Objective:To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation.Methods:A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241).Results:MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c. 1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c. 2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP1) and likely pathogenic (PM2_Supporting+ PM3+ PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.

Objective To investigate the efficacy and safety of regional citrate anticoagulation(RCA)in continuous blood purification(CBP)treatment during the shock and infection phases of severe burns.Methods A retrospective analysis was conducted on the clinical data of 64 patients who received RCA-CBP treatment at the Burns Reseaich Institute,the First Affiliated Hospital of Army Medical University from Jan-uary 2015 to January 2024.The patients were divided into the burn shock phase(burn duration<2 days,n=18)and the burn infection phase(burn duration≥2 days,n=46)according to the start time of CBP treat-ment.General datas,total body surface area burned(TBSA),abbreviated burn severity index(ABSI),hemato-crit(HCT)at the start of CBP treatment,platelet count(PLT),activated partial thromboplastin time(APTT),serum creatinine,urea nitrogen,total bilirubin,acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,Child-Pugh score,filter usage time for each CBP treatment,the incidence of unplanned treatment termination,blood gas analysis,and adverse e-vents were compared between the two groups.Results Compared with the burn shock phase,the levels of HCT and PLT in the burn infection phase were lower,the levels of urea nitrogen and the incidences of shock,hyperlactatemia and hypoxemia were higher,the filter usage time was longer,and the incidence of unplanned treatment termination was lower,the differences were statistically significant(P<0.05).The results of mult-ivariate COX regression analysis showed that the burn shock phase was a protective factor for the filter usage time(P<0.05).Among the 64 patients,citrate accumulation occurred in 2 patients(3.1%),both of which were septic shock combined with hyperlactatemia during the burn infection stage.Patients with acid-base im-balance and electrolyte disorder were corrected after adjusting the treatment.There were 5 new bleeding e-vents,all of which were caused by the primary diseases.Conclusion RCA is safe and effective for CBP treat-ment in severe burned patients and can be used as a routine anticoagulant method.

Objective:To elucidate the expression of angiopoietin-like protein 4 (ANGPTL4) in LPS-induced septic cardiomyopathy tissue and cardiomyocyte, and to explore the mechanism of ANGPTL4 in septic cardiomyopathy.Methods:Fifty C57BL/6 mice, aged 8 weeks, were randomly(random number) divided into a treatment group (LPS) and a control group ( n = 25 each). The mice in the treatment group were intraperitoneally injected with LPS (10 mg/kg) to establish a sepsis model. After 24 h, the myocardial tissues of the mice in the sepsis group and the control group, which were caused by LPS, were collected for RNA sequencing to pick out the differentially expressed gene of ANGPTL4.Ventricular myocytes of neonatal mice were taken, and the silencing and overexpression vectors of ANGPTL4 were transfected. After 48 hours of transfection, the cells were collected for subsequent detection. Western blot method was used to detect the expression of apoptotic factors Bax, Bcl-2, and Caspase 3 in mouse ventricular myocytes; CCK8 method was used to detect the activity of ventricular myocytes; using the Annexin V-FITC and PI double staining method, the apoptosis of ventricular myocytes was detected. Results:RNA-seq analysis revealed a statistically significant upregulation of ANGPTL4 expression at both transcriptional and translational levels in the ventricular tissue of septic mice, as compared to the control group ( P<0.05). The results of qRT-PCR and Western blot indicated that the mRNA and protein levels of ANGPTL4 in the ventricular tissues and cardiomyocytes of mice treated with LPS were significantly increased ( P<0.05). After transfection of the silencing and overexpression vectors of ANGPTL4 in cardiomyocytes, it was found that compared with NC, the mRNA and protein expression levels of ANGPTL4 in the si-ANGPTL4 group significantly decreased ( P<0.05), the vitality of ventricular myocytes increased ( P<0.05), the expressions of apoptosis-related factors Bax and Caspase 3 significantly decreased ( P<0.05), and the expression of Bcl-2 significantly increased ( P<0.05), and the number of apoptotic cells significantly decreased ( P<0.05); while the transfection of the overexpression vector of ANGPTL4 showed an opposite trend. Conclusions:In septic myocardial tissue and cardiomyocyte, the expression of ANGPTL4 is elevated, resulting in the inhibition of ventricular myocyte viability and the promotion of cardiomyocyte apoptosis.

OBJECTIVE: To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation. METHODS: A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241). RESULTS: MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c.1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c.2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+PM2_Supporting+PM3+PP1) and likely pathogenic (PM2_Supporting+PM3+PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.
Humans ; Male ; Pedigree ; Cholestasis, Intrahepatic/diagnostic imaging* ; Adenosine Triphosphatases/genetics* ; Female ; Adult ; Exome Sequencing ; Mutation ; East Asian People

Objective:To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation.Methods:A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241).Results:MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c. 1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c. 2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP1) and likely pathogenic (PM2_Supporting+ PM3+ PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.

