OBJECTIVE To investigate the potential mechanism by which Juanxiao decoction improves bronchial asthma （hereinafter referred to as “asthma”） based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome signaling pathway. METHODS Female SD rats were randomly assigned to normal group， model group and Juanxiao decoction low-， medium- and high-dose groups （0.36， 0.72 and 1.44 g/kg， calculated based on crude drug weight）， as well as positive control group （Dexamethasone acetate tablets， 0.2 mg/kg）， with 10 rats in each group. Except for the normal group， asthma models were established in the remaining groups via intraperitoneal injection of ovalbumin combined with aluminum hydroxide， followed by nebulized inhalation of ovalbumin. On day 14 of the experiment， rats in each group received intragastric administration of the corresponding solution or normal saline， once a day， for 7 consecutive days. Following the final administration， the following parameters were measured in each group： lung function indexes （forced vital capacity， forced expiratory volume in 0.3 second， peak expiratory flow）， serum levels of inflammatory markers （interleukin-1β， interleukin- 18）， and the percentages of inflammatory cells （lymphocytes， eosinophils， neutrophils） in bronchoalveolar lavage fluid. Histopathological changes in lung tissue were observed， and the protein and mRNA expressions of nuclear factor-kappa B （NF- κB）， NLRP3 and caspase-1 in lung tissue were detected. RESULTS Compared with the normal group， pathological changes such as alveolar wall thickening and inflammatory cell infiltration were observed in rats in the model group. All pulmonary function indicators were significantly reduced in rats in the model group and the administration groups. The levels of inflammatory markers， the percentages of inflammatory cells， and the protein and mRNA expressions of NF-κB， NLRP3 and caspase-1 were significantly elevated or up-regulated （P＜0.05）. Compared with the model group， pathological changes in rats in each dosage group of Juanxiao decoction were significantly alleviated， and all quantitative indicators showed dose-dependent improvements （P＜0.05）. CONCLUSIONS Juanxiao decoction can reduce airway inflammatory responses in asthmatic rats， alleviate lung function impairment， and improve pathological changes such as inflammatory cell infiltration. Those effects may be related to the inhibition of the NLRP3 inflammasome signaling pathway.

Objective To investigate the relationship between pre-liver transplantation plasma soluble programmed cell death protein 1 (sPD-1) levels and prognosis in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICI). Methods A total of 38 HCC liver transplant recipients who received ICI treatment at Beijing Tsinghua Changgung Hospital from January 2021 to February 2024 were included in the study. The use of ICI drugs was reviewed, and the clinical and pathological characteristics of patients with and without postoperative HCC recurrence were compared. Kaplan-Meier analysis was used to evaluate postoperative survival. Pre-transplant plasma samples were collected from patients treated with ICI, and the sPD-1 levels were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic curves were plotted to explore the relationship between sPD-1 expression and clinical pathological features and to analyze the prognosis. The effects of different preoperative ICI discontinuation times on sPD-1 expression were also compared. Results Among the patients, 28 (74%) received anti-programmed cell death protein 1 (PD-1) monoclonal antibodies, 9 (24%) received anti-programmed cell death protein ligand 1 (PD-L1) monoclonal antibodies, and 1 (3%) received bispecific antibodies. Patients were grouped based on whether they had HCC recurrence within 1 year after surgery. Significant differences were found between the two groups in preoperative alpha-fetoprotein levels, tumor number, maximum tumor diameter, capsular invasion, differentiation grade, Ki67 index, conform to Milan criteria, conform to University of California at San Francisco (UCSF) criteria and tumor, node, metastasis (TNM) staging (all P<0.05). The median pre-transplant plasma sPD-1 level was 902 (318, 4 406) pg/mL, and the sPD-1 level was higher in the recurrence group than in the non-recurrence group (P<0.05). Using 2 073 pg/mL as the cut-off value, patients were divided into high and low sPD-1 level groups. Significant differences were found between the two groups in tumor number, postoperative hospital stay and total hospital stay (all P<0.05). Kaplan-Meier analysis showed that the disease-free survival rate was lower in the high sPD-1 level group than in the low sPD-1 level group (P=0.004), while the overall survival rate did not differ significantly between the two groups (P=0.381). In addition, patients who discontinued ICI treatment ≤ 5 half-lives before surgery had higher sPD-1 levels than those who discontinued ICI treatment for >5 half-lives before surgery. Conclusions Pre-transplant plasma sPD-1 levels are closely related to prognosis and may reflect the dynamic changes in the immune microenvironment. For patients with high pre-transplant plasma sPD-1 levels, the indications for liver transplantation should be carefully evaluated, and postoperative management and follow-up should be strengthened. Early intervention should be provided to improve patients' quality of life and prolong their survival.

