A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

Objective To investigate the anti-tumor effect of Job's tears oral solution on lung cancer mice.Methods Observe the histopathological morphology of the tumor;Flow cytometry detected the changes in the levels of CD4+T and CD8+T in splenic lymphocytes;Elisa detected the contents of immunoglobulins IgA,IgG,IL-2 and IFN-γ;Blood routine was detected;the kit determined the levels of liver and kidney glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)content;Serum alanine aminotransferase(ALT),alkaline phosphatase(ALB),azelaic transaminase(AST),urea nitrogen(BUN),and blood creatinine(CRE)were measured in each group of mice.The transcriptome was found differential genes and pathway enrichment was performed.Western blot was used to detect the expression of proteins related to IL-17 signaling pathway(STAT3,NF-κB,VEGF)and TNF signaling pathway(PI3K/AKT,MAPK,JNK).Results Tumor histopathological and morphological changes were obvious in each administration group,and the heterogeneity was gradually reduced.Compared with the cisplatin group,the levels of CD4+T,CD8+T,CD4+T/CD8+T,IL-2,IFN-γ,and IgG in the Job's tears group were significantly increased(P<0.01).The blood routine results:compared with the model group,WBC,RBC,HGB,PLT,Lym%and GR%in the Job's tears group decreased significantly(P<0.01);Compared with the cisplatin group,WBC,RBC,PLT,HGB and Lym%in the Job's tears group increased significantly(P<0.01).The antioxidant indexes of liver and kidney showed that the levels of GSH and SOD in the liver and kidney tissues of the Job's tears group increased significantly(P<0.01),and the level of MDA decreased significantly(P<0.01).Effects on liver and kidney function indexes in mice AST,ALT,BUN and CRE decreased significantly in the Job's tears group(P<0.01),and ALB level increased significantly in the Job's tears group(P<0.01).Transcriptome results,Job's tears high-dose group mainly exerted anti-tumor effects by affecting TNF signaling pathway and IL-17 signaling pathway.Western blot results,in the IL-17 signaling pathway,S-TAT3 and VEGF decreased in the cisplatin group and the Job's tears group compared with the model group(P<0.01),and NF-κB decreased in the Job's tears high-dose group(P<0.01);Compared with the cisplatin group,STAT3 and NF-κB were decreased in the Job's tears group(P<0.01);VEGF was decreased in the Job's tears low-dose group(P<0.01);In the TNF signaling pathway,PI3K and MAPK were decreased in the cisplatin group and Job's tears group(P<0.01);AKT and P-AKT were decreased in the Job's tears group(P<0.01).Compared with the cisplatin group,the Job's tears group AKT,PI3K,and MAPK decreased(P<0.01);P-AKT decreased in the high dose group of Job's tears(P<0.01).Conclusion High-dose Job's tears oral solution inhibits tumor proliferation,attenuates inflammatory response,enhances immunity,improves blood routine and reduces liver and kidney injury in lung cancer mice mainly by inhibiting IL-17 and TNF signaling pathway.

