1.Proteomics and Network Pharmacology Reveal Mechanism of Xiaoer Huatan Zhike Granules in Treating Allergic Cough
Youqi DU ; Yini XU ; Jiajia LIAO ; Chaowen LONG ; Shidie TAI ; Youwen DU ; Song LI ; Shiquan GAN ; Xiangchun SHEN ; Ling TAO ; Shuying YANG ; Lingyun FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):69-79
ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough (AC) by Xiaoer Huatan Zhike granules (XEHT) based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin (OVA) and 100 mg aluminum hydroxide, a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model, low-, medium- and high-dose (1, 5, 20 g·kg-1, respectively) XEHT, and sodium montelukast (1 mg·kg-1) groups (n=6), and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage, and those in the blank and model groups received the same volume of normal saline by gavage, 1 time·d-1. After 10 consecutive days of drug administration, the guinea pigs were stimulated by 1% OVA nebulization, and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) in the bronchoalveolar lavage fluid (BALF) and immunoglobulin G (IgG) and immunoglobulin A (IgA) in the serum. Immunohistochemistry (IHC) was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6, interleukin-1β (IL-1β), and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group, the model group showed increased coughs (P<0.01), elevated levels of CRP, TNF-α, IL-6, and MDA and lowered level of SOD in the BALF (P<0.05, P<0.01), elevated levels of IgA and IgG in the serum (P<0.05, P<0.01), congestion of the lung tissue and infiltration of inflammatory cells, increased expression of IL-6 and TNF-α (P<0.01), large areas of low electron density edema in type Ⅱ epithelial cells, obvious swelling and vacuolization of the organelles, karyopyknosis or sparse and dissolved chromatin, and up-regulated mRNA levels of IL-6, IL-1β, and TNF-α (P<0.01). Compared with the model group, the drug administration groups showed reduced coughs (P<0.01), lowered levels of CRP, TNF-α, IL-6, and MDA and elevated level of SOD in the BALF (P<0.05, P<0.01), alleviated lung tissue congestion, inflammatory cell infiltration, and type Ⅱ epithelial cell injury, and decreased expression of IL-6 and TNF-α (P<0.01). In addition, the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG (P<0.05, P<0.01). The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6, IL-1β, and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α (P<0.05, P<0.01). Phospholipase D, mammalian target of rapamycin (mTOR), and epidermal growth factor receptor family of receptor tyrosine kinase (ErbB) signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D, mTOR, and ErbB signaling pathways.
2.Improvement of myocardial injury by traditional Chinese medicine:mitochondrial calcium homeostasis mediates macrophage autophagy and pyroptosis pathway
Lingyun LIU ; Guixin HE ; Weibin QIN ; Hui SONG ; Liwen ZHANG ; Weizhi TANG ; Feifei YANG ; Ziyi ZHU ; Yangbin OU
Chinese Journal of Tissue Engineering Research 2025;29(6):1276-1284
BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.
3.Mechanism of action of microorganisms in tumor neoantigen immunotherapy and its application progress
International Journal of Biomedical Engineering 2025;48(5):516-522
Due to its high immunogenicity and tumor specificity, tumor neoantigen has emerged as an important target for tumor immunotherapy. The capacity of microorganisms to modulate the immune system, thereby activating neoantigen-specific T cells and utilizing the phenomenon of molecular mimicry, underscores their potential for broad application in the development of cancer vaccines. In this review, the mechanisms of action of microorganisms in neoantigen immunotherapy were examined, and the applications of bacteria and their derivatives, viral vectors, and fungal vectors in delivering tumor neoantigens were summarized. The significance of microorganisms in tumor neoantigen immunotherapy was underscored, and a reference for future research and clinical application was provided.
