ObjectiveTo investigate the preventive effect and mechanism of Dendrobium officinale （DO） on non-alcoholic fatty liver disease （NAFLD） by network pharmacology and animal experiments. MethodsDO components in blood after administration were identified and analyzed using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-QE-HF-MS/MS）. Network pharmacology and molecular docking methods were employed to obtain active ingredients and potential targets of DO for NAFLD control. High-fat feeds were used to replicate the NAFLD rat model. Biochemical kits were used for detecting the expression levels of blood lipids， hepatic lipids， and liver functions of rats. Hematoxylin-eosin （HE） staining and oil red O staining were employed to observe pathological changes in rat liver， and real-time fluorescence quantitative PCR （Real-time PCR） assay was performed to validate potential targets obtained from the network pharmacology analysis. ResultsA total of 13 DO components were identified in blood， including berberine， dihydrosanguinarine， and oxypeucedanin. A total of 14 potential targets were screened through network pharmacology， including Forkhead box protein O1 （FoxO1）， epidermal growth factor receptor （EGFR）， and insulin-like growth factor 1 （IGF-1R）， involving pathways such as the advanced glycation end product （AGE）/receptor for AGE （RAGE） signaling pathway， blood lipids and atherosclerosis， insulin resistance， and FoxO signaling. The results of animal experiments showed that the NAFLD rat model was successfully replicated. After the preventive treatment with DO for NAFLD rats， the indexes of blood lipids， hepatic lipids， and liver function were normalized； lipid deposition and lesions in the liver were significantly improved； the expression level of FoxO1 mRNA in the liver was significantly reduced （P<0.05）， and the mRNA expression levels of phosphatidylinositide 3-kinases （PI3K）， protein kinase B （Akt）， EGFR， and IGF-1R were significantly increased （P<0.05）. ConclusionDO has a preventive effect on NAFLD rats， and the mechanism of action may be related to the modulation of IGF1R and EGFR targets and activation of the PI3K/Akt/FoxO1 signaling pathway.

Objective To quantitatively assess the association of short-term exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient fine particulate matter (PM2.5) with residents mortality. Methods A time-stratified case-crossover study was conducted from 2020 to 2022 among 10606 non-accidental residents by using the Guangzhou Cause of Death Surveillance System in Conghua District, Guangzhou. Exposure levels of PAHs in PM_2.5 and meteorological data during the study period were obtained from the Center for Disease Control and Prevention in Conghua District and the China Meteorological Administration Land Data Assimilation System (CLDAS-V2.0), respectively. Conditional Poisson regression model was used to estimate the exposure-response association between PAHs and the mortality risk. Results Fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene, and indeno[1,2,3-cd]pyrene were significantly associated with an increased risk of mortality. For every one interquartile range increase in exposure levels, the non-accidental mortality risks increased by 8.33% (95% CI: 1.80%, 15.27%), 4.67% (95% CI: 1.86%, 7.57%), 6.07% (95% CI: 2.08%, 10.21%), 4.62% (95% CI: 1.85%, 7.47%), and 4.70% (95% CI: 0.53%, 9.03%), respectively. The estimated non accidental deaths attributable to exposure to fluoranthene, chrysene, benzo[k]fluorine, benzo[a]pyrene and indine[1,2,3-cd]pyrene were 5.91%, 6.08%, 6.51%, 6.46%, and 4.21%, respectively. Conclusions Short-term exposure to PAHs in PM_2.5, including fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene and indine[1,2,3-cd]pyrene, was significantly associated with an increased risk of mortality among residents.

