This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Gastrointestinal graft versus host disease is one of the most severe complications after hematopoietic stem cell transplantation, which can occur in patients of any age groups. Its clinical manifestations include nausea, vomit, abdominal pain, diarrhea and the like. Severe gastrointestinal graft versus host disease could directly influence the patients' clinical prognosis and therapeutic efficacy of transplantation. Here we had a review of the research progress on nutritional support and diet management strategies for gastrointestinal graft versus host disease. It is of great clinical significance to form a step-wise nutritional support model to reduce the risk of malnutrition in patients with gastrointestinal graft versus host disease, which would contribute to improving patients' general condition, relieving digestive tract symptoms, and reducing the risk of complications.

Objective:To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring′s birth weight and risk of small for gestational age (SGA) infant.Methods:The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers′ demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results:A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β=-2.30, 95% CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β=-7.39, 95% CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR=1.05, 95% CI 1.01-1.08, P=0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions:Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

Objective To explore the clinical efficacy of low molecular weight heparin combined with insulin in the treatment of hyper-triglyceridemic-acute pancreatitis(HTG-AP).Methods A total of 106 patients diagnosed with HTG-AP who were admitted to the department of gastroenterology of Huaibei People's Hospital from May 2022 to July 2023 were selected as the research objects.According to the random number table method,the low-molecular heparin group(35 cases,received a 5 000 U subcutaneous injection low-molecular heparin once every 12 hours for 6 days),the insulin group(35 cases,received intravenous insulin pumping at a rate of 2 U/h,with careful monitoring of the patient's random blood glucose levels to prevent hypoglycemia),and the combination therapy group(36 cases,received both low-molecular heparin and insulin).Before treatment and at 1,2,and 6 days after treatment,the difference of serum triacylglycerol(TG),total cholesterol(TC),blood amylase,inflammatory factors[C-reactive protein(CRP),interleukin-6(IL-6)],calcium ions,and creatinine levels among the three groups were compared.The modified computed tomography severity index(MCTSI)scores,acute physiology and chronic health evaluationⅡ(APACHEⅡ),hospital length of stay,and hospital costs before and after 6 days of treatment were observed.Results After treatment,the TC of all three groups significantly decreased compared to before treatment(P<0.05),but there was no significant difference among the three groups.The calcium ion levels of the three groups did not show a statistically significant difference before and after treatment.After 6 days of treatment,the creatinine levels of the three groups significantly decreased compared to before treatment,but there was no significant difference among the three groups.After 2 days of treatment,serum TG levels were significantly lower in the combination therapy group and insulin group compared to the low-molecular heparin group(mmol/L:4.6±1.7,4.4±1.8 vs.5.6±2.0,both P<0.05).However,there was no statistically significant difference between the combination therapy group and the insulin group.After 6 days of treatment,the combination therapy group showed significantly lower levels of serum TG,blood amylase,CRP,and IL-6 compared to the insulin group and the low-molecular heparin group[TG(mmol/L):2.8±1.9 vs.4.3±1.9,5.0±2.2,blood amylase(U/L):36.0(32.0,45.0)vs.59.0(43.0,71.0),52.0(45.0,64.0),CRP(mg/L):12.9(8.8,29.7)vs.35.3(21.7,50.3),31.4(23.0,45.1),IL-6(ng/L):15.4(9.8,23.5)vs.25.6(16.4,51.5),32.9(14.7,41.4),all P<0.05].After 6 days of treatment,the APACHEⅡscores of all three groups decreased significantly(all P<0.05).The MCTSI scores of the insulin group and the combined treatment group also decreased significantly compared to before treatment.Furthermore,the MCTSI and APACHEⅡscores of the combination therapy group were significantly lower than those of the low-molecular heparin group and the insulin group(MCTSI score:2.3±0.7 vs.3.3±1.7,2.9±1.3,APACHEⅡscore:1.3±1.2 vs.2.5±2.4,2.6±2.5,all P<0.05).The combination therapy group had significantly lower length of hospital stay and treatment cost compared to the low molecular heparin and insulin groups[length of hospital stay(days):6.9±1.6 vs.8.8±3.4,8.5±2.8,and cost of treatment(yuan):6 040.5(5 239.4,7 105.9)vs.6 696.4(5 791.5,11 026.2),6 918.5(6 087.9,10 080.8),all P<0.05].Conclusions The combination of low-molecular heparin and insulin treatment can significantly reduce serum TG and inflammatory factor levels,as well as the severity and duration of the disease.This approach can also reduce the cost of treatment.Therefore,it is worth promoting and applying in clinical settings.

