ObjectiveTo investigate the mechanism by which Shenqi Yiliu prescription reverses cisplatin resistance in ovarian cancer cells by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway-mediated glycolysis. MethodsThe human ovarian cancer A2780 cell line was intervened with progressively increasing doses of cisplatin （1 g·L^-1） to establish the cisplatin-resistant cell line A2780cisR， and the cell sensitivity to cisplatin was examined by the cell counting kit-8 （CCK-8） assay. High， medium， and low （39.9， 19.95， 9.98 g·kg^-1） doses of Shenqi Yiliu prescription-containing sera were used to treat A2780cisR cells for 48 h. Glucose consumption and lactate production were measured by the cuvette assay. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the activities of glucose transporter （GLUT）， phosphofructokinase （PFK）， and pyruvate kinase （PK）. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was used to detect apoptosis. Western blot was employed to quantify the protein levels of phosphorylated （p）-PI3K， p-Akt， p-mTOR， hexokinase 2 （HK2）， pyruvate kinase M2 （PKM2）， B-cell lymphoblastoma-2 （Bcl-2）， Bcl-2-associated X-protein （Bax）， and B-lymphoblastoma-2 gene-related promoter （Bad）. Real-time PCR was conducted to determine the mRNA levels of HK2， PKM2， Bax， Bcl-2， and Bad. ResultsThe median inhibitory concentration （IC₅₀） of cisplatin on A2780cisR cells was nearly 3 times that on A2780P cells. Compared with A2780P cells， A2780cisR cells showed increased glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax （P<0.05）， and decreased apoptosis rate and Bcl-2 expression （P<0.05）. Compared with A2780cisR cells， medium- and high-dose Shenqi Yiliu prescription reduced the glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax， and Bad （P<0.05）， while increasing the apoptosis rate and Bcl-2 expression （P<0.05）. ConclusionShenqi Yiliu prescription can inhibit glycolysis mediated by the PI3K/Akt/mTOR pathway to promote apoptosis， thereby reversing cisplatin resistance in ovarian cancer cells.

Osteoporosis is a systemic disease, and epidemiological projections indicate that by 2050, approximately 23.43% of the Chinese population over 50 years of age will be affected. Given the poor prognosis associated with osteoporosis, the exploration of safe and effective natural products is of considerable significance. Studies investigating the chemical constituents of traditional Chinese medicine in cellular and/or animal models have demonstrated bone-protective effects. Although most of these compounds lack clinical data, they hold considerable potential as lead candidates for drug development. In-depth study of the structure-activity relationship of these natural products not only contributes to elucidating the mechanisms of action but also provides a theoretical basis for the development of novel antiosteoporosis therapies. This review summarizes natural products with potential antiosteoporotic effects reported between 2020 and 2024. Overall, plant-derived natural compounds exhibit antiosteoporotic effects by regulating bone remodeling, inflammation, and oxidative stress, highlighting their promise as multitarget therapeutic candidates.

Kynurenine pathway (KP) is a major catabolic route of tryptophan, generating a series of bioactive metabolites including kynurenine, kynurenic acid (KA), quinolinic acid, and 3-hydroxykynurenine. Beyond its fundamental role in amino acid metabolism, KP exerts critical regulatory functions in neurodevelopment, synaptic plasticity, and immune modulation. Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with onset in early childhood, characterized by persistent deficits in social communication and restricted, repetitive behaviors. Despite extensive research, the etiological mechanisms underlying ASD remain highly complex and incompletely understood, involving genetic, environmental, and immunological factors. Emerging clinical evidence has consistently revealed a significant imbalance in KP metabolites in individuals with ASD, often accompanied by altered ratios of neuroprotective versus neurotoxic byproducts. However, the primary drivers of this metabolic dysregulation and its causative contribution to ASD pathogenesis are not yet fully elucidated. In this review, we systematically review the enzymatic steps of KP and the principal physiological functions of its major metabolites, with particular emphasis on their dual roles in neuroprotection and neurotoxicity. We then analyze the potential pathogenic mechanisms through which KP dysfunction may contribute to ASD, focusing on two interconnected etiological dimensions. First, KP imbalance can promote oxidative stress, which in turn triggers chronic inflammatory responses via microglial activation and release of pro-inflammatory cytokines, thereby disrupting neuronal homeostasis. Second, aberrant KP metabolism affects neurotransmitter systems, particularly glutamatergic and dopaminergic signaling, leading to impaired neural circuit development and synaptic pruning. By integrating current findings on the KP-ASD association, this review offers a comprehensive etiological framework and a clinically relevant paradigm. Furthermore, we highlight that specific KP metabolites, such as the KA/quinolinic acid ratio, hold promise as peripheral biomarkers for early diagnosis and disease stratification. Finally, we discuss the therapeutic potential of targeting KP enzymes or receptors for personalized intervention strategies, while acknowledging the challenges in translating these findings into clinical practice.

