1.Necroptosis-related diagnostic biomarkers of bronchopulmonary dysplasia and their relationships with immune microenvironment
Haixia TU ; Changjiang FANG ; Ping GAN ; Nana PENG ; Yunyun GU ; Honghua JIANG ; Weiwei HOU ; Guihua SHU
Journal of Clinical Medicine in Practice 2025;29(14):80-87
Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P<0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P<0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P<0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.
2.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
3.Feasibility of undergoing day surgery at 3rd week after infection with SARS-CoV-2 in children
Yuting SONG ; Weiwei CAI ; Wei GU ; Shan ZHONG
Chinese Journal of Anesthesiology 2024;44(1):31-35
Objective:To retrospectively analyze the feasibility of undergoing day surgery at 3rd week after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children.Methods:The clinical data from children who underwent day surgery from November 1, 2022 to February 28, 2023, with operation time ≤1 h, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, regardless of gender, aged≤14 yr, with body mass index of 10-30 kg/m 2, were divided into SARS-CoV-2 group and control group according to whether the children had been infected with the SARS-CoV-2. The main outcome measure was the incidence of respiratory system-related complications within 30 days after surgery. Secondary outcome measures included the rate of unplanned ventilation, delayed discharge and secondary admission within 30 days after surgery. Preoperative creatine kinase isoenzyme (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), white blood cell count, C-reactive protein (CRP) level, grade of oropharyngeal mucosa inflammation, operation time, emergence time, intraoperative respiratory depression, laryngeal spasm, hypoxemia, hypotension, incidence of sinus bradycardia and rate of additional rescue drugs were recorded. Results:There were 337 cases in SARS-CoV-2 group and 1 396 cases in control group. Compared with control group, CK-MB concentrations were significantly increased, and the Hb concentration was decreased before surgery in SARS-CoV-2 group ( P<0.05). There were no statistically significant differences in the incidence of respiratory system-related complications, unplanned ventilation, delayed discharge and rate of postoperative secondary admission, preoperative AST and ALT concentrations, white blood cell count, CRP concentrations, grade of oropharyngeal mucosa inflammation, operation time, intraoperative respiratory depression, laryngeal spasm, hypoxemia, hypotension, incidence of sinus bradycardia, rate of additional rescue drugs and emergence time between the two groups ( P>0.05). Conclusions:Feasibility of undergoing day surgery is good at the third week after being infected with the SARS-CoV-2 in children.
4.Preliminary clinical application of novel magnetic navigation and ultrasound-guided percutaneous transhepatic cholangiography drainage through the right liver duct for malignant obstructive jaundice
Han ZHUO ; Chen WU ; Zhongming TAN ; Weiwei TANG ; Deming ZHU ; Yan XU ; Jie ZHAO ; Jianping GU ; Xuehao WANG ; Jinhua SONG
Chinese Journal of Internal Medicine 2024;63(3):284-290
Objective:To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice.Methods:Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People′s Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group ( n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group ( n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results:The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35, P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81, P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion:Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.
5.Mechanism of circSKA3/miR-3163/ADAM9 gene axis regulating proliferation,migration,invasion and expressions of immune factors in ovarian cancer SKOV3 cells
Jian ZHANG ; Weiwei GE ; Donghua GU ; Kai GUO ; Xialiang LU
Chinese Journal of Immunology 2024;40(11):2304-2309
Objective:To explore mechanism of regulation of proliferation,migration,invasion and expressions of immune factors of ovarian cancer SKOV3 cells by circSKA3/miR-3163/disintegrin-metalloproteinase 9(ADAM9)gene axis.Methods:qRT-PCR was used to detect circSKA3 and miR-3163 expressions in ovarian cancer tissues and paracancerous tissues.Western blot was used to detect ADAM9 protein level in tissues.SKOV3 cells were selected for cell experiment in vitro,and divided into sh-NC group,sh-circSKA3 group,miR-NC group,miR-3163 group,sh-circSKA3+anti-miR-3163 group,sh-circSKA3+pcDNA-ADAM9 group.circSKA3 and miR-3163 expressions in SKOV3 cells were detected by qRT-PCR.CCK-8,scratch test and Transwell were used to detect cell proliferation activity,migration and invasion ability.ELISA was used to detect expressions of TNF-α,IL-6 and IL-10.Double luciferase report experiment verified targeting relationship between circSKA3 with miR-3163,miR-3163 and ADAM9.Western blot was used to detect levels of ADAM9,matrix metalloproteinase-2(MMP-2)and MMP-9 in SKOV3 cells.Results:Com-pared with paracancerous tissues,circ-SKA3 and ADAM9 expressions were increased,and miR-3163 expression was decreased in ovarian cancer tissues(P<0.05).Compared with sh-NC group/miR-NC group,sh-circSKA3 group/miR-3163 group showed decreased cell proliferative activity and healing rate,decreased number of invasive cells,MMP-2,MMP-9 proteins and TNF-α and IL-6 expres-sions were decreased,expression of IL-10 was increased(P<0.05).circSKA3 could targeting regulate expression of miR-3163,and miR-3163 could targeting bind to ADAM9(P<0.05).Compared with sh-circSKA3 group,cell proliferation activity and scratch healing rate in sh-circSKA3+anti-miR-3163 and sh-circSKA3+pcDNA-ADAM9 groups were increased,number of invasive cells was in-creased,MMP-2,MMP-9 protein and TNF-α,IL-6 expressions were increased,while expression of IL-10 was decreased(P<0.05).Conclusion:Silencing circSKA3 expression can reduce expression of ADAM9 by up-regulating miR-3163 expression,inhibit ovarian cancer cell proliferation,migration and invasion,and regulate immune factor expression.
