ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

The major components of Olaflur raw material were characterized using ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry(UPLC-Q-TOF/MS).The results revealed that cetyl amine fluoride(C16-AmF),octadecene amine fluoride(C18:1-AmF),and octadecyl amine fluoride(Olaflur)were the main components.The contents of C16-AmF,C18:1-AmF,and Olaflur in oral care products were determined via ultra performance liquid chromatography-charged aerosol detector coupled with solid-phase extraction(SPE-UPLC-CAD).The oral care sample was dispersed evenly with a 50%ethanol aqueous solution,and then vortexed with ethanol.The supernatant was collected by centrifugation,concentrated to near dryness,and redissolved with ultrapure water.The re-dissolved sample was loaded onto a Poly-Sery HLB Pro SPE column for purification and elution.The acetonitrile eluate was collected and concentrated to 1.0 mL.Finally,a prepared test solution was separated on a Thermo Acclaim Surfactant Plus chromatographic column(2.1 mm×150 mm,3 μm).Acetonitrile and 100 mmol/L acetic acid-ammonium acetate aqueous solution(pH=4.8)were used as the mobile phases for gradient elution.The flow rate was 0.3 mL/min and cloumn temperature was maintained at 40℃.The sample was detected using a charged aerosol detector,and quantified using an external standard method.The experimental results indicated that the three organic fluorinated amines showed good linear relationship in their respective concentration ranges.The correlation coefficients(r)were greater than 0.99.The limit of detection(LOD)and the limit of quantification(LOQ)of C16-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of C18:1-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of Olaflur were 3.0 μg/mL and 10.0 μg/mL,respectively.The spiked recoveries of the three organic fluorinated amines were 84.3%-104.2%,with relative standard deviations(RSDs)of 4.93%-5.82%.The 28 batches of commercial oral care samples were detected by this method and the results indicated that three organic fluorinated amines were detected in 18 samples and the total content were 22.2-11477.8 μg/g.This method had high sensitivity and good reproducibility.It was suitable for verifying the authenticity of the claims of oral care products promoted with Olaflur as the main efficacy ingredient and selling point,and provided a valuable reference for establishing and improving the standard analytical method for Olaflur.

In recent years,micro photoionization detectors(μPID),with their rapid response speed and excellent sensitivity,have attracted widespread attention in both scientific research and industry.This study developed a portable gas chromatograph based on μPID technology(GC-μPID),and examined its key performance characteristics such as reproducibility,sensitivity,and online analytical capability.The results showed that the method's relative standard deviation(RSD)was controlled within 2.7%,demonstrating good reproducibility;for the standard curves of 27 kinds of volatile organic compounds(VOCs),the linearity was excellent(R2≥0.99),with detection limits of≤10 μg/m3 and benzene series compounds reaching detection limits as low as 0.5 μg/m3.In field applications at an industrial park,this method successfully identified and quantified 17 kinds of VOCs,accurately capturing their diurnal concentration variations.The results above validated that the method developed here had the capability of onsite real-time monitoring and provided an effective tool for in situ monitoring atmospheric pollutants.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

Objective:To explore the efficacy of atezolizumab combined with anlotinib in treating advanced non-small cell lung cancer (NSCLC) .Methods:A total of 80 patients with advanced NSCLC treated in the Baoding No.2 Central Hospital from September 2019 to September 2023 after second-line treatment were selected as research subjects. Patients who received only anlotinib treatment were included in the monotherapy group ( n=40), while patients who received atezolizumab combined with anlotinib treatment were included in the combination group ( n=40). The clinical efficacy and serum levels of carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) of the two groups were compared. Kaplan-Meier survival curve was used to analyze the survival of the two groups. The functional assessment of cancer therapy-lung cancer (FACT-L) was used to assess the quality of life of patients in both groups before and after treatment. The incidence of adverse reactions was compared between the two groups. Results:After four cycles of treatment, the objective response rate (ORR) of the combination group was 37.50% (15/40), which was higher than that of the monotherapy group [17.50% (7/40) ], with a statistically significant difference ( χ2=4.01, P=0.045). The disease control rates (DCRs) of the two groups were 85.00% (34/40) and 75.00% (30/40), respectively, with no statistically significant difference ( χ2=1.25, P=0.264). Before treatment, the CEA levels in combination group and monotherapy group were (10.18±2.15) and (10.14±2.02) μg/L, and the VEGF levels were (804.04±46.58) and (809.10±43.63) ng/L, respectively, with no statistically significant difference (both P>0.05). After treatment, the serum CEA levels of patients in combination group and monotherapy group were (4.35±1.05) and (6.63±1.37) μg/L, and the VEGF levels were (431.26±50.19) and (549.92±55.27) ng/L, respectively, with statistically significant differences ( t=8.35, P<0.001; t=10.05, P<0.001), and the levels of serum CEA and VEGF in the two groups after treatment were lower than before treatment ( t=32.47, P<0.001; t=21.73, P<0.001; t=88.65, P<0.001; t=58.27, P<0.001). Survival analysis showed that the median progression-free survival (PFS) of the monotherapy group and the combination group were 4.12 and 6.06 months, respectively, with a statistically significant difference ( χ2=17.70, P<0.001), the median overall survival (OS) were 11.8 and 12.7 months, respectively, with no statistically significant difference ( χ2=3.09, P=0.079). Before treatment, the FACT-L scores of patients in combination group and monotherapy group were 61.20±6.98 and 60.52±7.14, respectively, with no statistically significant difference ( t=0.43, P=0.668). After treatment, the FACT-L scores of the two groups were 83.24±9.38 and 74.58±7.86, respectively, with a statistically significant difference ( t=4.48, P<0.001), and the FACT-L scores of the two groups after treatment were all higher than before treatment ( t=29.36, P<0.001; t=21.51, P<0.001). During treatment, the total incidence of drug-related adverse reactions in two groups was 42.50% (17/40) and 55.00% (22/40), respectively, with no statistically significant difference ( χ2=1.25, P=0.263) . Conclusions:Atezolizumab combined with anlotinib in the treatment of advanced NSCLC can enhance the short-term efficacy, prolong the PFS of patients, improve the quality of life, and the related adverse reactions are tolerable.

