1.Association between preoperative serum β 2-microglobulin concentrations and postoperative delirium in elderly patients
Yuanlong WANG ; Qian HE ; Shuhui HUA ; Shanling XU ; Jian KONG ; Hongyan GONG ; Rui DONG ; Yanan LIN ; Chuan LI ; Yanlin BI ; Bin WANG ; Xu LIN
Chinese Journal of Anesthesiology 2024;44(2):145-149
Objective:To evaluate the association between preoperative serum β 2-microglobulin (β 2MG) concentrations and postoperative delirium (POD) in elderly patients. Methods:The study selected patients who underwent knee or hip arthroplasty under spinal-epidural anesthesia on an elective basis at Qingdao Municipal Hospital from May 2021 to November 2022. The patients were divided into a POD group and a non-POD group based on the occurrence of POD. The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. The study collected baseline data from two groups of patients and analyzed the differences between them. Logistic regression was used to identify the risk factors for POD. The stability of the regression model was tested using sensitivity analysis. The mediation model was used to examine whether cerebrospinal fluid (CSF) biomarkers mediated the relationship between β 2MG and POD. The receiver operating characteristic curve was drawn and the area under the curve was calculated to evaluate the accuracy of preoperative β 2MG concentrations and CSF biomarker concentration in predicting POD. Results:There were 57 cases in POD group and 449 cases in non-POD group. The results of logistic regression analysis showed that the increased β 2MG and CSF total tau protein (t-tau) concentrations were risk factors for POD, and the increased CSF β-amyloid 42 concentration was a protective factor for POD after adjustment for multiple confounders such as age, gender, education, Mini-Mental State Examination, history of hypertension and infusion volume ( P<0.05). The results of mediation analysis showed that the serum β 2MG′s effect on POD was partly mediated by t-tau (18.1%). The results of the receiver operating characteristic curve showed that the area under the curve of the β 2MG concentration combined with the CSF biomarker concentration was 0.742. Conclusions:Elevated preoperative serum β 2MG concentration is a risk factor for POD in elderly patients, and the relationship may be partly mediated by CSF t-tau.
2.Genetic analysis of a case with Al Kaissi syndrome and a literature review
Gege SUN ; Ganye ZHAO ; Shuang HU ; Hua′nan REN ; Li WANG ; Li′na LIU ; Xiangdong KONG
Chinese Journal of Medical Genetics 2024;41(2):193-198
Objective:To explore the genetic etiology of a child with delayed growth and development and carry out a literature review.Methods:A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy.Results:The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion.Conclusion:The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.
3.Protective effect and mechanism of quercetin on cardiac and renal functions in rats with cardiorenal syndrome
Lujiao KONG ; Hua LU ; Xin WANG ; Shuai LI ; Jing LIU ; Xiaoyang GUO
China Pharmacy 2024;35(13):1612-1617
OBJECTIVE To investigate the protective effect and mechanism of quercetin on the cardiac and renal functions of rats with cardiorenal syndrome (CRS) based on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa- B (NF-κB) signaling pathway. METHODS CRS model of SD rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion. Model rats were randomly separated into model group, quercetin low-dose group (35 mg/kg), quercetin high-dose group (70 mg/kg), high-dose of quercetin+740Y-P group (70 mg/kg quercetin+3.5 mg/kg PI3K/Akt/ NF-κB signaling pathway activator 740Y-P), with 12 rats in each group. Another 12 normal rats were selected as sham operation group. They were given relevant drugs, once a day, for 14 consecutive days. After administration, the cardiac function indexes [left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), isovolumic relaxation time (IVRT)] and renal function indicators [blood urea nitrogen (BUN), 24-hour urine protein, and serum creatinine (Scr)] were detected, and fibrosis in the cardiac and renal tissues was observed; the levels of inflammatory indexes [interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)] in the serum and cardiac and renal tissues as well as the expression of PI3K/Akt/NF-κB pathway-related proteins in the cardiac and renal tissues were detected. RESULTS Compared with sham operation group, the levels of BUN, 24-hour urine protein and Scr, collagen volume fraction of cardiac and renal tissues, the levels of IL-1β and TNF-α in serum and cardiac and renal tissues, and the phosphorylation of PI3K, Akt and NF-κB p65 protein in cardiac and renal tissues were increased significantly in model group (P<0.05); the levels of LVEF, IVRT and EDV were reduced significantly (P<0.05). Compared with the model group, the above indexes were reversed significantly in quercetin low-dose and high-dose groups (P<0.05), and the reversal effect was better in the high-dose group (P<0.05). 740Y-P restored the reverse effect of high-dose quercetin on the indexes (P<0.05). CONCLUSIONS Quercetin can alleviate cardiac and renal fibrosis and function injury, the mechanism of which may be 20232016) associated with inhibiting the activation of the PI3K/Akt/NF-κB signaling pathway.
