1.Kaixuan Jiedu Core Prescription Ameliorates Psoriasis Induced by IMQ Combined with Restraint Stress in Mice by Regulating Neuro-immune Axis and Inhibiting Skin Homing of Th17 Cells
Haoruo YANG ; Ningxin ZHANG ; Qiubai JIN ; Jiaqi LI ; Xue XIAO ; Meiqi SUN ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):55-68
ObjectiveTo observe the effect and therapeutic effect of Kaixuan Jiedu core prescription (KXJD) on skin homing of Th17 cells in the mouse model of imiquimod (IMQ) combined with restraint stress-induced psoriasis-like skin damage, and to explore its potential mechanism from the perspective of neuro-immune axis. MethodsThirty male C57BL/6J mice were randomly allocated into five groups (n=6): Control, model (IMQ), restraint stress model (IMQ+RS), KXJD, and methotrexate (MTX). The mouse model of psoriasis-like skin damage was established by 5% IMQ combined with restraint stress. At the same time of modeling, each treatment group was treated with corresponding doses of drugs, and the control, IMQ, and IMQ+RS groups were treated with the same amount of normal saline by gavage once a day for 5 days. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the skin tissue and Baker scoring was performed. Serum levels of interleukin-1β (IL-1β) and angiopoietin-2 (Ang-2) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), C-C motif chemokine ligand 20 (CCL20), and C-C motif chemokine receptor 6 (CCR6) in the skin tissue were determined. Immunohistochemistry (IHC) was employed to determine the protein expression of cutaneous lymphocyte-associated antigen (CLA), integrin αE (CD103), cytokeratin 10 (CK10), and nuclear factor-kappa B (NF-κB) in the skin. Immunofluorescence double staining (DIF) was adopted to detect the expression and co-localization of vascular endothelial cadherin (VE-cadherin) and platelet-endothelial cell adhesion molecule (CD31), CCR6, CD103, substance P (SP), calcitonin gene-related peptide (CGRP), and protein gene product 9.5 (PGP9.5) in the skin tissue. Real-time PCR was employed to quantify the mRNA levels of IL-10, IL-17A, and IL-23. ResultsCompared with the control group, the IMQ group and IMQ+RS group showed significant inflammatory cell infiltration, abnormal proliferation of epidermal cells, keratinization and other pathological changes in the skin tissue, and a significant increase in Baker score, elevated levels of IL-1β and Ang-2 in the serum and MMP-9, CCL20 and CCR6 in the skin lesions, upregulated expression of CLA, CD103, CK10, NF-κB, IL-17A mRNA, and IL-23 mRNA in the skin lesions, and downregulated expression of TIMP-1 and IL-10 mRNA. In addition, the fluorescence intensities of VE-cadherin and CD31 co-localization, CCR6 and CD103 co-localization, SP and PGP9.5 co-localization, and CGRP and PGP9.5 co-localization were increased (P<0.05). Compared with the IMQ group, the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ group, the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ+RS group, KXJD and MTX significantly alleviated the pathological damage of skin lesions, significantly decreased the Baker score, lowered the levels of IL-1β and Ang-2 in the serum and MMP-9, CCL20 and CCR6 in skin lesions, downregulated the expression of CLA, CD103, CK10, NF-κB, IL-17A mRNA and IL-23 mRNA in skin lesions, and upregulated the expression of TIMP-1 and IL-10 mRNA. Furthermore, KXJD and MTX reduced the fluorescence intensities of VE-cadherin and CD31 co-localization, CCR6 and CD103 co-localization, CGRP and PGP9.5 co-localization, and SP and PGP9.5 co-localization (P<0.05). ConclusionKXJD can significantly ameliorate the psoriasis-like skin damage induced by IMQ combined with restraint stress in mice by regulating the neural-immune axis and inhibiting the skin homing of Th17 cells.
