OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Objective To investigate the effects of plateau hypoxia on the growth and tumor microenvironment of colorectal carcinoma in vivo.Methods A total of 16 male BALB/C mice(6 weeks old,weight 18-20 g)were randomly divided into plateau hypoxic group and plain normoxic group,with 8 mice in each group,while 14 male C57BL/6 mice were grouped in same way,with 7 mice in each group.The mice in the plateau hypoxic group were housed in a low-pressure oxygen(10%)chamber to simulate an altitude of approximately 5 600 m,while the mice of the other group was maintained in SPF-grade normal atmospheric conditions(21%oxygen,at an altitude of about 300 m).Colorectal tumor MC38 cells and colon adenocarcinoma CT26 cells were subcutaneously implanted into C57BL/6 mice and BALB/C mice,respectively to construct subcutaneous tumor-bearing mouse models.Then the tumor size and weight were measured in 4 groups of mice.After the tumor tissues,spleen and blood samples were collected in the C57BL/6 mice.Flow cytometry was used to determine the percentages of macrophages,T lymphocytes,IFN-γ+T lymphocytes,and myeloid-derived suppressor cells(MDSC).The differences in these immune cells were compared between the cells from the plateau hypoxic group and those from the plain normoxic group.Results The weight of subcutaneous tumor mass was significantly inhibited in both C57BL/6 and BALB/C mice from the plateau hypoxic group than those from the 2 plain normoxic groups(0.17 vs 0.09 g,1.38 vs 0.51 g,P<0.01).When compared with the immune cells from the tumor mass of the plain normoxic C57BL/6 mice,the percentage of M2-type macrophages was reduced in the tumor tissue from the plateau hypoxic mice(22.13%vs 15.90%,P<0.05),so was that of MDSC(2.06%vs 1.05%,P<0.01),particularly in the monocytic(M)-MDSC subgroup(60.97%vs 41.13%,P<0.01).While,no significant change was observed in the proportion of the polymorphonuclear(PMN)-MDSC subgroup(10.97%vs 9.70%,P>0.05).Additionally,the percentage of CD4+T cells was significantly reduced(48.70%vs 41.93%,P<0.05),whereas that of CD8+T cells was obviously increased(41.25%vs 51.18%,P<0.05),along with a notable rise in the proportions of IFN-γ+T,IFN-γ+CD4+T and IFN-γ+CD8+T cells(28.58%vs 59.65%,23.33%vs 53.65%,36.9%vs 66.48%,P<0.01).However,between the peripheral blood samples of the 2 groups of C57BL/6 mice,the proportions of M1-type macrophages and CD4+T cells were reduced(84.98%vs 78.43%,5.86%vs 4.01%,P<0.01),and those of MDSC and PMN-MDC were increased(4.47%vs 16.43%,36.56%vs 62.97%,P<0.01).In the spleen tissues,notable decreases were observed in the proportions of CD8+T cells and IFN-γ+CD8+T cells between the 2 groups(33.05%vs 27.68%,5.13%vs 1.58%,P<0.01).Conclusion Plateau hypoxia improves the immune response within the tumor microenvironment,and inhibits subcutaneous tumor growth of colorectal cancer,but suppresses systemic immune response.

Objective To investigate the expression of serum exosomal long non-coding RNA X chromo-some inactivation specific transcript(LncRNA XIST)and microRNA(miR)-130a-3p in gestational diabetes mellitus(GDM)patients and its relationship with pregnancy outcome.Methods A total of 149 GDM patients(GDM group)and 149 healthy pregnant women(control group)admitted to the hospital from January 2021 to January 2024 were selected.Serum exosomal LncRNA XIST,miR-130a-3p and glucose and lipid metabolism indexes of the two groups were detected and compared.The correlation of LncRNA XIST and miR-130a-3p levels with glycolipid metabolism indexes was analyzed by Pearson method.Univariate and multivariate Logis-tic regression models were used to analyze the influencing factors of pregnancy outcomes in GDM patients.Re-ceiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of serum exosomal Ln-cRNA XIST and miR-130a-3p levels alone and in combination for pregnancy outcomes in GDM patients.Results Serum exosomal LncRNA XIST levels,fasting insulin(FINS),fasting blood glucose(FBG),insulin resistance index(HOMA-IR),2-hour postprandial glucose(2 hPG),total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)levels in GDM group were higher than those in control group(P＜0.05),and the levels of miR-130a-3p and high density lipoprotein cholesterol(HDL-C)were lower than those in the control group(P＜0.05).LncRNA XIST was positively correlated with FINS,FBG,HOMA-IR,2 hPG,TC,TG and LDL-C,and negatively correlated with HDL-C(P＜0.05).miR-130a-3p was negatively correlated with FINS,FBG,HOMA-IR,2 hPG,TC,TG and LDL-C,and positively correlated with HDL-C(P＜0.05).Among the 149 GDM patients,43 cases showed adverse pregnancy outcome,accounting for 28.86％.The increase level of FBG,the increase level of LncRNA XIST and the increase of HOMA-IR were risk factors for adverse pregnancy outcome in GDM patients,while the increase of miR-130a-3p was a protec-tive factor.The ROC curve analysis showed that the predictive efficacy of combined detection was superior to that of single indicator detection.Conclusion The serum exosomal LncRNA XIST of GDM patients is highly expressed,and miR-130a-3p is lowly expressed,and the combined detection of the above indexes has a high predictive value for pregnancy outcome.

