ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

Chemical constituents of n-butanol fraction of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied. Ten compounds were purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography. Based on the physicochemical properties and spectroscopic data, these compounds were identified as (4S)-4,8-dihydroxy-α-tetralone-5-[6′-(3′′,5′′-dimethoxy-(E)-p-coumaroyl)]-β-D-glucopyranoside (1), (4S)-4,8-dihydroxy-α-tetralone-5-[6′-(E)-feruloyl]-β-D-glucopyranoside (2), (1S,3R,4S,5R)-4,5-di-O-caffeoyl quinic acid methyl ester (3), (1R,3R,4S,5R)-3,4-di-O-caffeoyl quinic acid methyl ester (4), (3R,5R)-3,4,5-tri-O-caffeoylquinic acid methyl ester (5), (1R,3R,4S,5R)-3-O-caffeoyl-5-O-p-coumaroyl quinic acid methyl ester (6), (1R,3R,4S,5R)-3-O-p-coumaroy-4-O-caffeoyl quinic acid methyl ester (7), (1R,3R,4S,5R)-3-O-caffeoyl-4-O-p-coumaroy quinic acid methyl ester (8), (3R,5R)-3,5-di-O-caffeoyl quinic acid methyl ester (9) and (1S,3R,4R,5R)-4-O-caffeoyl-5-O-feruloyl quinic acid methyl ester (10). Among them, compound 1 was a new compound, and compounds 3–10 were isolated from the genus Cyclocarya for the first time.

BackgroundSuicide is the second leading cause of death in adolescents. Patients with depression have a high risk of suicide， and family dysfunction is an important contributing factor of suicide. However， the mechanisms among these variables remain unclear. ObjectiveTo explore the influence of family cohesion and adaptability on the risk of suicide in adolescent inpatients with depression， and the mediating effect of depressive symptoms and the moderating effect of resilience， so as to provide references for suicide prevention and intervention. MethodsA total of 335 adolescent inpatients with depression were consecutively enrolled from October 2024 to August 2025 in a tertiary Grade A psychiatric hospital in Guangzhou. All participants met the diagnostic criteria for depression in the International Classification of Diseases， tenth edition （ICD-10）. They were assessed using the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version （FACES Ⅱ-CV）， the Self-rating Depression Scale （SDS）， the Connor-Davidson Resilience Scale （CD-RISC）， the Suicidal Behaviors Questionnaire-Revised （SBQ-R） and the suicide module of the Mini-International Neuropsychiatric Interview （MINI）. A comprehensive suicide risk index was constructed. Model 4 and model 7 in the SPSS macro program Process 4.1 were used to test the mediating effect and the moderating effect， respectively. ResultsCorrelation analysis revealed that the SDS score was positively correlated with the composite suicide risk index （r_s=0.663， P<0.01） but negatively correlated with the family cohesion and adaptability dimensions scores of the FACES II-CV and the CD-RISC score （r_s=-0.448， -0.386， -0.576， P<0.01）. Depressive symptoms fully mediated the association between family cohesion and suicide risk， with an indirect effect of -0.491 （95% CI： -0.646–-0.352）， accounting for 89.76% of the total effect. Depressive symptoms also fully mediated the association between family adaptability and suicide risk， with an indirect effect of -0.442 （95% CI： -0.603–-0.293）， accounting for 89.11% of the total effect. Resilience significantly moderated the effect of family cohesion on depressive symptoms （β=-0.006， P<0.01） and the effect of family adaptability on depressive symptoms （β=-0.007， P<0.05）. ConclusionIn adolescent inpatients with depression， depressive symptoms may play a fully mediating role in the relationships between family cohesion/family adaptability and suicide risk， respectively， and resilience moderated the first stage of this mediating pathway. ［Funded by Guangzhou Science and Technology Plan Project （number， 2024A03J0299）］

