Objective To explore the protective effect of polydatin and its mechanism on secondary liver injury in silicosis rats based on network pharmacology and animal experiments. Methods i) Network pharmacology study. Based on multiple databases, the targets of polydatin effect related to silicosis and liver injury were collected, and the common targets of polydatin-silicosis-liver injury were screened to construct a protein-protein interaction network. Enrichment analyses were performed to identify core targets involved in the effects of polydatin on silicosis-associated secondary liver injury. The mechanism of action of polydatin in relieving silicosis and silicosis-associated secondary liver injury was investigated, in which polydatin served as molecular docking ligand. ii) Animal experimental validation. Specific pathogen free male SD rats were randomly divided into three groups, with 10 rats per group. Rats in the model and intervention groups received 1 mL of a silica suspension at a mass concentration of 50 g/L for modeling using a one-time non-tracheal exposure method. Then rats in the intervention group were injected intraperitoneally with polydatin solution at 30 mg/kg body weight, once daily starting from the first day after silica exposure, whereas rats in the control group received no treatment. Lung and liver histopathology of rats, which were randomly sacrificed on days 28 and 56 post-exposure in both groups, were examined. Biomarkers of liver injury and hepatic oxidative stress were measured, and hepatic expression of nuclear factor erythroid 2-related factor 2 (NRF2) related proteins was detected by Western blotting. Results i) Network pharmacology study results. A total of 137 polydatin-related targets, 14 812 silicosis-related targets, and 3 038 liver injury-related targets were identified, among which 69 were common targets and 28 were key targets. Gene Ontology analysis indicated that the key targets were involved in 1 883 pathways. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified 137 pathways related to the targets. Molecular docking showed good binding affinities between polydatin and B-cell lymphoma 2 (BCL2), interleukin 6 (IL-6), tumor necrosis factor (TNF), and NRF2. ii) Animal experimental validation results. Compared with the control group, rats in the model group showed increased collagen deposition in both lung and liver tissues, with hepatic degeneration, necrosis, and inflammatory cell infiltration on days 28 and 56 after silica exposure. The collagen in lung and liver tissues of rats on days 28 and 56 after silica exposure increased in the model group compared with the control group (all P<0.05). Meanwhile, serum alanine aminotransferase and aspartate aminotransferase activities, hepatic lactate dehydrogenase 5 activities and NADPH: quinone oxidoreductase 1 (NQO1) expression in liver tissue increased (all P<0.05), whereas hepatic superoxide dismutase activity and NRF2 expression were decreased (all P<0.05). The level of malondialdehyde and the relative expression of heme oxygenase-1 (HO-1) protein in liver tissue in rat of model group were higher than those in the control group (all P<0.05). These alterations were ameliorated in rats of the intervention group compared with the model group (all P<0.05). Conclusion Polydatin exerts protective effects against secondary liver injury in rats with silicosis. These effects may be mediated by regulation of core targets such as BCL2, IL6, TNF, and NRF2, modulation of inflammatory pathways including TNF and IL17 signaling, and activation of the NRF2/HO-1 pathway, thereby exerting synergistic anti-inflammatory, antioxidant, and antifibrotic effects via the "lung-liver axis".

