OBJECTIVE To investigate the mechanism by which aloin （ALO） ameliorates atherosclerosis （AS）. METHODS Eight C57BL/6J mice were assigned to the control group （CON group） and fed a standard diet； thirty-two apolipoprotein E-knockout （APOE－/－） mice were randomly divided into model group （MOD group）， ALO low-dose and high-dose groups [ALO-L group， ALO-H group， 20， 40 mg/（kg·d）]， and atorvastatin positive control group [ATO group， 4 mg/（kg·d）]， with 8 mice in each group， establishing the AS model through feeding with a high-fat diet. The mice were administered the drug via gavage or given an equal volume of deionized water for 8 consecutive weeks. The lipid levels in the serum of mice were measured， and the pathological structural changes in their aortas were observed. The expressions of macrophage polarization markers （CD86+ ， CD206+） in the aorta were determined， along with the mRNA expressions of inducible nitric oxide synthase （iNOS）， tumor necrosis factor-α （TNF-α）， arginase-1 （Arg-1）， and interleukin-10 （IL-10）， as well as the protein expressions of iNOS and Arg- 1， and the phosphorylation levels of nuclear factor κB p65 （NF-κB p65） and signal transduction and activator of transcription 3 （STAT3） proteins. Additionally， a macrophage polarization model was established using lipopolysaccharide （LPS）-induced RAW264.7 cells， and the effect of ALO （400 μmol/L） on the cellular polarization phenotype was investigated. RESULTS Compared with the MOD group， administration groups all showed significant improvement in dyslipidemia （except for high-density lipoprotein cholesterol in the serum of ALO-L group） （P＜0.05）； aortic intimal structure improved significantly， plaque area was reduced significantly （P＜0.01）； the CD86+ relative fluorescence intensity in the aorta decreased significantly， the CD206+relative fluorescence intensity increased significantly （P＜0.01）， while the expressions of iNOS and TNF-α mRNA were down-regulated significantly （P＜0.05）； mRNA expressions of Arg-1 and IL-10， and protein expression of Arg-1 were increased significantly in ALO-H group and ATO group （P＜0.05）； the protein expressions of iNOS， and the phosphorylation levels of NF-κB p65 and STAT3 protein were decreased significantly （P＜0.05）. In vitro experiments further confirmed that ALO significantly reduced the proportion of LPS-induced M1-type macrophages but increased the proportion of M2-type macrophages （P＜0.01）. CONCLUSIONS ALO inhibits M1-type macrophage polarization and promotes M2-type polarization， ameliorates dyslipidemia and reduces arterial plaque formation in AS model mice， improve the structure of the aortic intima potentially through suppression of the NF-κB/STAT3 signaling pathway.

BACKGROUND: The epidemiological pattern and disease burden of type 2 diabetes have been shifting in China over the past decades. This analysis described the epidemiological transition of type 2 diabetes in the past three decades and projected the trend in the future three decades in China. METHODS: Age-, sex-, and year-specific incidence, prevalence, death, and disability-adjusted life years (DALYs) for people with 15 years or older and diabetes or high fasting glucose in China and related countries from 1990 to 2021 were obtained from the Global Burden of Disease. We obtained the trends of age-, sex-, and year-specific rates and absolute numbers of incidence, prevalence, deaths, and DALYs attributable to type 2 diabetes in China from 1990 to 2021. Using the Lee-Carter model, we projected the incidence, prevalence, death, and DALYs attributable to type 2 diabetes to 2050 stratified by age and sex. RESULTS: The age-standardized incidence of type 2 diabetes was 341.5 per 100,000 persons (1.6 times in 1990) and the age-standardized prevalence was 9.96% (9960.0 per 100,000 persons, 2.5 times in 1990) in China 2021. In 2021, there were 0.9 million deaths and 26.8 million DALYs due to type 2 diabetes or hyperglycemia, as 2.9 and 2.7 times the data in 1990, respectively. The age-standardized rates of type 2 diabetes and hyperglycemia were projected to raise to 449.5 per 100,000 persons for incidence, 18.17% for prevalence, 244.6 per 100,000 persons for death, and 4720.2 per 100,000 persons for DALYs by 2050. The incidence of type 2 diabetes kept growing among individuals under the age of 20 years in the past three decades (128.7 per 100,000 persons in 1990 and 439.9 per 100,000 persons in 2021) and estimating 1870.8 per 100,000 in 2050. CONCLUSIONS The incidence, prevalence, and disease burden of type 2 diabetes grew rapidly in China in the past three decades. The prevention of type 2 diabetes in young people and the care for elder adults will be the greatest challenge for the country.
Humans ; Diabetes Mellitus, Type 2/mortality* ; China/epidemiology* ; Prevalence ; Female ; Male ; Incidence ; Middle Aged ; Adult ; Aged ; Adolescent ; Young Adult ; Disability-Adjusted Life Years ; Aged, 80 and over

