Objective To explore the mechanism of Quhan Zhufeng Mixture on proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocyte(RA-FLS)based on NDRG2/JAK2/STAT3 signaling pathway.Methods RA-FLS cells were cultured in vitro,and were divided into ① blank serum group,methotrexate group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups;② blank serum group,AG490 group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups.Different concentrations of drug-containing serum were used to intervene cells.Cell proliferation was detected by CCK-8 method,apoptosis was detected by flow cytometry,and mRNA expressions of Bax,Bcl-2,Caspace-3,Caspace-9,N-myc downstream regulatory gene 2(NDRG2),Janus kinase 2(JAK2)and signal transduction and transcription activator 3(STAT3)were detected by RT-qPCR,Western blot was used to detect the protein expressions of Bax,Bcl-2,Caspace-3,Caspace-9,NDRG2,JAK2,STAT3,p-JAK2 and p-STAT3 in cells.Results Compared with the blank serum group,cell survival rate in methotrexate group,Quhan Zhufeng Mixture all dosage groups significantly decreased(P<0.01),the apoptosis rate significantly increased(P<0.01),the mRNA and protein expressions of Bax and Caspase-9 significantly increased(P<0.05,P<0.01),while the mRNA and protein expression of Bcl-2 significantly decreased(P<0.01),and Caspase-3 mRNA and protein expression in methotrexate group and Quhan Zhufeng Mixture medium-and high-dosage groups significantly increased(P<0.01).Compared with the blank serum group,the mRNA and protein expression of NDRG2 significantly increased in Quhan Zhufeng Mixture all dosage groups(P<0.05,P<0.01),the mRNA and protein expressions of JAK2 and STAT3 were significantly reduced in AG490 group and Quhan Zhufeng Mixture medium-and high-dosage groups(P<0.05,P<0.01),and the expressions of p-JAK2 and p-STAT3 proteins were significantly reduced(P<0.01).Conclusion Quhan Zhufeng Mixture can regulate the proliferation and apoptosis of RA-FLS by regulating the activity of NDRG2/JAK2/STAT3 signaling pathway,playing a role in treating rheumatoid arthritis.

Objective To explore the mechanism of Quhan Zhufeng Mixture on proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocyte(RA-FLS)based on NDRG2/JAK2/STAT3 signaling pathway.Methods RA-FLS cells were cultured in vitro,and were divided into ① blank serum group,methotrexate group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups;② blank serum group,AG490 group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups.Different concentrations of drug-containing serum were used to intervene cells.Cell proliferation was detected by CCK-8 method,apoptosis was detected by flow cytometry,and mRNA expressions of Bax,Bcl-2,Caspace-3,Caspace-9,N-myc downstream regulatory gene 2(NDRG2),Janus kinase 2(JAK2)and signal transduction and transcription activator 3(STAT3)were detected by RT-qPCR,Western blot was used to detect the protein expressions of Bax,Bcl-2,Caspace-3,Caspace-9,NDRG2,JAK2,STAT3,p-JAK2 and p-STAT3 in cells.Results Compared with the blank serum group,cell survival rate in methotrexate group,Quhan Zhufeng Mixture all dosage groups significantly decreased(P<0.01),the apoptosis rate significantly increased(P<0.01),the mRNA and protein expressions of Bax and Caspase-9 significantly increased(P<0.05,P<0.01),while the mRNA and protein expression of Bcl-2 significantly decreased(P<0.01),and Caspase-3 mRNA and protein expression in methotrexate group and Quhan Zhufeng Mixture medium-and high-dosage groups significantly increased(P<0.01).Compared with the blank serum group,the mRNA and protein expression of NDRG2 significantly increased in Quhan Zhufeng Mixture all dosage groups(P<0.05,P<0.01),the mRNA and protein expressions of JAK2 and STAT3 were significantly reduced in AG490 group and Quhan Zhufeng Mixture medium-and high-dosage groups(P<0.05,P<0.01),and the expressions of p-JAK2 and p-STAT3 proteins were significantly reduced(P<0.01).Conclusion Quhan Zhufeng Mixture can regulate the proliferation and apoptosis of RA-FLS by regulating the activity of NDRG2/JAK2/STAT3 signaling pathway,playing a role in treating rheumatoid arthritis.

