BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

The prevalence of allergic diseases is increasing year by year.The phenotype of allergic diseases changes in stages as children age，following an allergic march from atopic dermatitis，food allergy in infancy to allergic rhinitis and allergic asthma in school age.Common influences on the development of allergic diseases include genetics，environment，and diet.Reducing the risk of developing new allergic diseases during the allergic march is one of the goals of prevention.It has now been found that diet during pregnancy may affect the foetal immune response，and that the early addition of complementary foods and increased dietary diversity may influence the development of allergic diseases in children.This article provides a review of the impact of dietary interventions early in life on the allergic march in children.

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Acute kidney injury(AKI)is characterized by high morbidity,high mortality,high disability rate and high treatment cost,its pathological mechanism has not been fully elucidated and there is a lack of ef-fective treatment methods.Klotho,a kidney-specific protective protein,is mainly expressed in renal tubular ep-ithelial cells,regulates the AKI progression and mitigates the renal injury through multiple pathways,inclu-ding the regulation of the renin-angiotensin-aldosterone system(RAAS),antioxidant stress,anti-inflamma-tion,modulation of cell death and anti-fibrotic effects.At present,the Klotho-based strategies for AKI preven-tion and treatment remain in the preclinical stage,requiring further investigation.This article reviews the mo-lecular regulatory mechanisms of Klotho in AKI and its diagnostic and therapeutic potential,aiming to provide new idea for the pathological mechanisms and clinical translation of AKI.

Objective:To establish the ultra high performance liquid chromatography (UPLC) fingerprints of Mume flos at different flowering stages; To provide reference for the quality research of Mume flos.Methods:The fingerprints of Mume flos were established by UPLC method, and the common peaks were identified by high performance liquid chromatography high resolution mass spectrometry (LC-MS). Chemometrics analysis was carried out with the fingerprints' common peak area of plum blossom at different flowering stages as a variable. Semiquantitative analysis of changes in flavonoids and phenolic acids in Mume flos at different flowering stages was conduct using peak area calculation method.Results:Totally 31 common peaks were identified in the fingerprints of plum blossom medicinal materials at different flowering stages and 9 components were identified. Clustering analysis (HCA) and principal component analysis (PCA) both classified plum blossom medicinal herbs at different flowering stages into three categories. Among them, there were significant differences between the groups at the bud stage, blooming period, and final flowering period, while the differences between the groups at blooming period and final flowering period were relatively small. The orthogonal partial least squares discriminant analysis (OPLS-DA) screened 16 different components with VIP>1.0. The contents of phenolic acids in different flowering stages were as follows: bud stage>blooming period>final flowering period, while the contents of flavonoids were as follows: blooming period>final flowering period>bud stage.Conclusions:This method is simple and reliable, and can provide reference for the quality evaluation of plum blossom medicinal materials at different flowering stages.

Objective To investigate the effect of Xinma Granules on respiratory mucosal immune function in chronic asthmatic mice.Methods Fifty female BALB/C mice were randomly divided into normal group,model group,low-dose Xinma Granules group,high-dose Xinma Granules group and Dexamethasone group,with 10 mice in each group.Except for the normal group,the mice in the other groups were sensitized and challenged with ovalbumin(OVA)to establish a chronic asthma model.After corresponding treatment,the levels of secretory immunoglobulin A(sIgA)and immunoglobulin E(IgE)in bronchial lavage fluid were measured by enzyme-linked immunosorbent assay(ELISA).The pathological changes of lung tissue were observed by hematoxylin-eosin(HE)staining.The expression of E-cadherin in lung tissue was detected by Western Blot.Results HE staining showed obvious airway inflammation in asthmatic mice.The concentration of sIgA in the bronchial lavage fluid of the model group was lower than that of the normal group(P＜0.05);the concentration of sIgA in the high-dose and the low-dose of Xinma Granules groups and the Dexamethasone group was higher than that in the model group(P＜0.05);the concentration of IgE in bronchial lavage fluid of model group was higher than that of normal group(P＜0.05);the concentration of IgE in the high-dose and the low-dose Xinma Granules groups and the Dexamethasone group was lower than that in the model group(P＜0.05).The relative expression of E-cadherin protein in lung tissue of the model group was lower than that of the normal group(P＜0.05);the relative expression of E-cadherin protein in lung tissue of mice in the high-dose and low-dose Xinma Granules groups and Dexamethasone group was higher than that in model group(P＜0.05).The improvement effect on above various indexes in high-dose Xinma Granules group and Dexamethasone group were superior to that in low-dose Xinma Granules group(P＜0.05),the differences between the both groups were statistically insignificant(P＞0.05).Conclusion Xinma Granules may improve the airway mucosal immune function of asthmatic mice by improving airway inflammation,increasing the concentration of sIgA in the respiratory tract,and enhancing the expression of E-cadherin protein in the respiratory tract.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the safety and efficacy of thoracic radiotherapy (TRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy.Methods:Medical records of 56 patients with ES-SCLC who received thoracic radiotherapy after first-line platinum-based chemotherapy plus immunotherapy in Cancer Hospital Chinese Academy of Medical Sciences from January 2018 to December 2021 were retrospectively analyzed. The control group was not established for clinical causes. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were employed to identify prognostic factors using the Cox proportional hazards model. The cumulative incidence of local regional recurrence (LRR) was estimated using the Fine-Grey competing risks regression model.Results:Among 56 patients in our cohort, 47 patients received consolidative TRT (cTRT) before progression and 9 patients received salvage TRT after progression. The median follow-up time was 21 months (95% CI=19.8-22.2 months), the median OS was not reached, the median PFS was 9 months (95% CI=7.0-13.0 months), and the 1-year and 18-month OS rates were 84.9%, 62.1%. In the cTRT group, the 1-year and 18-month OS rates were 84.1%, 64.5%, with the median PFS of 10 months; 1-year and 18-month LRFS rates were 73.6% and 66.0%, respectively; the cumulative incidence of LRR at 1-year and 2-year were 24.9% and 30.8%, respectively. No other 4-5 grade adverse events (AE) were reported except 6 patients presenting with 4 grade hematologic toxicities. Three grade radiation esophagitis occurred in 3 patients (5%). Ten patients (18%) developed 1-2 grade treatment-related pneumonitis, including 5 (9%) patients with immune related pneumonitis and 5 (9%) patients with radiation pneumonitis. Conclusion:The application of TRT after first-line chemoimmunotherapy is safe and may has potential survival benefit for patients with ES-SCLC.