Objective To determine the median effective dose (ED₅₀) of remimazolam for preoperative sedation in pediatric patients aged 1-6 years using the modified Dixon sequential method. Methods This is a prospective clinical study. Pediatric patients scheduled for elective short surgery (surgery time ≤1 h) under general anesthesia from January to July 2023 were selected. Inclusion criteria were age 1-6 years, an ASA physical status Ⅰ-Ⅱ and the preoperative parent separation anxiety scale (PSAS) score ≥3 points. Remimazolam was administered intravenously preoperatively, and its sedative effect was assessed. The modified Dixon sequential method was used to determine the ED₅₀ of remimazolam, with the initial dose set at 0.10 mg/kg and the dose increment set at 0.02 mg/kg. Sedation was considered successful (positive, included in positive group) if the child with sedation score ≥2 points, preoperative PSAS score <3 points,and the mask acceptance score of 4 points during anesthesia induction. If any criterion was not met, sedation was considered failure (negative, included in negative group), and the next patient's dosage was increased by 0.02 mg/kg based on the previous patient's dosage. The test was completed after 7 consecutive positive and negative turning points appeared alternately. Probabilistic unit regression analysis was used to determine the ED₅₀, ED₉₅ and the corresponding 95% confidence interval (CI) of remimazolam for preoperative sedation. Postoperative recovery time and adverse events such as airway spasm, respiratory depression, hypotension, nausea and vomiting during anesthesia were recorded. Results A total of 23 pediatric patients were included, with 13 in positive group and 10 in negative group. There were no statistically significant differences in mean arterial pressure, pulse oxygen saturation or heart rate before and after sedation (P>0.05). Compared with negative group, positive group showed a significant reduction in preoperative parent separation anxiety and an increase in mask acceptance during anesthesia (P<0.05). There was no significant difference in sedation score and anesthesia awakening time between two groups (P>0.05). The ED₅₀ of remimazolam for preoperative sedation in pediatric patients aged 1-6 years was 0.051 mg/kg (95%CI 0.033-0.065 mg/kg), and the ED₉₅ was 0.077 mg/kg (95%CI 0.064-0.161 mg/kg). No adverse events such as airway spasm, respiratory depression, hypotension, nausea and vomiting occurred during anesthesia in any of pediatric patients. Conclusion The ED₅₀ of intravenous administration of remimazolam for preoperative sedation in pediatric patients aged 1-6 years is 0.051 mg/kg (95%CI 0.033-0.065 mg/kg).

Hemodynamics numerical simulation, a multidisciplinary research approach integrating fluid dynamics, clinical medicine, and computer simulation techniques, offers an objective and quantitative analysis of cardiovascular blood flow dynamics through calculating data such as flow rate, pressure, resistance, and wall stress. This review provides a comprehensive overview of the modeling methods and characteristics of numerical simulations within the cardiovascular system. Additionally, it also summarizes the research advancements and potential clinical applications of numerical simulations in the context of various cardiovascular diseases, including vascular aneurysms, aortic dissection, atherosclerosis, structural heart diseases, heart failure, ventricular assist devices, cardiogenic shock, and extracorporeal membrane oxygenation. The goal is to facilitate the deep integration of clinical medicine with engineering technologies, thereby fostering innovative solutions for the precise diagnosis and treatment of cardiovascular disease.