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

This study explored the growth-promoting effect and mechanism of the endophytic bacterium Kocuria rosea on Rehmannia glutinosa, aiming to provide a scientific basis for the development of green bacterial fertilizer. R. glutinosa 'Jinjiu' was treated with K. rosea, and the shoot parameters including leaf length, leaf width, plant width, and stem diameter were measured every 15 days. After 120 days, the shoots and roots were harvested. The root indicators(root number, root length, root diameter, root fresh weight, root dry weight, root volume, and root vitality) and secondary metabolites(catalpol, rehmannioside A, rehmannioside D, verbascoside, and leonuride) were determined. The R. glutinosa growth-promoting mechanism of K. rosea was discussed from the effect of K. rosea on the nutrient element content in R. glutinosa and rhizosphere soil and the genome information of this plant. After application of K. rosea, the maximum increases in leaf length, leaf width, plant width, and stem diameter were 35.67%(60 d), 25.39%(45 d), 40.17%(60 d), and 113.85%(45 d), respectively. The root number, root length, root diameter, root volume, root fresh weight, root dry weight, and root viability increased by 41.71%, 45.10%, 48.61%, 94.34%, 101.55%, 147.61%, and 42.08%, respectively. In addition, the content of rehmannioside A and verbascoside in the root of R. glutinosa increased by 76.67% and 69.54%, respectively. K. rosea promoted the transformation of nitrogen(N), phosphorus(P), and potassium(K) in the rhizosphere soil into the available state. Compared with that in the control, the content of available N(54.60 mg·kg~(-1)), available P(1.83 μmol·g~(-1)), and available K(83.75 mg·kg~(-1)) in the treatment with K. rosea increased by 138.78%, 44.89%, and 14.34%, respectively. The content of N, P, and K in the treatment group increased by 293.22%, 202.63%, and 23.80% in the roots and by 23.60%, 107.23%, and 134.53% in the leaves of R. glutinosa, respectively. K. rosea carried the genes related to colonization(rbsB, efp, bcsA, and gmhC), N, P, and K metabolism(narG, narH, narI, nasA, nasB, GDH2, pyk, aceB, ackA, CS, ppa, ppk, ppk2, pstS, pstA, pstB, and pstC), and indole-3-acetic acid and zeatin synthesis(iaaH and miaA). Further studies showed that K. rosea could colonize the roots of R. glutinosa and secrete indole-3-acetic acid(3.85 μg·mL~(-1)) and zeatin(0.10 μg·mL~(-1)). In summary, K. rosea promotes the growth of R.ehmannia glutinosa by enhancing the nutrient uptake, which provides a theoretical basis for the development of plant growth-promoting microbial products.
Rehmannia/metabolism* ; Endophytes/metabolism* ; Plant Roots/growth & development* ; Micrococcaceae/genetics* ; Data Mining ; Plant Leaves/metabolism* ; Genomics ; Rhizosphere

Objective Based on the multi-software visual analysis of the literature on the effect of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway on rheumatoid arthritis in the past decade,the development trend and research hotspot in this field are summarized.To provide researchers with new directions and ideas to promote the innovative development of the field.Methods The literatures related to JAK/STAT signaling pathway in rheumatoid arthritis were collected from the Web of Science Core Collection database from 2013 to 2023.CiteSpace and VOSviewer software were used to analyze the number of publications,countries,authors and keywords of 354 articles retrieved.Results The number of published papers in this field continues to increase.According to the author's research direction,the presentation of high-frequency words,and the attention to the preface and hot topics,it is suggested that this field focuses on gene expression,immune mechanism,inflammatory mechanism,pathway inhibitors,drug therapy,etc.Future research will focus on the safety,mechanism and controlled trials of pathway inhibitors and antirheumatic drugs.Conclusion The effect of JAK/STAT signaling pathway on rheumatoid arthritis has attracted much attention in the past,present and future.There are differences in the research of different teams in this field,and the regional development is unbalanced,suggesting that we should strengthen cooperation and exchanges,focus on the international frontier,and carry out more high-quality research to promote the development and progress of this field,and provide clinical basis.

