Objective To investigate the increased cytotoxicity induced by luteolin and cisplatin cotreatment and validate its mechanism.Methods HepG2 cells were pretreated with luteolin for 1 hour or remained untreated and followed by exposure to cisplatin.Cells were stained with Hoechst,and Caspase-3 activity was detected by spectrophotometry.Cell death was detected by LDH release assay.Phosphated C-jun N-terminal kinase (JNK) and total JNK1 were detected by Western blot.Results Luteolin significantly enhanced Caspase-3 activity and HepG2 cells apoptosis by cisplatin.The cell death rates by co-treatment with different concentration of luteolin (0-20 μmol/L) and cisplatin (10 μg/ml) were much higher than cisplatin or luteolin alone treatment.Combined treatment of luteolin (20 μmol/L) with cisplatin (10 μg/ml) killed 47.66 ％ of HepG2 cells.There were significant differences on cell death between combination group and single reagent group (F =535.48,P ＜ 0.01).Combination group showed better efficacy than single reagent group.The Caspase-3 activity of HepG2 cells treated by luteolin (20 μmol/L),cisplatin (10 μg/ml) or luteolin (20 μmol/L)plus cisplatin (10 μg/ml) were 1.94,1.74 and 8.12 times of negative control group respectively.Combination treatment induced sustained activation of JNK signaling pathway.Conclusions Enhancing cisplatin-induced JNK activation by luteolin leads to increased cytotoxicity in HepG2 cells.The combination of luteolin and cisplatin is an effect apporch for improving the anticancer value of cisplatin,which has implications in cancer prevention and therapy.

Objective: To analyze the prevalence of obesity and its influencing factors among residents aged 40 years and over in Taizhou,so as to provide reference for obesity prevention and control. Methods: From June 2014 to May 2015,people who were aged 40 years or above and received routine physical examination in six centers for disease control and prevention in Taizhou were recruited. Demographic characteristics and health relates behaviors were collected by a questionnaire survey;height,weight,waist circumference and hip circumference were collected by physical examination. Logistic regression analysis was conducted to explore the influencing factors for overall obesity and central obesity. Results : Totally 1 216 people were investigated,and 1 192 (98.03%) questionnaires were valid. The age of them ranged from 40 to 86 years old,with （51.92±8.91） years old on average. There were 547 males （45.89%） and 645 females （54.11%）. The prevalence rates of overall obesity and central obesity were 6.54% and 60.32%,respectively. The Results of multivariate logistic regression analysis showed that regular physical exercise （OR=0.597, 95%CI： 0.359-0.992） was a protective factor for overall obesity;female （OR=2.352,95%CI： 1.685-3.283）was a risk factor of central obesity;public servants or staff from enterprise and institution（OR=0.508, 95%CI： 0.289-0.892）,drinking （OR=0.637,95%CI：0.471-0.860）,salt intake of less than five grams per day （OR=0.590,95%CI：0.434-0.802）and regular physical exercise （OR=0.760,95%CI：0.583-0.991） were protective factors for central obesity. Conclusion The prevalence rates of overall obesity and central obesity among residents aged 40 years or above in Taizhou were 6.54% and 60.32%, respectively. Gender,occupation,drinking,salt intake and physical exercise were the influencing factors for obesity.

Severe acute pancreatitis (SAP) is accompanied with complex pathogenic course and high mortality. The imbalance of immune response is an important cause which leads the SAP patients to the severe situation and even death. The immunomodulatory therapy can regulate the imbalance of inflammation, alleviate SAP-associated organ injury, and improve the prognosis of patients. Previous immunomodulatory therapy had some problems, such as single-object and simple-method. In recent years, some new methods of immunomodulatory therapy, such as regulating the apoptosis and mature of immune cells, applying of mesenchymal stem cells (MSCs) and multi-regulation methods, provide some new ideas and hopes for SAP therapy. This paper reviewed the history and recent research progresses of SAP immunomodulatory therapy.