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

BACKGROUND:The type of graft selected during anterior cruciate ligament revision is considered one of the main factors affecting the postoperative outcome,but there are few reports on the comparison between different graft materials. OBJECTIVE:To explore the medium-to-long-term clinical efficacy after anterior cruciate ligament revision with autologous ligament,allogeneic ligament,and LARS artificial ligament. METHODS:A total of 67 patients with the first anterior cruciate ligament revision admitted to the Department of Joint and Sports Medicine,The Second Hospital of Tangshan from May 2011 to May 2020 were selected,including 41 males and 26 females,with a mean age of(45.83±7.39)years.They were divided into three groups according to different grafts used:autologous ligament group(n=24),allogeneic ligament group(n=22),and LARS artificial ligament group(n=21).Follow-up for more than 36 months after revision was performed to evaluate the effect of revision. RESULTS AND CONCLUSION:(1)International Knee Documentation Committee(IKDC)score,Lysholm knee score,and Tegner motor score 1 year after surgery and at the last follow-up in the three groups were higher than those before surgery(P<0.05).There were no significant differences in IKDC score,Lysholm knee score,and Tegner motor score among the three groups 1 year after surgery and the last follow-up(P>0.05).(2)The lateral differences of KT-1000 at 1 year after surgery and the last follow-up among the three groups were lower than those before surgery(P<0.05).The lateral difference of KT-1000 and the positive rate of the axial shift test in the last follow-up of the LARS artificial ligament group were higher than those in the autologous ligament group and allogeneic ligament group(P<0.05).(3)At the last follow-up,X-ray films showed no obvious enlargement of the reconstructed bone tunnel and no obvious failure of the graft fixation device.There was no obvious aggravation of osteoarthritis,but bone density decreased significantly in some elderly patients.(4)These findings suggest that anterior cruciate ligament revision with LARS artificial ligaments can obtain good initial stability,but with the extension of time,the stability of partial cases tends to decrease,even with reconstructed ligament failure.Both allogeneic and autogenous ligaments can obtain good clinical efficacy in anterior cruciate ligament revision.

