ObjectiveTaking classical herbal pair compatibility research as the entry point， this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine （TCM） formula Zhizi Houpotang， and to elucidate its antidepressant mechanism， with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 （NLRP3）/gasdermin D （GSDMD） signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group， a chronic unpredictable mild stress （CUMS） depression model group， a Zhizi Houpotang full-formula group （6 g·kg^-1·d^-1）， a Magnoliae Officinalis Cortex （MOC）-Aurantii Fructus Immaturus （AFI） herbal pair group （4.2 g·kg^-1·d^-1）， a Gardeniae Fructus （GF）-MOC herbal pair group （4.2 g·kg^-1·d^-1）， a GF-AFI herbal pair group （3.6 g·kg^-1·d^-1）， and a positive drug group （fluoxetine， 12 mg·kg^-1·d^-1）. Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 （Ibal） and the purinergic receptor P2X ligand-gated ion channel 7 （P2RX7） in the prefrontal cortex （PFC）. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of inflammatory cytokines interleukin-1β （IL-1β） and interleukin-18 （IL-18） in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 （Panx1）， P2RX7， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， GSDMD， postsynaptic density protein 95 （PSD95）， and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group， the depression model group exhibited significant depressive-like behaviors. In addition， the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased （P<0.01）， the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated （P<0.01）， and the protein expression levels of Panx1， P2RX7， NLRP3， ASC， Caspase-1， and GSDMD in the PFC were significantly upregulated （P<0.01）. In contrast， the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated （P<0.01）， and neuronal dendritic spine density was significantly reduced （P<0.01）. Compared with the model group， the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators （P<0.01）. The GF-AFI herbal pair group improved all the above indicators except P2RX7， Caspase-1， GSDMD， and PSD95 （P<0.05， P<0.01）. In contrast， the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair， GF-MOC， can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling， thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously， it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density， promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula， and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.

Atherosclerosis （AS） is a vascular disease primarily affecting large and medium-sized arteries. It serves as the pathological basis for many cardiovascular and cerebrovascular diseases and is associated with a relatively high incidence of complications and mortality worldwide. Traditional Chinese medicine （TCM） plays an important role in the prevention and treatment of AS， demonstrating unique therapeutic advantages through multiple targets and pathways. Ligusticum chuanxiong， a commonly used Chinese medicine in clinical practice， contains key active components against AS， including ligustrazine， senkyunolide， ligustilide， quercetin， ferulic acid， vanillic acid， chlorogenic acid， gallic acid， protocatechuic acid， caffeic acid， chrysophanol， and β-sitosterol. Recent literature indicates that these active components can regulate AS through multiple mechanisms， including improving endothelial cell dysfunction， alleviating lipid metabolism disorders， inhibiting macrophage foam cell formation， suppressing the invasion， proliferation， and migration of smooth muscle cells， inhibiting apoptosis， exerting anticoagulant effects and inhibiting platelet activation， protecting mitochondrial function， and modulating intestinal flora and its metabolites， demonstrating significant pharmacological activity and clinical potential. Clinically， L. chuanxiong is often combined with Salvia miltiorrhiza， Paeonia lactiflora， Angelica sinensis， and borneol to form compound formulations， enhancing therapeutic effects and achieving synergistic anti-AS activity. Compound treatment with L. chuanxiong primarily focuses on promoting blood circulation and shows significant efficacy for different AS syndrome types. This article provides an in-depth review of the active components， drug pairs， and compound preparations of L. chuanxiong in the prevention and treatment of AS， aiming to lay a foundation for subsequent theoretical research and clinical applications in managing AS and its related complications.

ObjectiveTo investigate the status of overlapping hepatitis B virus （HBV） infection in patients with chronic hepatitis C virus （HCV） infection and the serological characteristics of such patients. MethodsA total of 8 637 patients with HCV infection who were hospitalized from January 1， 2010 to December 31， 2020 and had complete data of HBV serological markers were enrolled， and the composition ratio of patients with overlapping HBV serological markers was analyzed among the patients with HCV infection. The patients were divided into groups based on age and year of birth， and serological characteristics were analyzed， and the distribution of HBV-related serological characteristics were analyzed across different HCV genotypes. ResultsThe patients with HCV/HBV overlapping infection accounted for 5.85%， and the patients with previous HBV infection accounted for 48.10%； the patients with protective immunity against HBV accounted for 14.67%， while the patients with a lack of protective immunity against HBV accounted for 31.39%. The patients were divided into groups based on age： in the 0 — 17 years group， the patients with protective immunity against HBV accounted for 61.41% （304 patients）； the 18 — 44 years group was mainly composed of patients with previous HBV infection （698 patients， 37.31%）， the 45 — 59 years group was predominantly composed of patients with previous HBV infection （1 945 patients， 50.38%）， and the ≥60 years group was also predominantly composed of patients with previous HBV infection （1 486 patients， 61.66%）. The patients were divided into groups based on the year of birth： in the pre-1992 group， the patients with previous HBV infection accounted for 51.63% （4 112 patients）； in the 1992 — 2005 group， the patients with protective immunity against HBV accounted for 54.72% （168 patients）； in the post-2005 group， the patients with protective immunity against HBV accounted for 64.38% （235 patients）. In this study， 6 301 patients underwent HCV genotype testing： the patients with genotype 1b accounted for the highest proportion of 51.71% （3 258 patients）， followed by those with genotype 2a （1 769 patients， 28.07%）， genotype 3b （63 patients， 1.00%）， genotype 3a （10 patients， 0.16%）， genotype 4 （21 patients， 0.33%）， and genotype 6a （5 patients， 0.08%）. ConclusionWith the implementation of hepatitis B planned vaccination program in China， there has been a significant reduction in the proportion of patients with previous HBV infection among the patients with HCV/HBV overlapping infection， but there is still a relatively high proportion of patients with a lack of protective immunity against HBV.