OBJECTIVE: To analyze RELT gene mutation found in a pedigree with clinical features and inheritable pattern consistent with amelogenesis imperfecta (AI) in China, and to study the relationship between its genotype and phenotype. METHODS: Clinical and radiological features were recorded for the affected individuals. Peripheral venous blood samples of the patient and family members were collected for further study, and the genomic DNA was extracted to identify the pathogenic gene. Whole exome sequencing (WES) was performed to analyze the possible pathogenic genes, and Sanger sequencing was performed for validation. SIFT and PolyPhen-2 were used to predict and analyze the mutation effect. Comparison of RELT amino acids across different species were performed by using Uniprot website. In addition, the three-dimen-sional structures of the wild type and mutant proteins were predicted by Alphafold 2. RESULTS: The proband exhibited typical hypocalcified AI, with heavy wear, soft enamel, rough and discolored surface, and partial enamel loss, while his parents didn ' t have similar manifestations. WES and Sanger sequencing results indicated that the proband carries a homozygous frameshift mutation in RELT gene, NM_032871.3: c.1169_1170del, and both of his parents were carriers. This mutation was predicted to be pathogenic by SIFT and PolyPhen-2. Up to now, there were 11 mutation sites in RELT gene were reported to be associated with AI, and all of the patients exhibited with hypocalcified AI. Compared with the wild-type RELT protein, the mutant protein p. Pro390fs35 conformation terminated prematurely, affecting the normal function of the protein. CONCLUSION Through phenotype analysis, gene sequencing, and functional prediction of a Chinese family with typical amelogenesis imperfecta, this study found that RELT gene frameshift mutation can lead to protein dysfunction in AI patients. Further research will focus on the role and mechanism of RELT in enamel development at the molecular and animal levels, providing molecular biology evidence for the genetic counseling, prenatal diagnosis, and early prevention and treatment of AI.
Humans ; Amelogenesis Imperfecta/genetics* ; Frameshift Mutation ; Male ; Pedigree ; Female ; China ; Exome Sequencing ; Phenotype ; Adult

Background Exposure to air pollutants increases the risk of diseases in multiple systems, including respiratory and cardiovascular systems, yet its association with neurological diseases remains unclear. Objective To quantitatively evaluate the association between short-term exposure to air pollutants and outpatient and emergency visits for neurological diseases, identify potential susceptible populations, and quantify associated disease burden. Methods Daily 24-hour average concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO), daily maximum 8-hour average concentration of ozone (O₃), daily meteorological data (24-hour average temperature, 24-hour average relative humidity), and data on daily outpatient and emergency department visits for neurological diseases from two hospitals in Conghua District, Guangzhou, China, were collected from 2015 to 2022. A time-stratified case-crossover design was adopted, and a conditional Poisson regression model was constructed to analyze the association between air pollution exposure and neurological disease visits. Two-pollutant models and sensitivity analysis were used to validate model stability. Stratified analyses by season (cold season: from November to March; warm season: from April to October), sex (male, female), and age (≤45 years, 46–60 years, ≥61 years) were performed to identify vulnerable group. Additionally, the number and proportion of neurological disease visits attributable to short-term air pollutant exposure were calculated. Results A total of 72 673 outpatient and emergency department visits for neurological diseases were included during the study period. Most of the patients were middle-aged and elderly individuals (69.89% were over 45 years old) and females (60.25%). The results of single-pollutant models showed that for each interquartile range (IQR) increase in exposure to PM_2.5, PM₁₀, SO₂, NO₂, CO, and O₃, the risk of outpatient and emergency department visits for neurological diseases increased by 7.54% (95%CI: 4.69%, 10.46%), 6.66% (95%CI: 3.92%, 9.46%), 16.72% (95%CI: 10.58%, 23.19%), 8.12% (95%CI: 4.82%, 11.53%), 5.60% (95%CI: 2.34%, 8.97%), and 6.11% (95%CI: 2.91%, 9.40%), respectively. The results of the two-pollutant model showed that the association between PM_2.5 and SO₂ exposure and outpatient and emergency department visits for neurological diseases were relatively stable. The stratified analyses showed that the effect of SO₂ was stronger in the cold season. It was estimated that 8.32% (95%CI: 5.55%, 10.96%) and 6.65% (95%CI: 4.27%, 8.96%) of the outpatient and emergency department visits were attributable to short-term exposure to SO₂ and PM_2.5, respectively. Conclusion Exposure to PM_2.5 and SO₂ is associated with increased risks of outpatient and emergency visits for neurological diseases. SO₂ shows stronger effects during the cold season, and exposure to air pollution contributes to up to 8.32% of neurological disease visits.