6.Correlation between interleukin-2 receptor and CD4+/CD8+ on the activity of lupus nephritis
Huihui GU ; Weiwei WANG ; Anni SHI ; Xiaoxia CHENG
China Modern Doctor 2024;62(10):13-16
Objective To investigate the correlation between serum interleukin-2 receptor(IL-2R),CD4+/CD8+ and disease activity in patients with lupus nephritis(LN).Methods A total of 38 patients with LN who were treated in Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from March 2021 to December 2022 were enrolled in LN group,and 40 healthy persons who underwent physical examination in the hospital during the same period were included in healthy control group.General clinical data,systemic lupus erythematosus disease activity index(SLEDAI)and pathological classification were collected.LN patients were divided into active group and inactive group according to SLEDAI score,and the difference of clinical indicators between two groups was compared.Results The hemoglobin(Hb),platelet count,albumin(ALB),complement C3 and C4 in LN group were significantly lower than those in healthy control group,the positive rates of antinuclear antibody and anti-double strand DNA antibody(anti-ds-DNA antibody),serum creatinine(SCr)and C-reactive protein were significantly higher than those in healthy control group(P<0.05).The ALB of active group was significantly lower than that of inactive group,and IL-2R,erythrocyte sedimentation rate,24h urinary protein quantity and anti-ds-DNA antibody positive rate were significantly higher than those of inactive group(P<0.05).Serum IL-2R levels in LN patients were positively correlated with SLEDAI,SCr,blood urea nitrogen and 24h urinary protein quantity,and negatively correlated with Hb and complement C3(P<0.05).Conclusion Serum IL-2R can be used as an indicator to judge the degree of LN activity and provide a basis for the judgment of clinical disease activity.
7.Effects of irinotecan combined with XELOX regimen on immune status, intestinal microecology and prognostic risk in elderly patients with colorectal cancer
Kunyan CHEN ; Juan DU ; Yuwei JI ; Weiwei GU ; Hanzhi PENG
Journal of International Oncology 2024;51(11):690-695
Objective:To analyze the effects of irinotecan combined with XELOX regimen on immune status, intestinal microecology and prognostic risk in elderly patients with colorectal cancer.Methods:A total of 105 elderly patients with advanced colorectal cancer admitted to Qidong People's Hospital of Jiangsu Province from October 2018 to April 2023 were included as the study objects. They were divided into control group ( n=45) and observation group ( n=60) according to different chemotherapy regimen. The control group was treated with XELOX regimen alone, and the observation group was treated with irinotecan combined with XELOX regimen. The short-term efficacy, changes of indexes related to immune status and intestinal microecology before and after treatment were compared between the two groups. The patients were followed up from the end of treatment. With death or recurrence and metastasis as the end event during the follow-up, 105 patients were divided into poor prognosis group ( n=32) and good prognosis group ( n=73). The clinical data of the two groups were compared, and multivariate logistic regression was used to analyze the prognostic factors in elderly patients with advanced colorectal cancer. Results:The total effective rate of the observation group was 53.33% (32/60), which was higher than that of the control group (20.00%, 9/45) ( χ2=12.01, P=0.001). One week after treatment, the ratios of CD4 + T cells and CD4 +/CD8 + in the observation group were (38.59±1.50) % and 1.81±0.20, respectively, higher than those in the control group (36.25±1.82) % and 1.59±0.15 ( t=7.22, P<0.001; t=6.19, P<0.001). The ratio of CD8 + T cells was (21.27±2.70) %, lower than that of the control group (22.80±2.92) % ( t=2.78, P=0.007). The numbers of Bifidobacterium, Lactobacillus and Enterococcus were (9.44±0.82), (9.89±0.79), (9.14±0.66) lg CFU/g, respectively, which were higher than those in the control group (8.20±0.70), (9.05±0.72), (8.25±0.62) lg CFU/g ( t=8.16, P<0.001; t=5.60, P<0.001; t=7.02, P<0.001). There were statistically significant differences in the proportion of smoking and drinking history ( χ2=7.61, P=0.006), the proportion of low differentiation ( χ2=6.54, P=0.011), the proportion of lymph node metastasis ( χ2=5.86, P=0.016) and the level of carcinoembryonic antigen (CEA) before chemotherapy [ (5.80±0.89) μg/L vs. (7.48±1.02) μg/L, t=8.51, P<0.001], the level of carbohydrate antigen 199 (CA199) [ (29.54±1.85) U/ml vs. (34.52±2.50) U/ml, t=11.36, P<0.001] in good prognosis group and poor prognosis group. Multivariate analysis showed that smoking and drinking history ( OR=1.74, 95% CI: 1.53-2.15, P<0.001), low differentiation ( OR=1.80, 95% CI: 1.60-2.15, P<0.001), lymph node metastasis ( OR=1.82, 95% CI: 1.68-2.33, P<0.001), high CEA level before chemotherapy ( OR=1.81, 95% CI: 1.62-2.38, P<0.001), high CA199 level before chemotherapy ( OR=1.80, 95% CI: 1.66-2.37, P<0.001) were risk factors for the prognosis of advanced colorectal cancer in the elderly. Conclusion:Irinotecan combined with XELOX regimen can effectively improve immune function and intestinal microecology in elderly patients with advanced colorectal cancer, but the risk of poor prognosis after chemotherapy is higher. Smoking and drinking history, low differentiation, lymph node metastasis, high CEA level before chemotherapy, and high CA199 level before chemotherapy are risk factors affecting the prognosis of elderly patients with advanced colorectal cancer.
