1.Epidemiological characteristics of hand-foot-mouth disease in China: A retrospective analysis
Chinese Journal of Biologicals 2025;38(02):155-160
Objective To understand the epidemiological characteristics of hand-foot-mouth disease(HFMD) in China, and provide evidence for the prevention and control of HFMD and vaccine clinical research design.Methods Using PubMed,China National Knowledge Infrastructure(CNKI) and Wanfang databases as retrieval sources, the Chinese and English articles on epidemiological characteristics of HFMD in China published from 2012 to 2021 were systematically retrieved, and relevant information was extracted. Chi-square test was used for the statistical analysis of the enterovirus detection rate, type composition, the distribution of gender, age, year, season, region and symptoms.Results A total of 327 articles were included in this study, of which 295 were included in the overall detection rate of HFMD enterovirus. The total number of people involved was 4 786 389, the number of enterovirus nucleic acid positive cases was 709 086, and the laboratory-diagnosed cases accounted for about 14. 81% of the total number. The four types with the highest detection rates were Coxsackievirus A6(CA6), enterovirus 71(EV71), CA16 and CA10. A total of 327 articles with 61 serotypes were included in the type proportion, and the four types more than 1% were EV71, CA16, CA6 and CA10, and other types such as CA4, CA2 and CA5accounted for a lower proportion. Among the laboratory-diagnosed cases, there were more men than women, with a sex ratio of about 1. 72∶1; children under 5 years of age were at high risk of HFMD, with 1 year of age being the most and 0 year of age being the least; the composition ratio of enteroviruses varied with the year and season, the proportion of EV71 showed an overall downward trend from 2008 to 2019, and the peak season for HFMD was from April to June. The distribution of HFMD exhibited geographical differences, and the top 5 provinces were: Guangdong, Jiangsu, Hebei, Hunan and Zhejiang; HFMD was mainly common type/mild type, and the proportion of EV71 in severe cases and deaths was significantly higher than that of other types.Conclusion The type composition of HFMD enteroviruses in China was mainly EV71, CA16, CA6 and CA10,while other types such as CA4, CA2 and CA5 accounted for a relatively low proportion. Type distribution varied in sex, age,year, season, region and symptoms.
2.A Case of Infliximab-Induced Paradoxical Psoriasis
Mei WANG ; Wurihan BAO ; Zhijing ZHANG ; Huiyun LI
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1425-1428
Paradoxical psoriasis is a special adverse drug reaction characterized by the new onset, exacerbation, or phenotypic change of psoriatic lesions during treatment with biological agents. In recent years, with the increasing use of biologics, this condition has garnered growing attention from clinicians. The pathogenesis of paradoxical psoriasis is complex and its clinical manifestations are highly heterogeneous. Diagnosis currently relies primarily on clinical features and medication history due to the lack of unified diagnostic criteria. Furthermore, treatment strategies—such as whether to discontinue the original biologic agent or switch therapies—remain controversial, posing significant challenges in clinical management.This article presents a case of paradoxical psoriasis occurring in a patient with ankylosing spondylitis following treatment with the tumor necrosis factor-α inhibitor (TNFi) infliximab. By discussing the clinical characteristics of this case, we aim to enhance clinicians' understanding of this condition, reduce misdiagnosis and underdiagnosis, and provide valuable insights for its diagnosis and treatment.