2.Kaixuan Jiedu Core Prescription Alleviates Restraint Stress-exacerbated Imiquimod-induced Psoriasis-like Skin Lesions via Regulation of HPA Axis and Neuroinflammation
Ningxin ZHANG ; Haoruo YANG ; Jiaqi LI ; Mengyao JIANG ; Jiarong WU ; Xinqian LIU ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):79-88
ObjectiveTo investigate the ameliorative effect and potential mechanisms of Kaixuan Jiedu core prescription (KXJD) on imiquimod (IMQ)-combined restraint stress-induced psoriasis-like skin lesions in mice. MethodsA total of 36 C57BL/6J mice were randomly assigned to six groups (n=6 per group): Normal group, restraint stress blank group, model group, restraint stress model group, KXJD group (30.42 g·kg-1), and methotrexate group (0.001 g·kg-1). Psoriasis-like lesions were induced by topical IMQ application combined with restraint stress. After 5 days of intervention, the severity of skin lesions was evaluated using the Psoriasis Area and Severity Index (PASI). The following parameters were assessed: Hypothalamic-pituitary-adrenal (HPA) axis-related hormones, including adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), and corticosterone (CORT), central neuronal markers, including neuronal nuclei antigen (NeuN), microtubule-associated protein 2 (MAP2), and beta Ⅲ-tubulin (β-Ⅲ tubulin), microglial activation markers, including ionized calcium-binding adapter molecule-1 (Iba-1) and cluster of differentiation 11b (CD11b), and skin nerve fiber markers, including protein gene product 9.5 (PGP9.5) and serotonin (5-HT), as well as the expression levels of inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). ResultsCompared with the normal group, both the model group and the restraint stress model group exhibited more severe psoriasis-like skin lesions, with significantly elevated serum levels of ACTH, CRH, and CORT (P<0.01). The expression of glucocorticoid receptor (GR) and corticotropin-releasing hormone receptor 1 (CRHR1) in the skin was significantly downregulated. The expression of NeuN, MAP2, β-Ⅲ tubulin, Iba-1, and CD11b in the hypothalamus and hippocampus was significantly upregulated, suggesting abnormal changes in neuronal number or structure and aberrant activation of glial cells (P<0.05, P<0.01). In addition, the expression of PGP9.5 and 5-HT in the skin, as well as the mRNA levels of TNF-α, IL-6, and IL-1β were all markedly elevated (P<0.05, P<0.01). Compared with the model group, the restraint stress model group showed further exacerbation in most parameters. Compared with the restraint stress model group, the KXJD group exhibited significantly reduced PASI scores (P<0.01), significantly decreased serum CRH, ACTH, and CORT levels (P<0.05, P<0.01), upregulated skin GR and CRHR1 expression, inhibited abnormal neuronal changes and microglial activation in the hypothalamus and hippocampus, attenuated skin nerve fiber hyperplasia and amine signaling molecule release, and significantly reduced pro-inflammatory cytokine mRNA expression (P<0.05, P<0.01). ConclusionKaixuan Jiedu Core prescription can effectively ameliorate IMQ combined with restraint stress-induced psoriasis-like skin lesions in mice by modulating HPA axis function, inhibiting central neuropathological changes, and attenuating skin nerve fiber hyperplasia, amine signaling molecule (5‑HT) release and local inflammatory responses.
3.Kaixuan Jiedu Core Prescription Alleviates Psoriatic Skin Lesions in Mice by Modulating Cold-sensitive TRPM8 Neuron-derived Signaling
Xue XIAO ; Bin YANG ; Meiqi SUN ; Haoruo YANG ; Ningxin ZHANG ; Jiaqi LI ; Huan LIU ; Mengyao JIANG ; Yuanyao SHE ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):89-101
ObjectiveTo investigate the ameliorative effects of Kaixuan Jiedu core prescription (KXJD) on skin lesions in psoriasis-like mouse models under cold environment exposure, and to analyze its influences on transient receptor potential (TRP) channels and related neuroimmune regulatory factors. MethodsThirty-six C57BL/6J mice were randomized into 6 groups, with 6 mice in each group. Two feeding conditions were set: Normal temperature and cold [simulating a cold environment at (10±0.5) ℃, for 6 h daily]. Mice were induced to develop psoriasis-like lesions by applying imiquimod externally. The model mice were allocated into model groups and KXJD (30.42 g·kg-1, continuous gavage for 5 days) groups. Normal mice were used as the control group. Specifically, mice were allocated into normal temperature, normal temperature model, normal temperature+KXJD, cold exposure control, cold exposure model, and cold exposure+KXJD groups. The pathological changes in skin lesions were observed by hematoxylin-eosin (HE) staining. The expression of cluster of differentiation (CD) 3+ T lymphocytes, CD11c+ dendritic cells (DCs), phosphorylated