1.Therapeutic role of miR-26a on cardiorenal injury in a mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway.
Weijie NI ; Yajie ZHAO ; Jinxin SHEN ; Qing YIN ; Yao WANG ; Zuolin LI ; Taotao TANG ; Yi WEN ; Yilin ZHANG ; Wei JIANG ; Liangyunzi JIANG ; Jinxuan WEI ; Weihua GAN ; Aiqing ZHANG ; Xiaoyu ZHOU ; Bin WANG ; Bi-Cheng LIU
Chinese Medical Journal 2025;138(2):193-204
BACKGROUND:
Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD.
METHODS:
We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data.
RESULTS:
Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes.
CONCLUSIONS
Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals
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MicroRNAs/metabolism*
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Angiotensin II/toxicity*
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Mice
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Renal Insufficiency, Chronic/chemically induced*
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Mice, Knockout
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Disease Models, Animal
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Male
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Signal Transduction/genetics*
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LIM Domain Proteins/genetics*
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Mice, Inbred C57BL
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Cell Line
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Humans
2.Clinical Characteristics and Prognosis Analysis of Patients with Extranasal NK/T-Cell Lymphoma: A Multicenter Retrospective Study of Huaihai Lymphoma Working Group.
Hui-Rong SHAN ; Qing ZHANG ; Ling WANG ; Yu-Ye SHI ; Yu-Qing MIAO ; Tai-Gang ZHU ; Jing-Jing YE ; Xu-Dong ZHANG ; Liang WANG ; Zi-Yuan SHEN ; Wei SANG
Journal of Experimental Hematology 2025;33(1):93-100
OBJECTIVE:
To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL).
METHODS:
The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis.
RESULTS:
A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005).
CONCLUSION
The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Asparaginase/therapeutic use*
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Lymphoma, Extranodal NK-T-Cell/pathology*
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Prognosis
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Retrospective Studies
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Survival Rate
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Polyethylene Glycols
3.Expert consensus on the prevention and treatment of radiochemotherapy-induced oral mucositis.
Juan XIA ; Xiaoan TAO ; Qinchao HU ; Wei LUO ; Xiuzhen TONG ; Gang ZHOU ; Hongmei ZHOU ; Hong HUA ; Guoyao TANG ; Tong WU ; Qianming CHEN ; Yuan FAN ; Xiaobing GUAN ; Hongwei LIU ; Chaosu HU ; Yongmei ZHOU ; Xuemin SHEN ; Lan WU ; Xin ZENG ; Qing LIU ; Renchuan TAO ; Yuan HE ; Yang CAI ; Wenmei WANG ; Ying ZHANG ; Yingfang WU ; Minhai NIE ; Xin JIN ; Xiufeng WEI ; Yongzhan NIE ; Changqing YUAN ; Bin CHENG
International Journal of Oral Science 2025;17(1):54-54
Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans
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Chemoradiotherapy/adverse effects*
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Consensus
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Risk Factors
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Stomatitis/etiology*
4.Association of Dietary Preferences with All-Cause and Cause-Specific Mortality: Prospective Cohort Study of 1,160,312 Adults in China.
Wen Ru SHI ; Si Tong WEI ; Qing Mei HUANG ; Huan CHEN ; Dong SHEN ; Bo Feng ZHU ; Chen MAO
Biomedical and Environmental Sciences 2025;38(9):1120-1128
OBJECTIVE:
Although dietary preferences influence chronic diseases, few studies have linked dietary preferences to mortality risk, particularly in large cohorts. To investigate the relationship between dietary preferences and mortality risk (all-cause, cancer, and cardiovascular disease [CVD]) in a large adult cohort.
METHODS:
A cohort of 1,160,312 adults (mean age 62.48 ± 9.55) from the Shenzhen Healthcare Big Data Cohort (SHBDC) was analyzed. Hazard ratios ( HRs) for mortality were estimated using the Cox proportional hazards model.