3.Chaihu Shugansan Combined with Ferulic Acid Regulates BDNF/TrkB Signaling Pathway and Monoamine Neurotransmitters in Frontal Cortex of Rat Model of CUMS
Yuexin LI ; Zhijing ZHANG ; Ziyi GUO ; Di YAN ; Xueyan HU ; Jianping YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):28-37
ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress (CUMS) and explore the mechanism from the histomorphology of frontal cortex, expression of key molecules in the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway, and changes in monoamine neurotransmitter levels. MethodsSixty adult male SD rats were randomized into six groups (n=10): blank control, depression model, Chaihu Shugansan (3.3 g·kg-1·d-1), ferulic acid (50 mg·kg-1·d-1), Chaihu Shugansan (3.3 g·kg-1·d-1) + ferulic acid (50 mg·kg-1·d-1), and fluoxetine (2.1 mg·kg-1·d-1). Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used, including fasting with free access to water for 24 h, water deprivation with free access to food for 24 h, wetting the bedding with water in the cage, restraint for 3 h, tail clamping for 1 min, swimming in ice water at 4 ℃, and day and night reversal. Each stimulus was used 1 to 3 times, and the modeling lasted for a total of 21 days. At the same time of stimulation, rats in each medication group were treated with corresponding agents by gavage, while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test, sucrose preference test, and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium, and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF, TrkB, and cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex. ResultsCompared with the blank control group, the depression model group showed reduced body mass (P<0.05, P<0.01), decreased number of crossings and rearings in the open field test and sucrose preference (P<0.01), prolonged time of immobility in the forced swimming test (P<0.01), reduced neuronal cells, increased necrotic cells, and darkening cell staining in the frontal cortex, down-regulated mRNA and protein levels of BDNF, TrkB, CREB, and lowered levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Compared with the depression model group, each intervention group showed improved general state, increased body mass (P<0.05), increased number of crossings (P<0.05), shortened immobility time in the forced swimming test (P<0.01), increased neuronal cells, reduced necrotic cells, and lightened cellular staining in the frontal cortex, up-regulated mRNA and protein levels of BDNF, TrkB and CREB, and elevated levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Moreover, the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex (P<0.05). The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex (P<0.05), and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test, up-regulating the mRNA levels of BDNF, TrkB, and CREB and the protein levels of BDNF and CREB in the frontal cortex, and increasing the DA content in the frontal cortex (P<0.05). ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover, the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.
4.Effect of pulmonary hypertension on the prognosis of patients with severe aortic stenosis after transcatheter aortic valve replacement: A systematic review and meta-analysis
Zhili WEI ; Yang CHEN ; Shuai DONG ; Hao CHEN ; Yang CHEN ; Zhijing AN ; Yalan ZHANG ; Bing SONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1173-1180
Objective To systematically evaluate the impact of pulmonary hypertension (PH) on the prognosis of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods A computerized search was conducted in CNKI, Wanfang Data, VIP, CBM, PubMed, The Cochrane Library, EMbase, and Web of Science databases from inception to June 2023 for cohort studies on the prognostic impact of PH in severe AS patients undergoing TAVR. Two researchers independently screened the literature, extracted data, and assessed the quality of included studies. Stata 17.0 software was used for meta-analysis. Results A total of 16 cohort studies were included, all with Newcastle-Ottawa Scale scores≥7. Meta-analysis results showed that, compared with AS patients without PH, those with PH had significantly higher 1-year all-cause mortality after TAVR [OR=2.10, 95%CI (1.60, 2.75), P<0.01], 30-day all-cause mortality [OR=2.09, 95%CI (1.54, 2.83), P<0.01], and cardiovascular mortality [OR=1.49, 95%CI (1.18, 1.90), P<0.01]. The differences between the two groups in major bleeding events, stroke, myocardial infarction, pacemaker implantation, and postoperative renal failure were not statistically significant. For outcome indicators with significant heterogeneity, subgroup analyses were performed based on PH measurement methods, diagnostic criteria, and different types of PH. The results showed that most subgroup combined results were consistent with the overall findings and that heterogeneity was significantly reduced. Conclusion PH significantly increases the 30-day all-cause mortality, 1-year all-cause mortality, and cardiovascular mortality in patients with severe AS undergoing TAVR.
5.Suppression of METTL3 expression attenuated matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the extracellular matrix in pelvic organ prolapse.
Xiuqi WANG ; Tao GUO ; Xiaogang LI ; Zhao TIAN ; Linru FU ; Zhijing SUN
Chinese Medical Journal 2025;138(7):859-867
BACKGROUND:
Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP.
METHODS:
Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF).
RESULTS:
Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05).
CONCLUSIONS
Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans
;
Female
;
Extracellular Matrix/metabolism*
;
Cell Differentiation/genetics*
;
Methyltransferases/metabolism*
;
Pelvic Organ Prolapse/pathology*
;
Fibroblasts/metabolism*
;
Myofibroblasts/metabolism*
;
Vagina/metabolism*
;
Cell Proliferation/physiology*
;
Cells, Cultured
;
Middle Aged
6.Analysis of the effect and safety of autologous blood reinfusion during venous-arterial extracorporeal membrane oxygenation weaning under controlled rotational speed.