Objective:To investigate the clinical features, diagnostic methods, treatment modalities, and prognosis of parathyroid multiglandular disease (PTMGD) in primary hyperparathyroidism (PHPT) .Methods:The clinical data of 29 patients with PTMGD who underwent surgery at the General Surgery Department of the Tianjin Medical University General Hospital from Dec. 2015 to Jul. 2023 were retrospectively analyzed, including the patients' preoperative and postoperative blood calcium and parathyroid hormone, the main clinical manifestations, the involvement of other systems, the main types of pathology, the accuracy of the various examinations, and the postoperative prognosis, etc., and were compared with the 291 patients who had undergone surgery for single-glandular lesion patients were compared. SPSS25 was used to analyze the data.Results:The age of onset of PTMGD was 52.7±1.9 years compared to 56.6±0.7 years in patients with monoglandular disease, P=0.047. Tumor diameter of PTMGD was (2.05±0.1) cm and (2.34±0.6) cm of monoglandular disease, P=0.006. The preoperative blood calcium was (2.56±0.59) mmol/L in PTMGD and (2.70±0.58) mmol/L in monoglandular disease, P=0.045. Preoperative parathyroid hormone (PTH), blood calcium, and Win values were positively correlated with maximum tumor diameter in patients with PTMGD (R-values of 0.362, 0.223, and 0.352, respectively) .Neck ultrasound, neck-enhanced CT and parathyroid nuclear imaging were used to localize and diagnose the diseased parathyroid glands in this group of cases.The accuracy rates were (14/25) 56%, (10/19) 53% and (11/24) 46% in patients with PTMGD, while in patients with monoglandular disease, the accuracy rates were (233/250) 89%, (131/152) 96% and (223/232) 86%. PTMGD accuracy rate was less than that of monoglandular disease,and was statistically significant ( P-value was less than 0.001 in all cases) .The accuracy of the combined localization diagnosis of the three tests in patients with PTMGD was then improved to (13/18) 72%. The pathology of PTMGD was predominantly parathyroid hyperplasia, 45/72 (63%), compared to that of monoadenopathy 18/291 (6%), P<0.001. Parathyroid adenomas predominated in patients with monoadenopathy compared to that of PTMGD, 237/291 (82%) vs. 24/72 (33%), and the proportion of parathyroid adenomas in patients with monoadenopathy was higher than that in patients with PTMGD, P<0.001. 23 patients with PTMGD were followed up, of whom 9 showed mild elevation of parathyroid hormone postoperatively, and 1 patient showed signs of hypoparathyroidism. Conclusion:The low age of onset of multiglandular lesions in primary hyperparathyroidism, mild biochemical tests, and the difficulty of accurately locating all lesions preoperatively warrant adequate preoperative evaluation to promptly identify patients with familial multiple endocrine adenomas, as well as intraoperative bilateral parathyroid exploration in patients with suspected multiglandular lesions.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Objective:To investigate the incidence characteristics and influencing factors of non-alcoholic fatty liver disease (NAFLD) in rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps and to provide scientific evidence for early identification and prevention of NAFLD for residents.Methods:A total of 10 158 participants were included from the Xinjiang Uygur ethnic group population cohort. A prospective cohort study and Cox proportional hazards regression model analysis were used to explore the influencing factors and clustering of NAFLD, and the dose-response relationship between related biochemical indicators and the risk of NAFLD was studied using a restricted cubic spline.Results:The cumulative incidence rate of NAFLD was 6.9%, and the incidence density of NAFLD was 12.06/1 000 person-years. The incidence density of NAFLD in females was higher than in males (14.72/1 000 person-years vs. 9.17/1 000 person-years, P<0.001). The incidence density of NAFLD gradually increased with age in the total population, both men and women (all P<0.001). In the general population, an education level of junior high school or above was a protective factor for NAFLD, while older age, divorce, widowhood, overweight, obesity, hypertension, increased glomerular filtration rate, decreased HDL-C, increased LDL-C, and increased ALT were risk factors for NAFLD. Estimated glomerular filtration rate (eGFR), HDL-C, LDL-C, and ALT were non-linearly correlated with the incidence of NAFLD, and there was a significant dose-response relationship between them. Only 19.1% of residents had no NAFLD risk factors; over 80.9% had ≥1 NAFLD risk factors. The risk of NAFLD increased with the number of risk factors. Conclusions:The incidence of NAFLD in rural Uygur ethnic group residents in Xinjiang Production and Construction Corps was relatively low, but most residents had one or more risk factors for NAFLD. Prevention and control of NAFLD in this population cannot be ignored. In addition, people of older age, divorced or widowed, low education level, overweight or obese, hypertension, and abnormal eGFR, HDL-C, LDL-C, and ALT were the high-risk groups of NAFLD that need to be paid attention to in this population.

Objective:To search, evaluate, and summarize the best evidence for difficult peripheral intravenous catheterization in children.Methods:Following the "6S" evidence pyramid model, literature related to the management of difficult peripheral veins in children was searched in both English and Chinese databases including UpToDate, BMJ Best Practice, National Guidelines Clearinghouse, the Joanna Briggs Institute Evidence-Based Health Care Database, PubMed, Medlive, SinoMed, CNKI, and Wanfang Database. The search period was from the establishment of the database to January 2023. Two researchers trained in systematic evidence-based nursing, independently evaluated the quality of included literature and extracted relevant evidence.Results:Five articles were included: two guidelines, two expert consensuses, and one systematic review. 19 best evidence were summarized, covering five aspects: difficult vein quality management, difficult vein assessment, difficult intravenous catheterization site and needle type selection, difficult intravenous catheterization auxiliary methods, and handling of failed difficult intravenous catheterization.Conclusions:This study summarizes the best evidence for difficult peripheral intravenous catheterization in children, demonstrating clinical nursing practicality. It provides evidence-based guidance for pediatric nursing staff performing difficult intravenous catheterization.