As early mobilization of patients in the intensive care unit(ICU)is increasingly recognized as a key measure for improving patient prognosis and reducing complications,related research is increasing.However,conventional early mobilization methods are often limited by factors such as patient condition,nursing resources,and environmental factors,making it difficult to achieve optimal results.In recent years,virtual reality(VR)technology,owing to its unique immersion and interactive features,has emerged as a focus of research in the field of ICU patient rehabilitation.This review summarizes the advances in the application of VR technology in the early mobilization of ICU patients,focusing on its advantages over traditional methods,specific implementation approaches,clinical outcomes,and challenges encountered during application.By synthesizing existing evidence,this review aims to provide valuable references for clinical practice and to explore future directions for VR technology in ICU rehabilitation,with the goal of promoting its widespread application in the early mobilization of critically ill patients.

OBJECTIVES: To explore potential keywords, research clusters, collaborative pattern, and research trends in the field of medical technology management (MTM) through bibliometric analysis, providing insights for researchers, policy makers, and hospital administrators. METHODS: A retrieval formula was applied to the title, abstract, and keywords in the Web of Science (WoS) Core Collection, along with system-recommended terms, to identify articles on MTM. A total of 181 articles published between 1974 and 2022 were retained for quantitative analysis. The global trend of research output; total citations, average citations, and H-index; and bibliographic coupling, co-authorship, and keyword co-occurrence were analyzed using VOSviewer. RESULTS: The number of articles on MTM has been steadily increasing year by year. The focus of research has shifted from addressing basic medical needs to prioritizing emergency response and medical information security. The United States, Italy, and the United Kingdom emerged as the main contributors, with the United States leading in both volume of publications (60 articles) and academic impact (H-index = 21). Authors from the United Kingdom and the United States led the way in cross-border cooperation. The top five institutions, ranked by total link strength among cross-institutional authors, were primarily located in Canada and Spain. CONCLUSIONS The field of MTM has experienced stable growth over the past three decades (1993-2022). The shift of research focus has prompted a heightened emphasis on protecting patient privacy and ensuring the security of medical data. Future research should emphasize interdisciplinary and professional collaboration, as well as international cooperation and open sharing of knowledge.
Bibliometrics ; Humans ; Biomedical Technology

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 effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism* ; Animals ; Diabetic Nephropathies/metabolism* ; Saponins/therapeutic use* ; Triterpenes/therapeutic use* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Male ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endoribonucleases/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; Rats ; Diabetes Mellitus, Experimental/complications* ; Endoplasmic Reticulum/metabolism* ; Multienzyme Complexes

OBJECTIVE: To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro. METHODS: Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo. RESULTS: Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05). CONCLUSION Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals ; Sirtuin 1/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Autophagy/drug effects* ; Male ; Intestinal Mucosa/drug effects* ; Rats, Sprague-Dawley ; Epithelial Cells/metabolism* ; Colon/drug effects* ; Humans ; Kidney Failure, Chronic/drug therapy* ; Signal Transduction/drug effects* ; Renal Dialysis ; Rats ; Kidney/drug effects*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

The male patient,one day old,was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth.The patient had transient hypoglycemia early after birth,and acute heart failure suddenly occurred on the eighth day after birth.Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol,and pituitary magnetic resonance imaging was normal.Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene(c.917-2A＞G+c.608C＞T),inherited respectively from the parents.The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene.Upon initiating hydrocortisone replacement therapy,cardiac function rapidly returned to normal.After being discharged,the patient continued with the hydrocortisone replacement therapy.By the 18-month follow-up,the patient was growing and developing well.In neonates,unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases,and timely cortisol testing and genetic testing should be conducted.[Chinese Journal of Contemporary Pediatrics,2024,26(3):321-324,V]