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.

Allergic diseases exhibited the characteristics of latent concealment and dynamic transmutation， which highly align with the pathogenic features of "latency and transformative change" described in the theory of latent pathogens. Based on the "latent pathogens with transformative potential" theory， this paper systematically explored the mechanisms of occurrence， transmission， and outcome of allergic diseases. It proposed that the insufficiency of kidney essence is the root cause enabling pathogens to lurk internally， leading to disease onset due to deficient healthy qi and lurking pathogens； the dysfunction of sanjiao serves as the pathway for pathogen stagnation， driving multi-system transmission； the accumulation of phlegm， stasis， and toxins constitutes the predicament of a protracted course， ultimately resulting in intractable pathological entanglement. Accordingly， a tiered intervention strategy is formulated，i.e. during the latency period， treatment should tonify the kidney and replenish essence to consolidate the foundation and halt the tendency of pathogens to lurk internally； during the transmission period， treatment should regulate sanjiao to intercept disease transmission and curb multi-system proliferation； during the protracted period， treatment should purge phlegm and resolve stasis to eliminate stubborn lesions， and break the vicious cycle of chronic accumulation and damage.

Traditional Chinese medicine （TCM）， through its multi-target and systematic regulatory effects， has demonstrated unique advantages in the treatment of gastric precancerous lesions （GPL）. At present， TCM theoretical research on GPL is mainly reflected in three aspects， the integration of macroscopic syndrome differentiation， the inflammation-carcinoma transformation mechanism， as well as the systematization and scientization of theoretical inheritance from famous TCM practitioners. High-quality evidence-based research findings serve as the foundation for clinical practice guidelines on GPL， and TCM has gained international academic recognition in the field of GPL prevention and treatment. Research on TCM mechanisms has yielded a series of important outcomes in the aspects of signaling pathways， gene expression regulation， cellular epigenetics， histone modification， and intestinal microecology. It is proposed that future research on GPL should focus on four key directions， establishing multi-omics data， exploring targeted intervention strategies on key regulatory nodes， advancing the standardization process of integrated traditional Chinese and western medicine prevention and treatment technologies， and constructing stratified screening and intervention platforms. The in-depth integration of TCM microcosmic mechanism of action with its macroscopic syndrome differentiation and treatment system， coupled with interdisciplinary research， will provide valuable references for the clinical treatment and scientific research of GPL.

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 underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Objective To investigate the mechanism by which SLC38A1 promotes hepatocellular carcinoma(HCC)progression through glutamine transport-mediated activation of the PI3K/AKT signaling pathway.Methods Bioinformatics analysis was employed to assess the correlation between SLC38A1 expression and clinicopathological features/prognosis in HCC patients,with functional enrichment analysis of SLC38A1 conducted.SLC38A1 was silenced or over expressed via transfection in Huh-7 cells,with glutamine inhibited using DRP-104 and the PI3K/AKT pathway suppressed using LY294002.Cell viability,proliferation,migration,invasion,and glutamine concentration were evaluated using CCK-8,EdU staining,scratch wound healing assay,Transwell chamber assay,and glutamine assay kits,respectively.PI3K/AKT pathway activity was assessed by Western blotting.Results SLC38A1 mRNA and protein levels were significantly higher in HCC tumor tissues than in adjacent normal tissues(P<0.05).HCC patients with high SLC38A1 expression exhibited significantly lower overall survival than those with low expression(P<0.05).SLC38A1 expression correlated significantly with pathologic T-stage(pT),N-stage(pN),M-stage(pM),survival status,and immune infiltration in HCC patients(P<0.05).SLC38A1 silencing markedly reduced glutamine uptake in HCC cells(P<0.001),suppressing cell viability,proliferation,migration,invasion,and PI3K/AKT pathway activity(P<0.001).Conversely,SLC38A1 overexpression promoted proliferation,migration,invasion,and PI3K/AKT activation(P<0.001).DRP-104-mediated glutamine inhibition suppressed HCC cell malignancy and PI3K/AKT signaling while abolishing the oncogenic effects of SLC38A1 overexpression(P<0.001).PI3K/AKT pathway inhibition blocked the pro-tumorigenic effects of SLC38A1 overexpression(P<0.001).Conclusion SLC38A1 promotes proliferation,migration,and invasion in HCC by activating the PI3K/AKT pathway through enhanced glutamine transport.

Bismuth iodide(BiOI)with different crystal plane ratios of(110)to(001)was synthesized,and typeⅡheterojunction formed between(001)and(110)crystal planes of BiOI was used to improve the separation efficiency of photogenerated electrons and holes.Then the BiOI(001)/(110)was composited with nitrogen-doped graphene quantum dots(N-GQDs)to prepare a ternary composites,which could enhance the range and intensity of light absorption,and prolonged the lifetime of photogenerated electrons due to the formation of Z-scheme heterojunctions between BiOI and N-GQDs,thereby leading to the excellent photoelectric performance of the BiOI/N-GQDs for generating sensitive photoelectric response signals.A photoelectrochemical sensor for sensitive detection of chlorpyrifos(CPF)was designed with BiOI/N-GQDs-modified FTO electrode as a photocathode.The S and N atoms contained in CPF were coordinated with Bi(Ⅲ)on the surface of BiOI,which reduced the photocurrent of BiOI/N-GQDs.The photocurrent change was linear with logarithm of concentration of CPF in the range of 1.5×10-12-5.0×10-9 mol/L,and the detection limit was 1.5×10-12 mol/L.The sensor was highly sensitive,selective and stable,and could be used for determination of trace CPF in environmental and food samples.