Objective To analyze the classification characteristics of rheumatoid arthritis (RA)-related antibodies and to investigate the factors influencing the development of RA-related interstitial pulmonary diseases (RA-ILD) in RA patients using latent class analysis (LCA). Methods A retrospective analysis of 712 RA patients treated at the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University from December 2019 to October 2022 was conducted. According to whether patients had RA-ILD or not, they were divided into simple RA group (n=523) and RA-ILD group (n=189). Then, the differences in general data, clinical features, medication use and laboratory indicators were compared between the two groups. Based on the differences in RA-related antibody indicators, 712 patients were divided into 3 latent categories using LCA: high-risk group (n=364), medium-risk group (n=205), and low-risk group (n=143).One-way analysis of variance was employed to compare clinical characteristics of the 3 groups, and the prevalence of RA-ILD was calculated. Multivariate logistic regression analysis was utilized to identify independent affect factors of RA-ILD. Results Significant differences in gender, age, and smoking history were observed between simple RA group and RA-ILD group (P<0.05). The high, medium and low risk groups exhibited significant differences in gender, age, prednisone (PRED) and methotrexate (MTX) medication history, Red blood cell count (RBC), interleukin-2 (IL-2), IL-4, IL-10, IL-17, TNF-α, interferon-γ (INF-γ), serum globulins, and white blood albumins (P<0.05). The high-risk group had a higher proportion of males, RBC, IL-2, IL-4, IL-10, IL-17, TNF-α, INF-γ, and serum globulin levels, and a lower proportion of MTX medication compared with medium- and low-risk groups (P<0.05 or P<0.01). The medium-risk group had a higher proportion of MTX administration than that in high- and low-risk groups (P<0.05 or P<0.01). The low-risk group had a higher proportion of females and older age than those in other two groups (P<0.05 or P<0.01). The prevalence of RA-ILD was 30.5%, 23.9% and 20.3% in the three groups, respectively. Multivariate logistic regression analysis indicated that male (OR=2.920, 95%CI 1.722-4.952), age (OR=1.055, 95%CI 1.035-1.074), IL-17 (OR=1.013, 95%CI 1.003-1.023), TNF-α (OR=1.050, 95%CI 1.017-1.083), INF-γ (OR=0.962, 95%CI 0.932-0.993), Serum albumin (OR=0.919, 95%CI 0.869-0.971) and high risk antibody indicators (OR=1.725, 95%CI 1.084-2.745) were independent predictors for RA-ILD. Conclusions RA patients exhibit distinct categories of antibody indicators, with a higher prevalence in high-risk patients with RA-ILD. RA-ILD is more likely to occur in male, elderly patients with abnormal liver function and high-risk antibody indictors. More attention should be paid to these patients and individualized interventions should be developed and implemented in a timely manner to improve the quality of patient survival.

Objective To investigate the mechanism by which Senegenin (SEN) alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2 (Nrf2)/NOD-like receptor protein 3 (NLRP3) pathway. Methods BV2 mouse microglia cells were randomly divided into control group, model group, SEN group and MCC950 group. Cells in control group were not treated, and cells in model group were added with 1 μg/ml lipopolysaccharide (LPS); Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN, and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours. CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells. Griess method was used to determine the release amount of nitric oxide (NO) in the supernatant. Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3, lymphocyte apoptosis-associated spect-like protein containing a CARD (ASC), caspase-1, interleukin (IL)-1β and IL-18 mRNA. Immunofluorescence staining was used to detect the expression levels of ASC, IL-1β, Nrf2 and heme oxygenase-1 (HO-1). Western blotting was used to detect the expression levels of NLRP3, caspase-1, ASC, IL-1β, IL-18, Nrf2, HO-1, nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS). Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2~20 μmol/L SEN compared with control group (P>0.05). Compared with control group, the viability of BV2 cells in model group decreased significantly (P<0.05). Compared with model group, the viability of BV2 cells in 4 μmol/L SEN group was significantly restored (P<0.05). Compared with control group, the results of Griess method showed that the release amount of NO in cells of model group increased significantly (P<0.05); the results of real-time PCR showed that the expression levels of NLRP3, ASC, caspase-1, IL-1β and IL-18 mRNA in cells of model group increased significantly (P<0.05); the results of Western blotting showed that the protein expression levels of NLRP3, ASC, caspase-1, IL-1β and IL-18 proteins in cells of model group increased significantly (P<0.05), and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased, and the expression levels of Nrf2 and HO-1 decreased, with statistically significant differences (P<0.05). Compared with model group, the release amount of NO in cells of SEN group and MCC950 group decreased, and the expression levels of NLRP3, ASC, caspase-1, IL-1β and IL-18 mRNA and proteins decreased, with statistically significant differences (P<0.05); in the SEN group, the expression levels of iNOS and NF‑κB decreased, and immunofluorescence staining showed that Nrf2 was translocated into the nucleus, and the expression levels of Nrf2 and HO-1 proteins increased significantly, with statistically significant differences (P<0.05). Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome, with an effect comparable to that of the inflammasome inhibitor MCC950. The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Objective To explore the correlation of bilateral knee joint strength asymmetry with balance, walking ability, and motor function in hemiplegic stroke patients, providing a reference for clinical assessment of stroke patients. Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected. According to the Berg Balance Scale (BBS) scores, patients were divided into Group A (BBS score ≤20, n=23) and Group B (BBS score >20, n=23). The peak torque and differences of bilateral knee flexors and extensors were compared between two groups. Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s. BBS, Functional Ambulation Classification (FAC), and Fugl-Meyer Assessment of Lower Extremity (FMA-LE) were used to evaluate patients' balance, walking ability, and lower limb motor function. The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed. Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B (P<0.05). At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B (P<0.05). At 60°/s, the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS, FAC, and FMA-LE (r=-0.569, -0.582, -0.606, P<0.01), as did the knee flexors (r=-0.534, -0.386, -0.458, P<0.05). At 120°/s, similar negative correlations were observed for both knee extensors (r=-0.304, -0.304, -0.443, P<0.05) and flexors (r=-0.337, -0.349, -0.370, P<0.05). Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability. The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.

Prehabilitation is a novel rehabilitation strategy, mainly including sports intervention, psychological intervention, nutrition support, and other specific measures. It extends the concept of accelerated rehabilitation surgery by enhancing patients' organ function and metabolic reserve through preoperative intervention, thereby accelerating postoperative recovery. This concept has been applied to various surgical procedures, including cancer, orthopedics, thoracic surgery, and cardiac surgery. The majority of spinal surgery patients are elderly, exhibiting significant physiological decline and frailty, necessitating a multi-modal rehabilitation program that addresses body and nutrition, pain, and brain health awareness. As a subspecialty of orthopedics, there have been increasing reports on the application of prehabilitation in spinal surgery in recent years. This review summarizes the application and research progress of prehabilitation in spinal surgery, providing a reference for clinical medical staff to correctly implement prehabilitation.

Objective To evaluate the clinical value of 18F-fibroblast-activation protein inhibitor (¹⁸F-FAPI) PET/CT in malignant tumors exhibiting low uptake of 18F-fluorodeoxyglucose (18F-FDG). Methods We prospectively analyzed 62 patients with malignant tumors and low ¹⁸F-FDG uptake who underwent ¹⁸F-FAPI PET/CT in the Affiliated Cancer Hospital and Institute of Guangzhou Medical University from January 2021 to November 2022. Patient demographics information, clinical and radiological data were collected. Tumor lesions were categorized based on ¹⁸F-FAPI and 18F-FDG uptake relative to surrounding tissues into low-, moderate-, and high-uptake, with high uptake indicating positivity. The number and tracer uptake levels of primary tumors and metastatic lesions visualized by both ¹⁸F-FDG and ¹⁸F-FAPI were recorded and compared. Results Of the 62 primary tumors, 18(29.0%) showed low-uptake and 44 (71.0%) moderate-uptake on ¹⁸F-FDG PET, while 1(1.6%), 6(9.7%), and 55(88.7%) showed low, moderate, and high uptake on ¹⁸F-FAPI, respectively. The maximum standardized uptake value (SUV_max) for primary tumors was significantly higher with ¹⁸F-FAPI than with ¹⁸F-FDG (7.5±5.6 vs. 3.9±2.1, P<0.01). The number of positive lymph node foci revealed by ¹⁸F-FAPI was noticeably higher than that by ¹⁸F-FDG (77 vs. 38, P<0.01). A total of 16 distant organ metastases were identified, with 11(68.8%) detected by ¹⁸F-FDG and 15(93.8%) by ¹⁸F-FAPI, showing no significant difference in detection rates (P>0.05). Conclusions ¹⁸F-FAPI PET/CT effectively visualizes primary and metastatic lesions in malignant tumors with low ¹⁸F-FDG uptake, suggesting its potential as a promising radiotracer for such malignancies.