Objective To investigate the current distribution and predict the future suitable habitats of Haemaphysalis longicornis in Nanjing City, so as to provide insights into control and early warning of ticks and management of tick-borne diseases in Nanjing City. Methods The electronic map of Nanjing City was obtained from the National Platform for Common GeoSpatial Information Services. The distribution of H. longicornis and the longitude and latitude of distribution points from 2022 to 2024 were obtained from centers for disease control and prevention across each district in Nanjing City. Climatic and environmental variable data in Nanjing City were captured from the Worldclim database. Initially, 19 bioclimatic variables in this database were selected, including annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the warmest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter. The elevation and normalized difference vegetation index were obtained from Data Sharing Platform of the Center for Resources and Environmental Sciences, Chinese Academy of Sciences. Then, the distribution points of H. longicornis, elevation, vegetation index and 19 bioclimatic variables were loaded into the software MaxEnt 3.4.4 to evaluate and screen out the variables with a contribution rate of 1% and higher. ArcGIS 10.8.1 software was used to extract the elevation, vegetation index and 19 bioclimatic variables of the distribution points of H. longicornis for a correlation analysis. If the absolute value of the correlation coefficient was 0.8 and higher, the variable with the higher contribution was retained. The 2050 dataset of the BCCCSM2-MR atmospheric circulation model in the coupled model intercomparison project phase 6 (CMIP6) were obtained from the Worldclim database as climate data for 2050. Screened H. longicornis species data and environmental and climate data were loaded into the maximum entropy (MaxEnt) model with the software MaxEnt 3.4.4 for training and validation, and then, all data generated from the model were imported into the software ArcGIS 10.8.1 to generate raster data and yield the map pertaining to the distribution of H. longicornis risk in Nanjing City. The accuracy of the model was evaluated with a receiver operating characteristic (ROC) curve, and the predictive effect of the model was assessed with area under the ROC curve (AUC). The suitable habitats of H. longicornis were classified in Nanjing City with the software ArcGIS 10.8.1, and the areas of distribution of suitable habitats in various categories were recorded to create the map of current H. longicornis suitable habitats classification in Nanjing City. The climatic and geographic information data in 2050 were employed as future environmental and climatic factors, and current environmental and climatic factors and current H. longicornis distribution data were additionally used to predict the future suitable habitats of H. longicornis in Nanjing City. In addition, the contributions of environmental and climatic factors to distribution of suitable habitats of H. longicornis was evaluated with the Jackknife method in Nanjing City. Results A total of 10 environmental and climatic variables were screened for analysis of the suitability of H. longicornis in Nanjing City based on correlation analyses and contributions of the MaxEnt model, including annual mean temperature, precipitation of the warmest quarter, vegetation index, precipitation of the wettest month, temperature annual range, annual precipitation, mean temperature of the warmest quarter, elevation, mean temperature of the wettest quarter, and maximum temperature of the warmest month, and annual mean temperature (34.8%), precipitation of the warmest quarter (17.3%), vegetation index (13.1%), and precipitation of the wettest month (10.8%) contributed relatively highly to the distribution of suitable habitats of H. longicornis in Nanjing City. The mean AUC of the ROC curve was 0.810 ± 0.055 for 10 repeated modeling results of the MaxEnt model, indicating high predictive performance of the model. The potential distribution areas of H. longicornis were predicted to be mainly located in Luhe District, Pukou District, Jiangning District, Lishui District, and Gaochun District in Nanjing City with the MaxEnt model. Under current climatic conditions, the area of potential suitable habitats of H. longicornis was 4 182.42 km² in Nanjing City, including 1 252.94 km² highly suitable habitats, which accounted for 19.00% of the total area of Nanjing City. Under the climate scenario in 2050, the area of potential suitable habitats of H. longicornis was projected to increase to 5 467.58 km² in Nanjing City, accounting for 82.95% of the total area of the city, and these habitats were mainly concentrated in Luhe District, Pukou District, Jiangning District, Lishui District, and Gaochun District. The areas of suitable habitats of H. longicornis at various categories were predicted to vary greatly in 2050, and the area of highly suitable habitats of H. longicornis was projected to increase to 2 378.82 km², accounting for 36.08% of the total area of Nanjing City. Based on jackknife tests and contributions of environmental and climatic variables, 6 dominant environmental and climatic factors were screened, including annual mean temperature (34.8% contribution), precipitation of the warmest quarter (17.3% contribution), vegetation index (13.1% contribution), precipitation of the wettest month (10.8% contribution), temperature annual range (5.4% contribution), and mean temperature of the warmest quarter (5.0% contribution), with cumulative contributions of 86.4%. Conclusion The distribution of H. longicornis is strongly associated with vegetation, temperature and precipitation in Nanjing City. Future climate change may lead to an expansion of the distribution area of H. longicornis in Nanjing City.

