Objective To investigate the biological activity of raddeanin A(RA) against nasopharyngeal carcinoma(NPC)and the molecular mechanism of anti-NPC mediated by ERK/MAPK signaling pathway.Methods CCK-8 assay was used to detect the inhibitory effect of RA on the growth of NPC cells. Bioinformatics was utilized to predict the targets of RA acting on NPC and their associated signaling pathways. The binding affinity between RA and core target was analyzed by molecular docking. Annexin V-FITC/PI, JC-1 staining, flow cytometry, combined with Western blot were used to further investigate the anti-proliferation mechanism of RA in NPC cells.Results RA effectively inhibited the proliferation of NPC cell lines 6-10B and 5-8F, with IC_(50)values of 5. 770 and 5. 068 ??mol/L, respectively. The pharmacological effects were primarily associated with cell apoptosis and the MAPK signaling pathway. The binding affinities between RA and core target proteins, such as MAPK1 and caspase 3, predicted through molecular docking, were less than-5 kcal/mol. RA induced apoptosis and mitochondrial membrane potential changes in 6-10B cells. The expression levels of apoptosis-related proteins, including cleaved PARP, cleaved caspase 3, and cleaved caspase 9, significantly increased(F = 229. 60, 136. 60 and 73. 67, P < 0. 001,< 0. 001 and < 0. 01, respectively). Additionally, the expression of the mitochondrial pathway-related protein Bax was marked-ly upregulated, while Bcl-2 expression was significantly downregulated(F = 47. 42 and 17. 54, P < 0. 001 and P < 0. 05,respectively). Furthermore, the expression levels of ERK/MAPK pathway-related proteins, including p-p90 RSK, p-ERK1/2,and p-MSK1, were significantly reduced(F = 106. 90, 27. 73 and 101. 50, P < 0. 05, < 0. 01 and < 0. 05, respectively).Conclusion RA regulates the ERK/MAPK signaling pathway, reduces mitochondrial membrane potential, triggers mitochondrial pathway to induce apoptosis, and then exerts the activity of inhibiting NPC cell proliferation.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Background: This study was performed to characterize the incidence, costs, and risk factors associated with renal and cardiovascular adverse outcomes following primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Patients with STEMI who underwent pPCI using iso-osmolar contrast were enrolled at 39 centers. The incidence of acute kidney injury (AKI) and major adverse renal and cardiovascular events (MARCE) was analyzed, as well as inpatient costs. Logistic regression analysis was performed to identify risk factors. Results: Among 2,293 patients, the incidence of AKI and MARCE within 72 hours post-pPCI was 4.14% (n = 95) and 4.40% (n = 101), respectively. AKI and/or MARCE were associated with systolic blood pressure (AKI: odds ratio [OR], 1.009; 95% confidence interval [CI], 1.000–1.018), hypertension (AKI: OR, 1.815; 95% CI, 1.133–2.906; MARCE: OR, 1.760;95% CI, 1.118–2.769), anterior wall infarction (AKI: OR, 1.895; 95% CI, 1.196–3.004; MARCE:OR, 1.939; 95% CI, 1.240–3.032), Killip class (AKI: OR, 1.465; 95% CI, 1.117–1.922; MARCE:OR, 1.467; 95% CI, 1.131–1.903), and serum creatinine (SCr; MARCE: OR, 1.006; 95% CI, 1.000–1.012). Hospitalization costs for patients with STEMI who developed AKI or MARCE were significantly higher than for those without AKI (9,595 ± 5,795 vs. 8,279 ± 3,872 USD, P = 0.003) or without MARCE (9,890 ± 5,616 vs. 8,255 ± 3,859 USD, P < 0.001). Conclusions In patients with STEMI undergoing pPCI with iso-osmolar contrast, the incidence of AKI and MARCE was associated with higher hospitalization costs. Systolic blood pressure, hypertension, anterior wall infarction, Killip class, and SCr were identified as risk factors for these outcomes.