Objective To report the genetic analysis of a family with a fetus suspected of Ellis-van Creveld (EVC) syndrome based on ultrasound findings such as ventricular septal defect (VSD), short long bones in the limbs and polydactyly, and to conduct a literature review to clarify the pathogenic cause. Methods A 27-year-old pregnant woman, who was pregnant for the first time and had no prior deliveries, was admitted to the prenatal diagnosis center of Shijiazhuang Obstetrics and Gynecology Hospital in October 2021. At 17 weeks of gestation, ultrasound detected multiple fetal malformations. The genomic DNA of the fetal proband's amniotic fluid cells and the parents' peripheral blood samples were sequentially subjected to chromosomal karyotype analysis, chromosomal microarray analysis (CMA), and whole exome sequencing (WES). Suspected pathogenic mutations were verified by Sanger sequencing in the proband and its parents. Subsequently, a Minigene in vitro experiment was used to analyze one splicing mutation. Meanwhile, databases such as PubMed were searched, and literature reports were combined for genetic analysis. Results Chromosomal karyotype analysis of the fetus showed no abnormalities, and CMA did not detect any copy number variation (CNV) with clinical significance. WES results revealed two mutations in the EVC gene (NM_153717.2) of the fetus: a nonsense mutation c.1405G>T(p.E469X) in exon 10 and a splicing mutation c.1886+5G>A in intron 13. Family verification using Sanger sequencing showed that the father was a carrier of the c.1405G>T(p.E469X) mutation in exon 10, and the mother was a carrier of the c.1886+5G>A mutation in intron 13. The compound heterozygous mutation of the fetus was inherited from the parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) for classifying genetic variations, c.1405G>T (p.E469X) was classified as likely pathogenic mutation (PVS1+PM2), and c.1886+5G>A was classified as likely pathogenic mutation (PM2+PM3_Strong). The Minigene experiment results showed that the c.1886+5G>A mutation caused a 115-bp segment retention in intron 13, further supporting its pathogenicity. Review of the literature showed that the typical clinical manifestations of EVC syndrome include short limbs, short ribs, postaxial polydactyly, nail and tooth dysplasia, and congenital heart defects. Gene mutations in EVC/EVC2 were found to be the main pathogenic cause through whole exome sequencing, with mutation types including missense mutations, large-scale duplications/deletions, in-frame microdeletions, nonsense mutations, frameshift mutations, and splicing mutations. Conclusions The compound heterozygous mutations in the EVC gene are the pathogenic cause of the fetus. The detection of these mutations expands the genetic variation spectrum of Ellis-van Creveld syndrome.