Objective To compare the efficacy and safety of computed tomography (CT)-guided percutaneous versus electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation (MWA) for the treatment of pulmonary nodules. Methods A retrospective analysis was conducted on the data of high-risk pulmonary nodule patients who underwent MWA at the Nanjing Drum Tower Hospital between 2022 and 2023. The pathological diagnosis rate, complications, and progression-free survival (PFS) rate were compared between the CT group and the ENB group. Results There were 61 patients in the CT group, including 30 males and 31 females, with an average age of (67.22±9.13) years. There were 53 patients in the ENB group, including 29 males and 24 females, with an average age of (65.29±13.76) years. The pathological diagnosis rate in the CT group was slightly higher than that in the ENB group (88.52% vs. 71.69%, P=0.03). However, the ENB group exhibited a lower incidence of perioperative complications, including pneumothorax (16.39% vs. 3.77%, P=0.03), hemoptysis (19.67% vs. 5.66%, P=0.05), and pain (22.95% vs. 7.55%, P=0.03). There was no statistically significant difference in PFS rate between the two groups [HR=1.17, 95%CI (0.23, 5.81), P=0.85]. Conclusion Both CT-guided and ENB-guided MWA are effective treatment modalities for high-risk pulmonary nodules.

Objective To observe the clinical efficacy of Fuyuan Capsules combined with Xingnao Kaiqiao acupuncture in the treatment of vascular dementia(VD),and to explore its possible mechanism of action.Methods A total of 204 cases of patients with a definitive diagnosis of VD admitted to the wards and outpatient clinics of Hengshui Hospital of Traditional Chinese Medicine from October 2019 to October 2022 were selected for the study.The patients were randomly divided into observation group and control group according to the random number table method,with 102 cases in each group.The patients in both groups were treated with symptomatic treatments such as blood pressure-controlling,glucose-lowering,blood lipids-regulating,along with cognitive function training.The control group was treated with Xingnao Kaiqiao acupuncture,and the observation group was given oral administration of Fuxing Capsules on the basis of the treatment in the control group.One week constituted a course of treatmen,and eight consecutive courses of treatment were carried out.After two months of treatment,the clinical efficacy of the two groups was evaluated.The changes in the scores of the Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA),Revised Hasegama's Dementia Scale(HDS-R),and Clinical Dementia Rating Scale(CDR)were observed in the patients of the two groups before and after treatment.The changes in the scores of the Activity of Daily Living Scale(ADL),Hachinski Ischemic Scale(HIS),and the traditional Chinese medicine(TCM)syndrome scores before and after treatment were compared in patients of the two groups.The changes in the expression level of neuregulin 1(NRG1)before and after treatment in patients of the two groups were detected.Results(1)During the study,two cases fell off from both groups,respectively.Finally,100 cases in the observation group and 100 cases in the control group were included in the efficacy statistics.(2)After treatment,the MMSE and MoCA scores of the patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the HDS-R and CDR scores of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(4)After treatment,the ADL and HIS scores of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(5)After treatment,the TCM syndrome scores of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(6)The total effective rate was 84.00％(84/100)in the observation group and 67.00％(67/100)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P＜0.05).(7)After treatment,the NRG1 levels of patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).Conclusion Fuyuan Capsules combined with Xingnao Kaiqiao acupuncture in the treatment of VD can significantly improve the clinical symptoms of patients,enhance the cognitive function,and effectively increase the serum NRG 1 level,so as to improve their quality of life.

The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.