RESULTS:
The study identified 12,308 all-cause deaths, of which 3,865 (31.4%) were cancer-related and 3,576 (29.1%) were attributed to CVD. Compared with a mixed diet of meat and vegetables, a mainly meat-based diet (hazard ratio [ HR] = 1.13; 95% confidence interval [ CI]: 1.02, 1.27) associated with a higher risk of all-cause mortality, while mainly vegetarian ( HR = 0.87; 95% CI: 0.78, 0.97) was linked to a reduced risk. Furthermore, there was a stronger correlation between mortality risk and dietary preference in the > 65 age range.
CONCLUSION
A meat-based diet was associated with an increased risk of all-cause mortality, whereas a mainly vegetarian diet was linked to a reduced risk.
Humans
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China/epidemiology*
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Middle Aged
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Male
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Female
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Prospective Studies
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Aged
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Cardiovascular Diseases/mortality*
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Diet/statistics & numerical data*
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Neoplasms/mortality*
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Adult
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Cause of Death
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Food Preferences
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Proportional Hazards Models
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Mortality
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Cohort Studies
5.Associations of Genetic Risk and Physical Activity with Incident Chronic Obstructive Pulmonary Disease: A Large Prospective Cohort Study.
Jin YANG ; Xiao Lin WANG ; Wen Fang ZHONG ; Jian GAO ; Huan CHEN ; Pei Liang CHEN ; Qing Mei HUANG ; Yi Xin ZHANG ; Fang Fei YOU ; Chuan LI ; Wei Qi SONG ; Dong SHEN ; Jiao Jiao REN ; Dan LIU ; Zhi Hao LI ; Chen MAO
Biomedical and Environmental Sciences 2025;38(10):1194-1204
OBJECTIVE:
To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease.
METHODS:
This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used.
RESULTS:
During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity.
CONCLUSION
Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans
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Pulmonary Disease, Chronic Obstructive/epidemiology*
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Exercise
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Male
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Female
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Middle Aged
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Prospective Studies
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Aged
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Genetic Predisposition to Disease
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Risk Factors
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United Kingdom/epidemiology*
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Incidence
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Adult
6.Evaluation value of TRIM21 expression in alveolar macrophages for the serverity and prognosis of patients with severe pneumonia complicated by ARDS
Kai-Kai SHEN ; Yu-Qing WEI ; Jia-Jia JIN ; Xin-Yu ZHOU ; Hao XU ; Tang-Feng LYU ; Yong SONG
Medical Journal of Chinese People's Liberation Army 2025;50(7):817-823
Objective To evaluate the value of tripartite motif-containing protein 21(TRIM21)mRNA expression in alveolar macrophages for the serverity and prognosis of patients with severe pneumonia complicated by acute respiratory distress syndrome(SP-ARDS).Methods A retrospective analysis was conducted on 42 SP-ARDS patients(SP-ARDS group)and 15 outpatient healthy controls(control group)admitted to the Department of Respiratory and Critical Care Medicine,Jinling Hospital Affilicated to Medical School of Nanjing University,from November 2023 to June 2024.Bronchoalveolar lavage fluid was collected,and alveolar macrophages were isolated.The expression levels of TRIM21 mRNA were quantified using qPCR.Differences in TRIM21 mRNA expression levels,clinical characteristics,and relevant laboratory test results were compared between the two groups.Correlations between TRIM21 mRNA expression and SP-ARDS severity,28-day mortality,inflammatory indicators,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores,duration of mechanical ventilation,and ICU stay were analyzed using Pearson or Spearman correlation analysis.Logistic regression analysis was used to identify risk factors for 28-day mortality,and the predictive value of each factor was evaluated using receiver operating characteristic(ROC)curves.Results Compared with control group,the expression levels of TRIM21 mRNA,white blood cell counts,neutrophil-to-lymphocyte ratio(NLR),and C-reactive protein(CRP),and procalcitonin(PCT)levels increased(P<0.05),and hemoglobin levels decreased(P<0.05)in SP-ARDS group.No significant differences were observed in gender,age,smoking history,alcohol consumption,underlying disease history,and platelet count between the two groups(P>0.05).TRIM21 mRNA expression level in SP-ARDS patients was positively correlated with ARDS severity(P<0.05).Additionally,non-survivors within 28 days had a significantly higher expression level of TRIM21 mRNA compared to survivors(P<0.001).Correlation analysis indicated that the relative expression level of TRIM21 mRNA in SP-ARDS patients was positively correlated with CRP(r=0.309,P<0.05),NLR(r=0.422,P<0.01),PCT(r=0.561,P<0.001),APACHE Ⅱ score(r=0.615,P<0.001),and duration of mechanical ventilation(r=0.665,P<0.001).Logistic regression analysis revealed that elevated expression levels of TRIM21 mRNA(OR=2.886,P=0.043)and higher APACHE Ⅱ scores(OR=1.546,P=0.037)were independent risk factors for 28-day mortality in SP-ARDS patients.The areas under the ROC curves(AUCs)for predicting 28-day mortality using TRIM21 mRNA expression level and APACHE Ⅱ score were 0.889 and 0.874,respectively,with optimal cut-off values of 5.21 and 20.5 points,respectively.The combined AUC for prediction was 0.962.Conclusion Increased TRIM21 mRNA expression in alveolar macrophages of SP-ARDS patients is positively correlated with disease severity and may serve as a potential predictive marker for 28-day survival in SP-ARDS patients.