Objective:To explore the feasibility of predicting complexity of intensity modulated radiotherapy(IMRT)plan through adopted machine learning method to extract planomics features of radiotherapy,so as to provide a new method for comprehensive evaluation of the complexity of IMRT plan.Methods:The medical case data of 3203 patients with pelvic tumor,or abdominal tumor or head and neck tumor,who admitted to The First Affiliated Hospital with Nanjing Medical University from December 2022 to November 2023,were selected.All patients adopted Monaco system to conduct design for plan,and underwent treatment on Precise and Axesse accelerators.The evaluation indicator of complexity of 10 plans was calculated by using Python software,and the planomics features in the files of radiotherapy plans were extracted through format conversion and pyradiomics tool of imaging omics.The planomics features of radiotherapy were selected through data cleaning,filtering method and embedding method of machine learning.The corresponding predictive model of the evaluation indicator of complexity of 10 common plans was respectively constructed through used Gradient Boosting Decision Tree algorithm.The goodness of fit(R2)was adopted to evaluate the prediction performance of the model,and the 5-fold cross-validation method was adopted to detect the generalization ability of the model.Results:There were statistically significant differences between Precise accelerator and Axesse accelerator in average leaf to area(LA),plan irregularity(PI)of beam shape and standard circle,modulation complexity score(MCS)of the variability between shape and area of subfield,and the advantage value of leaf travel(LT)(t=63.894,-63.678,72.582,-48.858,P＜0.01),respectively.A total of 107 planomics features were extracted through pyradiomics tool,and 38 features were remained after filtering method conducted screening,and 4 to 11 features were remained after embedding method conducted screening.The goodness of fits of mean field area(MFA),LA and leaf gap average(LGA)value were better in the validation set,with R2＞0.970,however the goodness of fits of the proportion of small aperture score 20 mm(SAS20)was poor in validation set,with R2=0.917.The 5-fold cross-validation results showed that the average value of prediction accuracy of all indicators of complexity was＞90％.Conclusions:The extracted planomics features of radiotherapy based on radiomics method can accurately predict the complexity of IMRT plan,which are expected to play a greater role in improving the ensure efficiency of individual quality of patient,and screening radiotherapy plan with higher-quality.

Objective:To explore the application effects of mind mapping combined with scenario simulation training on the ability training of junior nurses in hospital transfer of patients with critical burns and trauma.Methods:A prospective randomized controlled study was conducted. From December 2019 to December 2020, 55 female junior nurses from the Institute of Burn Research of the First Affiliated Hospital of Army Medical University (the Third Military Medical University) who met the inclusion criteria were enrolled in this study and divided into routine group (27 nurses, aged (24.0±0.9) years) and combined group (28 nurses, aged (24.2±0.8) years), according to the random number table. The nurses in routine group were trained with hospital transfer of patients with critical burns and trauma by theory combined with operational skill, and the nurses in combined group were trained with hospital transfer of patients with critical burns and trauma by mind mapping combined with scenario simulation training. Before and after the training, the self-made theoretical examination papers and skill assessment items were used for the examination and assessment to nurses, and their scores were calculated and compared. The self-made emergency ability scoring system was used to evaluate the emergency disposal ability of nurses from five dimensions, including team cooperation ability, emergency response ability, operative technique ability, specialized business ability, and nurse-patient communication ability, and their scores were calculated and compared. The non-standard implementation rates of transfer nursing measures, such as incomplete preparation of goods, poor communication effect of patients, inadequate pipeline nursing, unclear handover, and inadequate final treatment, were calculated and compared in the process of transporting highly simulated human (hereinafter referred to as simulated human) by nurses before and after training; and the rate of disease change and successful rate of transport of simulated human were calculated and compared after training. After assessment, self-made satisfaction questionnaire was used to compare nurses' satisfaction with the training mode, content, and effects. Data were statistically analyzed with independent sample t test, Pearson chi-square test, or Yates corrected chi-square test. Results:Fifty-five enrolled nurses were fully involved in the training, examination, assessment, and questionnaire filling. Before training, there were no statistically significant differences in theoretical examination and skill assessment scores between the 2 groups ( P>0.05); After training, the theoretical examination and skill assessment scores of nurses in combined group were significantly higher than those in routine group (with t values of -3.89 and -4.24, respectively, P<0.05). Before training, there were no statistically significant differences in the scores of each item of emergency disposal ability between the 2 groups ( P>0.05); after training, the scores in terms of team cooperation ability, emergency response ability, operative technique ability, specialized business ability, and nurse-patient communication ability of nurses in combined group were significantly higher than those in routine group (with t values of -6.49, -6.44, -2.21, -2.85, and -2.34, respectively, P<0.05). Before training, there were no statistically significant differences in the non-standard implementation rates of transfer nursing measures of nurses between the 2 groups ( P>0.05); after training, the non-standard rates of incomplete preparation of goods, unclear handover, and inadequate final treatment of nurses in combined group were significantly lower than those in routine group (with t values of 3.87, 5.89, and 5.28, respectively, P<0.05). After training, the rate of disease change of simulated human of nurses in combined group was 7.14% (2/28), which was significantly lower than 33.33% (9/27) in routine group ( χ2=5.89, P<0.05); the successful rate of transport was 96.43% (27/28), which was significantly higher than 74.07% (20/27) in routine group ( χ2=3.87, P<0.05). After assessment, the total score of training satisfaction and scores of satisfaction with training mode and training effect of nurses in combined group were significantly higher than those in routine group (with t values of 5.22, 4.67, and 10.71, respectively, P<0.05). There was no statistically significant difference in the satisfaction score on training content between the two groups ( P>0.05). Conclusions:Evidence-based mind mapping combined with scenario simulation training significantly improves the nursing skills and emergency handling capabilities of junior nurses in transferring patients with critical burns and trauma.

