ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2％pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4％paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P＜0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P＜0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P＜0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P＜0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P＜0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.

Objective To analyze the developmental trends and research hotspots of anoikis in cancer research from 2005 to 2024.Methods Relevant literature was retrieved from the Web of Sci-ence Core Collection.Visualization tools including CiteSpace,VOSviewer and SCImago Graphica were employed to analyze publication volume,countries,institutions,authors,journals,keywords and other bibliometric indicators.Results A total of 2,252 articles were included in this study,showing an overall upward trend in publication volume,with a notable increase after 2012.China and the United States ranked highest in terms of publication volume and citation frequency.Representative institutions included Shanghai Jiao Tong University,Chulalongkorn University and MD Anderson Cancer Center,while a representative scholar was CHANVORACHOTE Pithi.The core journal was Oncogene.Keyword and co-citation analyses revealed that research focused on genetic characteristics,cancer treatment,prognostic prediction and metabolic reprogramming,with core terms including"ex-pression""metastasis"and"anoikis".Conclusion Research interest in the field of anoikis contin-ues to rise,with future directions focusing on drug resistance mechanisms,the tumor microenvironment,immunotherapy,signaling pathways and epithelial-mesenchymal transition(EMT).

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective To study the tongue manifestation of patients with different syndromes in non-small cell lung cancer(NSCLC)and the correlation between tongue characteristics of different syndromes and tumor markers and coagulation indicators.Methods Totally 497 patients with NSCLC were grouped according to syndrome differentiation,and the differences in tongue characteristics of different syndromes were compared.Bivariate correlation analysis was used to study the correlation between tongue characteristics and serum tumor markers and coagulation indicators in patients with NSCLC of different syndromes.Results Compared with healthy people of different syndromes,in TB-a,yin deficiency and phlegm-heat syndrome>healthy group>qi-yin deficiency syndrome>spleen deficiency and phlegm-dampness syndrome>lung stagnation and phlegm-stasis syndrome(P<0.001).In TB-L,healthy group>spleen deficiency and phlegm-dampness syndrome>qi-yin deficiency syndrome>lung stagnation and phlegm-stasis syndrome>yin deficiency and phlegm-heat syndrome(P<0.001).In TB-b,yin deficiency and phlegm-heat syndrome>qi-yin deficiency syndrome>spleen deficiency and phlegm-dampness syndrome>healthy group>lung stagnation and phlegm-stasis syndrome(P<0.001).Yin deficiency and phlegm-heat syndrome had the highest TB-a and the lowest Per-all.Spleen deficiency and phlegm-dampness syndrome had the highest TB-L and Per-all.Lung stagnation and phlegm-stasis syndrome had lower TB-b and TC-b than other groups,lower TB-a than the healthy group,and a high Per-all index(P<0.05).In terms of tumor markers,Per-all in spleen deficiency and phlegm-dampness syndrome was positively correlated with Ca199,Ca50 and Ca242(P<0.05).In terms of coagulation indicators,the tongue texture index of lung stagnation and phlegm-stasis syndrome had a high correlation with the coagulation indicator Fg(P<0.01).Conclusion Different TCM syndromes of NSCLC have their own typical tongue characteristics.Tongue manifestations of different syndromes are correlated with tumor markers and coagulation indicators,respectively,which can reflect changes in clinical status.

AIM To investigate the effects of Heixiaoyao Powder on neuroinflammation in APP/PS1 transgenic mice.METHODS The 16-week-old male APP/PS1 transgenic mice were randomly divided into the model group,the BBG group(P2X7R specific antagonist,30 mg/kg)and high,medium and low dose Heixiaoyao Powder groups of(22.10,11.05,5.53 g/kg),in contrast to the male C57BL/6J mice of the same age and the same strain of the blank groups,with 12 mice in each group.When normal saline by gavage was dosed upon the blank group and the model group,and the other groups were treated with corresponding drug by gavage.After 90 days of administration,the mice had their learning and memory ability detected by Morris water maze test;their hippocampal pathological changes observed with HE staining;their MyD88 expression detected by immunofluorescence staining;their hippocampal levels of pro-inflammatory factors(TNF-α,IL-6),anti-inflammatory factors(IL-10),ATP and amyloid protein β(Aβ)detected by ELISA;their hippocampal mRNA expressions of P2X7R,TLR4,MyD88 and NF-κB-P65 detected by RT-qPCR method;and their hippocampal protein expressions of P2X7R,TLR4,MyD88,NF-κB-P65 and p-NF-κB-P65 detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated prolonged escape latency and reduced frequency in crossing platform(P＜0.01);decreased number of hippocampal neurons,deranged neurons,and darker cytoplasm staining;increased immunofluorescence expression of hippocampal MyD88(P＜0.01);decreased IL-10 level(P＜0.01);increased levels of TNF-α,IL-6,ATP and Aβ(P＜0.01);increased mRNA and protein expressions ofP2X7R,TLR4 and MyD88(P＜0.01),and increased protein expression of p-NF-κB-P65(P＜0.01).Compared with the model group,the groups intervened with Heixiaoyao Powder or BBG demonstrated shortened escape latency and increased frequency in crossing platform(P＜0.01);more number of neatly arranged hippocampal neurons;increased hippocampal IL-10 level(P＜0.01),decreased levels of TNF-α,IL-6,ATP and Aβ(P＜0.05,P＜0.01);decreased mRNA and protein expressions of P2X7R,TLR4 and MyD88(P＜0.05,P＜0.01);and decreased protein expression of p-NF-κB-P65(P＜0.05,P＜0.01).Except the low dose Heixiaoyao Powder group,the other treatment groups shared decreased immunofluorescence expression of MyD88(P＜0.05,P＜0.01).CONCLUSION Heixiaoyao Powder can significantly improve the learning and memory ability of APP/PS1 model mice,and its mechanism may lie in its function in alleviating cerebral neuroinflammation by reducing the abnormal Aβ aggregation via inhibiting the activation of ATP/P2X7R/NF-κB signaling pathway.

Aim To investigate the effect of angioten-sin Ⅱ type 1a receptor(AT1aR)knockout on cardiac dysfunction in rats with obesity and its possible molecu-lar mechanism.Methods SD rats(n=24)were used to generated the whole-body AT1 aR-deficiency rats by sgRNA and the CRISPR/Cas9 system,and the obesity model was constructed by feeding with high-fat diet(HFD).They were divided into four groups:wildtype(WT)and knockout(KO)groups with nor-mal feeding and their respective high-fat diets groups.Color ultrasound diagnostic instrument was uses to e-valuate the cardiac function;oil red O staining was a-dopted to stain the myocardial lipids;RT-PCR was used to detect the levels of GPX4 and Ptgs2 genes in myocardial tissue.Western blot was employed to detect the expression of GPX4,ferritin,Nrf2,HO-1 and NQO1 in rat myocardial tissue.ELISA and other kits were used to determine the lipid contents in serum and myocardium.Results It was found that high-fat feed-ing caused cardiac dysfunction,serum lipid disorders,oxidative stress and ferroptosis in SD rats.However,these changes were attenuated in AT1aR knockout rats fed with high-fat diet.Furthermore,compared with WT-HFD group,KO-HFD rats showed enhanced acti-vation of the Nrf2/HO-1 pathway in the myocardium,reduced ferroptosis,decreased lipid accumulation,and reduced cardiac dysfunction.Conclusion AT1aR knockout can improve HFD-induced cardiac dysfunc-tion by enhancing antioxidant capacity and reducing the degree of ferroptosis.