Objective:To investigate the efficacy of neutrophil elastase inhibitor in children with acute respiratory distress syndrome（ARDS）.Methods:A total of 168 children with moderate to severe ARDS who were hospitalized in the Department of Pediatric Intensive Care Unit，the Affiliated Children′s Hospital of Xi′an Jiaotong University and Children's Emergency Center of Gansu Provincial Central Hospital from January 2022 to December 2023 were selected. Eighty-seven children receiving neutrophil elastase inhibitors were treated as the treatment group and 81 children receiving conventional treatment as the control group. The dynamic changes of general data，clinical indicators and ventilator parameters at 24 h，48 h and 72 h were compared between the two groups. Mortality at 28 days was the primary endpoint. Kaplan-Meier curve and Log-Rank test were used to evaluate cumulative survival.Results:There was no significant difference in general information and clinical characteristics between the two groups.Compared with the control group，arterial partial pressure of oxygen（PaO 2）/fraction of inspired oxygen（FiO 2）in the treatment group increased significantly at 48 h［（160.28±5.90）mmHg（1 mmHg=0.133 kPa）vs（141.04±4.01）mmHg， P<0.05］and 72 h［（227.58±6.85）mmHg vs（180.86±4.08）mmHg， P<0.05］，and the differences were statistically significant.The platform pressure in the treatment group were lower than that of the control group at 24 h［（28.18±3.95）cmH 2O（1cmH 2O=0.098 kPa）vs（30.15±7.75）cmH 2O， P<0.05］，48 h［（25.56±4.06）cmH 2O vs（29.07±5.01）cmH 2O， P<0.05］，72 h［（24.95±2.82）cmH 2O vs（27.12±6.51）cmH 2O， P<0.05］，and the differences were statistically significant. IL-8 in the treatment group were lower than that of the control group at 48 h［（78.26±14.05）ng/L vs（86.02±15.01）ng/L， P<0.05］and 72 h［（58.38±15.56）ng/L vs（68.68±18.05）ng/L， P<0.05］，and the differences were statistically significant.The survival curve showed that the cumulative survival rate of the treatment group was higher than that of the control group，the difference between the two groups was statistically significant（ χ2=4.549， P=0.033）. Conclusion:Neutrophil elastase inhibitors can reduce the lung injury of ARDS patients by inhibiting the inflammatory response induced by neutrophils，and ultimately improve the prognosis of the disease.

Objective:To analyze the risk factors for in-hospital malignant ventricular arrhythmia (MVA) in acute myocardial infarction (AMI) and to construct and validate a risk prediction model.Methods:This study was a retrospective cohort study. Patients aged≥18 years who were admitted to Qilu Hospital of Shandong University with a diagnosis of AMI and underwent coronary angiography (CAG) from May 2016 to March 2023 were selected, and the patients' clinical routine test indicators and CAG results were collected. Univariate and bidirectional stepwise logistic regression were used to screen out the risk factors for constructing the best prediction model. The prediction model was constructed by combining the results of multivariate logistic regression. The Hosmer-Lemeshow test and ROC curve, calibration curve, and decision curve were drawn to evaluate the model. The nomogram was drawn to visualize the model, and the Bootstrap self-sampling method was used for internal validation. The ROC curve was drawn to evaluate the predictive performance of each risk factor and prediction model. Finally, a multicollinearity test was performed.Results:Among the 4 205 patients finally included in the study, 115 patients (2.735%) developed MVA during hospitalization. The predictive factors screened out included age (X1), diastolic blood pressure (X2), respiratory rate (X3), blood glucose (X4), serum potassium (X5), logarithmic NT-proBNP (X6), myocardial infarction type (NSTEMI=X7, unclassified=X8), J wave (X9), Killip grade (Ⅱ=X10, Ⅲ=X11, Ⅳ=X12), and the regression equation was ln(p/1-p)=-4.699+0.029×X1-0.012×X2+0.059×X3+0.148×X4-1.175×X5+0.866×X6-1.427×X7-0.475×X8+0.758×X9+0.294×X10+0.902×X11+1.815×X12. The area under the ROC curve (AUC) of the model was 0.855 (95% CI: 0.816-0.894), and the Hosmer-Lemeshow test ( χ2=14.178, P=0.077) and the calibration curve showed that the predicted probability was consistent with the actual probability. The probability threshold of 0% to 65% had a better clinical net benefit. The area under the internal validation ROC curve (AUC) was 0.855, 95% CI: 0.813-0.891. The prediction performance of the nine variables was stronger than that of any single variable. There was no multicollinearity between the variables. Conclusions:Age, diastolic blood pressure, respiratory rate, blood glucose, serum potassium, NT-proBNP, type of AMI, J wave, and Killip class are forecasting indicator for in-hospital MVA in AMI. The risk prediction model based on the above factors has good predictive performance.