Objective To analyze the risk factors of poor prognosis in patients with extended-spectrum β-lactamase producing enterobacterales(ESBL-E)bloodstream infection,and establish a nomogram prediction model to provide help for clinical diagnosis and treatment.Methods A total of 235 patients with ESBL-E bloodstream infection were collected from the First People's Hospital of Jiande City.According to their prognosis,the patients were divided into survival group(n=211)and death group(n=224).The clinical data of the patients were collected,and the independent risk factors of poor prognosis were screened by multivariate Logistic regression analysis.The nomogram was established and verified.Results The mortality of ESBL-E bloodstream infection patients with shock,respiratory failure,diabetes and leukemia,ICU admission,hypoproteinemia,increased or decreased white blood cells,and thrombocytopenia was higher(P＜0.05).Multivariate Logistic regression analysis showed that combined shock,respiratory failure and leukemia were independent risk factors for death from ESBL-E bloodstream infection.Conclusion The nomogram prediction model of adverse prognostic risk factors in patients with ESBL-E bloodstream infection can provide help for clinicians to judge the poor prognosis in the early stage,and it is of reference significance to take early intervention measures to reduce the mortality of patients.

Objective To investigate the relationship between serum autotaxin(ATX),energy balance re-lated protein(Adropin)and inflammatory factors and poor prognosis in patients with dilated cardiomyopathy(DCM).Methods A total of 105 DCM patients admitted to Qingdao Huangdao District Traditional Chinese Medicine Hospital from June 2017 to February 2020 were selected as the DCM group,and 100 healthy volun-teers who came to the hospital for physical examination during the same period were selected as the control group.The levels of serum ATX,Adropin and inflammatory factors[hypersensitive C-reactive protein(hs-CRP)and interleukin-6(IL-6)]in the two groups were detected,and the correlation between serum ATX,Adropin and inflammatory factors was analyzed by Pearson correlation analysis.Patients in DCM group were divided into good prognosis group and poor prognosis group according to the occurrence of endpoint events during follow-up.Logistic regression was used to analyze the risk factors of poor prognosis in DCM patients,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum ATX and Adropinfor poor prognosis in DCM patients.Results The serum levels of ATX,hs-CRP and IL-6 in DCM group were higher than those in control group,and the level of Adropin was lower than that in control group,with statistical significance(P＜0.05).Pearson correlation analysis showed that serum ATX level was posi-tively correlated with hs-CRP and IL-6,and serum Adropin level was negatively correlated with hs-CRP and IL-6(P＜0.05).New York Heart Association(NYHA)functional classification m to Ⅳ and serum ATX lev-el in the poor prognosis group were higher than those in the good prognosis group,the heart failure duration and left ventricular end-diastolic diameter were higher than those in the good prognosis group,the left ventric-ular ejection fraction(LVEF)and serum Adropin levels were lower than those in the good prognosis group,the difference was statistically significant(P＜0.05).Logistic regression model analysis showed that NYHA functional classification Ⅲ to Ⅳ and high ATX were risk factors for poor prognosis in DCM patients,and high Adropin and high LVEF were protective factors for poor prognosis in DCM patients(P＜0.05).ROC curve a-nalysis showed that the area under the curve(AUC)of serum ATX and Adropin in predicting poor prognosis of DCM patients was 0.841 and 0.793,respectively,and the AUC of combined prediction of poor prognosis of DCM patients was greater than that of single prediction.Conclusion Serum ATX is abnormally elevated and serum Adropin is abnormally decreased in DCM patients,both of which are closely related to inflammatory factors.Detection of serum ATX and Adropin levels can provide reference for prognosis assessment of DCM patients.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.