Zhijing XU ; Yu'an GENG ; Congmei WANG ; Lu QI ; Yangang SHI ; Zishu XU ; Linkai HUANG ; Qian XU ; Ruifang LIU
Chinese Critical Care Medicine 2025;37(6):595-598
OBJECTIVE:
To investigate the efficacy and safety of autologous blood transfusion during weaning from venous-arterial extracorporeal membrane oxygenation (VA-ECMO) under controlled rotational speed.
METHODS:
A retrospective study was conducted, selecting patients who underwent extracorporeal membrane oxygenation (ECMO) and successfully weaned at the emergency and critical care medicine center of Henan Provincial Third People's Hospital from January 2023 to May 2024. General data including gender, age, body mass index (BMI), European system for cardiac operative risk evaluation (EuroScore), and disease types were collected. Vital signs at weaning [heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and peripheral oxygen saturation], parameters before and after weaning [B-type natriuretic peptide (BNP), hemoglobin (Hb), partial pressure of arterial oxygen (PaO2), partial pressure of arterial carbon dioxide (PaCO2), arterial lactate, central venous pressure (CVP), inferior vena cava collapsibility index, left ventricular ejection fraction (LVEF), and right heart load], post-weaning inflammatory markers at 1-day and 3-day [body temperature, white blood cell count (WBC), neutrophil percentage (NEU%), C-reactive protein (CRP), procalcitonin (PCT), interleukin-10 (IL-10)], as well as complications (infection, thrombosis, renal failure, gastrointestinal bleeding) and post-weaning blood return status were recorded. Patients were divided into an observation group (with post-weaning blood return) and a control group (without post-weaning blood return) based on the presence of blood return after weaning. The changes in the aforementioned parameters were compared between the two groups.
RESULTS:
A total of 62 patients were included, with 31 cases in each group. No statistically significant differences were observed between the two groups in baseline characteristics including gender, age, BMI, and EuroScore. At weaning, the observation group exhibited relatively stable vital signs, with no significant differences in heart rate, SBP, DBP, or peripheral oxygen saturation compared to the control group. After weaning, the observation group showed significantly lower levels of BNP, PaCO2, arterial lactate, CVP, and right heart load compared to pre-weaning values [BNP (ng/L): 2 325.96±78.51 vs. 4 878.48±185.47, PaCO2 (mmHg, 1 mmHg≈0.133 kPa): 35.23±3.25 vs. 40.75±4.41, arterial lactate (mmol/L): 2.43±0.61 vs. 6.19±1.31, CVP (cmH2O, 1 cmH2O≈0.098 kPa): 8.32±0.97 vs. 15.34±1.74, right heart load: 13.24±0.97 vs. 15.69±1.31, all P < 0.05], while Hb, PaO2, inferior vena cava collapsibility index, and LVEF were significantly higher than pre-weaning values [Hb (g/L): 104.42±9.78 vs. 96.74±6.39, PaO2 (mmHg): 94.12±7.78 vs. 75.51±4.39, inferior vena cava collapsibility (%): 28±7 vs. 17±3, LVEF (%): 62.41±6.49 vs. 45.30±4.51, all P < 0.05]. No statistically significant differences were found between the observation group and control group in these parameters. At 3 days post-weaning, the observation group demonstrated significantly lower levels of body temperature, WBC, NEU%, CRP, PCT, and IL-10 compared to 1 day post-weaning [body temperature (centigrade): 36.83±1.15 vs. 37.94±1.41, WBC (×109/L): 7.82±0.96 vs. 14.34±2.15, NEU%: 0.71±0.05 vs. 0.80±0.07; CRP (mg/L): 4.34±0.78 vs. 8.94±1.21, PCT (μg/L): 0.11±0.02 vs. 0.26±0.05, IL-10 (ng/L): 8.93±1.52 vs. 13.51±2.17, all P < 0.05], with no significant differences compared to the control group. No statistically significant differences were observed between the two groups in the incidence of complications including infection, thrombosis, renal failure, and gastrointestinal bleeding.