4.Protective effects of cryptotanshinone on heart and kidney function in rats with cardiorenal syndrome by regulating PI3K/Akt/mTOR signaling pathway
Xin WANG ; Hua LU ; Lujiao KONG ; Xiaoyang GUO ; Tingting MA ; Yue LU
China Pharmacy 2024;35(17):2096-2101
OBJECTIVE To investigate the protective effect and mechanism of cryptotanshinone (CTS) on heart and kidney function in rats with cardiorenal syndrome (CRS) by regulating phosphoinositide kinase-3 (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway. METHODS CRS model of rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion injury. Model rats were randomly divided into CRS model group (CRS group), low-dose CTS group (CTS-L), high-dose CTS group (CTS-H group), high-dose CTS+PI3K activator 740Y-P group (CTS-H+740Y-P group), with 12 rats in each group. Another 12 rats were selected as the normal control group (Normal group) and were carried out surgery without modeling. CTS-L group and CTS-H group were respectively given CTS 30 and 60 mg/kg intragastrically, once a day, for consecutive 14 d. Besides the intervention of CTS 60 mg/kg intragastrically, CTS-H+740Y-P group was given 10 mg/kg 740Y-P intraperitoneally, once a day, for 14 consecutive days. After the last medication, the levels of cardiac function [left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left ventricular fraction shortening (LVFS)] and renal function [24 h urinary protein, blood urea nitrogen (BUN), serum creatinine (Scr), brain natriuretic peptide (BNP)] were detected in rats. The pathological changes and fibrosis of the heart and kidney in rats were observed; the expressions of PI3K/Akt/mTOR signaling pathway in heart and renal tissue were all detected. RESULTS Compared with Normal group, the levels of LVEF and LVFS in rats were all decreased significantly in CRS group (P<0.05); the levels of LVESD, LVEDD, 24 h urinary protein, serum levels of BUN, Scr and BNP, collagen area and the phosphorylation of PI3K, Akt and mTOR protein in heart and renal tissue were all increased significantly (P<0.05). The morphology of myocardial cells was enlarged and disordered; the structure ofrenal tubules was disordered, epithelial cells were wrinkled, and there was infiltration of inflammatory cells. Compared with CRS group, the above indexes of rats were reversed significantly in CTS-L group and CTS-H group (P<0.05); heart and kidney function had been restored, and pathological damage and fibrosis had been reduced. PI3K activator 740Y-P weakened the protective effect of CTS on cardiac and renal function in CRS rats. CONCLUSIONS CTS can protect heart and kidney function in CRS rats, the mechanism of which may be associated with inhibiting the PI3K/Akt/mTOR signaling pathway.
5.Two new isocoumarins from cave-derived Metarhizium anisopliae NHC-M3-2
Rong-xiang WU ; Jie-lan GUO ; Hua HUANG ; Jing-jing LIAO ; Yi HAO ; Fan-dong KONG ; Li-man ZHOU ; Chao-jun ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2588-2593
Extracting extracts of secondary metabolites from the karst cave fungus
6.Application of IgG antibody combination of wild strain and epidemic strain of COVID-19 in identifying epidemic Omicron BA.5 strain infection
Jinjin CHU ; Hua TIAN ; Chuchu LI ; Zhifeng LI ; Chen DONG ; Xiaoxiao KONG ; Jiefu PENG ; Ke XU ; Jianli HU ; Changjun BAO ; Liguo ZHU
Chinese Journal of Preventive Medicine 2024;58(9):1354-1359
Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.
