ObjectiveTo investigate the effects of Maxing Kugan decoction （MKD） on inflammatory response and apoptosis in rats with oleic acid （OA）-induced acute lung injury （ALI） and explore its mechanism of action. MethodsSixty Sprague-Dawley （SD） rats were randomly assigned into six groups： a control group， a model group， a dexamethasone-treated group （2 mg·kg^-1）， and three MKD-treated groups at low， medium， and high doses （3.1， 6.2，12.4 g·kg^-1）. Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA （0.2 mL·kg^-1）. Twelve hours after modeling， blood gas analyses were conducted， and the wet-to-dry （W/D） weight ratio of lung tissue was measured for each group. Additionally， enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the bronchoalveolar lavage fluid （BALF） of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin （HE） staining and TdT-mediated dUTP-biotin nick end labeling （TUNEL） assays， and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor kappa-B （NF-κB） signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the control group， the model group exhibited a significant decrease in partial pressure of oxygen （PaO₂）， blood oxygen saturation （SaO₂）， and oxygenation index （PaO₂/FiO₂）， along with a marked increase in partial pressure of carbon dioxide （PaCO₂） and lung W/D ratio （P<0.01）. Additionally， levels of TNF-α， IL-6， and IL-1β in BALF were significantly elevated （P<0.01）. Histopathological analysis of lung tissue showed significant inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK， NF-κB p65， inhibitor of NF-κB （IκBα）， B-cell lymphoma-2 associated x protein （Bax）， and Caspases-3， as well as the protein expression levels of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3， while the mRNA and protein expression of Bcl-2 was downregulated （P<0.01）. Compared with the model group， MKD significantly elevated PaO₂， SaO₂， and PaO₂/FiO₂ while reducing PaCO₂ and W/D ratio in rats （P<0.01）. It also greatly reduced TNF-α， IL-6， and IL-1β levels in BALF （P<0.01） and alleviated inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Additionally， it downregulated the mRNA expression of p38 MAPK， NF-κB p65， IκBα， Bax， Caspases-3， as well as protein expression of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3 in lung tissue （P<0.05， P<0.01）， while significantly upregulating mRNA and protein expression of Bcl-2 （P<0.01）. ConclusionMKD exerts a protective effect on OA-induced ALI rats， potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.

ObjectiveTo investigate the effects of Maxing Kugan decoction （MKD） on inflammatory response and apoptosis in rats with oleic acid （OA）-induced acute lung injury （ALI） and explore its mechanism of action. MethodsSixty Sprague-Dawley （SD） rats were randomly assigned into six groups： a control group， a model group， a dexamethasone-treated group （2 mg·kg^-1）， and three MKD-treated groups at low， medium， and high doses （3.1， 6.2，12.4 g·kg^-1）. Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA （0.2 mL·kg^-1）. Twelve hours after modeling， blood gas analyses were conducted， and the wet-to-dry （W/D） weight ratio of lung tissue was measured for each group. Additionally， enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the bronchoalveolar lavage fluid （BALF） of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin （HE） staining and TdT-mediated dUTP-biotin nick end labeling （TUNEL） assays， and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor kappa-B （NF-κB） signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the control group， the model group exhibited a significant decrease in partial pressure of oxygen （PaO₂）， blood oxygen saturation （SaO₂）， and oxygenation index （PaO₂/FiO₂）， along with a marked increase in partial pressure of carbon dioxide （PaCO₂） and lung W/D ratio （P<0.01）. Additionally， levels of TNF-α， IL-6， and IL-1β in BALF were significantly elevated （P<0.01）. Histopathological analysis of lung tissue showed significant inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK， NF-κB p65， inhibitor of NF-κB （IκBα）， B-cell lymphoma-2 associated x protein （Bax）， and Caspases-3， as well as the protein expression levels of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3， while the mRNA and protein expression of Bcl-2 was downregulated （P<0.01）. Compared with the model group， MKD significantly elevated PaO₂， SaO₂， and PaO₂/FiO₂ while reducing PaCO₂ and W/D ratio in rats （P<0.01）. It also greatly reduced TNF-α， IL-6， and IL-1β levels in BALF （P<0.01） and alleviated inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Additionally， it downregulated the mRNA expression of p38 MAPK， NF-κB p65， IκBα， Bax， Caspases-3， as well as protein expression of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3 in lung tissue （P<0.05， P<0.01）， while significantly upregulating mRNA and protein expression of Bcl-2 （P<0.01）. ConclusionMKD exerts a protective effect on OA-induced ALI rats， potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.

Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

ObjectiveTo evaluate the efficacy and safety of first-line transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy in the treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma （HCC） based on China Liver Cancer Staging （CNLC）. MethodsA total of 198 patients who received first-line TACE combined with targeted therapy and immunotherapy or received TACE alone from January 2015 to December 2022 in the First Affiliated Hospital of Soochow University were enrolled in this study， and after propensity score matching， there were 50 patients in combination group and 50 patients in TACE group. The Kaplan-Meier method was used to calculate median overall survival （mOS） and median progression-free survival （mPFS）. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate objective response rate （ORR） and disease control rate （DCR）， and Common Terminology Criteria for Adverse Events v5.0 was used to evaluate adverse events. The chi-square test was used for comparison of categorical data between two groups； the t-test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate survival time and calculate 95% confidence interval （CI）， and the Log-rank test was used for comparison of mOS and mPFS between two groups. ResultsThe combination group had an mOS of 30.1 months （95%CI： 21.9‍ ‍—‍ ‍38.3）， and the TACE group had an mOS of 14.5 months （95%CI： 11.0 ‍—‍‍ ‍18.0）， with a significant difference between the two groups （χ²=17.8， P<0.001）； the combination group had an mPFS of 10.3 months （95%CI： 8.8‍ ‍—‍ ‍11.8）， and the TACE group had an mPFS of 7.1 months （95%CI： 5.8‍ — ‍8.4）， with a significant difference between the two groups （χ²=10.4， P<0.001）. There were significant differences between the combination group and the TACE group in ORR （84% vs 58%， P<0.05） and DCR （94% vs 80%， P<0.05）. There was no significant difference between the combination group and the TACE group in the incidence rate of adverse events （24% vs 16%， P=0.317）， and no adverse event-related deaths were observed in either group. ConclusionCompared with TACE alone， TACE combined with targeted therapy and immunotherapy has a better efficacy in the treatment of patients with CNLC stage Ⅱb/Ⅲa HCC， without increasing the incidence rate of severe adverse events.

ObjectiveTo investigate the ability of the modified albumin-bilirubin （mALBI） grade in predicting the prognosis of patients with Child-Pugh A unresectable hepatocellular carcinoma （uHCC） after transcatheter arterial chemoembolization （TACE） combined with immunotherapy and anti-angiogenic drugs （hereafter referred to as targeted immunotherapy）. MethodsA retrospective analysis was performed for the data of 76 patients with Child-Pugh A uHCC who met the inclusion criteria and underwent TACE combined with targeted immunotherapy in The First Affiliated Hospital of Soochow University from January 2020 to January 2023， and according to the mALBI grade， they were divided into mALBI 1/2a group with 38 patients and mALBI 2b group with 38 patients. The primary endpoint was overall survival （OS）， and the secondary endpoints were progression-free survival （PFS）， objective response rate （ORR）， and disease control rate （DCR）. Evaluation criteria included complete remission， partial remission， stable disease， and progressive disease. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical variables between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of median OS （mOS） and median PFS （mPFS） between groups. The univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors for prognosis. ResultsThere were significant differences in albumin and tumor burden between the two groups （both P<0.05）. The 76 patients had an mOS of 25.2 months （95% confidence interval ［CI］： 18.4 — 32.0）， an mPFS of 9.4 months （95%CI： 7.1 — 11.7）， an ORR of 63.2%， and a DCR of 82.9%. The mOS was 30.1 months （95%CI： 19.8 — 40.4） in the mALBI 1/2a group and 19.5 months （95%CI： 7.1 — 31.9） in the mALBI 2b group， and there was a significant difference in mOS between the two groups （χ²=4.490， P=0.034）. The mALBI 1/2a group had an mPFS of 10.2 months （95%CI： 8.4 — 12.0）， an ORR of 71.1%， and a DCR of 86.8%， while the mALBI 2b group had an mPFS of 7.6 months （95%CI： 4.6 — 10.6）， an ORR of 55.3%， and a DCR of 78.9%； there were no significant differences in mPFS， ORR， and DCR between the two groups （all P>0.05）. ECOG status， tumor burden， mALBI grade， portal vein invasion， and extrahepatic metastasis were independent risk factors for mOS in patients undergoing TACE combined with targeted immunotherapy （all P<0.05）. There were no treatment-related deaths. ConclusionThe mALBI grade has a good value in predicting the survival of patients with Child-Pugh A uHCC undergoing TACE combined with targeted immunotherapy.