4.Effect of nourishing yin and tonifying yang method on inflammatory response and bone metabolism in patients with type 2 diabetes mellitus complicated with osteoporosis
Lingyun MA ; Defeng LIU ; Airu LIU ; Nana ZHANG ; Jiatong SONG ; Weiyu BIAN ; Yujuan JI ; Yunyan JI ; Wendong LI ; Xiu'e CHI
International Journal of Traditional Chinese Medicine 2025;47(3):312-317
Objective:To investigate the effect of nourishing yin and tonifying yang method on inflammatory response and bone metabolism in patients with T2DM complicated with osteoporosis (OP).Methods:A randomized controlled trial. From January 2022 to December 2023,80 patients with T2DM and OP in our hospital were selected as the observation objects, and they were divided into two groups by random number table method, with 40 cases in each group.On the basis of conventional treatment, the control group chewed vitamin D calcium chewable tablets, and the observation group added nourishing yin and tonifying yang Chinese medicine.Both groups were treated for 6 months. TCM syndrome scores were performed before and after treatment ;the levels of fasting blood glucose (FPG), 2 hPG and HbA1c were detected by intelligent blood glucose monitor;the levels of serum neutrophils and lymphocytes were detected by automatic blood analyzer, and the neutrophil/lymphocyte ratio (NLR) was calculated;the levels of serum IL-1β and TNF-α were detected by automatic chemiluminescence analyzer, the levels of type I procollagen amino terminal propeptide (PINP), type I collagen carboxy terminal peptide β special sequence (β-CTX) and 25-hydroxy vitamin D3 [25-(OH)D3] were detected by ELISA;Bone mineral density (BMD) was detected by bone mineral density detector. The adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 92.5 %(37/40) in the observation group and 75.0 % (30/40) in the control group,the difference between the two groups was statistically significant ( χ2=4.50, P=0.034).After treatment, the scores of soreness and weakness of waist and knees, soreness and pain of waist and back, clear and long urine, pale tongue and white coating in the observation group were lower than those in the control group ( t=3.11, 3.75, 3.51, 3.74, P<0.01);the levels of serum FPG, 2 hPG and HbA1c in the observation group were lower than those in the control group ( t=3.11,3.20,3.39, P<0.01).The levels of serum NLR (2.63 ± 0.68 vs. 3.24 ± 0.79, t=3.70), IL-1β [(81.65 ± 8.30) ng/L vs. (89.03 ± 8.98) ng/L, t=3.82] and TNF-α [(35.14 ± 5.11) μg/L vs. (39.96 ± 5.38) μg/L, t=4.11] in the observation group were lower than those in the control group ( P<0.01). After treatment, the levels of PINP [(29.83 ± 3.92) ng/L vs. (34.02 ± 4.03) ng/L, t=4.71] and β-CTX [(21.30 ± 3.95 ) ng/L vs. (25.32 ± 4.18) ng/L, t=4.42] in the observation group were lower than those in the control group ( P<0.01), the levels of 25-(OH)D3 [(42.86 ± 5.12) μg/L vs. (38.08 ± 4.55) μg/L, t=4.41] and BMD [(0.90 ± 0.18) g/cm 3vs. (0.78 ± 0.16) g/cm 3, t=3.15] were higher than those in the control group ( P<0.01).During the treatment, the incidence of adverse reactions was 12.5% (5/40) in the observation group and 10.0 % (4/40) in the control group,there was no significant difference between the two groups ( χ2=0.13, P=0.723). Conclusion:The method of nourishing yin and tonifying yang can effectively improve the TCM syndromes of T2DM patients with OP, reduce the levels of blood glucose and inflammatory factors, improve bone metabolism, improve clinical efficacy and have good treatment safety.