extracellular signal-regulated kinase (p-ERK), and substance P (SP) were detected by immunofluorescence assay. The protein level of transient receptor potential cation channel subfamily M member 8 (TRPM8) in the skin tissue was determined by Western blot. The expression of TRPM8, transient receptor potential cation channel subfamily V member 1 (TRPV1), transient receptor potential cation channel subfamily A member 1 (TRPA1), and transient receptor potential cation channel subfamily V member 2 (TRPV2) at the protein and mRNA levels was determined by immunohistochemistry and Real-time PCR, respectively. The levels of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in the serum were analyzed by enzyme-linked immunosorbent assay (ELISA). The enrichment analysis of differentially expressed genes (DEGs) and TRP pathway network construction were conducted based on the GEO database. The co-expression of TRPM8 and CGRP in the skin lesions was verified by immunofluorescence double labeling. ResultsBoth the normal temperature and cold exposure model groups showed typical psoriasis-like skin lesions. Compared with the normal temperature and cold exposure control groups, the model groups had excessive epidermal keratinization, thickened spinous layer, and inflammatory infiltration in the dermis, with increased pathological scores (P<0.05), increased infiltration of CD3+ and CD11c+ cells and expression of p-ERK and SP, upregulated mRNA levels of TRPM8, TRPA1, and TRPV2, downregulated mRNA level of TRPV1 (P<0.05), and reduced content of CGRP and increased content of NPY in the serum. Compared with the normal temperature and cold exposure model groups, KXJD reduced the pathological manifestations and pathological scores of psoriasis-like skin lesions (P<0.05), and inhibited the infiltration of CD3+ and CD11c+ cells and the expression of p-ERK and SP. Gene enrichment analysis suggested that the DEGs of psoriasis were significantly enriched in the interleukin (IL)-17 signaling pathway and TRP channel inflammatory regulation. Compared with the normal temperature and cold exposure model groups, KXJD reversed the abnormal mRNA levels of genes related to the TRP channel subfamilies (P<0.05), increased the CGRP level, and decreased the NPY level. Immunofluorescence double labeling further confirmed that compared with the model groups, KXJD down-regulated the co-expression of TRPM8 and CGRP in the skin lesions. ConclusionKXJD may ameliorate psoriasis-like skin lesions by downregulating the overexpressed cold-sensitive receptor TRPM8 in skin lesions and correcting the disorder of neuropeptide (such as SP and CGRP) release mediated by it, thereby inhibiting the IL-23/helper T cell 17 (Th17) core inflammatory pathway, suppressing the infiltration of inflammatory cells and the activation of the ERK signaling pathway, and regulating the Xuanfu (sweat pore)-TRPM8-neuroimmune response axis.
4.A real-world study of 15,644 patients undergoing D2 radical gastrectomy over 11 years at Shanxi provincial cancer hospital
Baoping JIAO ; Kai TAO ; Gang ZHAI ; Zefeng GAO ; Feng LI ; Kaiqing GUO ; Yutao ZHANG ; Nan QIAO ; Yi JIA ; Zongliang GUO ; Erli WANG ; Zhe BAI ; Xiangnan ZHAO ; Haoruo ZHANG ; Yuye GAO ; Jinfeng MA
Chinese Journal of Gastrointestinal Surgery 2025;28(11):1302-1313
Objective:To summarize the clinicopathological features, evolving trends in treatment and surgical approaches, and survival outcomes of patients who underwent D2 radical gastrectomy for gastric cancer in Shanxi Provincial Cancer Hospital over the past 11 years with the goal of providing a reference for the clinical practice of gastric cancer in this region.Methods:A retrospective observational study was conducted to analyze the clinicopathological data of patients who underwent D2 radical gastrectomy for pathologically confirmed gastric malignancy at the Department of Gastrointestinal Surgery, Shanxi Provincial Cancer Hospital from January, 2013 to December, 2023. Exclusion criteria consisted of: (1) residual gastric cancer or recurrent gastric cancer after surgery; (2) emergency gastric cancer resection due to bleeding, perforation, obstruction, or other causes; (3) comorbidity with other primary malignant tumors; (4) severe preoperative cardiopulmonary insufficiency or hepatic and renal insufficiency who cannot tolerate radical surgery; and (5) inconsistent main diagnosis information across the medical record system, pathological system, and gastric cancer-specific database. Patients were divided into three groups based on treatment methods: the surgery-only group, the perioperative chemotherapy group, and the adjuvant chemotherapy group. Endpoints included: (1) baseline patient characteristics; (2) trends in tumor location and pathological features; (3) evolution of treatment