Objective To investigate the effect and mechnism of betaine (BET) in reversing chemotherapy resistance in prostate cancer (PCa) by inhibiting ATP-binding cassette subfamily B member 1 (ABCB1). Methods The PCa chemotherapy-sensitive C4-2B cells were cultured, and the TaxR cells resistant to docetaxel (DTX) were established by gradient increase the concentration of DTX. The drug resistance of C4-2B and TaxR cells against DTX was assessed using CCK-8 and the colony formation experiment. Western blotting and qRT-PCR were used to detect ABCB1 expression. The TaxR cells were divided into: (1) Control group, negative control group (NC), siABCB1-1 group (transfected with siABCB1-1), and siABCB1-2 group (transfected with siABCB1-2). Western blotting was used to detect the effect of small interfering RNA on silencing ABCB1, and CCK-8 was used to detect the differences in DTX resistance between each group. (2) Different concentrations of BET (0, 100, 200, 400, 600, 800 mmol/L) groups. These groups were subjected to CCK-8 to detect cell viability, and Western blotting was used to detect the protein expression of ABCB1. (3) Control group, DTX group (20 nmol/L DTX), BET group (200 mmol/L BET), and DTX+BET group (20 nmol/L DTX+200 mmol/L BET), flow cytometry was used to detect apoptosis rate and cell cycle, and Western blotting to detect the protein expression of apoptosis-related proteins (Bcl2, BAX, c-caspase-3). (4) Control group, BET group (200 mmol/L BET), wortmannin (WM) group (100 μmol/L WM), and BET+WM group (200 mmol/L BET+100 μmol/L WM). Western blotting was used to detect the protein expression of PI3K, Akt, and ABCB1. (5) Control group, BET group (200 mmol/L BET), and BAY group (10 μmol/L BAY), BAY+BET group (200 mmol/L BET+10 μmol/L BAY). Western blotting was used to detect the protein expression of NF-κB p65, p-ikBα and ABCB1. Network pharmacology combined with transcriptome sequencing was used to predict the possible pathways for BET to reverse chemotherapy resistance. Results Compared with C4-2B cells, TaxR cells showed significantly increased resistance to DTX (P<0.01), and high expression of ABCB1 (P<0.01). After silencing ABCB1 with siRNA, TaxR cells' resistance to DTX was significantly inhibited (P<0.01). The inhibition rate of TaxR cells treated with 200 mmol/L BET was less than 20%, and it significantly decreased the expression of ABCB1 protein in TaxR cells (P<0.05). Compared with control group, the combination of 200 mmol/L BET and 20 nmol/L DTX resulted in higher apoptosis rate and higher S stage cell ratio, lower expression of Bcl-2 protein and higher expression of BAX and c-caspase-3 proteins than the two drugs used alone (P<0.05). Compared with control group, the combination of 200 mmol/L BET and 100 μmol/L WM significantly down-regulated the protein expression of PI3K, Akt and ABCB1 (P<0.01). The combination of 200 mmol/L BET and 10 μmol/L BAY significantly down-regulated the protein expression of NF-κB p65, p-ikBα and ABCB1 (P<0.01). Conclusion BET may reverse TaxR cells' chemotherapy resistance by down-regulating ABCB1 expression through the PI3K/Akt/NF-κB signaling pathway.

Objective To investigate the protective effect and its mechanism of low-dose interleukin-2 (IL-2) against hepatocyte injury in Concanavalin A (Con A)-induced autoimmune hepatitis (AIH) mice. Methods Eighteen SPF female C57BL/6 mice were randomly divided into normal group, model group and treatment group, each group with 6 mice. Mice in the treatment group were subcutaneously injected with 300 μl 10,000 U IL-2 for 12 d, once a day. 2 h after the last dose, Con A (15 mg/kg) was injected through the tail vein in the model group and treatment group. After 8 h of modeling, the histopathological changes in the mouse liver were observed using HE staining, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were detected using ELISA method; the expression of apoptotic protein caspase 8/9/3 was detected by Western blotting; and the percentages of Treg and Th1 cells were observed by flow cytometry. Results Compared with normal group, the liver index, spleen index, the percentage of necrotic area of liver tissue, the serum levels of ALT, AST, TNF-α and IFN-γ, and the expression of apoptosis protein caspase 8/9/3 significantly increased in the model group (P<0.05 or P<0.01); Compared with model group, the liver index, spleen index, the percentage of necrotic area of liver tissue, the serum levels of ALT, TNF-α and IFN-γ, and the expression of apoptosis protein caspase 8/9/3 significantly decreased in the treatment group (P<0.05 or P<0.01). The flow cytometry results showed that compared with normal group, the percentages of Treg and Th1 cells and Th1/Treg ratio increased in the model group (P<0.05 or P<0.01); Compared with the model group, the percentage of Treg cells further increased (P<0.01), Th1/Treg ratio decreased significantly in the treatment group (P<0.05), but there was no significant difference in the percentage of Th1 cells between two groups (P>0.05). Conclusion Low-dose of IL-2 can effectively improve liver injury in AIH mice, and the mechanism of action may be related to inducible Treg cell activation.