Objective:To analyze the predictive ability of HIV infection risk assessment tool for men who have sex with men (MSM). Sentinel surveillance data of MSM in Taizhou prefecture of Zhejiang province was used.Methods:MSM involved in AIDS sentinel surveillance program in Taizhou from 2013 to 2017 were included in the study and items listed in the HIV infection risk assessment tool for MSM was revised. Related data on questions and options involved in sentinel surveillance was collected and individual risk scores were calculated. We determined the predictive ability of this tool by comprehensive analyzing the HIV infection status and individual risk scores.Results:A total of 1 944 MSM were included in the study, with an average age of (35.04±13.28)years old. Most of them were recruited from the venues (55.7%) and 48.2% were never married. Among these MSM, HIV infection rate was 12.6%(245/1 944) with the median of risk score as 23.99, versus 20.36 from the HIV negative ones. Significant differences appeared on the risk scores between the target populations that with different HIV status (Mann-Whitney test, P=0.007). According to the principle of decision tree, MSM were divided into two groups according to risk scores: ≤18.66 and >18.66. It appeared that the risk scores were in parallel with the rates of HIV infection ( χ2=13.102, P<0.001). Results from the multivariate analysis showed that MSM with higher risk score were more likely to be infected with HIV (>18.66 vs. ≤18.66: a OR=1.72, 95% CI: 1.27-2.32, P<0.001). Area under the ROC curve (AUC) for HIV infection was 0.553 (95% CI: 0.516-0.590, P=0.007). At the point of risk score 19.01, Youden’s index appeared the maximum, with sensitivity as 0.69 and specificity as 0.43, of this tool. Conclusions:The HIV infection risk assessment tool for MSM developed based on Delphi method can predict the risk of HIV infection in MSM to some extent. MSM with higher risk score seemed likely to be infected with HIV. Items of this tool need to be adjusted for the verification of the tool through cohort studies in the near future.

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.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective:To evaluate the relationship between physical activity (PA) and postoperative delirium (POD) in elderly patients undergoing knee or hip arthroplasty.Methods:The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. Medical records from elderly patients undergoing elective knee or hip arthroplasty under spinal-epidural anesthesia at Qingdao Municipal Hospital from August 2022 to August 2023 were collected. The patients were divided into a POD group ( n=89) and a non-POD group ( n=221) based on the occurrence of POD. Peripheral blood samples were collected before surgery, and the cerebrospinal fluid (CSF) 2 ml was extracted after successful puncture under spinal-epidural anesthesia for determination of the concentrations of amyloid-β 42 (Aβ 42), total tau protein (t-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay. Logistic regression was used to analyze the influencing factors of POD, and the mediation analysis was conducted to examine the mediating role of CSF biomarker in the relationship between PA and POD. Results:Logistic regression analysis showed that the increased concentration of CSF biomarkers Aβ 42 ( OR=0.997, P=0.006), elevated ratio of Aβ 42/t-tau ( OR=0.642, P=0.003), elevated ratio of Aβ 42/p-tau ratio ( OR=0.872, P=0.001) and PA ( OR=0.374, P=0.001) were protective factors for POD, while the elevated concentrations of t-tau ( OR=1.006, P=0.001) and p-tau ( OR=1.030, P=0.011) were risk factors for POD after adjusting for multi-confounders such as hypertension, diabetes, history of drinking, years of education and Mini-Mental State Examination score. The results of the mediation analysis showed that Aβ 42 (20%), t-tau (16%), Aβ 42/t-tau (23%) and Aβ 42/p-tau (28%) played mediating roles in the relationship between PA and POD. Conclusions:PA is a protective factor for POD in elderly patients undergoing knee or hip arthroplasty and CSF biomarkers may play a mediating role in the relationship between PA and POD.