Background Pyrethroid pesticides (PYRs) can cross the placental barrier to cause intrauterine fetal exposure, which may lead to developmental immunotoxicity (DIT). However, the specific effect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. Objective To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. Methods A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites, including 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid (cis-DBCA), in the urine of pregnant women during the first trimester (gestational weeks 6-12), the second trimester (gestational weeks 21-24), and the third trimester (gestational weeks 33-36). Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry. Exposure levels of PYRs metabolites in each trimester were divided into low, moderate, and high exposure groups based on the 25th (P₂₅) and 75th (P₇₅) percentiles. Meanwhile, participants were classified as having repeated high or low exposure if their metabolite levels were > P₇₅ or <P₂₅ in at least two trimesters, respectively, while all others were categorized as having repeated moderate exposure. Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell (WBC) and lymphocyte counts in children aged 1 year. Results A total of 336 mother-child pairs were included in this study. For the pregnant women, the total detection rates of maternal urinary 3PBA, 4F3PBA, and cis-DBCA across the three trimesters of pregnancy were 80.5%, 100.0%, and 81.3%, respectively; and median creatinine-corrected concentrations were 0.24, 0.36, and 0.42 μg·g⁻¹, respectively. In children aged 1 year, the mean WBC and lymphocyte counts in peripheral blood were (8.9±2.0)×10⁹·L⁻¹ and (5.7±1.6)×10⁹·L⁻¹, respectively. The results of the generalized linear model analysis indicated that compared to the low exposure group, the high cis-DBCA exposure group during the third trimester of pregnancy had significantly lower peripheral blood WBC count (β=−0.87, 95%CI: −1.51, −0.23) and lymphocyte count (β=−0.64, 95%CI: −1.15, −0.13); and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count (β=−1.34, 95%CI: −2.34, −0.34) and lymphocyte count (β=−0.80, 95%CI: −1.60, −0.01) than the repeated low exposure group. Similarly, the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count (β=−0.83, 95%CI: −1.59, −0.07) than the repeated low exposure group. Conclusion High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year, and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring. The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during pregnancy.

Objective To investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

Objective To explore the effect of Osthole on neuroinflammation in Alzheimer's disease(AD)by regulating the lactylation of pyruvate kinase M2(PKM2).Methods(1)Animal experiments:18 mice were divided into three groups,namely wild-type(WT)group,APP/PS1 group and APP/PS1+Osthole group.Learning-and memory-related biobehavioral indicators were compared among the three groups.Immunohistochemistry was used to detect the positive expression of Iba1 in brain tissue,enzyme-linked immunosorbent assay(ELISA)was employed to detect the levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β in brain tissue,and Western Blot was used to detect the protein expression levels of Pan lactylation(Pan-kla)and PKM2 lactylation(PKM2-kla)in brain tissue.(2)Cell experiments:an in vitro AD model was constructed by treated in mouse microglia(BV2 cells)with LPS/Aβ1-42,and followed by treatment with Osthole.Cell viability was detected by methyl thiazolyl tetrazolium(MTT),expression of Iba1(a marker of microglial activation)was detected by Western Blot,nitric oxide(NO)production was assessed by Griess reagent,and levels of IL-6,TNF-α and IL-1β were detected by ELISA.BV2 cell-conditioned medium(CM)was co-cultured with neuroblastoma cells(Na2 cells)to assess the protective effect of Osthole on Na2 cells.(3)Molecular docking was performed between Osthole and PKM2,and experimental verification was conducted.Results In animal experiments,deficits of learning and memory in mice were aggravated in APP/PS1 group compared with that in WT group,which were improved upon treatment with Osthole.Furthermore,the APP/PS1 group mice showed an increase in Iba1 positive cells in brain tissue,an increase in the levels of pro-inflammatory factors IL-6,TNF-α and IL-1β,as well as an increase in the levels of Pan-kla and PKM2-kla compared with the WT group,while the above indexes were inhibited by the Osthole treatment.In cell experiments,Osthole had no significant effect on BV2 cell viability at concentrations up to 100 μmol/L.Treatment with LPS/Aβ1-42 upregulated the expression of Iba1,NO production,and levels of pro-inflammatory factors IL-6,TNF-α,and IL-1β in BV2 cells,while Osthole significantly inhibited the expression of these LPS/Aβ1-42-induced indicators.Meanwhile,Osthole attenuated the damage of BV2-CM on Na2 cells.The molecular docking results indicated a good binding affinity between Osthole and PKM2.Treatment with Osthole can down-regulated the levels of lactate,Pan-kla and PKM2-kla in the AD cell model.Conclusion Osthole can improve the condition of AD and reduce neuroinflammation by inhibiting the lactylation of PKM2.

Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.