU ; Mingwei HU ; Xisheng WENG ; Bin FENG
Medical Journal of Peking Union Medical College Hospital 2025;16(1):42-49
To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE). The data of patients who underwent THA at Peking Union Medical College Hospital from June 2012 to April 2024 were retrospectively and consecutively collected. The patients were categorized into SLE group and control group based on the presence or absence of SLE. Using propensity score matching, we matched patients in the two groups at a 1∶1 ratio according to gender, age, and surgical side. Subsequently, we compared the clinical characteristics, incidence of major complications within 30 days postoperatively, and allogeneic blood transfusion rates between the two groups. A total of 270 patients in the SLE group who met the inclusion and exclusion criteria were selected. Within 30 days postoperatively, 18 cases (6.67%) experienced major complications, including 2 cases (0.74%) of upper respiratory tract infection, 2 cases (0.74%) of pulmonary infection, 3 cases (1.11%) of urinary tract infection, 2 cases (0.74%) of other systemic infection, 5 cases (1.85%) of poor wound healing, 1 case (0.37%) of wound infection, 1 case (0.37%) of gastrointestinal complications, 1 cases (0.37%) of shock, and 1 case (0.37%) of SLE flare-up. The allogeneic blood transfusion rate was 22.59% (61/270). After propensity score matching, 163 cases from SLE and control groups were included for analysis. (1) Regarding medical complications, compared with control group, SLE group showed significant differences in osteoporosis, respiratory system disorders, gastrointestinal diseases, urinary system disorders, hematologic abnormalities, and secondary or concomitant rheumatic diseases (all The incidence of major complications within 30 days following THA in patients with SLE was significantly higher than that in non-SLE patients, while the rate of allogeneic blood transfusion remained comparable. To ensure the safety of THA surgery for patients with SLE, it is important to optimize the patient's condition and achieve stabilization prior to surgery. Additionally, strict perioperative management must be forced.
6.Implementation Strategy and Thinking of Clinical Diagnostic Operations Management Based on Closed-loop Management Model
Shaowei WU ; Shixiao XIA ; Chao YANG ; Bin LV ; Zhe HE ; Yesheng WANG ; Yuxiong WENG ; Jiahong XIA
Chinese Hospital Management 2025;45(3):60-62
Refinement and standardisation of the management of clinical diagnostic and treatment operations is a key aspect of achieving high-quality development in hospitals.By analysing the management status quo of clinical diagnosis and treatment operations in hospitals,it combed the problems existing in this field.Based on the closed-loop management model,it proposed measures and recommendations to promote the continuous optimisation of the management of clinical diagnostic operations in hospitals.Hospitals should establish hospital-level operation catalog and conduct classified management,authorize operators and dynamically adjust them,carry out operation quality management,pay attention to information management of operation management,and combine operation management with physician performance management.
7.Comparison of nutritional risk assessment in patients with digestive tract tumors during perichemotherapy assessed by different nutritional risk screening methods
Cong HAN ; Ai-Bin LIU ; Wei CHEN ; Zai-Hu MU ; Xiao-Jun JING ; Yan-Hong WENG
Parenteral & Enteral Nutrition 2025;32(2):90-94
Objective:To compare the application of Micronutritional Risk Assessment(MNA),Universal Screening Tool for Malnutrition(MUST)and Nutritional Risk Screening 2002(NRS2002)in nutritional risk assessment among patients with digestive tract tumors during perichemotherapy,based on the Global Leadership Initiative on Malnutrition(GLIM)standard.Methods:A prospective cross-section study was conducted,including 114 patients with digestive tract tumors hospitalized by Department of General Surgery,Huangshan Shoukang Hospital from January 2020 to December 2021.All patients were evaluated by GLIM assessment,the correlation between GLIM and MNA,MUST and NRS 2002 screening results was compared,and the consistency among different methods was compared.Patients were divided into malnourished group(nutritional risk group)or normal nourished group according to the results of the three tools.The differences in single anthropometric or test indicators between the groups were compared.Results:According to GLIM,the proportion of malnutrition was 36.8%.The proportion of malnutrition evaluated by MNA,MUST,and NRS2002 were 63.2%,47.4%,and 32.5%,respectively.The sensitivity and negative predictive value of MNA in assessing nutrition-related risks were the highest,while the specificity,Jorden index,Kappa value and positive predictive value of NRS2002 were the highest.There were statistical differences in levels of body mass index,hemoglobin(Hb),triglyceride,total cholesterol,albumin,prealbumin(P-ALB),blood creatinine,lymphocyte counts,and hospitalization costs between two groups assessed by three different tools(P<0.05).Levels of Hb and P-ALB were statistically different between the two groups of the three screening tools.Conclusion:Based on GLIM evaluation results,MNA and other nutritional screening tools are applicable to the assessment of nutritional risks of patients with gastrointestinal cancer during perichemotherapy due to the joint evaluation of measurement indicators.The MNA is more recommended with the highest detection rate and sensitivity for nutritional risks assessment.