Objective:To explore the active ingredients of shengxian and jinshuiliujun decoction with the method of network pharmacology, and to verify the experimental mechanism of its treatment of silicosis.Methods:In May 2023, the active ingredients and targets of drugs in shengxian and jinshuiliujun decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The target of silicosis disease was screened by databases such as Genecards, Disease Gene Network (DisGeNET), Comparative Toxicogenomics Database (CTD), etc. The screened drug targets and disease targets were intersected to obtain the target set of shengxian and jinshuiliujun decoction for the treatment of silicosis. Protein-protein interaction (PPI) network analysis was performed on the target set through STRING database, and core target genes were screened. GO enrichment analysis and KEGG pathway analysis of intersection genes were performed based on Metascape database, and molecular docking verification of key components and targets of shengxian and jinshuiliujun decoction was carried out. Twenty-four adult male SD rats with SPF grade were randomly divided into control group, model group and TCM intervention group, with 8 rats in each group. The dust-stained rat model was prepared by non-tracheal exposure of 1 ml silica suspension (50 mg/ml) in one go, and TCM intervention group was given shengxian and jinshuiliujun decoction[6 g/ (kg·d) ] on the second day. The CT of the lungs of each group was observed 28 days after the dust-stained rat model. Paraffin sections of rat lung tissues were prepared and stained with Hematoxylin-Eosin (HE) and Masson. Western blot was used to verify the expression of core target-related proteins in rat lung tissues after the intervention of shengxian and jinshuiliujun decoction for 28 days, and the differences in protein expression between groups were compared by one-way analysis of variance.Results:A total of 205 active ingredients and 3345 active compounds were selected from shengxian and jinshuiliujun decoction, corresponding to 281 targets, among which 240 targets were related to silicosis. Serine/threonine kinase 1 (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF) and interleukin (IL) 6 may be the key targets of shengxian and jinshuiliujun decoction in the treatment of silicosis. Through enrichment analysis, 30 GO entries and 20 potential signaling pathways were screened according to P-value, including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) and cancer signaling pathways. Molecular docking showed that the active compounds of shengxian and jinshuiliujun decoction had good binding with the core target proteins, and the strongest binding properties were beta-sitosterol and TNF-α (-10.45 kcal/mol). In animal experiments, the inflammatory infiltration and fibrosis of lung tissue of rats in TCM intervention group were significantly improved. Compared with control group, the levels of TNF-α, IL-1β, IL-6 and NF-κB in lung tissue of model group were significantly increased ( P<0.05). Compared with model group, the lung injury of rats in TCM intervention group was significantly improved, and the expressions of TNF-α, IL-1β, IL-6 and NF-κB were significantly decreased ( P<0.05) . Conclusion:Shengxian and jinshuiliujun decoction in the treatment of silicosis may play an anti-fibrosis role by inhibiting the NF-κB signal transduction pathway mediated by inflammatory factors such as TNF-α and IL-1β, which provides a reference for further exploring the material basis and mechanism of its action.

Objective:To explore the active ingredients of shengxian and jinshuiliujun decoction with the method of network pharmacology, and to verify the experimental mechanism of its treatment of silicosis.Methods:In May 2023, the active ingredients and targets of drugs in shengxian and jinshuiliujun decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The target of silicosis disease was screened by databases such as Genecards, Disease Gene Network (DisGeNET), Comparative Toxicogenomics Database (CTD), etc. The screened drug targets and disease targets were intersected to obtain the target set of shengxian and jinshuiliujun decoction for the treatment of silicosis. Protein-protein interaction (PPI) network analysis was performed on the target set through STRING database, and core target genes were screened. GO enrichment analysis and KEGG pathway analysis of intersection genes were performed based on Metascape database, and molecular docking verification of key components and targets of shengxian and jinshuiliujun decoction was carried out. Twenty-four adult male SD rats with SPF grade were randomly divided into control group, model group and TCM intervention group, with 8 rats in each group. The dust-stained rat model was prepared by non-tracheal exposure of 1 ml silica suspension (50 mg/ml) in one go, and TCM intervention group was given shengxian and jinshuiliujun decoction[6 g/ (kg·d) ] on the second day. The CT of the lungs of each group was observed 28 days after the dust-stained