7.Risk factors of central line-associated bloodstream infection in the inten-sive care unit based on propensity score matching
Zhi-Mei TENG ; Shang ZHU ; Han XUE ; Jin-Hua HUANG ; Xu-Hui KONG
Chinese Journal of Infection Control 2024;23(11):1405-1412
Objective To explore the independent risk factors for central line-associated bloodstream infection(CLABSI),provide basis for developing intervention measures for infection prevention and control as well as con-ducting targeted treatment.Methods Patients who were diagnosed with CLABSI in a hospital from January 2019 to December 2023 were recruited retrospectively and defined as the infection group.According to 1:4 propensity score matching method,patients who received central venous catheter(CVC)without infection were taken as the control group.With whether CLABSI occurred as the dependent variable,the possible risk factors of the matched two groups as the independent variables,logistic regression analysis was conducted,and independent risk factors for pa-tients developing CLABSI were explored.Results A total of 42 patients in the CLABSI group and 168 patients in the non-CLABSI group were matched.Multivariate logistic regression analysis showed that high score of acute physiology and chronic health evaluation(APACHE)Ⅱ(OR=1.217,95%CI[1.094-1.357],P<0.001),long duration of central venous catheterization(OR=1.273,95%CI[1.157-1.400],P<0.001),and femoral venous catheterization(OR=6.846,95%CI[1.511-31.014],P=0.013)were independent risk factors for CLABSI.A total of 118 strains of pathogens were isolated from 42 CLABSI patients,with Gram-negative bacteria being the ma-jority(n=56).Conclusion High score of APACHE Ⅱ,long duration of central venous catheterization,and femo-ral venous catheterization are independent risk factors for CLABSI.The main pathogens are Gram-negative bacilli.Strict prevention and control measures for CLABSI should be implemented to reduce the risk of infection.
8.A review of the studies on genomics of Candida auris
Huai-Yuan SUN ; Jia-Jia FENG ; Wei-Hua KONG ; Kun JIANG ; Li-Kai LIN
Chinese Journal of Infection Control 2024;23(11):1456-1462
Candida auris(C.auris)is a fungus with multidrug resistance.Current genomic studies indicate that C.auris shares similarities in genome size and evolution with other resistant yeast species.There are differences in genome size and structural variations among different geographical clades of C.auris,which may be related to differences in phenotype and drug resistance.C.auris exhibits resistance to multiple antifungal agents,including triazole,amphotericin B,and echinocandins.Genomic studies have found that resistance of C.auris may be related to factors such as membrane transport protein and mutation in the ergosterol pathway,its resistance can change fur-ther during evolution.In this paper,the relevant studies are reviewed,with a view to understanding the mechanism of drug resistance of C.auris,and providing important basis for formulating prevention and control strategies as well as treatment programs of C.auris.
9.Research on mechanism of Wenyang Huazhuo Tongluo formula inhibiting HIF-1a/Foxm1/smad3 pathway to improve pulmonary microvascular injury of systemic sclerosis
Bo BIAN ; Qing MIAO ; Fan-Wu WU ; Yi-Ling FAN ; Jin-Li KONG ; Hua BIAN ; Kai LI
Chinese Pharmacological Bulletin 2024;40(11):2119-2123
Aim To investigate the molecular mecha-nisms of the Wenyang Huazhuo Tongluo formula in in-hibiting endothelial-to-mesenchymal transition(En-doMT)of pulmonary microvascular endothelial cells and improving pulmonary microvascular injury in sys-temic sclerosis(SSc).Methods Pulmonary micro-vascular endothelial cells were cultured with serum from SSc patients to establish SSc pulmonary microvas-cular endothelial cells.A hypoxia model was estab-lished in SSc pulmonary microvascular endothelial cells using liquid paraffin sealing,and the cells were treated with the Wenyang Huazhuo Tongluo formula or HIF-1a inhibitor KC7F2.Western blot was used to detect the protein expression levels of VE-cadherin,CD31,vimen-tin,HIF-1α,Foxm1,smad3,Tie-1,and vWF.ELISA was used to measure the concentrations of E-selectin and ICAM-1 in cell culture medium.The luciferase re-porter gene system was used to detect the promoter ac-tivity of the Foxm1 gene.Results Compared to the control group,the levels of VE-cadherin,CD31,HIF-1α,Foxm1,smad3,Tie-1,and vWF significantly de-creased under hypoxic condition,while the levels of vi-mentin,E-selectin,and ICAM-1 significantly in-creased.In addition,the cell morphology exhibited a distinct"spindle-like"myoblast morphology.Treat-ment with the Wenyang Huazhuo Tongluo formula or KC7F2 reversed these changes in protein expression levels and cell morphology induced by hypoxia.Con-clusion The Wenyang Huazhuo Tongluo formula im-proves pulmonary microvascular injury in SSc by inhib-iting the HIF-1a/Foxm1/smad3 pathway-mediated En-doMT of pulmonary microvascular endothelial cells.
10.Application of IgG antibody combination of wild strain and epidemic strain of COVID-19 in identifying epidemic Omicron BA.5 strain infection
Jinjin CHU ; Hua TIAN ; Chuchu LI ; Zhifeng LI ; Chen DONG ; Xiaoxiao KONG ; Jiefu PENG ; Ke XU ; Jianli HU ; Changjun BAO ; Liguo ZHU
Chinese Journal of Preventive Medicine 2024;58(9):1354-1359
Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

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