Objective To establish a method for rapid determination of isovelleral,α-amanitin,β-amanitin,γ-amanitin,dihydroxy-phallotoxin and carboxy-dihydroxy-phallotoxin in plasma by ultra performance liquid chromatography-mass spectrometry.Methods Take plasma samples and add acetonitrile solution in a 1:3 ratio.The sample was vortex mixed for 1 min,then centrifugated at 10 000r/min and 4℃ for 3min.The supernatant was injected,while 0.03％ammonia water and acetonitrile were used as mobile phases for ultra high performance liquid phase separation.Multi reaction monitoring was carried out in the positive ion mode of electric spray.Results The separation and detection of isovelleral,α-amanitin,β-amanitin,γ-amanitin,dihydroxy-phallotoxin and carboxyl-dihydroxy-phallotoxin in plasma could be achieved within 4 min by one injection.The linear range of six mushroom toxins in plasma was 40-500μg/L,and the detection limits were 10.0μg/L 10.0μg/L,10.0μg/L,6.0μg/L,6.0μg/L and 6.0μg/L(S/N=3),respectively.The relative standard deviations were 0.60％-1.90％(n=11),and the recovery rates were 90.8％-127.0％.Conclusion This method realizes the rapid and simultaneous determination of 6 kinds of mushroom toxins in plasma,including isovelleral.The operation is simple and the result is accurate,which provides a technical platform for the rapid confirmation of mushroom toxins in poisoned patients.

Objective:To investigate the relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns, in order to explore the hemoglobin warning threshold for blood transfusion in patients with extensive burns.Methods:The research was a retrospective observational study. From October 2012 to October 2022, 288 patients with extensive burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University), including 243 males and 45 females, aged 18 to 65 years. These patients were assigned to the death group ( n=54) and the survival group ( n=234) based on their final prognosis. The clinical data including gender, age, body mass index, total burn area, full-thickness burn area, time of first operation after injury, preoperative prothrombin time (PT) and activated partial thromboplastin time (APTT) and hemoglobin level of the first surgery, complication of inhalation injury, number of surgeries, total surgical area, total surgical time, total length of hospital stay, and highest procalcitonin value, lowest platelet count and hemoglobin values, and occurrence of sepsis during hospitalization were compared between the two groups of patients. According to the lowest hemoglobin value during hospitalization, the patients were assigned to <65 g/L group, ≥65 g/L and <75 g/L group, ≥75 g/L and <85 g/L group, and ≥85 g/L group. The total length of hospital stay, mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury were compared among the four groups of patients. The relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns was analyzed using a restricted cubic spline model before and after adjusting covariates. A logistic regression model was adopted to analyze the relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns after adjusting covariates, with the lowest hemoglobin value during hospitalization as a continuous variable and a categorical variable, separately. Results:Compared with those in survival group, the total burn area, full-thickness burn area, and total surgical area of patients in death group were significantly increased, the preoperative APTT of the first surgery was significantly prolonged, the number of surgeries was significantly reduced, the total length of hospital stay was significantly shortened, the highest procalcitonin value during hospitalization was significantly increased, the lowest platelet count and hemoglobin values during hospitalization were significantly decreased, and the incidence proportion of sepsis during hospitalization was significantly increased (with Z values of -6.72, -5.40, -2.15, -2.99, -2.21, -7.84, -6.23, -7.03, and -3.43, respectively, χ2=161.95, P values all <0.05). There were no statistically significant differences in the other clinical data of patients between the two groups ( P>0.05). There were statistically significant differences in mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury of patients among the four groups divided according to the lowest hemoglobin value during hospitalization (with χ2 values of 12.12, 15.93, and 10.62, respectively, P<0.05). There was no statistically significant difference in the total length of hospital stay of patients among the four groups ( P>0.05). The restricted cubic spline model analysis revealed an approximately linear relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns before and after adjusting covariates (with χ2 values of 0.81 and 0.75, respectively, P>0.05). After adjusting covariates, the logistic regression model analysis showed that the mortality risk of patients with extensive burns increased with decreasing hemoglobin when the lowest hemoglobin value during hospitalization was analyzed as a continuous variable (with odds ratio of 0.96, with 95% confidence interval of 0.92 to 0.99, P<0.05). When using the median value of 75.5 g/L as the cut-off value for categorizing the lowest hemoglobin value during hospitalization, there was no statistically significant difference in the mortality risk between patients with hemoglobin <75.5 g/L and those with hemoglobin ≥75.5 g/L ( P>0.05). When the patients were divided into four groups based on the lowest hemoglobin value during hospitalization as above, using ≥85 g/L group as a reference, only patients in <65 g/L group had a significantly increased mortality risk (with odds ratio of 5.37, with 95% confidence interval of 1.57 to 18.29, P<0.05). Conclusions:There is an approximately linear correlation between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns. When the hemoglobin level drops to 65 g/L or lower, the mortality risk of patients increases significantly, suggesting that a hemoglobin level of 65 g/L could serve as a warning threshold for blood transfusion in patients with extensive burns.