8.Risk and protective factors associated with adolescent depression in Singapore: a systematic review.
Wei Sheng GOH ; Jun Hao Norman TAN ; Yang LUO ; Sok Hui NG ; Mohamed Sufyan Bin Mohamed SULAIMAN ; John Chee Meng WONG ; Victor Weng Keong LOH
Singapore medical journal 2025;66(1):2-14
INTRODUCTION:
Adolescent depression is prevalent, and teen suicide rates are on the rise locally. A systemic review to understand associated risk and protective factors is important to strengthen measures for the prevention and early detection of adolescent depression and suicide in Singapore. This systematic review aims to identify the factors associated with adolescent depression in Singapore.
METHODS:
A systematic search on the following databases was performed on 21 May 2020: PubMed, EMBASE and PsycINFO. Full texts were reviewed for eligibility, and the included studies were appraised for quality using the Newcastle Ottawa Scale. Narrative synthesis of the finalised articles was performed through thematic analysis.
RESULTS:
In total, eight studies were included in this review. The four factors associated with adolescent depression identified were: (1) sociodemographic factors (gender, ethnicity); (2) psychological factors, including childhood maltreatment exposure and psychological constructs (hope, optimism); (3) coexisting chronic medical conditions (asthma); and (4) lifestyle factors (sleep inadequacy, excessive internet use and pathological gaming).
CONCLUSION
The identified factors were largely similar to those reported in the global literature, except for sleep inadequacy along with conspicuously absent factors such as academic stress and strict parenting, which should prompt further research in these areas. Further research should focus on current and prospective interventions to improve mental health literacy, targeting sleep duration, internet use and gaming, and mitigating the risk of depression in patients with chronic disease in the primary care and community setting.
Humans
;
Singapore/epidemiology*
;
Adolescent
;
Risk Factors
;
Depression/etiology*
;
Protective Factors
;
Male
;
Female
;
Life Style
;
Suicide
9.Changing prevalence and antibiotic resistance profiles of carbapenem-resistant Enterobacterales in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Wenxiang JI ; Tong JIANG ; Jilu SHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yuanhong XU ; Ying HUANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yingchun XU ; Xiaojiang ZHANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hong ZHANG ; Chun WANG ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(4):445-454
Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43%(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38%,9.73%,and 8.47%,respectively.The prevalence of CRE strains in Escherichia coli was 1.99%.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)%,followed by blood(20.88±3.40)%and urine(18.40±3.45)%.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)%.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.
10.Changing distribution and antibiotic resistance profiles of the respiratory bacterial isolates in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Ying FU ; Yunsong YU ; Jie LIN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(4):431-444
Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6%of the isolates were Gram-negative bacteria and 17.4%were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)%and(94.0±0.1)%,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P<0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9%.The prevalence of penicillin-resistant S.pneumoniae was 1.4%.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8%and 41.3%,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7%,20.8%,9.4%,29.8%,and 73.3%,respectively.The prevalence of β-lactamase was 96.1%in Moraxella catarrhalis and 60.0%in Haemophilus influenzae.The H.influenzae isolates from children(<18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P<0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

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