5.Effect of Scutellariae Radix-Coptidis Rhizoma on Stabilization of Atherosclerotic Vulnerable Plaques via Inhibition of TLR4/MyD88/NF-κB Signaling Pathway
Lingyun JI ; Qiaolan WU ; Zetao CHEN ; Chunlei GE ; Weida CHEN ; Ting SONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):28-36
ObjectiveTo observe the effect of Scutellariae Radix-Coptidis Rhizoma on plaque stability in atherosclerotic (AS) mice and to explore its possible mechanism of action based on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. MethodTen normal C57BL/6J mice were used as the normal group, and the same strain of ApoE knockout (ApoE-/-) mice were fed with a high-fat diet for 12 weeks to construct an atherosclerosis model. Mice were randomly divided into five groups, namely the model group, the atorvastatin group, and the Scutellariae Radix-Coptidis Rhizoma low-, medium-, and high-dose groups, with ten mice in each group. Then normal and model groups were given equal volume of saline gavage, and the low-, medium-, high-dose Scutellariae Radix-Coptidis Rhizoma groups were given 1.95, 3.9, 7.8 g·kg-1 of the drug by gavage for 8 weeks, respectively. The general state of mice was observed. Hematoxylin-eosin staining was utilized to observe the pathology of aortic root plaques and calculate the percentage of plaque area. Masson staining and oil red O staining combined with immunohistochemistry of F4/80 and α-SMA were used to detect the plaque components of aortic root plaques and calculate the plaque vulnerability index. Enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western blot was applied to detect the protein expression levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), TLR4, MyD88, NF-κB p65, and phosphorylation (p) -NF-κB p65 in the aortic tissues of mice in each group. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) assay was employed to detect the expression levels of MMP-2, MMP-9, TLR4, and MyD88, NF-κB p65 mRNA. ResultCompared with the model group, the general state of the mice in each medication group was improved, and no obvious side effects were observed. Compared with the model group, the percentage of plaque area in the aortic root of AS mice was significantly reduced in the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups (P<0.05). The content of collagen fibers and smooth muscle cells in the plaques of the high-dose Scutellariae Radix-Coptidis Rhizoma group was significantly increased (P<0.01), and the content of lipids and macrophages was significantly reduced (P<0.05), the plaque vulnerability index of each dose group of Scutellariae Radix-Coptidis Rhizoma was significantly reduced, with significant reduction of the medium- and high-dose groups (P<0.01). MMP-2 and MMP-9 protein and mRNA expression levels in aortic tissues were significantly reduced in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups (P<0.05). The serum levels of TNF-α and IL-6 were significantly reduced in AS mice in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups (P<0.05). In the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups, the levels of TLR4, MyD88 protein, and mRNA expression in aortic tissues were significantly reduced (P<0.05), and the level of NF-κB p65 phosphorylation in aortic tissues was significantly reduced (P<0.05). ConclusionScutellariae Radix-Coptidis Rhizoma may play an anti-inflammatory and stabilizing role by inhibiting the TLR4/MyD88/NF-κB signaling pathway.
6.Construction of competitive endogenous RNA network mediated by lung ischemia-reperfusion core genes
Xiaofeng LI ; Mingzheng TANG ; Xixi LIU ; Ziqing SONG ; Guoxin ZHANG ; Kaiyin YANG ; Lingyun ZHANG
Organ Transplantation 2024;15(1):70-81
Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.
7.Scutellariae Radix-Coptidis Rhizoma Treats Atherosclerosis via NLRP3 Inflammasome-mediated Pyroptosis of Macrophages
Lingyun JI ; Qiaolan WU ; Zetao CHEN ; Chunlei GE ; Weida CHEN ; Ting SONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):121-130
ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma (SRCR) on atherosclerosis (AS) in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes. MethodApoE-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model, atorvastatin (5 mg·kg-1), and low-, medium-, and high-dose (1.95, 3.9, 7.8 g·kg-1, respectively) SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration, hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 (EMR1)/NLRP3 and EMR1/gasdermin D (GSDMD). The serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were determined by enzyme-linked immunosorbent assay (ELISA). The protein levels of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, cleaved Caspase-1, GSDMD, N-terminus of GSDMD (GSDMD-NT), pro-IL-1β, IL-1β, and IL-18 were determined by Western blot, and the mRNA levels of NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the control group, the model group showed obvious plaques, elevated serum levels of TG, TC, LDL-C, IL-1β, and IL-18 (P<0.01), lowered serum level of HDL-C (P<0.01), and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques (P<0.01). Compared with the model group, SRCR, especially at the medium and high doses, alleviated the plaque pathology, reduced the lipid content in plaques (P<0.05, P<0.01), recovered the serum lipid levels (P<0.05), reduced the macrophage recruitment (P<0.01), activation of NLRP3 inflammasomes, and pyroptosis in aortic root plaques (P<0.05), lowered the serum IL-1β and IL-18 levels (P<0.01), and down-regulated the protein levels of NLRP3, ASC, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-NT, pro-IL-1β, IL-1β, and IL-18 (P<0.05) and the mRNA levels of NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-18 in the aortic tissue (P<0.05). ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.
