To investigate the effect of Ginkgo biloba extract (GBE) on lipids accumulation and the progression of atherosclerosis(AS), ApoE-/- mice fed with HFD were injected i.g. with two different doses of GBE (GBE-L 50 mg/(kg·d) or GBE-H 150 mg/(kg·d)) for 9 weeks. The core targets and potential mechanisms of GBE therapy for AS were investigated using network pharmacological target prediction. Subsequently, oxidized low-density lipoprotein (ox-LDL)-induced THP-1 was used to investigate the effect of GBE on foam cell formation through oil red staining and Dil-oxLDL fluorescent staining. The mRNA alterations in cholesterol uptake and efflux receptors were detected by real-time quantitative PCR. Finally, the impact of GBE on the expression of PPARγ as the core target was assessed through Western blot and immunofluorescence. It was found that GBE improved serum lipid profile, reduced necrotic cores and lipid deposition in aortic root plaques, and decreased the level of inflammatory factors in serum of ApoE-/- mice. Moreover, GBE treatment reduced the level of intracellular lipid accumulation and inhibited cholesterol uptake and efflux to alleviate foam cell formation. GBE activated PPARγ to enhance ABCA1/ABCG1-induced cholesterol efflux in THP-1. These results suggest that GBE can suppress lipid accumulation and alleviate foam cell formation by activating PPARγ pathway.

Objective:To investigate the patterns of mutation evolution in patients with acute myeloid leukemia (AML) during treatment and the possible clinical significances.Methods:A retrospective case series study was conducted. A total of 103 AML patients who were hospitalized at the Affiliated Yuebei People's Hospital of Medical College of Shantou University from November 2019 to August 2021 and underwent high-throughput next-generation sequencing (NGS) technology to detect the mutations of 128 AML-related genes in bone marrow samples were selected. Based on the NGS results, the somatic gene mutations in samples of patients collected at initial diagnosis (73 cases), complete remission (CR) (30 cases), non-remission (NR) (23 cases), and recurrence (12 cases) were analyzed, and the targeted drugs involved in the gene mutations detected in NR and recurrence samples were summarized.Results:The median age [ M ( Q1, Q3)] of onset for 103 patients was 58 (48, 66) years, including 64 males (61%) and 39 females (39%); 86 cases (83%) were primary AML, and 17 cases (17%) were secondary AML; at the initial diagnosis, 51 cases (50%) had normal karyotypes, 34 cases (33%) had abnormalities, and 18 cases (17.5%) were unknown. Compared with the CR samples, the mutation frequencies of FLT3 [29% (21/73) vs. 3% (1/30)], NPM1 [27% (20/73) vs. 3% (1/30)], NRAS [22% (16/73) vs. 3% (1/30)], and IDH2 [14% (10/73) vs. 0 (0/30)] were all higher in the initial diagnosis samples, and the differences were statistically significant (all P < 0.05); compared with the initial diagnosis sample, the median number of gene mutations in each CR sample was lower [4 (2, 5) vs. 7 (5, 9)], and the difference was statistically significant ( P < 0.001). However, there was no statistically significant difference in the median number of gene mutations in each patient between the initial diagnosis samples and the NR samples, the initial diagnosis samples and the recurrence samples, and the NR samples and the recurrence samples (all P > 0.05). Analysis of 14 patients with NGS data at initial diagnosis and CR showed that the same gene mutations could be detected at initial diagnosis and CR, such as DNAH23 (3 cases), USH2A (3 cases), etc; partial gene mutations were detected at initial diagnosis but were not detected at CR, including NRAS (5 cases), FLT3 (3 cases), ANKRD26 (3 cases), NPM1 (3 cases), ETV6 (3 cases), etc; ARID1B (1 case) and DNMT3A (1 case) were negative for mutations at initial diagnosis but positive upon reaching CR. Analysis of 14 patients with NGS data at initial diagnosis and NR showed that most gene mutations persisted at initial diagnosis and NR, such as DNMT3A (5 cases), NRAS (5 cases), KRAS (3 cases), RUNX1 (3 cases), etc; the mutant genes detected at initial diagnosis but not detected at NR included USH2A (2 cases), PCLO (2 cases), ATM (2 cases), FAT1 (2 cases), etc; partial gene mutations were not detected at initial diagnosis but were detected at NR, such as FAT1 (2 cases), TCF3 (2 cases), etc. Analysis of 5 patients with NGS data at CR and recurrence showed that some gene mutations were detected at both CR and recurrence, such as BCORL1 (1 case), ARID2 (1 case), SETD2 (1 case), VEGFC (1 case), etc; FLT1 (1 case) and GNAS (1 case) gene mutations were detected at CR but not detected at recurrence; at recurrence, some gene mutations that were not detected at CR were also detected, such as ANKRD26 (1 case), WT1 (1 case), etc. Among the 23 NR samples and 12 recurrence samples, the targets of drugs approved by US Food and Drug Administration or in clinical trials were detected in 14 (61%) and 5 (42%) samples respectively, including IDH1, IDH2, FLT3, KIT, KRAS, NRAS, SF3B1, U2AF1, and SRSF2. Conclusions:The number of gene mutations in AML patients during CR is significantly less than that at initial diagnosis, some gene mutations disappear when CR is achieved through treatment, but the majority of gene mutations persist during the treatment period, including NR and recurrence, suggesting that monitoring through NGS technology can help understand the evolution of gene mutations during AML treatment and discover the potential therapeutic targets.

Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

Eosinophilic gastroenteritis(EG)is a rare disease characterized by abnormal infiltration of eosinophils(Eos)in gastrointestinal tissues.Due to the unclear pathogenesis of EG and the lack of effective therapeutic drugs,research on its novel mechanisms,targets and drugs is critical.This article starts by outlining the research progress in the pathogenesis of EG,involving IgE mediated typeⅠimmediate allergic reactions and T helper 2 cell(Th2)mediated delayed allergic reactions.Then,the related targets of EG are summarized,including Th2 cytokines and factors regulating Eos function,but there has been no breakthrough in the treatment of these targets.Finally,the therapeutic drugs for EG are reviewed,such as glucocorticoids,antiallergic drugs and biologics.The advantages and disadvantages of various drugs are also described.However,these drugs cannot meet the current demands of clinical treatment and there is an urgent need to develop novel therapeutic drugs.It is believed that multi-target therapy is an ideal treatment for EG,and that traditional Chinese medicine and natural products should be the priorities of research and development for EG therapeutic drugs in the future.This review is expected to provide new ideas for the clinical treatment strategies and drug development of EG.

OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.

Diabetes mellitus is a chronic metabolic disorder, currently affecting more than 530 million people worldwide. Based on differences in pathogenesis, it is classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM is primarily caused by autoimmune destruction of pancreatic β cells, whereas T2DM results from insulin resistance due to β cell failure and dysfunction. Current treatments for diabetes include insulin injections, oral medications, and islet transplantation. As a curative therapy, islet transplantation still faces challenges such as limited donor cell availability, systemic immunosuppression-related side effects, and low long-term survival of transplanted islets. Transplantation of stem cell-derived islet organoids is expected to replace primary human islet cells and overcome these issues, making it one of the most promising therapies for T1DM and advanced-stage T2DM. This review provides an in-depth overview of the development of islet transplantation, with a focus on recent progress in stem cell differentiation into islet organoids and the engineering of islet organoids. Meanwhile, we also discuss the current opportunities and future challenges in islet organoid transplantation. These explorations and efforts lay the groundwork for future clinical applications and offer hope for a potential cure for diabetes.

Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7％.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P＜0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95％CI:0.566-0.838],social support(aOR=0.979,95％CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95％CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P＜0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P＜0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.

Objective To Investigate the efficacy of modified electroconvulsive therapy(MECT)in patients with schizophrenia across different genders.Methods From May 2018 to August 2022,481 patients with schizophrenia were recruited from three psychiatric hospitals in Luzhou,Zigong,and Yibin.According to gender grouping,both groups received adjunctive MECT treatment for two consecutive weeks for a total of six treatments.The differences in positive and negative syndrome scale(PANSS)scores before and after treatment,UKU adverse reaction rating scale(UKU),and gastrointestinal symptom rating scale(GSRS)scores were compared between the two groups.Results After quality control,463 cases were followed up for analysis including 246 males and 217 females.Compared with pre-treatment,the total PANSS score and scores on each subscale were significantly reduced in both genders after treatment(P<0.001).When comparing the reduction rates between the groups,the male patients showed a higher reduction rate in negative symptoms than the female patients(31.24%±30.24%vs.25.80%±33.96%,P<0.05).However,there were no significant differences between the two groups in the reduction rates of the total score,positive symptoms,and general psychopathology(P>0.05).The comparison of adverse reactions showed that the frequency of other types of adverse reactions was higher in female patients than in male patients(47.47%vs.37.80%,P<0.05).However,no significant differences were observed in the adverse reactions related to the mental,neurological,autonomic nervous system,and gastrointestinal systems(P>0.05).Correlation analysis revealed that the reduction rate of the PANSS total score was positively correlated with smoking history(r=0.135,P=0.034)and alcohol history(r=0.160,P=0.012)in male patients,while the reduction rate of the PANSS total score was negatively correlated with the disease duration(r=-0.210,P=0.002)and positively correlated with the age of onset(r=0.145,P=0.032)in female patients.Conclusion MECT is significantly effective for both male and female patients with schizophrenia.Compared to female patients,MECT shows a more pronounced effect on negative symptoms in male patients.Additionally,the factors related to the efficacy of MECT differ between genders,indicating that it is necessary to consider the clinical characteristics of patients comprehensively when selecting an MECT treatment plan.

Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

Objective To explore the effect of different pontic designs in resisting stress interruption effect and roller coaster phenomenon through three-dimensional finite element analysis,providing clinical guidance for the application of clear aligners in extraction cases.Methods Four three-dimensional finite element models of different pontic designs in the extraction area of clear aligners were established,including the pontic-free connection design,the conventional hollow pontic design,the partially solid-filled pontic design and the fully solid-filled pontic design.All four aligner models were individually assembled with the dental arch model.A 0.2 mm distal movement of the canine was simulated to observe the initial displacement and periodontal ligament stress distribution of canine and second premolar in each group of models.Results The initial displacement tendency diagram revealed that in all experimental conditions,both the canine and second premolar exhibited tipping movement patterns.However,significant variations in initial displacement magnitudes were observed across different pontic designs.The fully solid-filled pontic-connected clear aligner model exhibited the greatest initial displacement values(both crown and root)and the maximum initial displacement magnitude.Notably,this kind of design displayed movement characteristics closer to bodily movement,indicating superior control efficacy in tooth positioning.Periodontal ligament stress analysis revealed that the fully solid-filled pontic-connected clear aligner model generated the highest maximum principal stress in the periodontal ligament.Conclusion This three-dimensional finite element study reveals that the application of solid-filled pontic in clear aligner therapy could improve biomechanical control at extraction sites by minimizing aligner distortion,reducing stress interruption effect and preventing the roller coaster phenomenon.