1.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.
2.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.
3.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.
4.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.
5.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.
6.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.
7.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.
8.Comparative study of exosome-mimetic nanovesicles and exosomes derived from human adipose mesenchymal stem cells on the biological function of human umbilical vein endothelial cells
Haoruo ZHANG ; Aizhen CHEN ; Caixiang CHEN ; Shijie TANG ; Junjing LI ; Xiangyu LI ; Xiaosong CHEN
Chinese Journal of Plastic Surgery 2022;38(5):517-527
Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.
9.Comparative study of exosome-mimetic nanovesicles and exosomes derived from human adipose mesenchymal stem cells on the biological function of human umbilical vein endothelial cells
Haoruo ZHANG ; Aizhen CHEN ; Caixiang CHEN ; Shijie TANG ; Junjing LI ; Xiangyu LI ; Xiaosong CHEN
Chinese Journal of Plastic Surgery 2022;38(5):517-527
Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.
10.Clinical observation of total laparoscopic radical gastrectomy for locally advanced esophagogastric junction carcinoma
Qingyao CHANG ; Jun XU ; Kai JIA ; Wenhui YANG ; Yidi WANG ; Haoruo ZHANG
Cancer Research and Clinic 2021;33(8):606-611
Objective:To investigate the efficacy of total laparoscopic radical gastrectomy for locally advanced esophagogastric junction carcinoma and its effect on patient's immune function and levels of tumor markers.Methods:A total of 106 patients who underwent total laparoscopic radical gastrectomy (total endoscopic group) in the Affiliated Cancer Hospital of Shanxi Medical University from January 2016 to April 2020 were collected, and 98 patients who underwent open radical gastrectomy (open group) in the same period were selected. The short-term efficacy, preoperative and postoperative immune function and tumor markers were compared between the two groups.Results:The operative time of the total endoscopic group was longer than that of the open group [(214±49) min vs. (165±32) min, t = 8.87, P < 0.01], the intraoperative blood loss was less than that of the open group [(86±50) ml vs. (113±53) ml, t = 3.59, P < 0.01], the postoperative first exhaust time was shorter than that of the open group [3.0 d (3.0 d, 4.0 d) vs. 3.5 d (3.0 d, 4.5 d), Z = 2.89, P < 0.01], and the incision length was shorter than that of the open group [(4.6±0.6) cm vs. (17.6±2.0) cm, t = 68.63, P < 0.01]. The postoperative proportion of CD4 + T cells, CD4 +/CD8 + and proportion of NK cells in the total endoscopic group were higher than those in the open group [(41±8)% vs.(36±8)%, t = 4.710, P < 0.01; 1.63 (1.19, 2.30) vs. 1.15 (0.87, 1.63), Z = 4.165, P < 0.01; 24.60 % (17.77 %, 32.50 %) vs. 19.25 % (13.35 %, 25.80 %), Z = 3.440, P < 0.01], while the postoperative proportions of CD8 + T cells and regulatory T cells in the total endoscopic group were lower than those in the open group [(26±11)% vs. (30±10)%, t = 2.375, P = 0.018; 3.37% (5.00%, 6.70%) vs. 4.48% (5.70%, 7.20%), Z = 3.057, P = 0.002]. Postoperative carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) in the total endoscopy were lower than those in the open group group [0.96 μg/L (0.54 μg/L, 1.50 μg/L) vs. 1.27 μg/L (0.70 μg/L, 2.98 μg/L), Z = 2.745, P = 0.036; 8.07 U/ml (5.48 U/ml, 13.07 U/ml) vs. 10.80 U/ml (6.54 U/ml, 19.93 U/ml), Z = 2.690, P = 0.043]. Conclusion:Compared with open surgery, total laparoscopic radical gastrectomy has less trauma and stress response, and has less impact on the gastrointestinal and immune function of patients, and the levels of tumor markers CEA and CA199 are low.

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