Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

OBJECTIVE: To investigate the role of NOV/CCN3 in regulating the proliferation of mesenchymal stem cells (MSCs) and its regulatory mechanism and assess the value of CCN3 as a proliferative factor in bone tissue engineering. METHODS: Mouse embryonic fibroblasts (MEFs) were used as the MSC model, in which CCN3 expression was up-regulated and downregulated by transfection with the recombinant adenovirus vectors Ad-CCN3 and Ad-siCCN3, respectively. Flow cytometry was used to analyze the changes in cell cycle and apoptosis of the transfected cells. Western blotting was used to detect the expression levels of the proliferation indicators (PCNA, cyclin E, and cyclin B1) and the apoptosis indicators (Bax and Bcl-2) to assess the effect of modulation of CCN3 expression on MEF proliferation and apoptosis. CCN3 protein secretion by the cells was detected using ELISA. RT-qPCR and Western blotting were employed to analyze the changes in the expressions of Notch1, ligand DLL1, the downstream key proteins or genes (Hey1, P300, H3K9) and MAPK pathway-related proteins ERK1+2 and p-ERK1+2. RESULTS: Flow cytometry showed that compared with the control cells, MEFs transfected with Ad-CCN3 exhibited significantly increased cell proliferation index ( CONCLUSIONS CCN3 over-expression promotes the proliferation and inhibits apoptosis of MEFs possibly by inhibiting the classical Notch signaling pathway and activating the MAPK pathway
Animals ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Fibroblasts ; Mice ; Nephroblastoma Overexpressed Protein

Objective To find small molecules binding specifically to signal transducer and activator of transcription3 (STAT3) based on surface plasmon resonance (SPR) technology and confirm their inhibitory activities to STAT3. Methods The biomolecular interaction analysis T200 system based on SPR technology was used to couple the purified protein STAT3 to CM5 chip under the optimal pH conditions. The compounds with high binding response value were screened out from 50 candidate compounds derived from traditional Chinese medicines and the binding specificity was then confirmed. Biological experiments were performed to confirm the inhibitory effects of the screened compounds on STAT3. The binding pattern of STAT3 and the compound was fitted by molecular docking technique. Results More than 10 candidate molecules exhibited binding activities to STAT3 and kinetics assays revealed that only one candidate molecule, apigenin, showed specific binding. Western-blot analysis exhibited that apigenin inhibited the phosphorylation of STAT3 dose-dependently. Luciferase reporter gene assays demonstrated that apigenin also inhibited IL-6-induced STAT3 transcriptional activity in a dose-dependent manner. Molecular docking results showed that apigenin binds to the SH2 domain of STAT3, and interacts with key residues Glu638, Gln644, Gly656 and Lys658 by hydrogen bonds and with Tyr657 through π-π interactions. Conclusion Apigenin was a direct inhibitor of STAT3.

Objective To analyze the relationship of neurocognitive impairments and 1 H MRS changes of the thalamus in patients with chronic hepatitis B virus related cirrhosis (HBV-RC).Methods Totally 28 patients with HBV-RC (cirrhosis group) and 28 well-matched healthy subjects (control group) were enrolled.All subjects underwent number connection test A (NCT-A) and the digit symbol test (DST) before MRS scanning.The ratios of peak area to each metabolite,including N-acetylaminosuccinic acid (NAA),choline (Cho),glutamine and glutamate (Glx),myoinositol (mI) and creatine (Cr) were calculated,respectively.Results Compared with control group,patients in cirrhosis group showed lower Cho/Cr and mI/Cr,higher Glx/Cr,prolonged NCT-A time and decreased DST scores (all P＜0.001).NCT-A completion time was negatively correlated with Cho/Cr and mI/Cr (r=-0.477,P =0.001;r=-0.695,P＜0.001) and positively correlated with Glx/Cr (r=0.665,P＜0.001).DST scores were positively correlated with Cho/Cr and mI/Cr (r =0.478,P =0.001;r=0.632,P＜0.001),and negatively correlated with Glx/Cr (r=-0.572,P＜0.001).Conclusion The neurocognitive impairments may be related to metabolic changes of the thalamus in patients with HBV RC.

OBJECTIVE:To provide reference for rational application of tigecyclinet and alert to the occurrence of severe ADR.METHODS:Fifity patients receiving tigecycline in a level 3 general hospital during 2013-2015 were analyzed retrospectively to observe the change of symptom,sign and lab indexes after using Tigecyclinet injfection.Possible ADR of tigecycline,processing and outcomes were summarized.RESULTS:Among 50 patients,there were 24 cases of ADR,including 10 cases of inducing or aggravating blood coagulation abnormality (41.67％),9 cases of liver function injury (37.50％),4 cases of vomiting and other gastrointestinal discomfort (16.67％),1 case of red erythra with itching (4.17％).ADR of digestive system were mild and recovered after symptomatic treatment as inhibiting acid,antiemetic.Severe ADR as Liver function injury could not be recovered after symptomatic treatment as protecting liver,reducing enzyme.Nine cases of liver function injury mainly manifested as the elevation of TBIL,DBIL,ALP,LDH;8 of which suffered from liver function injury before medication and the symptom was aggravated after medication;liver function injury appeared in 3 cases on 10th day after medication and in 2 cases on 9th day after medication.Ten cases suffered from coagulation function disorder before medication and the symptom was aggravated after medication,which mainly manifested as the prolongation of APTT and TT and the elevation of INR,PT,D-dimer,etc.The coagulation function disorder was aggravated abnormally on 2nd-22th day after using tigecycline,mainly appearing on 2nd-5th day (70.00％).CONCLUSIONS:Great importance should be attached to severe ADR as coagulation function disorder,liver function injury when using tigecycline,in order to ensure the safety of drug use.