modalities; and (4) survival outcomes.Results:A total of 15,644 patients were included in the analysis, with 12,591 males and 3,053 females, the male-to-female gender ration was approximately 4∶1; the mean age was (61.2±9.5) years. The tumor sites were mainly concentrated in the esophagogastric junction (EGJ) (57.4%), followed by the antrum (25.9%). The incidence of EGJ cancer initially rose and then declined. However, gastric antrum tumors remained stable, and gastric body tumors showed a slow upward trend after 2020, accounting for 16.7%. In terms of pathological types, poorly differentiated carcinoma was the most prevalent, accounting for 55.9%, followed by moderately differentiated carcinoma (24.2%), mucinous adenocarcinoma (or signet ring cell carcinoma,14.1%), neuroendocrine carcinoma (4.8%), and well-differentiated carcinoma (0.9%). The proportion of poorly differentiated adenocarcinoma showed a significant upward trend overall as well, peaking at 65.6% in 2022 and decreasing to 57.5% in 2023. Mucinous adenocarcinoma (or signet ring cell carcinoma) exhibited fluctuations with a first increase followed by a decrease: it peaked at 17.3% in 2018, dropped sharply to 8.4% in 2022, and rose back to 13.8% in 2023. The proportions of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, and neuroendocrine tumors remained stable year by year. In terms of pathological staging, the overall proportions of gastric cancer at Stage 0, Stage I, Stage II, Stage III, and Stage IVa were 0.5%, 17.3%, 25.1%, 54.9%, and 2.3%, respectively. For Stage III, its proportion was 74.6% in 2013, which decreased to 46.4% by 2023. Stages I and II gastric cancer showed an upward trend, with their proportions rising from 10.2% and 12.1% in 2013 to nearly 21.0% and 29.6% in 2023, respectively. Between 2013 and 2023, the proportion of patients who received surgery alone continued to decrease, with this proportion dropping to 34.7% in 2023. In contrast, the number of patients who received adjuvant chemotherapy increased year by year, reaching 54.2% in 2023. Since 2017, the application of perioperative chemotherapy has gradually increased, rising to 11.1% in 2023. Immunotherapy showed an almost synchronous growth trend with perioperative chemotherapy. However, targeted therapy exhibited a downward trend after a period of growth. There were 10,704 cases of open surgery (68.4%), 4,744 cases of laparoscopic surgery (30.3%), and 193 cases of transthoracic surgery (1.2%). Pathological margin positivity was observed in 443 cases (2.8%), and the volume of gastric cancer surgeries gradually increased, peaked in 2021 before subsequently decreasing gradually. However, the volume of laparoscopic surgeries did not decrease; instead, it showed an upward trend. The main resection method for EGJ tumors was total gastrectomy, accounting for 78.5% of the total, followed by proximal gastrectomy, which accounted for 21.5%. After total gastrectomy, esophagojejunal Roux-en-Y anastomosis was the primary anastomotic method, and for proximal gastrectomy, the main anastomotic method was esophagogastric anastomosis, which accounted for 68.0% of the total. For distal gastrectomy, Billroth II anastomosis was the most common anastomotic technique, accounting for 92.7% of these procedures. The overall incidence of postoperative complications was 14.5% (2,264/15,644), among which the incidence of severe complications (grades III-IV) was 4.5% (706/15,644). The entire cohort was followed up with for (47.1±36.8) months, and the 1-year, 3-year, and 5-year overall survival rates were 86.4%, 65.9%, and 58.1%, respectively. For patients with stage 0, I, II, III, and IV gastric adenocarcinoma, the 1-year overall survival rates were 95.7%, 98.0%, 89.4%, 81.0%, and 49.1%, respectively; the 3-year overall survival rates were 92.1%, 94.6%, 81.9%, 51.4%, and 14.7%, respectively; and the 5-year overall survival rates were 89.4%, 91.7%, 75.1%, 41.5%, and 10.0%, respectively. For patients with stage I, II, III, and IV gastric neuroendocrine carcinoma, the 1-year overall survival rates were 96.7%, 91.1%, 73.8%, and 52.6%, respectively; the 3-year overall survival rates were 87.2%, 69.6%, 46.1%, and 32.1%, respectively; and the 5-year overall survival rates were 87.2%, 62.2%, 36.7%, and 32.1%, respectively.Conclusions:Gastric cancer in Shanxi Province is characterized by a male predominance, a high prevalence of tumors at the esophagogastric junction, a large proportion of poorly differentiated adenocarcinoma, and presentation at advanced stages (predominantly Stage III). The detection rate of early gastric cancer has been increasing year by year, the volume of laparoscopic surgeries has been on the rise annually, and the treatment model has shifted from single surgery to comprehensive treatment.