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

Objective To explore the correlation between the systemic immune-inflammation index(SII)and the clinical and pathological characteristics of patients with IgA nephropathy(IgAN).Methods A total of 350 patients who underwent renal biopsy and were initially diagnosed with primary IgAN were selected.The clinical and pathological data of the patients were collected,and SII was calculated.According to the median SII level of 554.78 in peripheral blood,the IgAN patients were divided into the low SII group(SII≤554.78,175 cases)and the high SII group(SII>554.78,175 cases).Based on the presence or absence of endocapillary hyperplastic(E)lesion,350 patients were also divided into the E0 group(279 cases,79.7%)and the E1 group(71 cases,20.3%).Multivariate Logistic regression analysis was conducted to determine the influencing factors of E1 in IgAN patients.A predictive model was established,and the predictive value of the model was evaluated using the receiver operating characteristic(ROC)curve.Results There were higher systolic blood pressure(SBP),platelet count(PLT),neutrophil count(NEU),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),total cholesterol(TC),serum creatinine(Scr),serum C3 and 24-hour urine protein levels in the high SII group than those of the low SII group,while the lymphocyte count(LYM)was lower(P＜0.05).In terms of pathological manifestations,the proportion of E1 was higher in the high SII group than that of the low SII group(P＜0.05).There were lower PLT,NEU,NLR,PLR,Scr and 24-hour urine protein in patients of the E0 group than those of the E1 group,while higher Hb,LYM and ALB levels in the E0 group than those of the E1 group(P＜0.05).Multivariate Logistic regression analysis showed that elevated SII,Scr and 24-hour urine protein levels were independent risk factors for E1 lesion in IgAN patients(P＜0.05).The area under the curve(AUC)of the predictive model for E1 lesion in IgAN patients was 0.781(95%CI:0.722-0.840).Conclusion SII can reflect the clinical and pathological severity in IgAN patients,providing new insights for clinical evaluation of the disease progression in IgAN patients.

Objective:To investigate the pattern of Mesothelin(MSLN)-specific T-cell(CTLs)immune reconstitution after allogeneic hematopoietic stem cell transplantation.Methods:Two cases of Mesothelin-positive patients with acute myeloid leukemia(AML)were screened,and the number of MSLN-CTLs and its subpopulations,the expression of surface PD-1/CTLA-4/TIM-3 im-mune exhaustion molecules,and the functions of secreted cytokines TNF-α and IFN-γ were monitored by flow cytometry after trans-plantation.They were compared with WT1-CTLs and cytomegalovirus(CMV)CTLs.Meanwhile,the relationship between CTL recon-stitution and Minimal residual disease(MRD)and leukemia recurrence was analyzed.Results:After transplantation,MSLN-CTLs,WT1-CTLs and CMV-CTLs can be detected,and intracellular factors were secreted.The phenotypes of WT1 specific CD8+T cells,MSLN specific CD8+T cells and CMV specific CD8+T cells were mainly TEM subsets and TEMRA subsets,and the TEM subsets of CMV specific CD8+T cells were more obvious.Compared with CMV-CTLs,the proportions of T Naive,TCM and TEMRA subsets were relatively higher in MSLN-specific CD8+T cells and WT1-specific CD8+T cells,and the expression levels of PD-1,CTLA-4 and TIM-3 were higher in MSLN-CTLs and WT1-CTLs.The dynamic changes of MSLN-CTLs and WT1-CTLs after transplantation were related to leukemia load and the chimerism rate of donor and recipient.Conclusion:After allogeneic hematopoietic stem cell transplantation,im-mune recovery to MSLN is found,which is different from WT1-CTLs and CMV-CTLs.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree affected with Primary ciliary dyskinesia (PCD). METHODS: A child who presented at the ENT Department of Zhengzhou University Children's Hospital in March 2024 due to secretory otitis media, chronic sinusitis, adenoid hypertrophy, dextrocardia, and bronchiectasis was selected as study subject. Relevant clinical data were collected. Peripheral blood samples from the child and her family members were collected. Following DNA extraction, whole exome sequencing was carried out. Candidate variants were validated by Sanger sequencing, and the correlation between the variants and phenotype was analyzed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-K-135). RESULTS: The child and her elder siblings exhibited similar clinical manifestations including recurrent cough, secretory otitis media, chronic sinusitis, tracheobronchitis, and pneumonia. The child also presented with bronchiectasis and visceral situs inversus. Genetic testing results indicated that the child and her elder siblings had all harbored compound heterozygous variants of the DNAH11 gene, namely c.3000 1G>A and c.5775C>G (p.Tyr1925*), which were respectively inherited from their phenotypically normal parents. Both variants can affect mRNA splicing and protein translation integrity. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic. It was predicted that they may jointly lead to a functional defect in axonemal dynein, resulting in the phenotype of PCD, conforming to an autosomal recessive inheritance. CONCLUSION The compound heterozygous variants c.3000 1G>A and c.5775C>G (p.Tyr1925*) of the DNAH11 gene probably underlay the pathogenesis of PCD in this pedigree. The same variant in different individuals may lead to different clinical phenotypes, which has reflected significant heterogeneity in genetic background and clinical phenotype. Above findings have enriched the mutational spectrum of PCD gene and have important implications for the accurate diagnosis, treatment, prognosis, and genetic counseling.
Humans ; Pedigree ; Female ; Axonemal Dyneins/genetics* ; Male ; Child ; Asian People/genetics* ; Kartagener Syndrome/genetics* ; Mutation ; Phenotype ; China ; Adult ; East Asian People

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.