Objective To analyze the factors related to early allograft dysfunction(EAD)after liver transplantation and to construct a predictive model.Methods A total of 375 patients who underwent liver transplantation in our hospital from December 2008 to December 2021 were collected,including 90 patients with EAD and 266 patients without EAD.Thirty items of baseline data for the 2 groups were compared and analyzed.Aftergrouping in a ratio of 7∶3,univariate and multivariate logistic regression analyses were used in the training set to evaluate the factors related to EAD and construct a nomogram.Receiver operating characteristic(ROC)curve,decision curve analysis(DCA),sensitivity,specificity,positive predictive value,negative predictive value,Kappa value and other indicators were used to evaluate the model performance.Results The incidence of EAD after liver transplantation was 24%.Multivariate logistic regression analysis showed that preoperative tumor recurrence history(OR=3.15,95%CI:1.28～7.77,P=0.013)and operation time(OR=1.22,95%CI:1.04～1.42,P=0.015)were related to the occurrence of EAD after surgery.After predicting the outcome according to the cut-off point of 0.519 identified by the Youden index,the model performance in the both training set and validation set was acceptable.DCA suggested the model has good clinical applicability.Conclusion The risk factors for EAD after liver transplantation are preoperative tumor recurrence history and operation time,and the established model has predictive effect on prognosis.

Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Objective To investigate the effects of vitamin D mediated mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK)pathway on myocardial injury in rats with gestational diabetes mellitus.Methods Fifty SD rats were divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,and the gestational diabetes rat model was established.After successful modeling,experimental-L,experimental-M,experimental-H groups were given intragastric administration of 0.05,0.10 and 0.15 μg·kg-1 concentration of vitamin D,while control group and model group were given intragastric administration of 0.9％NaCl at the same dose once a day for 2 weeks.Fasting blood glucose concentration and insulin level were detected before intervention,1 week and 2 weeks after intervention.Echocardiography was used to detect cardiac function[left ventricular ejection fraction(LVEF),maximum rate of rise(+dp/dtmax)and maximum rate of decline(-dp/dtmax)of left ventricular pressure].Myocardial enzyme indexes[troponin Ⅰ(cTn Ⅰ)kit,creatine kinase isoenzyme(CK-MB)]and inflammatory factors[tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in serum and myocardial tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA),and MEK/ERK pathway protein expression was detected by western blot.Results The levels of cTn Ⅰ in cardiac tissue of control group,model group,experimental-L group,experimental-M group,experimental-H group were(10.50±1.08),(42.26±4.30),(31.85±2.44),(23.31±2.15)and(14.85±1.19)ng·mL-1;serum cTn Ⅰ levels were(23.79±3.46),(63.59±5.52),(51.02±4.27),(42.75±3.19)and(29.20±2.11)ng·mL-1;myocardial tissue levels of CK-MB were(8.52±0.90),(17.65±1.75),(15.62±1.27),(13.11±1.24)and(9.85±0.87)ng·mL-1;serum levels of CK-MB were(11.32±0.98),(21.24±1.45),(18.75±1.32),(15.11±1.02)and(12.27±1.11)ng·mL-1;phosphorylated-MEK protein expression were 0.24±0.03,0.85±0.09,0.72±0.06,0.57±0.07 and 0.35±0.04;phosphorylated-ERK1/2 protein expression were 0.18±0.02,0.66±0.07,0.52±0.06,0.40±0.07 and 0.24±0.05,respectively.There were statistically significant differences of above indexes between control group and model group(all P＜0.05);the difference between model group and experimental-L,experimental-M,experimental-H groups were all statistically significant(all P＜0.05).Conclusion Vitamin D may reduce myocardial injury in rats with gestational diabetes by inhibiting the activation of MEK/ERK pathway.