5.Clinical efficacy of radical gastrectomy with mesangientization via the inferior margin of the pancreas approach
Weiguo ZHANG ; Haoruo ZHANG ; Gang ZHAI ; Baoping JIAO ; Yutao ZHANG ; Kaiqing GUO ; Nan QIAO ; Zefeng GAO ; Kai TAO
Chinese Journal of Digestive Surgery 2025;24(10):1298-1304
Objective:To investigate the clinical efficacy of radical gastrectomy with mesan-gientization via the inferior margin of the pancreas approach (GMIP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 255 patients of Siewert Ⅱ and (or) Ⅲ adenocarcinoma of esophagogastric junction (AEG) who were admitted to Cancer Hospital Affiliated to Shanxi Medical University from March 2024 to March 2025 were collected. There were 191 males and 64 females, aged (62 ±7)years. Of 255 patients, 152 cases undergoing GMIP were allocated into the mesangientization radical resection group, 103 cases undergoing D 2 radical resection of gastric cancer were allocated into D 2 radical resection group. Observation indicators: (1) surgical and post-operative situations; (2) lymph node dissection status. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Wilcoxon test. Comparison of count data between groups was conducted using the chi-square test or corrected chi-square test. Compari-son of ordinal data was conducted using the rank sum test. Results:(1) Surgical and postoperative situations. In the mesangientization radical resection group, the time of lymph node dissection was (115±14)minutes, volume of intraoperative blood loss was (81±37)mL. In the D 2 radical resection group, the above indicators were (97±13)minutes, (104±39)mL, respectively. There were significant differences in the above indicators between the two groups ( t=-8.68, -4.64, P<0.05). In the mesan-gientization radical resection group, the total number of examined lymph node was 40.00(10.00), the number of lymph node dissected (the total number of each group) was 29.00(5.00), the number of lymph node metastasis (the total number of each group) was 2.00(1.00). In the D 2 radical resection group, the above indicators were 27.00(9.00), 8.00(4.00), 1.00(1.00), respec-tively. There were significant differences in the above indicators between the two groups ( Z=-10.68, -13.57, -6.80, P<0.05). (3) Lymph node dissection status. There were significant differences in number of lymph node dissected of No.14v, 12a, 12p, 11d, 11p, 10, postgastric, 9, 8a, 8p lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). There were significant differences in number of lymph node metastasis of No.11d and postgastric lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). Conclusion:Compared with D 2 radical resection, the GMIP for Siewert Ⅱ or Ⅲ AEG has less volume of intraoperative blood loss and more complete lymph node dissection.