Background With the rapid development of the food delivery industry, take-away deliverymen become an essential component of urban logistics. However, high labor intensity, unstable income, and extended working hours place them at considerable risk of occupational burnout. Available studies have paid insufficient attention to the mental health of this population, and effective predictive or preventive approaches remain limited. Objective To understand the status of occupational burnout among take-away deliverymen, identify influencing factors based on restricted cubic spline analysis, and develop a predictive model to provide a theoretical basis for improving their mental health. Methods A cross-sectional survey was conducted among full-time take-away deliverymen registered to the "Ele.me" and "Meituan" platforms in Hangzhou between September 1 and November 30, 2024, using both online and offline approaches. A questionnaire covered sociodemographic, household, and occupational information, and the Maslach Burnout Inventory–General Survey were used in this survey. Univariate analyses and logistic regression were used to identify factors associated with burnout and to construct a predictive model. Model performance was evaluated using receiver operating characteristic (ROC) curve and calibration curve. Furthermore, restricted cubic spline was used to further explore the relationship between age, working hours, and occupational burnout. Results Among the 1192 participants, 735 (61.66%) experienced occupational burnout. The logistic regression model indicated that older age (OR=1.021, P=0.010), educational attainment of college level or above compared to junior high school or below, (OR=2.837, P<0.001), and longer daily working hours (OR=1.081, P=0.001) were positively associated with occupational burnout. In contrast, work experience of 3−5 years (OR=0.666, P=0.016) and more than 5 years (OR=0.382, P<0.001) compared to those with <3 years, as well as providing three social insurances (OR=0.655, P=0.006) or five social insurances (OR=0.478, P<0.001) compared to those without any social insurances coverage, were negatively associated with occupational burnout. The predictive model based on these variables achieved an area under the curve (AUC) of 0.783 (95% CI: 0.756~0.809), and good agreement between calibration curves. The restricted cubic spline analysis revealed that the risk of occupational burnout was highest among delivery workers aged 33−46 years. Those with daily working hours between 3.5 and 8.1 h had a lower risk, while the risk significantly increased when working hours exceeded 8.1 h per day. Conclusion The prevalence of reporting occupational burnout among take-away deliverymen in Hangzhou is high. The developed predictive model provides valuable insights for the prevention and control of burnout in this population. Measures such as optimizing social security systems, rational work schedule allocation, and enhancing psychological support may help reduce occupational burnout among take-away deliverymen.

As a noval class of nucleic acid drugs,messenger ribonucleic acid(mRNA)has great application potential in vaccines,immunotherapy,regenerative medicine,gene editing and so on.In particular,coronavirus disease 2019(COVID-19)in 2020 has greatly accelerated the mRNA technology development globally.However,mRNA being negatively charged,face challenges in cell entry and is easy to be phagocytized by cells of the innate immune system or degraded by nucleases in vivo.The instability and low delivery efficiency hinder widespread application of mRNA-based therapy.Therefore,safe,effective and stable delivery was needed carriers to protect mRNA from degradation and break through the barrier of cell membrane in order to ensure it express in intracellular.This paper systematically reviews the latest research progress of mRNA delivery carriers and briefly describes lipid carriers,polymer carriers,peptide carriers and viral carriers.The future directions of mRNA delivery carriers research are prospected so as to provide reference for the development of new mRNA drug delivery carriers.

Objective:To investigate the influence of sulforaphane(SFN)on ventricular remodeling in myocardial infarction(MI)rat model by regulating extracellular regulated protein kinase(ERK)/nuclear respiratory factor 1(NRF1)signaling pathway.Methods:Among 48 SD male rats,12 were randomly selected as Sham group.The remaining rats were treated with ligation of left ante-rior descending coronary artery to establish myocardial infarction model.After modeling,36 rats were randomly divided into MI model group,SFN treatment group(10 mg/kg),SFN+SCH772984(ERK inhibitor)group(10 mg/kg+15 mg/kg),with 12 rats in each group.Animal ultrasound was performed to detect cardiac structure and function.Histological analysis was performed to evaluate myo-cardial fibrosis and cell apoptosis.ELISA was used to measure pro-inflammatory factor levels in serum,and Western blot assay was used to observe the expression of ERK/NRF1 pathway related proteins in myocardium of rats in each group.Results:Compared with rats in Sham group,rats in MI model group showed a loss of myocardial compliance and disarray of ventricular myocardial fibers,along with increased myocardial fibrosis and myocardial cell apoptosis.Moreover,rats in MI model group also exhibited overactive inflammatory response and inhibition of the ERK/NRF1 signaling pathway in cardiac tissues(P<0.05).Notably,SFN treatment signifi-cantly not only improved cardiac function,but also ameliorated myocardial fibrosis and cell apoptosis(P<0.05).SFN treatment inhib-ited inflammatory cytokine expression and activated the ERK/NRF1 pathway as well(P<0.05).However,SCH772984 significantly abrogated the protective effect of SFN against myocardial fibrosis and apoptosis in MI rats.Conclusion:SFN may protect against ventricular remodeling in MI rat by activating ERK/NRF1 pathway.