Objective To investigate the anti-tumor effect of Job's tears oral solution on lung cancer mice.Methods Observe the histopathological morphology of the tumor;Flow cytometry detected the changes in the levels of CD4+T and CD8+T in splenic lymphocytes;Elisa detected the contents of immunoglobulins IgA,IgG,IL-2 and IFN-γ;Blood routine was detected;the kit determined the levels of liver and kidney glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)content;Serum alanine aminotransferase(ALT),alkaline phosphatase(ALB),azelaic transaminase(AST),urea nitrogen(BUN),and blood creatinine(CRE)were measured in each group of mice.The transcriptome was found differential genes and pathway enrichment was performed.Western blot was used to detect the expression of proteins related to IL-17 signaling pathway(STAT3,NF-κB,VEGF)and TNF signaling pathway(PI3K/AKT,MAPK,JNK).Results Tumor histopathological and morphological changes were obvious in each administration group,and the heterogeneity was gradually reduced.Compared with the cisplatin group,the levels of CD4+T,CD8+T,CD4+T/CD8+T,IL-2,IFN-γ,and IgG in the Job's tears group were significantly increased(P<0.01).The blood routine results:compared with the model group,WBC,RBC,HGB,PLT,Lym%and GR%in the Job's tears group decreased significantly(P<0.01);Compared with the cisplatin group,WBC,RBC,PLT,HGB and Lym%in the Job's tears group increased significantly(P<0.01).The antioxidant indexes of liver and kidney showed that the levels of GSH and SOD in the liver and kidney tissues of the Job's tears group increased significantly(P<0.01),and the level of MDA decreased significantly(P<0.01).Effects on liver and kidney function indexes in mice AST,ALT,BUN and CRE decreased significantly in the Job's tears group(P<0.01),and ALB level increased significantly in the Job's tears group(P<0.01).Transcriptome results,Job's tears high-dose group mainly exerted anti-tumor effects by affecting TNF signaling pathway and IL-17 signaling pathway.Western blot results,in the IL-17 signaling pathway,S-TAT3 and VEGF decreased in the cisplatin group and the Job's tears group compared with the model group(P<0.01),and NF-κB decreased in the Job's tears high-dose group(P<0.01);Compared with the cisplatin group,STAT3 and NF-κB were decreased in the Job's tears group(P<0.01);VEGF was decreased in the Job's tears low-dose group(P<0.01);In the TNF signaling pathway,PI3K and MAPK were decreased in the cisplatin group and Job's tears group(P<0.01);AKT and P-AKT were decreased in the Job's tears group(P<0.01).Compared with the cisplatin group,the Job's tears group AKT,PI3K,and MAPK decreased(P<0.01);P-AKT decreased in the high dose group of Job's tears(P<0.01).Conclusion High-dose Job's tears oral solution inhibits tumor proliferation,attenuates inflammatory response,enhances immunity,improves blood routine and reduces liver and kidney injury in lung cancer mice mainly by inhibiting IL-17 and TNF signaling pathway.

Objective:To investigate the differences in respiratory work load and oxygenation index improvement between intermittent sighing and progressive lung retraction strategies in patients with acute respiratory distress syndrome(ARDS)related to lung collapse.Methods:Sixty patients with ARDS related to lung collapse admitted from January 2020 to January 2024 were selected and divided into intermittent sighing group(IS group,n=30)and progressive lung re-expansion group(PLR group,n=30)according to different treatment methods.The IS group used an intermittent sighing ventilation mode,while the PLR group adopted a progressive lung re-expansion strategy.The changes in respiratory work load indicators[including work of breathing(WOB),maximum inspiratory pressure(Pmax),transcutaneous oxygen saturation(SpO2)],oxygenation index(PaO2/FiO2),lung compliance(Cst),and mechanical ventilation-related parameters were compared before and after treatment in both groups.Results:After treatment,the respiratory work load was significantly reduced in both groups,with a more pronounced decrease in WOB in the PLR group(P＜0.05);both groups showed significant improvements in oxygenation index,but the degree of improvement was more marked in the PLR group(P＜0.01);lung compliance improved more markedly in the PLR group(P＜0.05);the PLR group had significantly shorter mechanical ventilation time and ICU stay compared to the IS group(P＜0.05).Conclusions:The progressive lung recruitment strategy is better than the intermittent sighing ventilation in improving the respiratory work load,oxygenation index and lung compliance of patients with ARDS related to lung collapse.It can shorten the mechanical ventilation time and ICU hospital stay more effectively,which is worth clinical promotion and application.

Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.