6.Quercetin Attenuates Ferroptosis Against LPS-induced Acute Kidney Injury Rats via Modulating Keap1/Nrf2/ARE Pathway
Haoruo YANG ; Dajun YU ; Yu ZHANG ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):65-75
ObjectiveTo investigate the effect and therapeutic role of quercetin on ferroptosis in lipopolysaccharide (LPS)-induced acute kidney injury (AKI) rats based on the Kelch-like epichlorohydrin-related protein-1 (Keap1)/nuclear factor erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. MethodsSixty male SD rats were randomly divided into normal group, model group, quercetin high-dose (100 mg·kg-1) and low-dose (10 mg·kg-1) groups, ferroptosis inhibitor Ferrostatin 1 (FER1) group (5 mg·kg-1), and quercetin high-dose + Nrf2 inhibitor group (ML385, 30 mg·kg-1). Except for the normal group, the AKI rat model was established in each group by intraperitoneal injection of LPS (10 mg·kg-1). Following successful modeling, each treatment group received the corresponding dose of drug intervention, while the normal and model groups were administered an equal volume of normal saline. The intervention lasted for 3 weeks. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured biochemically to assess renal function. Serum tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). The levels of Fe2+, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in renal tissue were detected. Hematoxylin-eosin (HE), Masson, and periodic acid-Schiff (PAS) staining were employed to observe pathological morphological changes in renal tissue. Mitochondrial morphological changes were observed using transmission electron microscopy. Reactive oxygen species (ROS) levels in renal tissue were detected by immunofluorescence (IF). The protein and mRNA expression levels of Keap1, Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), transferrin receptor (TFR1), and kidney injury molecule-1 (KIM-1) were assessed by immunohistochemistry (IHC) and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the normal group, the model group exhibited significantly elevated serum levels of SCr, BUN, TNF-α, IL-1β, IL-6, Fe2+ and MDA in renal tissue, and significantly reduced SOD and GSH levels (P<0.01). Pathological injury in renal tissue was severe, with evident mitochondrial damage characteristic of ferroptosis and a reduced mitochondrial count. ROS levels in renal tissue were significantly increased. The protein and mRNA expression levels of Keap1, TFR1, and KIM-1 in renal tissue were significantly elevated, while those of Nrf2, HO-1, and GPX4 were significantly decreased (P<0.01). Compared with the model group, serum levels of SCr, BUN, TNF-α, IL-1β, IL-6, Fe2+ and MDA in renal tissue in the quercetin dosage groups and FER1 group showed varying degrees of reduction, while SOD and GSH levels were significantly increased (P<0.05). Pathological injury in renal tissue was markedly alleviated, mitochondrial damage improved, and mitochondrial counts increased. ROS levels in renal tissue were significantly reduced. The protein and mRNA levels of Keap1, TFR1, and KIM-1 in renal tissue were significantly decreased, while those of Nrf2, HO-1, and GPX4 were significantly increased, with the most notable improvement in the high-dose quercetin group (P<0.05). In comparison to the high-dose quercetin group, the ML385 group significantly weakened the protective effect of quercetin on AKI rats (P<0.05). ConclusionQuercetin effectively inhibits ferroptosis, improves renal tissue injury, and repairs renal function in AKI rats, and its mechanism may be related to the activation of the Keap1/Nrf2/ARE pathway.
7.Exploration of Kaixuan Jiedu Core Prescription's Efficacy in Alleviating Psoriasis Through Modulation of Ferroptosis Pathways: An Integrative Approach Involving Bioinformatics and Experimental Validation
Haoruo YANG ; Xue XIAO ; Jiaqi LI ; Ningxin ZHANG ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):69-78
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.
8.Exploration of Kaixuan Jiedu Core Prescription's Efficacy in Alleviating Psoriasis Through Modulation of Ferroptosis Pathways: An Integrative Approach Involving Bioinformatics and Experimental Validation
Haoruo YANG ; Xue XIAO ; Jiaqi LI ; Ningxin ZHANG ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):69-78
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.