Purpose: We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. Results: 2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. Conclusion EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

Objective To investigate the inhibitory effect of ursolic acid in Hippophae rhamnoides L. on hepatocyte apoptosis in rats with alcoholic liver disease based on the mitochondria-cytochrome c pathway. Methods A total of 50 specific pathogen-free male Wistar rats were divided into normal control group, alcohol model group, and low-, middle-, and high-dose ursolic acid groups using a random number table, with 10 rats in each group. The rats in the normal control group were given normal saline by gavage once a day for 8 weeks; the rats in the alcohol model group were given alcohol at increasing concentrations by gavage for 8 consecutive weeks; the rats in the low-, middle-, and high-dose ursolic acid groups were given ursolic acid at a dose of 50, 100, and 150 mg/kg, respectively, followed by an equal volume of alcohol as the model group 1 hour later. Serum liver function parameters were measured for each group; HE staining was used to observe liver histopathology; an electron microscope was used to observe hepatocyte ultrastructure; the TUNEL method was used to measure hepatocyte apoptosis; Western Blotting was used to measure the protein expression levels of cytochrome c and activated caspase-3 in hepatocyte mitochondria and cytoplasm. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significant reductions in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase (all P < 0.05). The rats in the alcohol model group had disordered arrangement of hepatic cords with marked hepatocyte edema and fatty degeneration, while those in the middle- and high- dose ursolic acid groups had basically normal arrangement of hepatic cords and a significant improvement in hepatocyte fatty degeneration, as well as a significant increase in the number of hepatocyte mitochondria and a significant improvement in morphology. Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significantly lower hepatocyte apoptosis rate and protein expression levels of cytochrome c and caspase-3 in cytoplasm (all P < 0.05). Conclusion Ursolic acid in Hippophae rhamnoides L. can improve the liver function and histomorphology of rats with alcoholic liver disease, possibly by inhibiting the release of cytochrome c in hepatocyte mitochondria, the activation of caspase-3, and the apoptosis of hepatocytes via the mitochondria-cytochrome c pathway.

Objective::The size and morphology of the right ventricular outflow tract (RVOT) in patients suffering from long-term pulmonary regurgitation (PR) after native RVOT (NRVOT) reconstruction are important factors affecting the feasibility, safety, and effectiveness of transcatheter pulmonary valve replacement. The purpose of this study was to evaluate the feasibility, safety, and effectiveness of a transthoracic Salus valve (Balance Medical Technology Co., Ltd, Beijing, China) in patients with moderate-to-severe PR after NRVOT reconstruction.Methods::Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital. Demographic data as well as preoperative, intraoperative, and follow-up data were reviewed.Results::Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination, transthoracic echocardiography, and cardiovascular magnetic resonance imaging. Seven patients were selected for transthoracic Salus valve replacement. Six patients underwent implantation of the Salus valve successfully. One valve migrated and was embolized during recovery of the delivery device; the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery. At a mean follow-up of (5.5 ± 1.1) months, dysfunction or migration of the Salus valve embolism was not observed.Conclusions::This early feasibility study demonstrates the feasibility, safety, and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction. The short-term effectiveness is clear, medium and long-term effectiveness requires longer follow-up.

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

Objective::The size and morphology of the right ventricular outflow tract (RVOT) in patients suffering from long-term pulmonary regurgitation (PR) after native RVOT (NRVOT) reconstruction are important factors affecting the feasibility, safety, and effectiveness of transcatheter pulmonary valve replacement. The purpose of this study was to evaluate the feasibility, safety, and effectiveness of a transthoracic Salus valve (Balance Medical Technology Co., Ltd, Beijing, China) in patients with moderate-to-severe PR after NRVOT reconstruction.Methods::Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital. Demographic data as well as preoperative, intraoperative, and follow-up data were reviewed.Results::Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination, transthoracic echocardiography, and cardiovascular magnetic resonance imaging. Seven patients were selected for transthoracic Salus valve replacement. Six patients underwent implantation of the Salus valve successfully. One valve migrated and was embolized during recovery of the delivery device; the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery. At a mean follow-up of (5.5 ± 1.1) months, dysfunction or migration of the Salus valve embolism was not observed.Conclusions::This early feasibility study demonstrates the feasibility, safety, and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction. The short-term effectiveness is clear, medium and long-term effectiveness requires longer follow-up.