Objective The HPLC-MS/MS is used to comprehensively monitor the feeding conditions of raw materials in Yuanhu analgesic capsules, and the content of the index components can be detected at the same time. Methods The Inertsil ODS-3 (4.6 mm×250 mm, 5 μm) was used with the column temperature 40 ℃, Flow phase: 0.1% formic acid-acetonitrile; the gradient elution program, active ingredients were separated by HPLC, and the Electrospray Ionization Mass (ESI) source was applied and operated in the negative ion mode, and reactions ion monitoring mode (MRM) for quantitative analysis were selected. Results Through analysis and contrast of the medicinal materials, reference substance of primary mass spectrogram showed the same characteristic peak, and the proprietary Chinese medicine can be judged by prescription feeding process. The tetrahydroxene and imperatorin had a good linear relationship in 5.08×10-5-30.45×10-5μg (r=0.999 4), 5.02×10-5-30.09×10-5μg (r=0.999 2). Precision test were 0.99% and 1.14%, the recovery rate were 97.02%-99.66%, 97.62%-99.94%. Conclusions The method is simple, accurate and reliable, high sensitive and fast. It is suitable to monitor the feeding condition and quality of yuanhu analgesic capsules.

Objective To develop a HPLC-MS/MS method for comprehensive monitoring and control of the raw material feeding (honeysuchle flowers extract and baikal skullcap root extract) , and simultaneous determination of chlorogenic acid and baicalin in Yinhuang capsules. Methods The separation was performed on an Inertsil ODS-3 (2.1 mm × 150 mm, 5 μm) analytical column with the mobile phase consisting of methanol- 10 mmol/L ammonium acetate solution by gradient elution program, and the column temperature was 40 ℃. Active ingredients were separated by HPLC, and the Electrospray Ionization Mass (API) source was applied and operated in the negative ion mode, and reactions ion monitoring mode (MRM) for quantitative analysis were selected. Results The samples and the mixed Extract have the same characteristic peak in MS and MS/MS. According to the prescription feeding process, the proprietary Chinese medicine wasdetermined. The results showed that the palladium residue of 6 batches samples were up to the standard by HPLC/MS/MS chromatographic peak areas. The calibration cruve of chlorogenic acid and baicalin were linear: 0.60-4.80 μg/ml (r = 0.9989),2.87-14.40 μg/ml (r = 0.9986), with the relative standard deviation of repeatability by 0.69% and 0.69% respectively, and the mean recovery rate were 95%-102%, 95%-103%, respectively. Conclusions The method was proven to be simple, accurate, reliable, high sensitive and can be used for determination and control of the raw material feeding (honeysuchle flowers extract and baikal skullcap root extract) and quality in Yinhuang capsules.

Objective The monitoring of the feeding situation of active pharmaceutical ingredient in Shendan-Chenpi tablet by HPLC-MS/MS,and the content of sodium taurocholate and hesperidin.Methods Using ZORBAX Eclipse Plus C18(4.6 mm×250 mm, 5 μm)Column temperature 40 ℃, Mobile phase with acetonitrile-10 mmol/sodium acetate solution, using gradient elution program. Active ingredients were separated by HPLC, and the Electrospray Ionization Mass (ESI) source was applied and operated in the negative ion mode, and reactions ion monitoring mode(MRM) for quantitative analysis were selected. Results The proprietary Chinese medicine is judged by the prescription feeding process, through analysis and contrast of the medicinal materials, reference substance of primary mass spectrogram, secondary mass spectrogram of peak. The aurocholic acid sodium and hesperidin had a good linear relationship in 0.242×10-2-1.45×10-2μg(r=0.996 0), 0.688×10-2-10.30×10-2μg(r=0.999 2), and the precision test were 0.78% and 1.56%, and the recovery rate were 102%-103%,96%-109%. Conclusions The method was simple, accurate and reliable, high sensitive and fast. The comprehensive monitoring was applied to the Shedan-Chenpi tablet in feeding analysis and quality.