9.Clinical efficacy of radical gastrectomy with mesangientization via the inferior margin of the pancreas approach
Weiguo ZHANG ; Haoruo ZHANG ; Gang ZHAI ; Baoping JIAO ; Yutao ZHANG ; Kaiqing GUO ; Nan QIAO ; Zefeng GAO ; Kai TAO
Chinese Journal of Digestive Surgery 2025;24(10):1298-1304
Objective:To investigate the clinical efficacy of radical gastrectomy with mesan-gientization via the inferior margin of the pancreas approach (GMIP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 255 patients of Siewert Ⅱ and (or) Ⅲ adenocarcinoma of esophagogastric junction (AEG) who were admitted to Cancer Hospital Affiliated to Shanxi Medical University from March 2024 to March 2025 were collected. There were 191 males and 64 females, aged (62 ±7)years. Of 255 patients, 152 cases undergoing GMIP were allocated into the mesangientization radical resection group, 103 cases undergoing D 2 radical resection of gastric cancer were allocated into D 2 radical resection group. Observation indicators: (1) surgical and post-operative situations; (2) lymph node dissection status. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Wilcoxon test. Comparison of count data between groups was conducted using the chi-square test or corrected chi-square test. Compari-son of ordinal data was conducted using the rank sum test. Results:(1) Surgical and postoperative situations. In the mesangientization radical resection group, the time of lymph node dissection was (115±14)minutes, volume of intraoperative blood loss was (81±37)mL. In the D 2 radical resection group, the above indicators were (97±13)minutes, (104±39)mL, respectively. There were significant differences in the above indicators between the two groups ( t=-8.68, -4.64, P<0.05). In the mesan-gientization radical resection group, the total number of examined lymph node was 40.00(10.00), the number of lymph node dissected (the total number of each group) was 29.00(5.00), the number of lymph node metastasis (the total number of each group) was 2.00(1.00). In the D 2 radical resection group, the above indicators were 27.00(9.00), 8.00(4.00), 1.00(1.00), respec-tively. There were significant differences in the above indicators between the two groups ( Z=-10.68, -13.57, -6.80, P<0.05). (3) Lymph node dissection status. There were significant differences in number of lymph node dissected of No.14v, 12a, 12p, 11d, 11p, 10, postgastric, 9, 8a, 8p lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). There were significant differences in number of lymph node metastasis of No.11d and postgastric lymph node between the mesangientization radical resection group and the D 2 radical resection group ( P<0.05). Conclusion:Compared with D 2 radical resection, the GMIP for Siewert Ⅱ or Ⅲ AEG has less volume of intraoperative blood loss and more complete lymph node dissection.
10.A real-world study of 15,644 patients undergoing D2 radical gastrectomy over 11 years at Shanxi provincial cancer hospital
Baoping JIAO ; Kai TAO ; Gang ZHAI ; Zefeng GAO ; Feng LI ; Kaiqing GUO ; Yutao ZHANG ; Nan QIAO ; Yi JIA ; Zongliang GUO ; Erli WANG ; Zhe BAI ; Xiangnan ZHAO ; Haoruo ZHANG ; Yuye GAO ; Jinfeng MA
Chinese Journal of Gastrointestinal Surgery 2025;28(11):1302-1313
Objective:To summarize the clinicopathological features, evolving trends in treatment and surgical approaches, and survival outcomes of patients who underwent D2 radical gastrectomy for gastric cancer in Shanxi Provincial Cancer Hospital over the past 11 years with the goal of providing a reference for the clinical practice of gastric cancer in this region.Methods:A retrospective observational study was conducted to analyze the clinicopathological data of patients who underwent D2 radical gastrectomy for pathologically confirmed gastric malignancy at the Department of Gastrointestinal Surgery, Shanxi Provincial Cancer Hospital from January, 2013 to December, 2023. Exclusion criteria consisted of: (1) residual gastric cancer or recurrent gastric cancer after surgery; (2) emergency gastric cancer resection due to bleeding, perforation, obstruction, or other causes; (3) comorbidity with other primary malignant tumors; (4) severe preoperative cardiopulmonary insufficiency or hepatic and renal insufficiency who cannot tolerate radical surgery; and (5) inconsistent main diagnosis information across the medical record system, pathological system, and gastric cancer-specific database. Patients were divided into three groups based on treatment methods: the surgery-only group, the perioperative chemotherapy group, and the adjuvant chemotherapy group. Endpoints included: (1) baseline patient characteristics; (2) trends in tumor location and pathological features; (3) evolution of treatment modalities; and (4) survival outcomes.Results:A total of 