High-flow nasal cannula (HFNC) is a respiratory support strategy,which delivers humidified and heated oxygen at a set oxygen concentration and speed to correct respiratory failure.The failure of HFNC ventilation involves many factors,and the failure of treatment may increase the mortality.At present,respiratory rate-oxygenation index and its related predictors or models are widely used as predictors of failure in HFNC treatment,which can help identify patients at risk of tracheal intubation,but there is no uniform critical value.When using HFNC,clinicians need dynamic evaluation,and make decisions with the help of predictive factors and the actual situation of patients to improve the prognosis.

The idea of disease prevention runs through the traditional medical diagnosis and treatment system,and also plays an important role in the prevention and treatment of gastric precancerous lesions.This article organically combines disease differentiation,syndrome differentiation,symptom differentiation,and constitution differentiation to form a four in one diagnosis and treatment model.Disease differentiation means identifying the name of the disease and grasping the progression stage of the disease;syndrome differentiation means combining the macroscopic and microscopic aspects to accurately grasp the pathogenesis;symptom differentiation means identifying complications and clinical problems that need to be solved urgently;constitution differentiation means predicting syn-drome type bias and disease development.This model not only enables systematic diagnosis and treatment of gastric precancerous le-sions,but also provides targeted diagnosis and treatment plans for patients,with the characteristics of comprehensiveness,full process,and personalization.Therefore,combining the four in one diagnosis and treatment model of disease differentiation-syndrome differentia-tion-symptom differentiation-constitution identification with the disease prevention theory is conducive to the early detection of gastric precancerous lesions,timely tracking of the progress of the lesions,and the adoption of correct,comprehensive,and full-process inter-vention methods to reverse gastric precancerous lesions,which can play a positive role in the diagnosis,treatment,and prevention of gastric precancerous lesions.

Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1). METHODS: A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing. RESULTS: The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously. CONCLUSION Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.
Female ; Humans ; Gas Chromatography-Mass Spectrometry ; Genetic Testing ; Mutation ; Phenotype ; Prenatal Diagnosis ; Tyrosinemias/genetics* ; Child

Objective:To investigate the distribution and epidemic characteristics of respiratory pathogens in children before and after COVID-19 epidemic in Lanzhou.Methods:Two hundred and eighty-six children hospitalized with acute upper respiratory tract infection in Central Hospital of Gansu Province and Gansu Maternal and Child Health Hospital from October to November of 2020 and October to November of 2021 were selected respectively as the research objects, and a retrospective analysis was made.IgM antibodies of nine pathogens, including influenza virus A(IVA), influenza virus B(IVB), parainfluenza virus(PIV), adenovirus(ADV), mycoplasma pneumoniae(MP), chlamydia pneumoniae(CP), respiratory syncytial virus(RSV), echovirus(ECHO)and coxsackie virus B(CVB), were detected, and the basic information and epidemic characteristics were statistically analyzed.Results:The total positive rates of IgM antibodies of nine pathogens before and after the epidemic in COVID-19 were 31.8%(91/286)and 5.9%(17/286)respectively, after the epidemic, the detection rates dropped significantly, and there was significant difference among them( χ2= 62.505, P<0.05); After the epidemic, the detection rates of ADV, MP and CVB were all lower than those before the epidemic, and there were significant differences among these groups( χ2= 39.281, 12.167, 10.155, all P<0.05). The positive detection rates in the age group of 1 month ~1 year, ~3 years, ~6 years and>6 years before the outbreak were 37.4%(37/99), 38.3%(36/94), 16.7%(12/72)and 28.6%(6/21)respectively, and there were significant differences among these groups( χ2=34.055, P<0.05); Among them, the detection rates of MP in the age group 1 month ~1 year, ~3 years, ~6 years and>6 years were 16.2%(6/37), 25.0%(9/36), 16.7%(2/12)and 100%(6/6)respectively, and there were significant differences among these groups( χ2=10.289, P<0.05); CVB was not detected in>6 years group, the positive detection rates of CVB were 16.2%(6/37), 22.2%(8/36)and 25.0%(3/12)in the age group of 1 month ~1 year, ~3 years, ~6 years respectively, and there were significant differences among these groups( χ2= 27.742, P< 0.05). After the epidemic, the positive detection rates of the patients in the age group of 1 month ~1 year, ~3 years, ~6 years and>6 years were 5.9%(4/68), 4.0%(3/75), 5.7%(6/106)and 10.8%(4/37), with no statistical significance( χ2=2.235, P>0.05); Among them, the positive rates of IVB were 25.0%(1/4), 33.3%(1/3)and 66.7%(4/6)in the age group of 1 month ~1 year, ~3 years, ~6 years respectively, and in the age group>6 years was not detected, and there were significant differences among these groups( χ2= 96.022, P< 0.05). The detection rates of mixed infection of pathogens before and after the epidemic were 5.6%(16/286)and 0.3%(1/286)respectively, with no statistical significance( χ2= 2.314, P>0.05). Conclusion:The distribution of common pathogens of acute upper respiratory tract infection among children in Lanzhou was different before and after COVID-19 epidemic.