rat model. Paraffin sections of rat lung tissues were prepared and stained with Hematoxylin-Eosin (HE) and Masson. Western blot was used to verify the expression of core target-related proteins in rat lung tissues after the intervention of shengxian and jinshuiliujun decoction for 28 days, and the differences in protein expression between groups were compared by one-way analysis of variance.Results:A total of 205 active ingredients and 3345 active compounds were selected from shengxian and jinshuiliujun decoction, corresponding to 281 targets, among which 240 targets were related to silicosis. Serine/threonine kinase 1 (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF) and interleukin (IL) 6 may be the key targets of shengxian and jinshuiliujun decoction in the treatment of silicosis. Through enrichment analysis, 30 GO entries and 20 potential signaling pathways were screened according to P-value, including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) and cancer signaling pathways. Molecular docking showed that the active compounds of shengxian and jinshuiliujun decoction had good binding with the core target proteins, and the strongest binding properties were beta-sitosterol and TNF-α (-10.45 kcal/mol). In animal experiments, the inflammatory infiltration and fibrosis of lung tissue of rats in TCM intervention group were significantly improved. Compared with control group, the levels of TNF-α, IL-1β, IL-6 and NF-κB in lung tissue of model group were significantly increased ( P<0.05). Compared with model group, the lung injury of rats in TCM intervention group was significantly improved, and the expressions of TNF-α, IL-1β, IL-6 and NF-κB were significantly decreased ( P<0.05) . Conclusion:Shengxian and jinshuiliujun decoction in the treatment of silicosis may play an anti-fibrosis role by inhibiting the NF-κB signal transduction pathway mediated by inflammatory factors such as TNF-α and IL-1β, which provides a reference for further exploring the material basis and mechanism of its action.

Objective:To examine the occurrence of complications in elderly patients who have undergone radical surgery for colorectal cancer.Additionally, this study aims to identify the various risk factors associated with these complications.Methods:This study included elderly patients with colorectal cancer who underwent radical surgery at Beijing Hospital between January 2013 and December 2020.These patients were divided into two groups based on their age.In this study, we examined a total of 906 patients who underwent surgery, with 695 patients under the age of 80 and 211 patients aged 80 and above.We classified postoperative complications into two categories: medical and surgical complications.Our analysis compared comorbidities, clinicopathological factors, perioperative variables, and postoperative morbidity and mortality between the two age groups.We utilized both univariate and multivariate analyses to identify any potential risk factors for postoperative morbidity.Results:When comparing patients under 80 years old to those aged 80 or older, it was found that the latter group had a lower body mass index, worse ASA scores, and more comorbidities.Additionally, the proportion of elderly patients with right colon cancer, pT3-4, and pN+ disease was higher compared to those under 80 years old.Furthermore, the elderly patients aged 80 or older had a lower rate of laparoscopic surgery compared to those under 80 years old.The study found that elderly patients aged 80 years and older had significantly shorter operation times compared to those younger than 80 years[(191.0±70.6)min vs.(214.0±83.3)min, t=3.642, P<0.001]. However, the overall complication rate was higher in the elderly group(32.7%)than in the younger group(22.6%)( χ2=8.839, P=0.004). Upon further analysis, it was found that medical complications increased significantly(20.9% vs.7.5%, χ2=30.547, P<0.001), whereas the rate of surgical complications did not show any statistical difference(15.6% vs.16.4%, χ2=0.069, P=0.832). The mortality rate during the perioperative period was found to be significantly higher in elderly patients aged 80 years and above compared to those below 80 years(1.9% vs.0.3%, χ2=6.316, P=0.029). Further analysis revealed that age was an independent risk factor for medical complications( HR=2.822, 95% CI: 1.804-4.414, P<0.001). Laparoscopic surgery has been shown to significantly decrease surgical complications( HR=0.475, 95% CI: 0.317-0.711, P=0.001). However, if the operation time exceeds 200 minutes, there is a significant increase in surgical complications( HR=1.942, 95% CI: 1.278-2.888, P=0.002). Conclusions:The incidence of postoperative medical complications in very elderly patients with colorectal cancer who undergo radical surgery has risen, although the rate of surgical complications has remained steady.Radical surgery for elderly patients with colorectal cancer is both safe and feasible, but it is important to prioritize the prevention and management of medical complications.