Objective:To investigate the differences in respiratory work load and oxygenation index improvement between intermittent sighing and progressive lung retraction strategies in patients with acute respiratory distress syndrome(ARDS)related to lung collapse.Methods:Sixty patients with ARDS related to lung collapse admitted from January 2020 to January 2024 were selected and divided into intermittent sighing group(IS group,n=30)and progressive lung re-expansion group(PLR group,n=30)according to different treatment methods.The IS group used an intermittent sighing ventilation mode,while the PLR group adopted a progressive lung re-expansion strategy.The changes in respiratory work load indicators[including work of breathing(WOB),maximum inspiratory pressure(Pmax),transcutaneous oxygen saturation(SpO2)],oxygenation index(PaO2/FiO2),lung compliance(Cst),and mechanical ventilation-related parameters were compared before and after treatment in both groups.Results:After treatment,the respiratory work load was significantly reduced in both groups,with a more pronounced decrease in WOB in the PLR group(P＜0.05);both groups showed significant improvements in oxygenation index,but the degree of improvement was more marked in the PLR group(P＜0.01);lung compliance improved more markedly in the PLR group(P＜0.05);the PLR group had significantly shorter mechanical ventilation time and ICU stay compared to the IS group(P＜0.05).Conclusions:The progressive lung recruitment strategy is better than the intermittent sighing ventilation in improving the respiratory work load,oxygenation index and lung compliance of patients with ARDS related to lung collapse.It can shorten the mechanical ventilation time and ICU hospital stay more effectively,which is worth clinical promotion and application.

Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.

Objective:To study the longitudinal trends and spatial clustering characteristics of healthcare service efficiency in China and in North,Northeast,East,Central,South,Southwest,and Northwest China.Methods:The Malmquist index model is used to measure China's healthcare service efficiency from 2012 to 2021,the Dagum Gini coefficient as well as the decomposition method are used to measure the magnitude and source of regional gaps in healthcare service efficiency,and the Kernel density estimation is used to study the longitudinal trend of change and spatial agglomeration characteristics of China's healthcare service efficiency.Results:China's overall healthcare service efficiency is growing,and the inter-regional gap is gradually narrowing,characterized by a concentration trend;the gap in the level of healthcare service efficiency between regions did not widen during the period under examination,but it was found that the gap within some regions was still significant.Conclusion:The national health service efficiency is growing slightly,and the regional gap is generally decreasing,but the Gini coefficient shows that the inter-regional contribution is still the main source of the gap.National health service efficiency is generally concentrated,but some regions are less efficient,with significant internal disparities.

Objective To investigate the protective effect of total saponins of Panax japonicus(TSPJ)against CCl4-induced acute liver injury(ALI)in rats and explore the underlying pharmacological mechanisms.Methods Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water,100 mg/kg biphenyl bisabololol,or 50,100,and 200 mg/kg TSPJ during modeling(n=8).Liver functions(AST,ALT,TBil and ALP)of the rats were assessed and liver pathologies were observed with HE staining.Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue;ELISA was used to determine the levels of T-SOD,GSH-Px,and MDA.Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue.Results Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI.In the rat models of ALI,treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST,ALT,ALP,TBil and MDA and decrease of T-SOD and GSH-Px levels(all P<0.01).The rat models of ALI showed significantly increased expression of p-NF-κB(P<0.01),decreased expressions of PI3K,p-Akt and SIRT6 proteins,and elevated expression levels of p-NF-κB,TNF-α and IL-6 proteins in the liver,which were all significantly improved in the treatment groups(P<0.05 or 0.01).Conclusion TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver viaregulating the PI3K/Akt and SIRT6/NF-κB pathways.

Objective:To study the longitudinal trends and spatial clustering characteristics of healthcare service efficiency in China and in North,Northeast,East,Central,South,Southwest,and Northwest China.Methods:The Malmquist index model is used to measure China's healthcare service efficiency from 2012 to 2021,the Dagum Gini coefficient as well as the decomposition method are used to measure the magnitude and source of regional gaps in healthcare service efficiency,and the Kernel density estimation is used to study the longitudinal trend of change and spatial agglomeration characteristics of China's healthcare service efficiency.Results:China's overall healthcare service efficiency is growing,and the inter-regional gap is gradually narrowing,characterized by a concentration trend;the gap in the level of healthcare service efficiency between regions did not widen during the period under examination,but it was found that the gap within some regions was still significant.Conclusion:The national health service efficiency is growing slightly,and the regional gap is generally decreasing,but the Gini coefficient shows that the inter-regional contribution is still the main source of the gap.National health service efficiency is generally concentrated,but some regions are less efficient,with significant internal disparities.