Objective To explore the adjuvant treatment options for elderly patients or those with low cardiopulmonary function who cannot tolerate lobectomy for peripheral solid pathological stage ⅠA (pⅠA) non-small cell lung cancer (NSCLC). Methods A retrospective analysis was conducted on the clinical data of patients with peripheral solid pⅠA stage NSCLC treated with lobectomy and compromised sublobar resection (CSR) in the Affiliated Hospital of Nantong University, from 2018 to 2019. The incidence of postoperative complications and independent predictors of postoperative recurrence were analyzed. Patients in the CSR group were divided into a targeted therapy group, a chemotherapy group, and an observation group based on postoperative treatment measures. The 3-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of the three subgroups before and after propensity score matching (PSM) were compared. Results A total of 586 patients were included, including 288 (49.15%) males and 298 (50.85%) females, with a median age of 64.00 years. There were 335 patients of lobectomy and 251 patients of CSR. There was no statistically significant difference in the incidence of postoperative complications between the lobectomy group and CSR group [RR=0.987, 95%CI (0.898, 1.085), P=0.789]. Multivariate analysis showed that gender, tumor location, and size were independent risk factors for recurrence after CSR. After PSM, 17 patients were enrolled in each of the three subgroups of CSR. Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 3-year RFS rate (P=0.115) and 5-year OS rate (P=0.101) between the targeted therapy group and chemotherapy group after PSM. The 3-year RFS rate and 5-year OS of the targeted group were significantly better than those of the observation group (P=0.041, P=0.009). Compared with lobectomy, there was no statistically significant difference in the 3-year RFS rate (P=0.069) and 5-year OS rate (P=0.540) in the targeted therapy group, while the chemotherapy group and observation group were significantly inferior to the lobectomy group (P<0.05). Conclusion CSR for treating stage pⅠA peripheral solid NSCLC in patients with advanced age or poor cardiopulmonary function does not increase the incidence of postoperative complications. Gender, tumor location, and size are independent risk factors for postoperative recurrence. In terms of 3-year RFS rate and 5-year OS rate, adjuvant targeted therapy after CSR is not only superior to observation but also not inferior to lobectomy.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To investigate the therapeutic effects and mechanisms of Huangqi Jianzhong Decoction(HJD)on gastric mucosal injury induced by Helicobacter pylori(Hp)infection.Methods A Wistar rat model of Hp-induced gastric mucosal injury was established.Successfully modeled rats were randomly divided into five groups:model group,low-,medium-and high-dose HJD groups,and quadruple therapy group(Omeprazole+Amoxicillin+Clarithromycin+Colloidal Bismuth pectin),8 rats per group,with an additional normal group.After 4 weeks of treatment,gastric mucosal pathological changes were assessed by hematoxylin-eosin(HE)staining.Serum levels of interleukin 1β(IL-1β),interleukin 18(IL-18),tumor necrosis factor α(TNF-α),chemokine(C-X-C motif)ligand 1(CXCL1),chemokine(C-X-C motif)ligand 9(CXCL9),and gastrin-17(G-17)were measured by enzyme-linked immunosorbent assay(ELISA).Protein expression levels of IRF8,IFN-γ,interferon-induced tetratricopeptide repeat protein 3(Ifit3)and uridine phosphorylase 1(Upp1)in gastric mucosal tissues were detected by Western Blot.Results Compared with the normal group,the model group exhibited significant gastric mucosal damage,serum levels of IL-1β,IL-18,TNF-α,CXCL1 and CXCL9 were significantly increased,G-17 was drcreased,and protein expression levels of IRF8,IFN-γ,Ifit3 and Upp1 in gastric mucosa were significantly increased,the differences being statistically significant(P＜0.05).Compared with the model group,the gastric mucosal tissue injury of rats in the medium-and high-dose of HJD groups and the quadruple therapy group was significantly improved,the levels of IL-1β,IL-18,TNF-α,CXCL1 and CXCL9 in serum were significantly decreased,G-17 was significantly increased,and the protein expression levels of IRF8,IFN-γ,Ifit3 and Upp1 in gastric mucosa were significantly decreased,the differences being statistically significant(P＜0.05).The effect in above indexes in high-does HJD groups was superior to the low-and mediun-groups.Conclusion HJD alleviates Hp-induced gastric mucosal injury by inhibiting the IRF8/IFN-γ signaling pathway and subsequent inflammatory responses.