15,644 patients were included in the analysis, with 12,591 males and 3,053 females, the male-to-female gender ration was approximately 4∶1; the mean age was (61.2±9.5) years. The tumor sites were mainly concentrated in the esophagogastric junction (EGJ) (57.4%), followed by the antrum (25.9%). The incidence of EGJ cancer initially rose and then declined. However, gastric antrum tumors remained stable, and gastric body tumors showed a slow upward trend after 2020, accounting for 16.7%. In terms of pathological types, poorly differentiated carcinoma was the most prevalent, accounting for 55.9%, followed by moderately differentiated carcinoma (24.2%), mucinous adenocarcinoma (or signet ring cell carcinoma,14.1%), neuroendocrine carcinoma (4.8%), and well-differentiated carcinoma (0.9%). The proportion of poorly differentiated adenocarcinoma showed a significant upward trend overall as well, peaking at 65.6% in 2022 and decreasing to 57.5% in 2023. Mucinous adenocarcinoma (or signet ring cell carcinoma) exhibited fluctuations with a first increase followed by a decrease: it peaked at 17.3% in 2018, dropped sharply to 8.4% in 2022, and rose back to 13.8% in 2023. The proportions of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, and neuroendocrine tumors remained stable year by year. In terms of pathological staging, the overall proportions of gastric cancer at Stage 0, Stage I, Stage II, Stage III, and Stage IVa were 0.5%, 17.3%, 25.1%, 54.9%, and 2.3%, respectively. For Stage III, its proportion was 74.6% in 2013, which decreased to 46.4% by 2023. Stages I and II gastric cancer showed an upward trend, with their proportions rising from 10.2% and 12.1% in 2013 to nearly 21.0% and 29.6% in 2023, respectively. Between 2013 and 2023, the proportion of patients who received surgery alone continued to decrease, with this proportion dropping to 34.7% in 2023. In contrast, the number of patients who received adjuvant chemotherapy increased year by year, reaching 54.2% in 2023. Since 2017, the application of perioperative chemotherapy has gradually increased, rising to 11.1% in 2023. Immunotherapy showed an almost synchronous growth trend with perioperative chemotherapy. However, targeted therapy exhibited a downward trend after a period of growth. There were 10,704 cases of open surgery (68.4%), 4,744 cases of laparoscopic surgery (30.3%), and 193 cases of transthoracic surgery (1.2%). Pathological margin positivity was observed in 443 cases (2.8%), and the volume of gastric cancer surgeries gradually increased, peaked in 2021 before subsequently decreasing gradually. However, the volume of laparoscopic surgeries did not decrease; instead, it showed an upward trend. The main resection method for EGJ tumors was total gastrectomy, accounting for 78.5% of the total, followed by proximal gastrectomy, which accounted for 21.5%. After total gastrectomy, esophagojejunal Roux-en-Y anastomosis was the primary anastomotic method, and for proximal gastrectomy, the main anastomotic method was esophagogastric anastomosis, which accounted for 68.0% of the total. For distal gastrectomy, Billroth II anastomosis was the most common anastomotic technique, accounting for 92.7% of these procedures. The overall incidence of postoperative complications was 14.5% (2,264/15,644), among which the incidence of severe complications (grades III-IV) was 4.5% (706/15,644). The entire cohort was followed up with for (47.1±36.8) months, and the 1-year, 3-year, and 5-year overall survival rates were 86.4%, 65.9%, and 58.1%, respectively. For patients with stage 0, I, II, III, and IV gastric adenocarcinoma, the 1-year overall survival rates were 95.7%, 98.0%, 89.4%, 81.0%, and 49.1%, respectively; the 3-year overall survival rates were 92.1%, 94.6%, 81.9%, 51.4%, and 14.7%, respectively; and the 5-year overall survival rates were 89.4%, 91.7%, 75.1%, 41.5%, and 10.0%, respectively. For patients with stage I, II, III, and IV gastric neuroendocrine carcinoma, the 1-year overall survival rates were 96.7%, 91.1%, 73.8%, and 52.6%, respectively; the 3-year overall survival rates were 87.2%, 69.6%, 46.1%, and 32.1%, respectively; and the 5-year overall survival rates were 87.2%, 62.2%, 36.7%, and 32.1%, respectively.Conclusions:Gastric cancer in Shanxi Province is characterized by a male predominance, a high prevalence of tumors at the esophagogastric junction, a large proportion of poorly differentiated adenocarcinoma, and presentation at advanced stages (predominantly Stage III). The detection rate of early gastric cancer has been increasing year by year, the volume of laparoscopic surgeries has been on the rise annually, and the treatment model has shifted from single surgery to comprehensive treatment.

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