7.Clinical value of DSA flat head CT in predicting symptomatic intracranial hemorrhage in patients with acute anterior circulation-large vessel occlusion cerebral infarction within 24 hours after operation
Qing SHEN ; Yinghua HUANG ; Kai ZHANG ; Wei JIANG ; Ganhui DING
Journal of Interventional Radiology 2025;34(8):877-881
Objective To discuss the clinical value of flat head CT of two-way digital flat angiography system(DSA)in predicting symptomatic intracranial hemorrhage in patients with acute anterior circulation-large vessel occlusion cerebral infarction occurring within 24 hours after operation.Methods A total of 264 patients with acute anterior circulation-large vessel occlusion cerebral infarction,who were admitted to the Shanghai Changhai hospital to receive treatment from January 2020 to January 2023,were selected for this study.Mechanical thrombectomy was carried out in all the patients,and DSA flat head CT examination was performed 24 hours after operation.According to whether the postoperative DSA plate head CT scan showed high-density shadow or not,the patients were divided into observation group(showing high-density shadow,n=176)and control group(showing no high-density shadow,n=88).The clinical data,therapeutic regimen,and intracranial hemorrhage within 24 hours after operation were compared between the two groups.Taking head CT results as the standard,the clinical value of DSA flat head CT scan performed immediately after operation in predicting symptomatic intracranial hemorrhage occurring within 24 hours after operation was evaluated.Results Among the 264 patients with acute anterior circulation-large vessel occlusion cerebral infarction,118 patients developed intracranial hemorrhage within 24 hours after operation,including 24 patients(20.34%)having symptomatic intracranial hemorrhage.No statistically significant differences in clinical data and therapeutic regimen existed between the two groups(P>0.05).The sensitivity,specificity and accuracy of DSA flat head CT scan performed immediately after operation in predicting intracranial hemorrhage occurring within 24 hours after operation in the observation group were 97.46%,58.22%and 75.76%respectively.The detection rate of symptomatic intracranial hemorrhage occurring within 24 hours after operation in the observation group was higher than that in the control group,the difference between the two groups were statistically significant(P<0.05).The sensitivity,specificity and accuracy of DSA flat head CT scan performed immediately after operation in predicting symptomatic intracranial hemorrhage occurring within 24 hours after operation were 87.50%,57.48%and 40.15%respectively.The sensitivity,specificity and accuracy of DSA flat head CT scan in predicting the transformation of cerebral hemorrhage were 95.67%,63.12%and 80.23%respectively.Conclusion In patients with acute anterior circulation-large vessel occlusion cerebral infarction,who develop intracranial hemorrhage within 24 hours after mechanical thrombectomy,DSA flat head CT scan performed immediately after operation often shows high-density shadow,which is very helpful in predicting the risk of postoperative intracranial hemorrhage,the clinicians should make an early diagnosis and response to a possible symptomatic intracranial hemorrhage.