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF-β1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- β1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
Rats ; Mice ; Animals ; Ureteral Obstruction/metabolism* ; Kidney/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Molecular Docking Simulation ; Rats, Sprague-Dawley ; Kidney Diseases/drug therapy* ; Extracellular Matrix/metabolism* ; Flavonoids/metabolism* ; Fibrosis

Objective:To explore the difference of high-risk factors between early-onset and late-onset pre-eclampsia, and to further understand high-risk factors of pre-eclampsia.Methods:Clinical data of pre-eclampsia pregnant women in 160 medical institutions in China in 2018 were retrospectively analyzed, including 8 031 cases of early-onset pre-eclampsia and 12 969 cases of late-onset pre-eclampsia. The proportion of high-risk factors, different body mass index (BMI) and age stratification between early-onset group and late-onset group were compared.Results:(1) Univariate analysis of high-risk factors: the proportions of high-risk factors in early-onset group and late-onset group were compared, and the differences were statistically significant (all P<0.05). Among them, the proportions of primipara and multiple pregnancy in early-onset group were lower than those in late-onset group, while the proportions of pregnant women with advanced age, irregular antenatal examination, obesity, family history of hypertension, pre-eclampsia, diabetes, kidney diseases, immune system diseases and assisted reproductive technology were higher than those in late-onset group. (2) Hierarchical analysis of BMI: the proportion of pregnant women with BMI≥24 kg/m 2 in early-onset group [48.2% (2 828/5 872) vs 45.5% (4 177/9 181), respectively; P=0.001] and the proportion of pregnant women with BMI ≥28 kg/m 2 in early-onset group [19.5% (1 143/5 872) vs 18.0% (1 656/9 181), respectively; P=0.028] were significantly higher than those in late-onset group. (3) Age stratification analysis: the proportion of pregnant women aged 35-39 years in the early-onset group [21.8% (1 748/8 023) vs 17.5% (2 110/12 068), respectively; P<0.01], the proportion of pregnant women 40-44 years old [6.8% (544/8 023) vs 5.4% (648/12 068), respectively; P<0.01], and the proportion of pregnant women ≥45 years old [0.7% (58/8 023) vs 0.5% (57/12 068), respectively; P=0.021] were significantly higher than those in the late-onset group. (4) Multivariate analysis: advanced age (≥35 years old), multiple pregnancy, irregular antenatal examination or transfer from other hospitals, family history of hypertension (including paternal, maternal and parental lines), previous history of pre-eclampsia, kidney diseases, immune system diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome) and assisted reproductive technology pregnancy were the risk factors affecting the severity of pre-eclampsia (all P<0.05). Conclusion:Pregnant women with high risk factors such as age ≥35 years old, BMI ≥24 kg/m 2 before pregnancy, family history of hypertension, history of pre-eclampsia, chronic kidney diseases, immune diseases (mainly including systemic lupus erythematosus and antiphospholipid syndrome) and assisted reproductive technology are more likely to have early-onset pre-eclampsia.

Objective:To investigate the role of 1, 25-dihydroxyvitamin D3 [1.25(OH) 2D 3] in liver lipid metabolism so as to provide the clues for elucidating the mechanism of non-alcoholic fatty liver. Methods:26 SD rats were randomly divided into control group (methionine-choline-sufficient diet, MCS), model group (methionine-choline-deficiency diet, MCD) and intervention group [MCD+1.25(OH) 2D 3]. The intervention, control, and model group was given 3 ng/100 g 1.25(OH) 2D 3 peanut oil solution per day by gavage according to body mass. After 4 weeks the experiment was ended up, and the blood was collected from the inferior vena cava to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The liver tissue was collected to observe the liver morphological and pathological changes (oil red O and HE staining). The changes in the level of liver total triglyceride (TG) content and liver lipid metabolism-related genes [fatty acid transfer protein (FAT/CD36), acetyl-coenzyme A carboxylase (ACC1)] mRNA and protein were detected. One-way analysis of variance was used to compare the means between groups. Results:Oil red O staining and HE staining showed that lipid droplet-vacuoles were significantly increased in the liver tissue of the model group than that of the intervention group. The liver TG content (2.23 ± 0.98) μmol/g of the intervention group was significantly lower than that of the model group (3.53 ± 1.06) μmol/g ( F = 5.930, P = 0.035). The ALT content of the intervention group (35.99±9.54) U/L was significantly lower than that of the model group (57.65 ± 19.42) U/L ( F = 13.790, P = 0.034). The AST content of the intervention group (16.9 ± 3.73) U/L was significantly lower than that of the model group (27.81 ± 13.31) U/L ( F = 3.084, P = 0.046). The relative expression levels of mRNA and protein (mRNA: 1.21 ± 0.61, protein: 1.54 ± 0.75) of FAT/CD36 in the intervention group were significantly lower than those of the model group (mRNA: 2.31 ± 0.81, protein: 2.83 ± 1.42) (mRNA: F = 8.370, P = 0.001, protein: F = 7.212, P = 0.043). The relative expression level of mRNA and protein of ACC1 (mRNA: 0.89 ± 0.54, protein: 0.28 ± 0.11) were also significantly lower than those in model group (mRNA: 1.39 ± 0.19, protein: 0.47 ± 0.24) (mRNA: F = 3.948, P = 0.036, protein: F = 10.933, P = 0.048). Conclusion:1.25(OH) 2D 3 can reduce liver fat deposition in rats fed with MCD by inhibiting the expression of fat / CD36 and ACC1.