Objective To explore the effect of forsythin on the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway in mice infected with respiratory syncytial virus(RSV).Methods A respiratory infection model was established by intranasal inoculation of RSV.Mice infected with RSV were randomly divided into model group,experimental group,and positive control group,while control group received an equal volume of DMEM medium by nasal drops.The experimental group was administered forsythin(200 mg·kg-1·d-1)by gavage,the positive control group received ribavirin(27.6 mg·kg-1·d-1)by gavage,and both the control and model groups were given an equal volume of 0.9％NaCl,with continuous intervention for 14 days.Interleukin-4(IL-4),IL-13,and interferon-gamma(INF-γ)levels in bronchoalveolar lavage fluid(BALF)were detected by enzyme-linked immunosorbent assay;transcription levels of TLR4 and MyD88 mRNA in lung tissue were detected by real-time fluorescent quantitative polymerase chain reaction;and the positive expression of TLR4 and MyD88 proteins in lung tissue were detected by immunohistochemistry.Results The levels of IL-4 in BALF of the control group,model group,experimental group,and positive control group were(490.63±27.45),(1 382.37±41.28),(970.32±36.01),(738.41±30.27)pg·mL-1,respectively;IL-13 levels were(4.02±2.63),(18.33±5.62),(12.97±3.73),and(7.51±2.74)pg·mL-1,respectively;INF-γ levels were(54.42±2.68),(30.26±4.68),(42.80±3.36),and(45.01±3.82)pg·mL-1,respectively;the expression of TLR4 mRNA in lung tissue were 0.43±0.06,1.63±0.12,0.98±0.10,and 0.86±0.06,respectively;the expression of MyD88 mRNA in lung tissue were 0.56±0.09,1.78±0.15,1.02±0.07,and 0.75±0.06,respectively;the average optical density of TLR4 protein in lung tissue were 0.02±0.00,0.11±0.02,0.06±0.01,and 0.03±0.00,respectively;the average optical density of MyD88 protein were respectively 0.01±0.00,0.09±0.02,0.05±0.01,and 0.03±0.01,respectively.Compared the model group with the control group,and compared the experimental and positive control groups with the model group,above indicators showed statistically significant differences(all P＜0.05).Conclusion Forsythin can alleviate lung damage in mice infected with RSV,possibly by regulating the balance of immune cells and inhibiting the TLR4/MyD88 signaling pathway.

Objective:To extract the early result of postoperative echocardiographic evaluation in patients underwent left ventricular assist device (LVAD) implantation, and to assess the efficacy of surgical treatment for end-staged heart failure.Methods:Between June 2019 and May 2023, the patients underwent left ventricular assist device implantation were enrolled in this study. Demographic baseline characteristics and perioperative echocardiographic parameters were collected and analyzed.Results:A total of 28 patients were included in the study. After LVAD implantation, the heart sizes of the patients obviously reduced and the left heart contractibility function improved. The right ventricular contractibility remained stable. The proportion of the patients with moderate to severe mitral regurgitation was significantly reduced, but patients with mild to moderate aortic insufficiency increased. No serious complications such as death, pericardial tamponade and thrombosis events were observed during the follow-up period.Conclusion:LVAD implantation improved the left cardiac function, while the right cardiac function remained stable. However, it should be paid attention that the aortic valve function was impaired after the surgery. Generally, the early results of LVAD implantation for the treatment of end-stage heart failure were satisfactory.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.

Objective:To explore the genetic etiology of a child with primary hypertrophic osteoarthropathy(PHO).Methods:A child who was admitted to Zhongnan Hospital of Wuhan University on July 27, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing. Suspected splicing variant was verified by Sanger sequencing of family members. In vitro function was validated through a minigene assay, whilst the suspected exonic deletion was validated by long-fragment PCR. This study was approved by the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-011). Results:Whole exome sequencing revealed that the child has harbored compound heterozygous variants of HPGD gene, including a heterozygous deletion (Exon 3 del) derived from his father and a splicing variant (c.421+ 1G>T) derived from his mother. Long-fragment PCR verified that the child and his father had both harbored a 7 565 bp heterozygous deletion (c.218-1304_324+ 6156del), whilst the minigene assay proved that the splicing variant has resulted in skipping of exon 4. Conclusion:The heterozygous c. 218-1304_324+ 6156del deletion and the c. 421+ 1G>T splicing variant of the HPGD gene probably underlay the pathogenesis in this child. Above finding has enriched the mutational spectrum of the HPGD gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.