INTRODUCTION: Sepsis is defined as a life-threatening complication that occurs when the body responds to an infection attacking the host. Sepsis rapidly progresses and patients deteriorate and develop septic shock, with multiple organ failure, if not promptly treated. Currently no effective therapy is available for sepsis; therefore, early diagnosis is crucial to decrease the high mortality rate. Genome-wide expression analyses of patients in critical conditions have confirmed that the expression levels of the majority of genes are changed, suggesting that the molecular basis of sepsis is at the gene level. This review aims to elucidate the role of circular (circ) RNAs in the pathogenesis of sepsis and sepsis-induced organ damage. In addition, the feasibility of using circRNAs as novel diagnostic biomarkers for sepsis is also discussed, as well as circRNA-based therapy. METHOD: This narrative review is based on a literature search using Medline database. Search terms used were "circular RNAs and sepsis", "circRNAs and sepsis", "non-coding RNAs and sepsis", "ncRNAs and sepsis", "circRNAs and septic pathogenesis", "circRNAs and septic model", "circRNAs and septic shock" and "circRNAs, biomarker, and sepsis". RESULTS: Numerous studies indicate that circRNAs might exert pivotal roles in regulating the immune system of the host against various pathogens, such as bacteria and viruses. Dysregulation of circRNA expression levels has been confirmed as an early event in sepsis and associated with the inflammatory response, immunosuppression and coagulation dysfunction. This impairment in regulation eventually leads to multiple organ dysfunctions, including of the kidneys, lungs and heart. CONCLUSION By investigating the regulation of circRNAs in sepsis, new molecular targets for the diagnosis and intervention of sepsis can be identified. Such an understanding will be important for the development of therapeutic drugs.
Biomarkers ; Humans ; RNA, Circular ; Shock, Septic/genetics*

Objective:To compare modified load-sharing rip-stop (mLSRS) technique with suture bridge (SB) for repair of massive rotator cuff tears.Methods:A retrospective analysis was conducted of the 68 patients who had been treated for massive rotator cuff tears from January 2017 to June 2019 at Department of Orthopedics, Dongyang People's Hospital. They were 26 males and 42 females, aged (63.4±1.0) years (from 45 to 84 years), with 56 right and 12 left sides affected. Of them, 32 were treated by mLSRS and 36 by double-line SB. The 2 groups were compared in terms of visual analog scale (VAS), Constant-Murley scoring, University of California Los Angeles (UCLA) scoring and American Shoulder and Elbow Surgeons (ASES) scoring at the final follow-ups, and Sugaya ultrasonic evaluation of the repair integrity at postoperative 12 months.Results:There was no statistically significant difference in preoperative general data between the 2 groups, showing they were comparable ( P>0.05). Operations were successful in all patients who were followed up for 13 to 44 months (average, 19.7 months). No patient suffered from such complications as joint infection or anchor withdrawal. At the final follow-up, the mLSRS group scored respectively 0.9±0.6, 85.3±4.8, 33.1±1.0 and 86.4±5.0 in VAS, Constant-Murley, UCLA and ASES scores, significantly improved than their preoperative values (7.2±0.8, 47.0±3.1, 15.8±3.0 and 48.5±4.5) ( P<0.05); the SB group scored respectively 1.1±0.6, 86.6±3.4, 33.2±1.1 and 86.9±4.6 in the above indicators, also significantly improved than their preoperative values (7.3±0.7, 46.5±4.7, 14.4±2.7 and 48.8±4.3) ( P<0.05); there were no significant differences between the 2 groups in preoperative or postoperative values ( P> 0.05). The Sugaya ultrasonic evaluation showed no significant difference in rotator cuff healing between the 2 groups at postoperative 12 months ( P>0.05); according to the positions of re-tears, the SB group had significantly more type Ⅱ re-tears (20%, 2/10) than the mLSRS group (0, 0/4) ( P<0.05). Conclusion:Although both mLSRS and SB techniques can achieve satisfactory and comparable clinical outcomes in arthroscopic repair of massive rotator cuff tears, mLSRS may lead to fewer postoperative type Ⅱ re-tears than SB.