Objective:To investigate the association of lipoprotein a (Lpa) in early pregnancy with gestational diabetes mellitus (GDM) risk.Methods:A total of 445 pregnant women in 12-14 gestational weeks from "Maternal Key Nutritional Factors and Offspring's Atopic Dermatitis" cohort were included in this study. The demographic characteristics of participants were collected by using questionnaires, and the fasting glucose and lipids levels in early pregnancy were measured. The results of oral glucose tolerance test (OGTT) between 24-28 gestational weeks were recorded. Multivariate logistic regression model was applied to analyze the association of Lpa with GDM by calculating the OR and 95% CI after adjustment for covariates. Results:The incidence number of GDM was 78 (17.5%). The Lpa level in pregnant women with GDM was significantly higher than that in pregnant women without GDM [105.5 (92.0, 122.0) vs. 97.0 (87.0, 109.0) mg/L], P<0.05. Lpa was significantly associated with GDM risk [ OR (95% CI) =1.21(1.08-1.36) per 10 mg/L], P<0.05. The association was still significant after adjustment for covariates including age, gestational weeks et al, the adjusted OR was 1.14 (95% CI: 1.01-1.30), P=0.03. Conclusions:The elevation of Lpa in early pregnancy is one of risk factor for GDM. Maintaining normal Lpa level during early pregnancy can benefit early prevention of GDM and offspring health.

Objective:To investigate the relationship between the methylation of apelin receptor early endogenous ligand ( APELA) gene promoter and preeclampsia. Methods:A systematic review was conducted to evaluate the cg02779075 locus methylation in APELA gene associated with preeclampsia in six previous studies on placenta genome-wide methylation based on the GEO gene expression database from 2007 to 2017. After testing the heterogeneity, the random-effects model was applied for meta-analysis. Placenta samples of 17 preeclamptic patients and 24 healthy gravidas were retrospectively collected in Obstetrics and Gynecology Hospital of Fudan University from 2008 to 2010. MassARRAY was used to quantify the methylation level of CpGs, and the expression of APELA gene was determined by qRT-PCR. All data were analyzed by t test or Mann-Whitney U test. Results:(1) Analysis of the six genome-wide methylation studies showed significant heterogeneity ( I2=0.64, P=0.016) and the meta-analysis using random-effects model showed that the methylation of cg02779075 locus in the placenta samples of preeclamptic women was down-regulated significantly ( Pmeta=6.7×10 -6). (2) Placenta tissue analysis revealed that the methylation of CpG1 [0.12 (0.00-0.25) vs 0.21 (0.09-0.33), U=-2.569] and CpG2 [0.07 (0.01-0.14) vs 0.17 (0.09-0.34), U=-4.160] in patients with preeclampsia was significantly reduced compared with those in healthy control (both P<0.05). The expression of APELA gene in the placenta was up-regulated in patients with preeclampsia, but no significant difference was observed between the two groups ( U=0.891, P=0.384). Conclusions:Aberrant methylation of APELA gene promoter was detected in the placentas of patients with preeclampsia.

Objective: To investigate the effect of siRNA silencing α1 antitrypsin (α1-AT) gene on the biological behavior of rheumatoid arthritis fibroblast-like synoviocytes (RA-SFs). Methods: Primary culture of knee synovial tissue from 5 patients with rheumatoid arthritis (RA) was performed. The artificially synthesized silencing α1-AT siRNA specifically inhibits the expression of α1-AT in RA-SFs. After 24 and 36 hours of transient transfection, the inhibition efficiency was detected by Quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the expression of related genes after α1-AT gene silencing was detected.Furthermore, ethyl thiazolyl tetrazolium (MTT) assay, Trans-well chamber, cell scratch and enzyme-linked immunosorbent assay (ELISA) were used to detect the effects of interfering α1-AT expression on cell proliferation, invasion and migration, and secretion of interleukin (IL)-17, Tumor necrosis factor (TNF)-α, IL-1α, IL-1β and other related inflammatory factors. At the same time, when the pathway inhibitor (ERK inhibitor, signal transducer and activator of transcription 3 (STAT3) inhibitor, NF-κB inhibitor) stimulated cells, the effect on α1-AT was changed. One-way analysis of variance was used for comparison between the two groups; further pairwise comparison using LSD-t test; The count data was checked by χ² test. Results: Compared with the negative control group, the siRNA α1-AT group was transfected for 24 hours, the α1-AT mRNA level was significantly inhibited (P<0.05), and the proliferation rate of RA-SFs was not affected (P>0.05), and the invasion and migration ability of cells decreased significantly (P<0.05). The secretion of IL-17 and IL-1β was slightly decreased (P>0.05), while TNF-α and IL-1α were not affected (P>0.05). In addition, the expression of α1-AT downstream genes Matrix metallop roteinases (MMP)-2 169, Hu-Bax1, MMP-9, Hu Bax and Hu Bcl-xl were significantly decreased (P<0.05). Moreover, the signaling pathway inhibitors ERK inhibitor (PD98059) and NF-κB inhibitor (PDTC) had significant effects on α1-AT (P<0.05). Conclusion The α1-AT gene silencing has potential effect on the biological behavior of RA SFs. Further study of this mechanism is helpful to provide evidence for the treatment of RA.