8.Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy
Kailian ZHENG ; Xinyu LIU ; Xiaohan SHI ; Huan WANG ; Xiaoyi YIN ; Xinqian WU ; Lingyun GU ; Penghao LI ; Yikai LI ; Wei JING ; Shiwei GUO ; Bin SONG ; Suizhi GAO ; Gang JIN
Chinese Journal of Surgery 2024;62(10):938-946
Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.
9.Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy
Kailian ZHENG ; Xinyu LIU ; Xiaohan SHI ; Huan WANG ; Xiaoyi YIN ; Xinqian WU ; Lingyun GU ; Penghao LI ; Yikai LI ; Wei JING ; Shiwei GUO ; Bin SONG ; Suizhi GAO ; Gang JIN
Chinese Journal of Surgery 2024;62(10):938-946
Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.
10.Predictive value of left ventricular global longitudinal peak strain for the prognosis of septic patients
Lingyun ZUO ; Wenliang SONG ; Yongjun LIU ; Jianfeng WU ; Xiangdong GUAN ; Xiang SI
Chinese Critical Care Medicine 2024;36(4):353-357
Objective:To investigate the predictive value of left ventricular global longitudinal peak strain (GLPS) for the prognosis of septic patients.Methods:A prospective cohort study was conducted. Patients diagnosed with sepsis and admitted to the intensive care unit (ICU) of the First Affiliated Hospital, Sun Yat-sen University from December 2018 to November 2019 were enrolled. The patient characteristics, cardiac ultrasound parameters [left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), four-dimensional ejection fraction (4DEF), GLPS] and cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT)] within 24 hours of ICU admission, organ support therapies, severity of illness, and prognostic indicators were documented. The differences in clinical parameters between patients with varying outcomes during ICU hospitalization were assessed. Pearson correlation analysis was employed to explore the correlation between GLPS and other cardiac systolic parameters, as well as the associations between various cardiac systolic parameters and sequential organ failure assessment (SOFA) score. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive capacity of cardiac ultrasound parameters and cardiac biomarkers for death during ICU hospitalization in septic patients.Results:A total of 50 septic patients were enrolled, with 40 surviving and 10 dying during ICU hospitalization, resulting in a mortality of 20.0%. All patients in the death group were male. Compared with the survival group, the patients in the death group were older, had a higher prevalence of diabetes mellitus, and received continuous renal replacement therapy (CRRT) more frequently, additionally, they exhibited more severe illness and had longer length of ICU stay. The levels of GLPS and cTnT in the death group were significantly elevated as compared with the survival group [GLPS: -7.1% (-8.5%, -7.0%) vs. -12.1% (-15.5%, -10.4%), cTnT (μg/L): 0.07 (0.05, 0.08) vs. 0.03 (0.02, 0.13), both P < 0.05]. However, no statistically significant difference was found in other cardiac ultrasound parameters or cardiac biomarkers between the two groups. Pearson correlation analysis revealed a negative correlation between GLPS and LVEF ( r = -0.377, P = 0.014) and 4DEF ( r = -0.697, P = 0.000), while no correlation was found with RVEF ( r = -0.451, P = 0.069). GLPS demonstrated a positive correlation with SOFA score ( r = 0.306, P = 0.033), while LVEF ( r = 0.112, P = 0.481), RVEF ( r = -0.134, P = 0.595), and 4DEF ( r = -0.251, P = 0.259) showed no significant correlation with SOFA score. ROC curve analysis indicated that the area under the ROC curve (AUC) of GLPS for predicting death during ICU hospitalization in septic patients was higher than other cardiac systolic parameters, including LVEF, RVEF, and 4DEF, as well as cardiac biomarkers NT-proBNP and cTnT (0.737 vs. 0.628, 0.556, 0.659, 0.580 and 0.724). With an optimal cut-off value of -14.9% for GLPS, the sensitivity and negative predictive value reached to 100%. Conclusion:GLPS < -14.9% within 24 hours of ICU admission in septic patients indicated a reduced risk of death risk during ICU hospitalization, while also correlating with the severity of organ dysfunction in this patient population.

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