Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

OBJECTIVES: This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement. METHODS: Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions. RESULTS: The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region. CONCLUSIONS Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling ; Animals ; Tooth Movement Techniques ; Rats ; Alveolar Process/physiology* ; Stress, Mechanical ; Humans ; Biomechanical Phenomena ; Cancellous Bone/physiology* ; Shear Strength

Objective To analyze the research status of in situ simulation in the medical field and explore its hotspots and trends. Methods Relevant literature was searched in China National Knowledge Infrastructure and Web of Science core collection from the inception to February 2024.CiteSpace 6.3.R1 was used to analyze the authors,institutions,and keywords and draw visual knowledge maps. Results A total of 25 Chinese articles and 438 English articles were included.Only 14 English articles were from China.In Chinese articles,the authors with the largest number of articles were Dai Hengmao and Liu Shangkun,and the institution with the largest number of articles was Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.There was little cooperation between the authors and institutions.In English articles,the author and institution with the largest number of articles was Auerbach Marc and Yale University,respectively,and the cooperation between authors and institutions was close.Emergency medicine,emergency event handling,and on-the-job training were the keywords with high frequency in Chinese articles.Patient safety,medical education,and cardiac arrest were the keywords with high frequency in English articles.A total of 4 clusters were generated for Chinese keywords and 13 clusters for English keywords. Conclusions The application of in situ simulation in the medical field is still in the initial stage,and the development is not balanced at home and abroad.The number of articles published and the cooperation between authors and institutions in China obviously lags behind those abroad.Treatment and care of emergency critical patients,emergency event handling and skill training,identification of latent safety threats,improvement of readiness,and promotion of medical quality improvement are the future research hotspots and research trends in this field.
Bibliometrics ; Humans ; China ; Simulation Training ; Education, Medical ; Emergency Medicine/education*

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective:To evaluate the efficacy of rhomboid inter-costal and sub-serratus (RISS) block with ropivacaine-dexmedetomidine-dexamethasone for analgesia after thoracoscopic lobectomy.Methods:This study was a prospective, randomized, double-blind, controlled trial. From January 2021 to November 2023, 46 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, undergoing elective video-assisted thoracoscopic lobectomy at the Second Affiliated Hospital of Nanjing Medical University, were selected and assigned into 2 groups ( n=23 each) using simple randomization: ropivacaine group (R group) and ropivacaine-dexmedetomidine-dexamethasone group (RDA group). RISS block was performed preoperatively, with 20 ml of the drug solution injected at the target points of the rhomboid-intercostal muscle and the serratus anterior-intercostal muscle. R group received 0.375% ropivacaine 40 ml, while RDA group received 40 ml of the mixture containing 0.375% ropivacaine, dexmedetomidine 1 μg/kg, and dexamethasone 8 mg. Postoperative analgesia was performed with oxycodone (When the patient′s numerical rating scale [NRS] score >4 in post-anesthesion care unit, oxycodone 2 mg was intravenously administered as needed until the NRS score <4, and then a patient-controlled analgesia pump was initiated). The time of the first postoperative analgesic requirement, NRS scores at rest and during coughing at 1, 3, 6, 12, 24 and 48 h postoperatively, cumulative consumption of oxycodone in the periods of 0-12 h, >12-24 h, and >24-48 h, time to first ambulation, and incidence of related adverse reactions within 48 h postoperatively were recorded. Results:Compared with R group, the time to the first analgesic requirement was significantly prolonged, the cumulative consumption of oxycodone in the first 0-12 h postoperatively was reduced ( P<0.001), and no statistically significant changes were found in the time to first ambulation, NRS scores at rest and during coughing, or the incidence of postoperative adverse reactions in RDA group ( P>0.05). Conclusions:RISS block using a combination of ropivacaine, dexmedetomidine and dexamethasone can significantly prolong block duration, reduce postoperative opioid analgesic consumption, and provide good safety for the patients undergoing thoracoscopic lobectomy.

Objective:To determine the median effective dose (ED 50) of oliceridine inhibiting the responses to the laryngeal mask airway insertion when combined with ciprofol in elderly patients. Methods:In this sequential trial, American Society of Anesthesiologists Physical Status classificationⅠ-Ⅲ elderly patients of either sex, aged ≥65 yr, with a body mass index of 18-30 kg/m 2, undergoing elective urological surgery under general anesthesia with laryngeal mask airway, were included in this study. Ciprofol 0.4 mg/kg was intravenously injected, the dose of oliceridine was determined by using modified Dixon′s up-and-down method (increment or decrement of 0.005 mg/kg), and the initial dose of oliceridine was 0.01 mg/kg. A positive response was defined as an increase in maximum mean arterial pressure or heart rate ≥20% within 3 min after inserting the laryngeal mask airway or occurrence of any one of these signs such as movement, coughing, frowning, mouth corner twitching, tearing, laryngospasm, or bispectral index value failing to drop below 60. The trial was terminated upon observing 7 positive-to-negative transition points, starting from the first occurrence of an alternation between positive and negative responses to laryngeal mask airway insertion. The ED 50 and 95% confidence interval of oliceridine inhibiting the responses to the laryngeal mask airway insertion was calculated when combined with ciprofol in elderly patients. Results:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion was 0.027 mg/kg, and the 95% confidence interval was 0.008-0.048 mg/kg when combined with ciprofol 0.4 mg/kg. Conclusions:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion is 0.027 mg/kg when combined with ciprofol 0.4 mg/kg in elderly patients.

Objective To observe the repair effect and mechanism of Danhuang Powder-containing serum on high glucose-induced vascular endothelial cell injury.Methods Danhuang Powder-containing serum was prepared.Human umbilical vein endothelial cells(HUVECs)were cultured to be divided into control group,recombinant human epidermal growth factor(called"growth factor"for short)group,Danhuang Powder group,high glucose group,high glucose+growth factor group,and high glucose+Danhuang Powder group.After corresponding intervention in each group for 48 hours,the cell ultrastructure and autophagy were observed under transmission electron microscope,apoptosis was detected by flow cytometry,and the protein expression levels of vascular endothelial growth factor(VEGF),epidermal growth factor(EGF)and basic fibroblast growth factor(bFGF)in the cells were detected by Western Blot.Results(1)The intra-mitochondrial ridges in the control group were clearly visible,autophagosomes and autolysosomes were fewer;mitochondria in the high glucose group were swollen and irregular,and appeared vacuolated;and the more typical autophagy-like structures were seen in the high glucose+Danhuang Powder group.(2)Compared with the high glucose group and high glucose+growth factor group,the apoptosis rate of cells in the high glucose+Danhuang Powder group was significantly decreased(P<0.05).(3)Compared with the high glucose group and the high glucose+growth factor group,the protein expression levels of VEGF,EGF and bFGF in the cells of the high glucose+Danhuang Powder group were significantly increased(P<0.05).Conclusion Danhuang Powder-containing serum can reduce the high glucose-induced damage in HUVEC cells,and its mechanism may be related to the activation of mitochondrial autophagy,and the inhibition of apoptosis,as well as the up-regulation of the expression of VEGF,EGF and bFGF.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.