Objective To analyze the status of willingness to participate in health science popularization (HSP) and its influencing factors among medical workers in Guangdong Province. Methods A total of 462 medical workers in Guangdong Province were recruited as the study subjects using a stratified convenience sampling method. The Questionnaire on Influencing Factors of Willingness to Participate in Health Science Popularization, developed by the research team, was used to investigate their willingness to participate in HSP and related variables, including previous communication experience, attitude, moral belief, descriptive norm, injunctive norm, self-efficacy, and social support. Hierarchical regression analysis was used to identify the influencing factors of willingness to participate in HSP. Results The median and 25^th and 75^th percentiles score of willingness to participate in HSP was 4.0 (3.8, 4.5), indicating a moderately high level of willingness. The HSP participation willingness score was positively correlated with scores for previous communication experience, attitude, moral belief, descriptive norm, injunctive norm, self-efficacy, and social support (Spearman correlation coefficients were 0.513, 0.384, 0.507, 0.533, 0.463, 0.556, and 0.435, respectively; all P<0.01). Hierarchical regression analysis showed that previous communication experience, moral belief, descriptive norm and self-efficacy positively predicted willingness to participate in HSP (all P<0.05). Medical workers in the non-Pearl River Delta region had lower willingness than those in the Pearl River Delta region for HSP participation (P<0.05). Conclusion There is still room for improving willingness for HSP participation among healthcare professionals in Guangdong Province. It is recommended to enhance self-efficacy through communication skills training, strengthen professional ethics education, foster a positive peer engagement atmosphere, and intensify resource support and capacity building for HSP in the non-Pearl River Delta region, to improve HSP participation willingness among medical workers in Guangdong Province.

OBJECTIVE To evaluate the quality of Lufu Pill （LFP）.METHODS The high-performance liquid chromatography （HPLC） fingerprint of LFP was established using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 Edition）， and similarity evaluation was performed. Hierarchical cluster analysis （HCA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed using SIMCA 14.1 software. The contents of strychnine， brucine， liquiritin， notoginsenoside R 1 ， ginsenoside Rg 1 ， ginsenoside Rb 1 ， licoricesaponin G 2 ， and ginsenoside Rd in 12 batches of samples were determined by the HPLC method.RESULTS A total of 26 common peaks were identified in the HPLC fingerprint of 12 batches of LFP samples， and eight common peaks were identified as strychnine （peak 3）， brucine （peak 4）， liquiritin （peak 6）， notoginsenoside R 1 （peak 7）， ginsenoside Rg 1 （peak 8）， ginsenoside Rb 1 （peak 15）， licoricesaponin G 2 （peak 17）， and ginsenoside Rd （peak 18）. The similarities of 12 batches of LFP samples were all greater than 0.90. The results of HCA and PCA both showed that the 12 batches of samples were divided into two categories： S2， S4-S6， and S12 were grouped into one category， while S1， S3， S7-S11 were grouped into another category. The upper control limits for Hotelling’s T 2 and DMod X were 16.631 and 1.578， respectively. The variable importance in projection values of ginsenoside Rg 1 （peak 8）， ginsenoside Rb 1 （peak 15）， peak 20， strychnine （peak 3）， peak 11， notoginsenoside R 1 （peak 7）， peak 2， peak 17， peak 13， peak 10， ginsenoside Rd （peak 18）， peak 23， peak 26， peak 21， and peak 24 were greater than 1.The content determination results showed that strychnine， brucine， liquiritin， notoginsenoside R 1 ， ginsenoside Rg 1 ， ginsenoside Rb 1 ， licoricesaponin G 2 ， and ginsenoside Rd were 0.005%-0.018%， 0.005%-0.010%， 0.050%-0.118%， 0.033%-0.073%， 0.132%-0.248%， 0.122%-0.242%， 0.021%-0.043%， and 0.016%-0.048%， respectively.CONCLUSIONS The established HPLC fingerprint and content determination method are accurate and reproducible， and can be used for the quality evaluation of LFP. Ginsenoside Rg 1 ， ginsenoside Rb 1 ， strychnine， notoginsenoside R 1 ， and ginsenoside Rd may be the differential components affecting its overall quality.