Objective:To evaluate the relationship between the preoperative sleep quality and postoperative delirium (POD) in elderly patients.Methods:Three hundred and eighty-nine patients of either sex, aged 65-90 yr, with American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who underwent elective knee/hip arthroplasty under combined spinal-epidural anesthesia in Qingdao Municipal Hospital from May 2022 to October 2023, were selected. The Pittsburgh Sleep Quality Index scale was applied at 1 day before surgery to assess the sleep quality within 1 month before surgery. The cerebrospinal fluid (CSF) specimens 2 ml were withdrawn from the subarachnoid space before anesthesia for determination of the concentrations of biomarkers (β-amyloid), total tau protein [t-tau], and phosphorylated tau protein [p-tau]) by enzyme-linked immunosorbent assay. Patients were divided into POD group and non-POD group based on whether delirium occurred within 7 days after surgery. Logistic regression was used to identify the risk factors for POD, and the sensitivity analysis was used to test the stability of the regression models. The mediation model was used to examine whether CSF biomarkers mediated the link between sleep quality and POD. The accuracy of preoperative sleep quality and CSF biomarker concentrations in predicting the occurrence of POD was evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve.Results:Two hundred and seventy-nine patients were finally included, with 33 patients in POD group and 246 patients in non-POD group. The results of logistic regression analysis showed that shorter sleep duration, use of hypnotics, daytime dysfunction within 1 month before surgery, elevated t-tau concentrations in CSF, and elevated p-tau concentrations in CSF were risk factors for POD after adjusting for multiple confounding factors such as age, sex, body mass index, years of education, Mini-Mental State Examination score, and VAS score. The results of mediating effect showed that the effect of use of hypnotics and daytime dysfunction within 1 month before surgery on POD was partially mediated by p-tau concentrations in CSF (>10%). The area under the curve of combination of daytime dysfunction, sleep duration, use of hypnotics within 1 month before surgery, and CSF biomarker concentrations in predicting POD was 0.979.Conclusions:Shortened sleep duration, use of hypnotic, and daytime dysfunction with 1 month before surgery are risk factors for POD in elderly patients, and the association between use of hypnotics and daytime dysfunction and POD is partially mediated by p-tau in CSF.

The new-generation non-invasive prenatal screening technology (NIPT2.0) is a new method successfully realized in recent years based on high-throughput sequencing to synchronously and accurately detect fetal chromosomal aneuploidies, microdeletion/microduplication syndromes and dominantly inherited monogenic disorders. NIPT2.0 can circumvent the shortcomings of previous non-invasive prenatal screening techniques (NIPT and NIPT Plus) including incapability to detect fetal monogenic disorders, insufficient accuracy of detection and low positive predictive values for certain chromosomal abnormalities (in particular trisomy 13, sex chromosomal abnormalities, and small-segment microdeletions and microduplication syndromes). How to apply NIPT2.0 reasonably and normatively to maximize its clinical value has become an issue which requires clarification. The Reproductive Health Branch of the Chinese Maternal and Child Health Care Association has organized experts to fully discuss and jointly drafted this consensus, which has put forwards suggestions over the clinical application strategy for NIPT2.0, including the scope of application, target disease, pre-test consultation, clinical application pathway, post-test genetic counseling and intervention, quality control and limitations, for the reference by peers, with a view to standardize its application and provide better clinical service.

OBJECTIVE: To explore the genetic basis for four patients suspected for Marfan syndrome (MFS). METHODS: Four male patients with suspected MFS and their family members who were treated at West China Second Hospital of Sichuan University from September 12, 2019 to March 27, 2021 were selected as the study subjects. Peripheral venous blood samples were collected from the patients and their parents or other pedigree members for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the variants was determined based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: Genetic testing revealed that all four patients have harbored variants of the FBN1 gene, including c.430_433del (p.His144fs) deletional variant in exon 5, c.493C>T (p.Arg165*) nonsense variant in exon 6, c.5304_5306del (p.Asp1768del) deletional variant in exon 44 and c.5165C>G (p.Ser1722Cys) missense variant in exon 42. According to the ACMG guidelines, the c.430_433del and c.493C>T were classified as pathogenic variants (PVS1+PM2_Supporting+PP4; PVS1+PS1+PS2+PM2_Supporting+PP4). c.5304_5306del and c.5165C>G were classified as likely pathogenic variants (PS2+PM2_Supporting+PM4+PP4; PS2_Moderate+PS1+PM1+PM2_Supporting). CONCLUSION The c.430_433del and c.5304_5306del variants of the FBN1 gene identified in this study were unreported previously. Above results have enriched the variation spectrum of the FBN1 gene and provided a basis for genetic counseling and prenatal diagnosis of patients with MFS and acromicric dysplasia.
Female ; Pregnancy ; Humans ; Male ; Exons ; China ; Family ; Genetic Counseling ; Genetic Testing ; Marfan Syndrome/genetics* ; Mutation ; Fibrillin-1/genetics*