[ ABSTRACT] AIM:To study the effect of livin gene-modified bone marrow mesenchymal stem cells ( BM-MSCs) transplantation on the cardiac function following acute myocardial infarction in a rat model and the expression of livin , caspase-3, caspase-7 and caspase-9 in the livin gene-modified BM-MSCs.METHODS: The MSCs were obtained by the whole bone marrow culture method , and the apoptosis of the MSCs after infection with adenovirus vector carrying enhanced green fluorescent protein ( EGFP) gene and livin recombinant vector ( rAd-livin) were detected by flow cytometry .The ex-pression of livin, caspase-3, caspase-7 and caspase-9 was detected by Western blot .After permanent left anterior descend-ing artery occlusion , the rats were randomized to receive intramyocardial injection of DMEM without cells ( vehicle group ) , or containing MSCs ( MSCs group ) , MSCs ( EGFP ) ( rAd-control/MSCs group ) or MSCs ( livin ) ( rAd-livin/MSCs group).Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum in-creased rate of left ventricular pressure ( -dp/dtmax ) and the maximum decline rate of left ventricular pressure ( +dp/dtmax ) were recorded for evaluating the cardiac functions .RESULTS: The apoptosis of rAd-livin/MSCs was significantly decreased as compared with MSCs and rAd-control/MSCs (P<0.05).Meanwhile, the expression of caspase-3, caspase-7 and caspase-9 was significantly downregulated as compared with the other 2 groups ( P<0.05 ) .The cardiac function in rAd-livin/MSCs group was significantly improved as compared with DMEM group , and those in the other 2 groups got the similar results, but the function in rAd-livin/MSCs group was better improved .Meanwhile, the number of surviving cells in rAd-livin/MSCs group was significantly improved as compared with the other 2 groups .CONCLUSION:The apoptosis of MSCs is decreased after rAd-livin transfection, and the expression of caspase-3, caspase-7 and caspase-9 is also significant-ly downregulated while the expression of livin is significantly upregulated .Transplantation of livin-modified BM-MSCs by lentiviral vector results in better prognosis for treating myocardial infarction by enhancing cell survival .

Objective To explore characteristics and significance of interferon-induced protein with tetratricopetide repeats 1 expressed in radiation injury and infection stress.Methods RNA was extracted from Raw264.7 cell,3T3 cell and 10T1 /2 cell after 5 hours stimulated with 5 μg/mL LPS.At the same time,to set up normal control group (untreated by LPS),and RNA of IFIT1 was detected by RT-PCR.Total-ly 20 C57 /BL6 mice were randomly divided into 4 groups,namely 0 h group,1 h group,4 h group and 12 h group.The mice were given 12 Gray60Co full-body exposure once,then liver IFIT1 was detected by western blot.Results Stimulated with LPS for 5 hours,IFIT1 was in-duced expression in Raw264.7 cell,3T3 cell and 10T1 /2 cell.The expression of normal control group was negative.The level of IFIT1 /Actin increased significantly 1 hour after radiation injury,and it reached the peak 12 hours after radiation injury (P <0.01).Conclusion LPS can stimulated a variety of cell lines expressed IFIT1,prompting that IFIT1 may participate in the occurrence and development of post-traumatic toxemia.IFIT1 of liver tissue increased significantly during the early stage in radiation mice.