Objective: To analyze the whole genome characteristics of Salmonella in diarrhea cases in Hohhot City, so as to provide the evidence for the prevention and control of Salmonella infection and rational clinical use of antibiotics. Methods: Salmonella strains were isolated and identified from fecal specimens of acute diarrhea cases at sentinel hospitals for national foodborne disease surveillance in Hohhot City from 2021 to 2023. DNA was extracted for whole genome sequencing. Bioinformatics analysis based on the Microobench Pathogen Genome Analysis System was conducted to determine serotypes, multi-locus sequence typing (MLST), drug resistance genes, and virulence genes. Additionally, 60 Salmonella genomic sequences from different regions across China were downloaded from the NCBI Genome database. A phylogenetic tree was constructed based on core-genome MLST (cgMLST) to analyze the phylogenetic relationship between strains from Hohhot City and those from other regions of China. Results: From 2021 to 2023, a total of 42 Salmonella strains isolated in Hohhot City were classified into 12 serotypes. Salmonella Enteritidis ST11, Salmonella I 4,[5],12:i:- ST34, and Salmonella Typhimurium ST19 were identified as the dominant strains, represented by 13, 10, and 6 isolates, which accounted for 30.95%, 23.81%, and 14.29%, respectively. Seventy-seven drug resistance genes belonging to 12 classes were detected. Among them, 17 Salmonella strains carried amino acid substitutions in the fluoroquinolone resistance-determining region caused by mutations at the gyrA and parC loci. Virulence genes covered all stages of Salmonella pathogenesis, with a predominance of genes associated with adhesion. Phylogenetic tree analysis results revealed that the 42 Salmonella strains from Hohhot City were distributed across evolutionary branches A, B, C, D, and F. They clustered with 60 strains from other regions of China, suggesting potential cross-regional transmission. Conclusions Salmonella strains isolated in Hohhot City exhibited diverse serotypes, carried multiple drug resistance genes and virulence genes, and displayed high genetic diversity. These findings indicate a potential risk of cross-regional transmission, highlighting the need for enhanced surveillance and prevention measures.

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.

Objective To explore the spatiotemporal expression patterns of Patched 1(Ptch1)and insulin enhancer binding protein-1(Isl 1)in mouse embryonic foregut and their relationship with the early development of trachea-main bronchus.Methods The foregut of 60 mouse embryos at E9.5-12.5 was separated for the detection of Isl1 and sonic hedgehog(Shh)protein by Western blotting.Serial paraffin sections of 6 mouse embryos at E9.5-14.5 were taken for immunohistochemical staining and immunofluorescence double staining with Isl1,Ptch1,forkhead box protein A2(Foxa2),type Ⅱ collagen α1 chain(Col2a1)and α-smooth muscle actin(α-SMA),as well as HE staining and Masson staining.Results The expression trend of Isl1 and Shh in foregut endoderm at E9.5-12.5 was similar,and the peak of Shh expression was later than Isl1.The foregut developed into the trachea at E9.5-12.5,Ptch1 was expressed in the thickening and protrusion of the respiratory endoderm,the laryngal-tracheal groove and the solid cell cord,accompanied by the increase and aggregation of Isl1-positive mesenchymal cells,forming a characteristic pyramidal structure centered on the respiratory endoderm and the solid cell cord;The main bronchus appeared at E12.5-13.5,Ptch1 was only expressed in its lateral wall,accompanied by the accumulation of Isl1-positive mesenchymal cells;The trachea-main bronchial epithelium lost Ptch1 expression and the surrounding Isl 1-positive mesenchymal cells also decreased rapidly at E13.5-14.5.Co12a1-positive chondrocytes first appeared in the Isl1-positive mesenchymal area adjacent to the Ptch1-positive epithelium at E12.5;Col2a1-positive cartilage was nested within the Isl1-positive mesenchymic area in a"C"shape and expanded in a proximal-distal pattern at E12.5-13.5;Col2a1-positive cartilage extended to the dorsal trachea beyond the Isl1-positive mesenchyma and encircles α-SMA positive smooth muscle in a circular manner at E14.5.Conclusion The expression of Ptch1 in the foregut endoderm is involved in the development and morphogenesis of the trachea-main bronchus epithelium,and is closely related to the proliferation and aggregation of Isl1-positive mesenchyme in the trachea-main bronchial wall,Subsequently,they jointly determine the time,location and extent of airway cartilage.

Objective To investigate the anatomical and microscopic structures of interstitial fluid flow channels in the skin tissue of hand dorsum in human cadavers.Methods Totally 7 fresh cadavers within 12 hours post-mortem were included.MRI was used to observe the distribution of interstitial fluid flow from the first phalanx of the fingers to the wrist,precisely locating the flow channels.Based on imaging results,histological analyses were conducted to determine the histological characteristics of the flow channels.Furthermore,multi-immunofluorescence and microcomputed tomography(Micro-CT)techniques were employed to analyze the channels,and image post-processing was used to elucidate their anatomical structures at the microscopic level.Results After injecting a contrast agent into the first phalanx of ten finger specimens and applying repeated pressure,MRI image revealed centripetal long-range interstitial fluid flow along channels distinct from blood vessels and lymphatic vessels.Histological analysis and Micro-CT further confirmed that the flow primarily occurred within the fibrous connective tissue and adventitia of the skin.Conclusion The orderly fibrous connective tissue and adventitia in the skin form the interstitial fluid flow channels in the human hand dorsum skin,named as"stromal membrane channels"in the skin.