CONCLUSION
Autologous blood reinfusion during VA-ECMO weaning under controlled rotational speed is safe and effective, without increasing risks of infection or thrombosis.
Humans
;
Retrospective Studies
;
Extracorporeal Membrane Oxygenation/methods*
;
Blood Transfusion, Autologous
;
Male
;
Female
;
Adult
;
Middle Aged
;
Natriuretic Peptide, Brain/blood*
7.Analysis on relationship between CALU and prognosis of hepatocellular carcinoma patients and its mechanism based on transcriptome and single cell sequencing data
Xiaoyan WANG ; Xuelian LI ; Bin LIANG ; Wenfei TIAN ; Hailin MA ; Zhijing MO
Journal of Jilin University(Medicine Edition) 2025;51(2):447-459
Objective:To analyze the relationship between the expression level of calumenin(CALU)and the prognosis of hepatocellular carcinoma(HCC)patients by bioinformatics tools and establish the prognostic prediction nomogram,and to clarify its possible mechanism.Methods:The data of 374 HCC tissue samples were downloaded from The Cancer Genome Atlas(TCGA)database and the data of 160 normal tissue samples were down loaded from Genotype-Tissue Expression(GTEx)database.Paired sample t-test was used to analyze the difference in CALU expression between the HCC tissue samples and the paired adjacent normal tissue samples.Human Protein Atlas(HPA)database was used to verify the results.DESeq2 package was used to screen the differentially expressed genes(DEGs)between CALU low expression group and CALU high expression group in the HCC tissue samples.R package pROC was used to analyze the receiver operating characteristic(ROC)curve.Univariate and multivariate Cox regression analyses were used to confirm the prognosis value of CALU in the HCC patients with different clinicopathological characteristics,and ggplot2 package was used to construct the forest plot.R packages rms and survival were used to construct the nomogram and its calibration curve,and the diagnostic value of CALU in distinguishing HCC tissue from normal tissue was analyzed.The data from Kaplan-Meier Plotter database were used to further verify the relationship between CALU and the prognosis of HCC patients.The gene transcriptional expression data of 216 HCC samples obtained from GSE14520 dataset were used to verify the prediction accuracy of the nomogram.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to determine the function and enrichment pathways of the DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the significantly enriched gene sets of the DEGs.Single-cell sequencing data of 10 HCC tissue samples and 8 adjacent normal tissue samples obtained from GSE149614 dataset were used to verify the relationship between CALU and the prognosis of HCC patients and its mechanism.Results:Compared with normal tissue,the expression level of CALU mRNA in HCC tissue was significantly increased(P<0.001),and the expression level of CALU protein in HCC samples was also increased.A total of 928 DEGs were identified between CALU low expression group and CALU high expression group in the HCC samples,including 784 upregulated DEGs and 144 downregulated DEGs.The ROC analysis results indicated that CALU showed high diagnostic value in distinguishing cancer tissue from adjacent non-cancer tissue with an area under curve(AUC)of 0.839.Kaplan-Meier survival analysis showed that the survival rate of HCC patients in CALU high expression group was significantly lower than that in CALU group low expression(P<0.001).Univariate and multivariate Cox regression analyses results demonstrated that high expression of CALU was an independent risk factor of the prognosis in HCC patients,and a prognosis prediction nomogram was constructed.The applicability of nomogram on the prognosis of HCC was verified by GSE14520 dataset.The GO enrichment analysis results showed that DEGs were mainly enriched in pathways related to the oxidative stress,ferroptosis and cuproptosis(P<0.05).The KEGG enrichment analysis results showed that DEGs were mainly enriched in the pathways related to extracellular matrix(ECM)receptor interaction,linoleic acid metabolism and neuroactive ligand receptor interaction(P<0.05).The GSEA results showed that high expression of CALU may promote the G1-S phase transition of the cell cycle,ubiquitination protein polymerization and HCC progression,while low expression of CALU may activate oxidative stress,ferroptosis and cuproptosis in HCC cells.Single-cell sequencing analysis results showed that the expression level of CALU mRNA was significantly increased in HCC cells with advanced tumor stages.HCC_CALU_High cell subset was mainly related to ubiquitination,p53 and cell cycle(P<0.01),and HCC_CALU_Low cell subset was mainly related to oxidative stress,ferroptosis,and histone binding(P<0.01).Conclusion:The high expression of CALU may be related to the poor prognosis of HCC patients.The constructed nomogram of HCC prognosis shows favourable effect in predicting the survival rate of the HCC patients.The up-regulation of CALU may promote HCC progression by regulating the G1-S phase of the cell cycle and ubiquitination of protein,while down-regulation of CALU may inhibit HCC progression by inducing oxidative stress,ferroptosis and cuproptosis in cells.