Objective To explore the changes of gut microbiota in response to abdominal and pelvic radiotherapy and its potential relationship with intestinal infection.Methods Irradiation was delivered to the abdominal region of BALB/c mice,following the regular human pelvic-radiotherapy protocol,2.0 Gy/d,continuous 5 d/week.Samples of ileum tissue and the intestinal content were collected at different time points of irradiation procedure,including after 3 and 5 weeks,and at 1 week after 6 weeks of irradiation.Quantitative RT-PCR was used to measure the mRNA level of antimicrobial peptides and pro-inflammtory factors.Bacterial translocation was determined by PCR.The gut microbiota was characterized by the denaturing gradient electrophoresis assay.Results The expressions of cryptdin-1 and cryptdin-4 were decreased after 3 weeks of irradiation and at 1 week after 6 weeks of irradiation(t =-7.43,-3.54,-4.72,-4.27,P ＜ 0.05),while they were significantly increased at the 5 weeks of radiation (t =6.15,5.75,P ＜ 0.05).The diversity index and richness of gut microbiota after 3 or 5 weeks irradiation were significantly decreased (t =-3.49,-4.19,-3.44,-4.97,P ＜ 0.05).The gut microbiota dysbiosis of the irradiated mice was characterized with the decrease of probiotics of Lactobacillus and the increasing of opportunistic pathogen of Escherichia coli,Shigella flexneri,et al.Bacterial translocation episodes were more frequently in the irradiated mice than that of control animal.The mRNA levels of IL-1β、IL-6 and TNF-α were significantly increased after 3 or 5 weeks of irradiation (t =4.85,6.16,7.71,4.60,4.86,5.97,P ＜ 0.05).Compared with the control,the expression levels of IL-1β and TNF-α at the 1 week after 6 weeks of irradiation ending was also obviously enhanced (t =3.67,5.88,P ＜0.05).Conclusions Pelvic radiotherapy can induce abnormality of enteric antimicrobial peptides and may result in gut microbiota dysbiosis.The disturbed gut microbial flora may further trigger an incurrence of bacterial translocation and enteritis.Therefore,the gut microbiota may be a potential interfering target to alleviate radiotherapy adverse effect.

Objective To assess the distribution of recombinant fusion protein dTMP-GH in mice and to determine whether it is of tar-geted distribution characteristics. Methods A laboratory scale preparation of dTMP-GH recombinant fusion protein was obtained. Protein dT-MP-GH was labeled with radioactive 125 I,then mice were sacrificed at 5 min,15 min,30 min,1 h,2 h,4 h,8 h,12 h,24 h after tail vein injec-tion of 125 I-dTMP-GH at a dose of 100 μg/kg,and the organs and tissues ( heart,liver,spleen,kidney,bone and thyroid) were collected for radioactive counting. Results Preparation of purified ( >98%) dTMP-G was obtained. 125 I labeling rate was 71. 53%,radiochemical purity was 96. 53%,and specific activity was 0. 22 MBq/μl. 30 min after tail vein injection of 125 I labeled dTMP-GH,radioactivity accounted for 10% of the total injected in femoral,and metabolism was carried via liver and kidney over time. Conclusion Fusion protein mainly distribu-ted in bone marrow via tail vein injection in mice,which expressed that dTMP-GH has the characteristics of selective distribution in bone mar-row tissue.

Objective To study the relationship between cellular immunity in vivo,humoral immunity and different iodine intakes in patients with hashimoto thyroiditis(HT).Methods Seventy-six HT patients were divided into two groups acconding to the median of urine iodine (MUI =491.20 μ g/L):HT I group (urine iodine≥MUI) with 37 cases and HT Ⅱ group (urine iodine ＜ MUI) with 39 cases.And 49healthy persons were selected as control group.The level of free three triiodothyronine (FT3),free thyroxine (FT4),thyroid stimulating hormone (TSH),thyroglobulin antibody (TGAb),thyroid peroxidase antibody (TPOAb),thyroid hormone receptor antibody ( TRAb ),tumor necrosis factor-alpha ( TNF- α )of all groups were detected.Results The levels of FT3 and FT4 in HT I group [ (2.67 ± 1.93 ),( 4.22 ± 3.77) pmol/L ]and HT Ⅱ group [ ( 3.19 ± 1.63 ),( 5.99 ± 3.97 ) pmol/L ] were significantly lower than those in control group [(5.30± 1.10),(16.50 ±2.70) pmol/L] (P ＜ 0.01).The levels of TNF-α in HT I group [(6.14 ± 1.83)ng/L] and HT Ⅱ group [ (6.09 ± 1.50) ng/L] were both obviously higher than that in control group [ ( 1.90 ±0.60) ng/L] (P ＜ 0.01 ).The levels of FT3 and FT4 were lower and TNF α was higher in HT I group than those in HT Ⅱ group,but there was no statistically significance (P ＞ 0.05 ).The positive rate of TPOAb,TGAb in HT I group [97.3％(36/37),81.1％(30/37)] and HT Ⅱ group [89.7％(35/39),74.4％(29/39)]were significantly higher than those in contnol group [ 18.4％(9/49),12.2％(6/49 ) ] (P ＜ 0.01 ).There was no statistically difference of the positive rate of TPOAb,TGAb and TRAb between HT I group and HT Ⅱ group (P ＞ 0.05).While the percentage of patients with high titer of TPOAb and TGAb in HT I group was higher than that in HT [Ⅱ group,and there was statistical difference(P ＜ 0.05 ).The level of TRAb in HT I group was higher than that in HT Ⅱ group [ ( 1.25 ± 0.14) mU/L vs.( 1.16 ± 0.21 ) mU/L ],but there was no significant difference (P ＞ 0.05).Correlated anlysis showed that FT3 was negatively correlated with TGAb and TPOAb (r =0.342,-0.397,P ＜0.05),and TNF-αwas positively correhted with TGAb and TPOAb (r =0.405,0.561,P ＜ 0.05).Conclusions High iodine intake influences the autoimmune mechanism of HT patients.The iodine intake should be limited in HT patients.