OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Objective To investigate the effect of a G-protein receptor 110(GPR110)ligand on retinal neuroinflam-mation in diabetic mice by regulating the Janus kinase 2/signal transduction and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods This experiment was divided into two parts.(1)Twelve C57BL/6J mice(24 eyes)were randomly divided into the control group,4-week streptozotocin(STZ)induction(STZ4-week)group,STZ 8-week group,and STZ 12-week group,with 3 mice in each group.The diabetic model was induced by intraperitoneal injection of STZ(150 mg·kg-1)in all groups except the control group.The expression of GPR110 and glutamine synthetase(GS)in the retinal tissue of mice was detected by immunofluorescence staining to screen the optimal acting time.(2)Thirty-two C57BL/6J mice(64 eyes)were divided into the control group,STZ 8-week group,the STZ+N-docosahexaenol ethanola-mine(SYN)group,and the STZ+SYN+adeno-associated virus-mediated GPR110(AAV-GPR110)group,with 8 mice in each group,and they were subjected to corresponding treatment.Immunohistochemistry was performed to detect the ex-pression of glial fibrillary acidic protein(GFAP)in mouse retinal tissues.ELISA was performed to detect the level of inter-leukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in mouse retinal tissues.Western blot was performed to detect the ratio of JAK2 to phosphorylated JAK2(p-JAK2)and that of STAT3 to phosphorylated STAT3(p-STAT3).Results(1)GPR110 in the retina of mice in the STZ 4-week group,STZ 8-week group,and STZ 12-week group was mainly expressed in Müller cells.The highest expression intensity of GPR110 was observed in the retina of mice in the STZ 8-week group;therefore,the diabetic mice in the STZ 8-week group were selected for subsequent experiments.(2)Compared with the control group,mice in the STZ 8-week group and the STZ+SYN+AAV-GPR110 group exhibited a decrease in the retinal thickness and the number of retinal ganglion cells,those in the STZ+SYN group displayed a de-crease in the retinal thickness(all P＜0.05),and those in the other three groups presented a significant increase in the in-tensity of GFAP-positive expression and an increase in the level of IL-6,IL-1β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Compared with the STZ 8-week group,the retinal thickness and the number of retinal ganglion cells in the STZ+SYN group increased,the intensity of GFAP-positive expression decreased,and the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values decreased(all P＜0.05).Compared with the STZ+SYN group,mice in the STZ+SYN+AAV-GPR110 group showed a decrease in the retinal thickness and the number of retinal ganglion cells,a significant increase in the intensity of GFAP-positive expression,and an increase in the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Conclusion The GPR110 ligand could alleviate retinal neuroinflammation in diabetic mice by inhibiting the JAK2/STAT3 signaling pathway.

Objective To evaluate the consistency of DNA coding region single nucleotide polymorphism(cSNP)genotyping at the DNA and RNA levels in common body fluid samples based on the next-generation sequencing platform.Methods After extensive literature retrieval,25 cSNP loci of 8 human tissue-specific mRNAs in peripheral blood,semen and vaginal secretion were selected.Two cSNP multiplex genotyping panels based on DNA and RNA,respectively,were developed for use on the MiSeq FGx sequencing platform.45 body fluid samples(including 14 peripheral blood samples,15 semen samples and 16 vaginal secretion samples)were sequenced and analyzed.The inconsistent typing results of DNA and RNA were rechecked by Sanger sequencing.Results The results of cSNP genotyping at the DNA and RNA levels in peripheral blood were completely consistent.Among the 15 semen samples,the genotypes of rs1995640 and rs 1995641 on the TGM4 gene were inconsistent in 3 cases.Among the 16 vaginal secretion samples,there were 2 cases,1 case and 2 case with inconsistent results of rs3869098,rs10947121 and rs12110470 in MUC22 gene,respectively.Conclusion In this study,MiSeq FGx sequencing and Sanger sequencing were used to test 25 cSNP loci with body fluid tissue specificity.The same typing results at the DNA and RNA levels were observed at 20 cSNPs.Inconsistent genotypes at the DNA and RNA levels were observed at 5 cSNPs on the TGM4 and MUC22 genes.This study provides experimental methods and data for forensic cSNP studies.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Purpose: This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication. Methods: The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols. Results: The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors. Conclusion The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:Measure the global longitudinal strain (GLS) of the left ventricle in trauma patients by beside speckle tracking echocardiography to explore the role of STE -GLS in evaluating left ventricular systolic function in trauma patients, and then explore the clinical value of GLS in judging the prognosis of trauma patients.Methods:Trauma patients admitted to intensive care unit from September 1, 2020 to April 1, 2021 with an Injury Severity Score (ISS) of ≥ 16 points. were consecutively enrolled. Moreover, those patients who met the following criteria were selected as the research subjects: aged between 18 and 80 years old, had no serious underlying diseases in the past, the time from trauma onset to admission was within 24 hours, and were able to complete an echocardiogram examination within 24 hours after the onset of the disease. Exclude patients who are unable to complete the ultrasound examination within 24 hours after the onset of the disease, or those with poor image quality, or those complicated with severe heart diseases and systemic comorbidities. The left ventricular global longitudinal strain (GLS) was measured by bedside speckle tracking echocardiography. According to the GLS values they were divided into abnormal group (GLS> -15%) and normal group (GLS≤ -15%). Independent sample t-tests and chi-square tests were applied to conduct a comparative analysis of the clinical characteristics between the two groups of patients. Furthermore, multiple linear regression analysis was conducted to explore the correlation between STE-GLS and the duration of intensive care unit stay.Results:A total of 32 trauma patients were eligible for this study. One patient was found to have abnormal left ventricular systolic function (LVEF<50%) detected by conventional echocardiography, however speckle tracking echocardiography detected decreased left ventricular systolic function (GLS> -15%) in 13 Patients. Multiple linear regression analysis showed that the global longitudinal strain of left ventricle and serum high sensitivity troponin I were independent risk factors affecting the time of intensive care in trauma patients.Conclusions:Speckle tracking echocardiography (STE) is more sensitive than traditional echocardiography and can detect left ventricular systolic dysfunction early. STE-GLS is an independent risk factor affecting hospitalization time of trauma patients in intensive care unit. Clinically, STE-GLS and serum Hs-TnI can be combined to determine the prognosis of trauma patients.

Ethanol detection plays an important role in food industry,environmental monitoring,medical health monitoring,prevention of drunk driving,etc.The development of low-cost,high-performance ethanol sensors has important application value.In this study,a ZnO/FeS nano heterojunction ethanol sensor was prepared on commercial ceramic silver electrode substrate.The sensing characteristics of the sensor for ethanol gas were systematically studied.The results showed that ZnO had a nanowire structure,and the FeS was coated on the ZnO nanowire in the form of nanosheets.The sensor performed well for ethanol detection in environments with relative humidity ranging from 30%to 60%,with a detection range from 0.2 mg/m3 to 50 mg/m3.At the optimum operating temperature of 300℃,the response of ZnO/FeS nano heterojunction sensor to 50 mg/m3 ethanol was 15.6,the response time was 5.0 s,and the detection limit was as low as 0.101 mg/m3,which was obviously better than that of commercial ethanol sensor.This sensor was highly selective for ethanol compared to other gases such as CO,NH3,acetone,etc,and could steadily work for 30 days.The fabricated sensor had good development potential in the field of low-cost and high-performance ethanol gas detection.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Purpose: This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication. Methods: The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols. Results: The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors. Conclusion The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.