8.Effectiveness of narrative exposure therapy for post-traumatic stress disorder in children and adolescents: a Meta-analysis
Junyu LIU ; Jianjian WANG ; Yuan LUO ; Liping ZHAO ; Zhijing LIU
Sichuan Mental Health 2024;37(2):179-186
BackgroundNarrative exposure therapy (NET), an integration of narrative therapy and exposure therapy, has been shown to be effective in relieving the symptoms of post-traumatic stress disorder (PTSD), which can help patients gain a deeper understanding of their trauma and is also considered to be quite safe. PTSD is highly prevalent in children and adolescents, while the effectiveness of NET intervention varies among the subjects. ObjectiveTo systematically evaluate the effectiveness of NET for PTSD in children and adolescents, so as to provide references for the clinical application of NET. MethodsOn August 1, 2022, the Cochrane Library, PubMed, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI), SinoMed, VIP and Wanfang database were searched from their inception to June 2022. Search was conducted with the use of a combination of medical subject heading and free text terms, and randomized controlled trials relevant to NET for PTSD in children and adolescents were collected. Then the quality of the controlled trials was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias (2011), and Meta-analysis was performed using RevMan 5.4 software. ResultsNine randomized controlled trials involving 394 children and adolescents with PTSD were included. Meta-analysis showed that NET and relaxation therapy reported comparable symptom relief in PTSD patients within 1 to 3 months after intervention (SMD=0.22, 95% CI: -0.84~1.28) and at 6 months after intervention (SMD=0.21, 95% CI: -0.75~1.17), while NET provided greater PTSD symptom relief than routine therapy both within 1 to 3 months after intervention (SMD=-0.66, 95% CI: -1.04~-0.27) and at 6 months after intervention (SMD=-0.77, 95% CI: -1.36~-0.19), with statistically significant differences. Regarding the alleviation of depressive symptoms, the effect was similar between NET and routine therapy within 1 to 3 months after intervention (SMD=-0.39, 95% CI: -0.98~0.21) and at 6 months after intervention (SMD=-0.74, 95% CI: -2.23~0.75). No statistical difference was demonstrated between NET and routine therapy in relieving psychological distress (SMD=-0.54, 95% CI: -2.14~1.07) and suppressing hyperorexia (SMD=-0.17, 95% CI: -0.54~0.19) 1 to 3 months after intervention. ConclusionNET yields a better outcome and a medium- and long-term effectiveness in alleviating symptoms of PTSD in children and adolescents compared with routine therapy, while it does not offer any significant advantages in improving depression symptoms, psychological distress and hyperorexia.
9.Establishment and analysis of an early prognosis model of patients with acute kidney injury in intensive care unit
Yu'an GENG ; Congmei WANG ; Zhijing XU ; Lu QI ; Yangang SHI ; Shiqiong SU ; Kai WANG ; Ruifang LIU
Chinese Critical Care Medicine 2024;36(2):178-182
Objective:To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance.Methods:A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI.Results:A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHEⅡ score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day " n", with y = 1.246?2 x1.164?9 and an R2 of 0.860?1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day " n", with y = -0.260?6 x2+3.010?7 x-1.612 and an R2 of 0.998?9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 μmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. Conclusion:The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.
10.Screening of UBE2S interacting protein and construction of prognostic model in hepatocellular carcinoma
Xiaoyan WANG ; Hao ZHANG ; Zehao GUO ; Jun CAO ; Zhijing MO
Journal of Jilin University(Medicine Edition) 2024;50(1):168-177
Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.


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