Objective:To analyze the short-term effects of prophylactic intraperitoneal hyperthermic chemotherapy(HIPEC)on elderly patients diagnosed with gastric cancer.Methods:The study enrolled patients with gastric cancer who underwent curative gastrectomy combined with postoperative HIPEC at Beijing Hospital between January 2017 and September 2022.The patients were divided into two groups based on age: young patients(age <65 years, n=45)and elderly patients(age≥65 years, n=32). The study evaluated the safety of HIPEC prophylactic application in elderly patients with gastric cancer by comparing their clinicopathological data, postoperative recovery, complications, and laboratory tests with those of another group of patients.Results:The study found that the elderly patients had a higher rate of comorbidities and higher ASA scores compared to the younger patients.Additionally, the elderly patients received HIPEC treatment less frequently than the younger patients( P=0.030). The proportion of young patients receiving one, two, and three times of HIPEC treatment was 8.9%, 57.8%, and 33.3%, respectively, while the proportion of elderly patients receiving the same was 28.1%, 59.4%, and 12.5%, respectively.The study found no significant differences in pathological characteristics between the two groups, including tumor stage, type, location, and differentiation degree.Additionally, there was no difference in the proportion of laparoscopic gastrectomy, type of resection, combined resection, duration of the operation, and intraoperative blood loss between elderly and young patients.The rate of complications between the two groups was also not significantly different(20.0% vs.21.9%; P=0.100). The mean duration of hospitalization after radical gastrectomy was 14.0 days in the young group and 15.5 days in the elderly group, respectively( P=0.480). Conclusions:Elderly patients with gastric cancer treated with radical gastrectomy combined with HIPEC did not experience increased postoperative complications or hospital stay compared to young patients, suggesting that prophylactic HIPEC was safe and feasible for elderly patients with locally advanced gastric cancer, as evidenced by favorable postoperative recovery and laboratory tests.

Objective:To investigate the short-term and long-term efficacy of laparoscopic surgery for colorectal cancer in elderly patients aged 80 and over.Methods:This study included patients aged 80 and over with sigmoid or rectal cancer who had undergone radical surgery in Beijing Hospital between January 2013 and December 2020.Of the enrolled patients, 47 underwent laparoscopic surgery, and 44 received open surgery.After 1∶1 propensity score matching(PSM), there were 32 cases in each group.Patient clinicopathological characteristics, surgery data, post-operative outcomes and long-term survival were compared.Results:Before PSM, there were significant differences in sex composition and tumor locations between the open surgery and laparoscopic surgery groups.After PSM, there was no significant difference in clinicopathological characteristics between the two groups.Before and after PSM, the operative time for laparoscopic surgery was statistically longer than that for open surgery.The intraoperative blood loss, the postoperative complication rate and the number of harvested lymph nodes were not significantly different between the two groups before and after PSM.Before and after PSM, the postoperative hospital stay in the laparoscopic operation group was shorter than that in the open surgery group, but the difference was not statistically significant.Before PSM, the 1-year, 3-year and 5-year survival rates of the open surgery group were 92.4%, 69.5% and 58.1%, respectively, and the 1-year, 3-year and 5-year survival rates of laparoscopic group were 91.3%, 79.8% and 69.5%, respectively.There was no significant difference in overall survival between the two groups before PSM( χ2=0.591, P=0.422). After PSM, the 1-year, 3-year and 5-year survival rates in the open surgery group were 89.3%, 67.1% and 52.2%, respectively, and the 1-year, 3-year and 5-year survival rates in the laparoscopic surgery group were 90.6%, 74.3% and 65.0%, respectively.There was no significant difference in the overall survival between the two groups after PSM( χ2=1.316, P=0.251). Conclusions:For elderly colorectal cancer patients aged 80 and over, laparoscopic surgery and open surgery have similar rates of complications and long-term survival.This study provides evidence for the safety of laparoscopic surgery.Further prospective randomized controlled clinical trials are needed to confirm these findings.