Objective:To investigate the effect of failure mode and effect analysis (FMEA) based catheter information platform in preventing catheter-related bloodstream infection (CRBSI) in intensive care unit to improve the current status of CRBSI.Methods:In this study, a retrospective cohort study was conducted using the purposive sampling method, and 140 patients with indwelling central venous catheters admitted to the ICU of Peking University Shenzhen Hospital from August to December 2021 were set as the control group; the 140 patients with indwelling central venous catheters admitted to the ICU from January to May 2022 were set as the observation group. The control group used electronic forms to record and manage at the bedside after CRBSI cluster nursing measures were given, and the observation group used the catheter information platform based on FMEA to conduct information management on catheter evaluation and maintenance process after CRBSI cluster nursing measures were given. Compared the implementation rate (6 items), implementation time, qualification rate, and incidence of CRBSI in ICU patients between two groups of ICU nurses.Results:The implementation rate of CRBSI cluster nursing measures among ICU nurses in the observation group: strict hand hygiene by nurses was 87%(122/140), maximum aseptic barrier during puncture was 97%(136/140), aseptic operation during catheter maintenance was 91%(128/140), 75% alcohol disinfection of connectors was 84%(118/140), 24-hour change of infusion lines was 95%(133/140), and timely change of patches/dressings was 89%(125/140), they were greater than those in the control group 70%(98/140), 87%(122/140), 71%(100/140), 61%(86/140), 71%(99/140), 69%(96/140), the differences were statistically significant ( χ2 values were 9.67 to 29.07, all P<0.05); the execution time and qualification rate among ICU nurses in the observation group were (9.11 ± 2.83) minutes and 91.4% (128/140), the control group were (10.00 ± 2.84) minutes and 60.7% (85/140), with statistically significant differences ( t value was -2.64, χ2 values was 36.28, all P<0.05). Conclusions:The FMEA-based catheterization information platform can help enhance the efficiency of the implementation of CRBSI clustering nursing measures by ICU nurses, improve the quality of care, and thus reduce the occurrence of CRBSI, and the feasibility of clinical promotion is high.

Background: The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM. Methods: Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb). Results: We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM. Conclusion These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

Objective:Under the guidance of evidence-based theory, the discharge preparation intervention plan for stroke patients was constructed, in order to provide a reference for improving the discharge preparation of stroke patients.Methods:To retrieve the relevant guidelines, consensus, literature and quality evaluation, summarize relevant evidence and evaluate the first draft of the intervention plan, implement two rounds of expert enquiry, according to the expert score and opinions, and improve the entries after the group discussion to form the final intervention plan.Results:In the two rounds of correspondence, the expert positive coefficient was 100%, the expert authority coefficient was 0.81 and 0.84 respectively, and the Kendall harmony coefficient of each entry was 0.165 and 0.453 respectively. The difference was statistical significant ( P<0.05). The ultimate in intervention plan included 6 primary entry, 23 secondary entries. Conclusions:The discharge preparation intervention plan for stroke patients constructed in this study is scientific, reliable and feasible, and is of great significance to improving the discharge preparation of stroke patients.