Objective:To explore the effect of virtual reality (VR) technology in postoperative pain management for surgical patients.Methods:The literature on VR technology for relieving postoperative pain in surgical patients was electronically retrieved from eight databases, including PubMed, Web of Science and so on. The search period was from database establishment to November 19, 2023. Two researchers independently screened literature, extracted data, and conducted literature quality evaluation, using RevMan 5.4 for Meta-analysis.Results:A total of 18 articles were included. Meta-analysis results showed that VR technology could reduce postoperative resting pain scores [ MD=-1.13, 95% CI (-1.29, -0.96), P<0.001], postoperative 12 hour pain scores [ MD=-0.49, 95% CI (-0.73, -0.24), P<0.001], postoperative 24 hour pain scores [ MD=-0.73, 95% CI (-0.92, -0.54), P<0.001], postoperative 48 hour pain scores [ MD=-0.69, 95% CI (-0.84, -0.53), P<0.001], postoperative 72 hour pain scores [ MD=-0.37, 95% CI (-0.59, -0.16), P<0.001], and postoperative pain scores during dressing changes [ MD=-1.11, 95% CI (-2.06, -0.16), P=0.02], and could improve patient postoperative comfort [ MD=8.31, 95% CI (6.57, 10.06), P<0.001] . Conclusions:As a non-pharmacological intervention, VR technology can alleviate postoperative pain and improve patient comfort in surgical patients. In the future, large-scale and high-quality research is still needed to further verify the effectiveness of VR technology.

Objective:To investigate the clinicopathological characteristics of dedifferentiated endometrial carcinoma/undifferentiated endometrial carcinoma (DDEC/UDEC) with loss of expression of SMARCA4.Methods:A total of 10 cases with loss of expression of SMARCA4 were diagnosed at Fujian Cancer Hospital between January 2019 and December 2023. A retrospective analysis was conducted on the clinical characteristics, morphology, immunophenotype, molecular classification, and prognosis.Results:(1) Clinical characteristics: among 10 cases of DDEC/UDEC with loss of expression of SMARCA4, the patients′ age ranged from 48 to 65 years, with a median age of 56 years.Five cases were classified as International Federation of Gynecology and Obstetrics (FIGO) stages Ⅰ-Ⅱ, while the remaining five were categorized as stages Ⅲ-Ⅳ. (2) Pathological features: tumor cells exhibited poor cell adhesion, with common intravascular tumor emboli (8/10), occasional vacuolated nuclei (6/10), rhabdoid cells (4/10), and starry sky phenomenon formed by tissue cell phagocytosis apoptosis bodies or fragments (4/10). Six cases (6/10) showed loss of mismatch repair (MMR) protein expression, two cases (2/10) exhibited p53 mutant expression, and five cases (5/10) tested positive for programmed cell death ligand 1 (PD-L1). (3) Molecular subtyping: molecular subtyping revealed POLEmut in 1 case (1/10), mismatch repair deficient (MMR-d) in 5 cases (5/10), p53 abn in 1 case (1/10), and no specific molecular profile (NSMP) in 3 cases (3/10). (4) Prognosis: the follow-up period ranged from 7 to 42 months, with a median of 20 months. Five patients succumbed to the tumor, whereas the remaining five exhibited no recurrence during subsequent postoperative evaluations. The 2-year progression-free survival rates and overall survival rates were 58.3% and 52.5%, respectively.Conclusions:Loss of expression of SMARCA4 occurs in approximately 1/5 of DDEC/UDEC, which presents with an aggressive clinical course and a poor prognosis. About half of them show MMR protein loss expression and PD-L1 positive expression, suggesting that there might be benefit from treatment with immune checkpoint inhibitors.

Surgery is the main clinical treatment for papillary thyroid carcinoma(PTC),and with the advancement of medical technology,PTC surgical treatment has made significant progress.However,there is still controversy in the academic community re-garding the scope of PTC surgical resection and lymph node dissection.Moreover,as PTC shows a trend towards youthfulness,patients′demands for surgical methods,surgical timing,surgical outcomes,and postoperative aesthetics are gradually increasing.Therefore,the choice of PTC surgical method needs to consider more aspects besides lesion resection and disease relief.This article reviews the pro-gress and limitations of surgical treatment for PTC.