Objective:To investigate the effects of Dexmedetomidine on postoperative pain and stress response in elderly patients undergoing laparoscopic colorectal cancer surgery.Methods:A total of 150 elderly patients who had undergone laparoscopic radical resection of colorectal cancer in our hospital from June 2019 to December 2020 were divided into two groups using the random number table method, the control group(n=75)and the study group(n=75). In the study group, Dexmedetomidine 0.5 μg/kg was injected intravenously over 10 min before induction of anesthesia and maintained at 0.5 μg/kg/h until 30 min before the end of surgery.Changes in heart rate, mean arterial pressure, postoperative pain and stress response index scores were compared between the two groups.Results:The MAP and HR in the study group at T1(10 min after administration), T2(immediately after endotracheal intubation), T3(30 min after pneumoperitoneum)and T4(leaving the operating room)were significantly lower than in the control group( P<0.05); The concentrations of norepinephrine and epinephrine in the study group were lower than those in the control group at T2, T3 and T4(all P<0.05); Pain scores of patients in the study group were lower than those in the control group at T4 and T5( P<0.05); Compared with the control group, the study group used less intraoperative Sufentanil[(65.5±7.0)μg vs.(76.2±7.6)μg, t=8.968, P=0.000], needed a lower number of PCIA compressions 24 h after surgery[(6.3±2.3) vs.(9.5±3.0), t=7.331, P=0.000]and had a shorter length of PACU stay[(23.4±4.0)min vs.(30.2±5.7)min, t=8.457, P=0.000]. Conclusions:Dexmedetomidine used in laparoscopic colorectal cancer surgery in elderly patients can reduce the use of sufentanil and the length of PACU stay time, improve postoperative pain scores and reduce stress response, and therefore should be recommended.

In Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using R-lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5μm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, V/V), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5-300 ng/mL for both, R- and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enantiomers. The relative standard deviation (RSD) of intra- and inter-day precision of R-ilaprazole and S-ilaprazole was less than 10.9％, and the relative error accuracy (RE) ranged from -0.5％-2.0％. Finally, the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate.

Objective To investigate the acute adverse reactions of craniospinal irradiation with helical tomotherapy in medulloblastoma patients and its risk factors. Methods A total of 20 patients with medulloblastoma who received craniospinal irradiation with helical tomotherapy between October 2012 and September 2016 in Air Force General Hospital were selected. The acute adverse events of 20 patients during the treatment were record. According to National Cancer Institute Common Terminology Criteria Adverse Events (NCI-CTCAE) version 4.0, the adverse reactions were divided into the mild group (grade 0-Ⅱ) and severe group (grade Ⅲ-Ⅳ) adverse reactions. And the risk factors were also analyzed. Results The non-hematological adverse reactions included fatigue (55％), vomiting (45％) and headache (25％). The hematological adverse reactions included leukopenia (95％), thrombocytopenia (55％) and lower hemoglobin (45％), and the incidence of severe adverse reactions was 35％ (7/20), 20％ (4/20) and 0 ( 0/20 ) , respectively . Leukopenia occurred in 18 patients ( 90％) at the beginning of radiotherapy within 2 weeks, and thrombocytopenia occurred in 8 patients (40％) at the beginning of radiotherapy after 2 weeks. Single factor analysis showed that there were no statistical differences in hematological adverse events of gender, age and radiation dose of spinal cord (all P>0.05). The incidence of leukopenia for the patients who received the chemotherapy before the radiotherapy was higher than that for the patients without the chemotherapy before the radiotherapy (P< 0.05). Conclusions The hematological adverse reactions were the major acute adverse events during the craniospinal irradiation with helical tomotherapy in patients with medulloblastoma. Theincidence of leukopenia and thrombocytopenia is common, and the incidence of hematological adverse reactions is higher after the chemotherapy. Thus, the close monitoring of hemogram change and treatment of hematological adverse reactions in time during the radiotherapy should be taken into the consideration.