Peroxynitrite anion(ONOO-),which is originated from the reaction of nitric oxide(NO)and superoxide anion(O2-),plays a pivotal role in immune defense and signal regulation.Excessive levels of ONOO-may induce the occurrence of various diseases such as Alzheimer's disease,inflammation,cardiovascular disease and cancer,etc.Existing detection methods for ONOO-have limitations such as complexity,time consumption,and low cell biocompatibility.In this study,a novel fluorescent probe QFPD was developed using quinoline and diphenylphosphinamide as fluorescent keleton and recognition group,respectively.The strong oxidizing property of ONOO-triggerd the cleavage of phosphoramide bond,leading to fluorescence quenching and a visible color change of the solution from yellow to purple,thereby enabling"ON-OFF"type recognition of ONOO-.QFPD exhibited excellent characteristics including good selectivity and high sensitivity in fluorescence detection(Limit of detection of 1.37 μmol/L),large Stokes shift(130 nm),rapid response(10 min),and strong anti-interference ability.Additionally,QFPD demonstrated good biocompatibility and could realize real-time dynamic monitoring of endogenous ONOO-.Furthermore,QFPD was successfully applied to environmental toxicology research by visualizing the oxidative stress effects induced by microplastics polymethyl methacrylate(PMMA)and Hg2+exposure,which might be a novel tool for the mechanism research on oxidative stress associated with microplastic pollution and heavy metal exposure.

Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear， and its pathogenesis is complex and refractory， collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment， traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis， and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis， this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu （stagnation） and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore， it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex， such as external wind and cold pathogens， emotional injuries， internal accumulation of dampness， and deficiency of healthy Qi， all of which can disrupt the ascending and descending movement of Qi， impede the circulation of Qi and fluids， close the pores and skin texture， and subsequently lead to stagnation. Based on the above understanding， "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind， warming cold， regulating Qi， eliminating dampness， tonifying deficiency， and external treatment， aiming to remove the causes， promote the circulation of Qi and fluids， and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms， reduce recurrence rate， and improve quality of life， which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu"， enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.

ObjectiveTo use bioinformatics technology to screen the molecular patterns and diagnostic biomarkers of ferroptosis closely related to psoriasis， observe the therapeutic effect of Kaixuan Jiedu core prescription on psoriasis and explore its potential mechanism through animal experiments. MethodsPsoriasis microarray data from GEO were analyzed to identify differentially expressed genes （DEGs）. Intersection with a ferroptosis gene set yielded psoriasis ferroptosis-related genes （FRGs）， which underwent correlation， consensus clustering， enrichment， and immune infiltration analyses. Core diagnostic FRGs （Hub-FRGs） were identified using random forest （RF）， support vector machine （SVM）， LASSO regression， Nomogram， and ROC analyses. In vivo， imiquimod （5% cream） induced psoriasis in mice （except controls）. Drug treatment groups received respective doses， while control and model groups received saline via daily gavage for 7 days. Back skin changes were recorded and PASI scored. Hematoxylin-eosin （HE） staining assessed histopathology. The levels of ferrous ion （Fe²⁺）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE） and free fatty acid （FFA） in skin tissue were detected. The level of reactive oxygen species （ROS） in skin tissue was detected by immunofluorescence. Immunohistochemistry was used to detect the expression of ChaC glutathione-specific γ-glutamyl transferase 1 （CHAC1）， arachidonic acid 12-lipoxygenase β （ALOX12B）， trimotif protein 21 （TRIM21）， proliferation marker （Ki67） and nuclear transcription factor-κB （NF-κB） protein. ResultsAnalysis of GSE30999 identified 2 100 DEGs and 24 FRGs. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment revealed 1 000 biological functions and 75 pathways. After cluster analysis， combined with three machine learning algorithms， Nomogram and ROC curve analysis， the core Hub-FRGs （CHAC1， ALOX12 B， TRIM21） were obtained. Immunoinfiltration showed inactive memory CD4⁺T cells and activated dendritic cells abundance significantly correlated with Hub-FRGs. In vivo， model group vs. control showed significantly increased PASI/Baker scores （P<0.05）， epidermal hyperkeratosis， inflammatory infiltration， and elevated levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， CHAC1， ALOX12B， TRIM21， Ki67， and NF-κB （P<0.05）. Drug groups vs. model group exhibited significantly reduced scores （P<0.05）， alleviated skin lesions， and decreased levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， Hub-FRGs， Ki67， and NF-κB （P<0.05）. ConclusionKaixuan Jiedu core prescription can significantly improve the skin pathological injury of psoriasis mice， showing good therapeutic and repair effects， and its mechanism may be related to regulating the expression of ferroptosis genes CHAC1， ALOX12B and TRIM21， which are closely related to the pathogenesis of psoriasis.