8.Analysis of characteristics of males with autologous sperm preservation in Anhui human sperm bank
Hang LI ; Qunshan SHEN ; Qing TAN ; Feifei FU ; Lei GE ; Xiaohong MAO ; Gang ZHAO ; Ping ZHOU ; Zhaolian WEI
Acta Universitatis Medicinalis Anhui 2024;59(6):957-960
Objective To analyze the characteristics of males with autologous sperm preservation(ASP)in Anhui human sperm bank,and to explore the future direction of ASP in human sperm bank.Methods The basic infor-mation of males applied for ASP in Anhui human sperm bank from January 2019 to December 2023 was retrospec-tively analyzed.Results During this period,there were 424 males applied for ASP.93.40%(396/424)came from Anhui Province,of which 46.46%(197/424)came from Hefei.The age range of them was 15 to 59 years old.66.04%(280/424)had a college degree or above.23.11%(98/424)were employees of public institutions or enterprises.26.89%(114/424)were unmarried and 89.39%(379/424)were childless.67.45%(286/424)patients applied for ASP because of assisted reproductive technology treatment.15.33%(65/424)patients did it due to tumors,among which testicular cancer,lymphoma,leukemia and seminoma were the main reasons.A total of 1 163 semen samples were saved,and 53 males had used their sperm.Conclusion Only a few people applied for ASP,and the characteristics of males with ASP can be used to further strengthen publicity for key groups,espe-cially cancer patients,so as to benefit more people with autologous sperm preservation.
9.Relationship between protein-energy wasting and parathyroid hormone levels in patients undergoing maintenance hemodialysis
Qing LI ; Shihua SHEN ; Weile WANG ; Jingjing LIU ; Yiya WANG ; Wei ZHU ; Jing YANG
Chinese Journal of Primary Medicine and Pharmacy 2024;31(4):553-559
Objective:To investigate the relationship between protein-energy wasting (PEW) and parathyroid hormone (PTH) levels in patients undergoing maintenance hemodialysis.Methods:A cross-sectional study was conducted to enroll 150 adult patients undergoing maintenance hemodialysis at The Third Affiliated Hospital of Anhui Medical University from January 2022 to May 2023. These patients were categorized into four groups based on their PTH levels: low PTH group (< 150 ng/L), standard PTH group (150-300 ng/L), very high PTH group (300-600 ng/L), and extreme high PTH group (> 600 ng/L). The diagnosis of PEW was determined using the diagnostic criteria proposed by the International Society of Renal Nutrition and Metabolism (ISRNM). Logistic regression analysis was performed to investigate the association between PEW and PTH levels.Results:Among the 150 patients undergoing maintenance dialysis, 52 (34.7%) were diagnosed with PEW. The prevalence of PEW was significantly higher in the low PTH group compared with the standard, very high, and extreme high PTH groups ( χ2 = 20.64, all P < 0.05). Univariate logistic regression analysis revealed a strong association between low PTH levels ( OR = 13.810, 95% CI: 2.907-65.603, P = 0.001) and an increased risk of PEW. The risk of PEW in the low PTH group was 13.810 times higher than that in the extreme high PTH group. Multivariate logistic regression analysis further confirmed that low PTH levels ( OR = 19.891, 95% CI: 1.810-218.620, P = 0.014) and low C-reactive protein levels ( OR = 1.056, 95% CI: 1.015-1.099, P = 0.007) were independently associated with an increased risk of PEW. Higher hemoglobin levels ( OR = 0.959, 95% CI: 0.931-0.988, P = 0.005) and a larger middle upper arm circumference ( OR = 0.544, 95% CI: 0.338-0.875, P = 0.012) were independently associated with a reduced risk of PEW. The risk of PEW in the low PTH group was 19.891 times higher than that in the extreme high PTH group. However, there was no significant difference in the risk of PEW in the standard and very high PTH groups compared with the extreme high PTH group (both P > 0.05). Conclusion:The risk of PEW is markedly elevated in patients with low PTH levels, emphasizing the importance of clinical attention to the prevention and treatment of low PTH levels. Addressing this issue may hold great value in reducing the risk of PEW.
10.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.


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