8.Effects of breast milk intake ratio during hospitalization on antibiotic therapy duration in preterm infants less than 34 gestational weeks: a multicenter retrospective cohort study
Chengpeng GU ; Wenjuan CHEN ; Shuping HAN ; Yan GAO ; Rongping ZHU ; Jihua ZHANG ; Rongrong CHEN ; Yan XU ; Shanyu JIANG ; Yuhan ZHANG ; Xingxing LU ; Mei XUE ; Mingfu WU ; Zhaojun PAN ; Dongmei CHEN ; Xiaobo HAO ; Xinping WU ; Jun WAN ; Huaiyan WANG ; Songlin LIU ; Danni YE ; Xiaoqing CHEN ; Weiwei HOU ; Li YANG
Chinese Journal of Perinatal Medicine 2023;26(7):546-553
Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d
9.Establishment of the predictive model of repeated admissions for community-acquired pneumoniain adults
Yuanyuan WEI ; Hongyan GU ; Weiwei WANG ; Yiru ZHAO ; Bin DAI
Acta Universitatis Medicinalis Anhui 2023;58(12):2113-2118
Objective To analyze the risk factors of repeated admissions for community-acquired pneumonia(CAP)in adults,and to build a nomogram model to predict individual risk.Methods A total of 2 306 adult hospitalized patients with CAP in Beijing Shijitan Hospital affiliated to Capital Medical University from January 2018 to Decem-ber 2020 were retrospectively selected and divided into repeated admission group and control group according to whether they were readmitted within one year after discharge.Univariate logistic analysis and multivariate logistic a-nalysis were used to determine the risk factors.The risk factors were introduced into R 3.5.3 software to construct the nomogram prediction model.The calibration curve was drawn and the Hosmer-Lemeshow goodness of fit test was performed to evaluate the accuracy of the nomogram prediction model.The receiver operating characteristic(ROC)curve was drawn to evaluate the discrimination of the nomogram prediction model.The decision analysis curve was drawn to measure patient benefits.Results The age,gender,length of stay,total score of comorbidity index,use of special grade antibiotics,history of blood transfusion,and Vaccination history were risk factors of repeated hospi-tal admissions for CAP in adults.The nomogram prediction model of adult CAP repeated admission was constructed based on the above risk factors.The Hosmer-Lemeshow goodness of fit test showed that the fitting effect of the no-mogram prediction model was good(x2=8.873,P=0.353).The ROC curve analysis showed that the area under the curve of the test dataset was 0.775.The results of the decision analysis curve showed that when the threshold was 0.21,the model could generate a net profit of 0.104.Conclusion The nomogram model established in this study has good discrimination and accuracy in predicting the risk of adult CAP repeated admissions and has high clinical application value.
10.Summary of the best evidence for non-pharmacological sleep management in adult critically ill patients
Tiantian GU ; Junxi CHEN ; Xiaohui LIU ; Benjin WANG ; Weiwei YUAN ; Yongmei ZHANG
Chinese Journal of Modern Nursing 2023;29(30):4127-4132
Objective:To retrieve and summarize evidence on non-pharmacological sleep management in adult critically ill patients, providing reference for sleep intervention by ICU medical and nursing staff.Methods:The literature on non-pharmacological sleep management in adult critically ill patients was systematically searched in domestic and foreign databases and guideline websites. The search period was from the establishment of the database to February 2023. After screening the literature based on inclusion and exclusion criteria, two evidence-based trained researchers independently evaluated the quality of the included literature, extracted and summarized evidence.Results:A total of 13 articles were included, including 3 clinical guidelines, 9 systematic reviews, and 1 randomized controlled trial. A total of 21 best pieces of evidence were summarized, covering 5 aspects, including strengthening nurse education and training, improving ward environment, reducing sleep interruption, selecting mechanical ventilation modes reasonably, and promoting physical and mental relaxation.Conclusions:The evidence summarized can provide reference for the development of non-pharmacological sleep management plans for adult critically ill patients. ICU medical and nursing staff should carefully apply evidence in clinical practice based on evidence, fully consider the human resources and actual situation of the department, and combine it with the needs of patients.

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