Objective:To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases.Methods:From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) .Results:① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups ( P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups ( P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively ( P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % ( P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion:The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

Objective:To investigate the clinical application value of triamcinolone acetonide combined with hyaluronidase injection and shallow X-ray in the treatment of multiple keloids.Methods:From March 2018 to October 2019, 144 cases of multiple keloids in outpatient department were analyzed retrospectively. There were 89 males and 55 females, aged from 16 to 68, with an average age of 28 years. The average duration was 6 years(ranged from 1 to 20 years). Among them, 65 cases were treated with superficial X-ray radiotherapy combined with local injection (group A) and 79 cases were treated only with local injection (group B). The Vancouver Scar Scale (VSS), t-test and chi-square test were used to evaluate the validity of the two groups. The patients were followed up for 6-18 months. Results:In group A, the VSS was changed from 11.9±0.9 to 6.5±1.1. 51 cases were improved and 14 cases showed obviously effective. The significant effect rate was 21.54%(14/65). The main side effect of group A was transient pigmentation. In group B, the VSS was changed varied from 12.1±1.0 to 8.3±1.0. 74 cases were improved, 2 cases were markedly effective, but 3 cases were ineffective. The significant effective rate was 2.63%(2/76). The side effects include telangiectasia, skin atrophy, even arousing abnormal menstrual cycles and hair growth in several females. The comparability between the two groups was confirmed by the VSS scores before treatment( t=-1.114, P=0.267). Then, the difference of VSS scores became significant after treatment( t=-10.208, P<0.001), the same to apparent efficiency( χ2=12.450, P<0.001). Conclusions:Triamcinolone acetonide combined with hyaluronidase injection and shallow X-ray radiation therapy for multiple keloids has ideal curative effect and low incidence of adverse reactions, which is a prospected clinical method.

Objective:To investigate the clinical application value of triamcinolone acetonide combined with hyaluronidase injection and shallow X-ray in the treatment of multiple keloids.Methods:From March 2018 to October 2019, 144 cases of multiple keloids in outpatient department were analyzed retrospectively. There were 89 males and 55 females, aged from 16 to 68, with an average age of 28 years. The average duration was 6 years(ranged from 1 to 20 years). Among them, 65 cases were treated with superficial X-ray radiotherapy combined with local injection (group A) and 79 cases were treated only with local injection (group B). The Vancouver Scar Scale (VSS), t-test and chi-square test were used to evaluate the validity of the two groups. The patients were followed up for 6-18 months. Results:In group A, the VSS was changed from 11.9±0.9 to 6.5±1.1. 51 cases were improved and 14 cases showed obviously effective. The significant effect rate was 21.54%(14/65). The main side effect of group A was transient pigmentation. In group B, the VSS was changed varied from 12.1±1.0 to 8.3±1.0. 74 cases were improved, 2 cases were markedly effective, but 3 cases were ineffective. The significant effective rate was 2.63%(2/76). The side effects include telangiectasia, skin atrophy, even arousing abnormal menstrual cycles and hair growth in several females. The comparability between the two groups was confirmed by the VSS scores before treatment( t=-1.114, P=0.267). Then, the difference of VSS scores became significant after treatment( t=-10.208, P<0.001), the same to apparent efficiency( χ2=12.450, P<0.001). Conclusions:Triamcinolone acetonide combined with hyaluronidase injection and shallow X-ray radiation therapy for multiple keloids has ideal curative effect and low incidence of adverse reactions, which is a prospected clinical method.

Background: Endoscopic submucosal dissection (ESD) has become the preferred treatment of early colorectal cancer. PDCD4 and autophagy have important clinical significance in the pathogenesis of colorectal cancer. Aims: To explore the expressions and significance of apoptosis factor PDCD4 and autophagy factors LC3Ⅱ and p62 in colorectal cancer. Methods: Fifty-four early colorectal adenocarcinoma patients treated by ESD from Jan. 2015 to Nov. 2020 at Binzhou Medical University Hospital were collected. The expressions of PDCD4, LC3Ⅱ and p62 were detected by immunohistochemistry, and the correlations with clinicopathological factors were analyzed. The differential expression of PDCD4 in pan-cancer was analyzed by bioinformatics analysis. Results: Expression of PDCD4 was associated with the long-diameter of paracancer adenoma (P<0.05), and expressions of LC3Ⅱ and p62 were associated with the long-diameters of adenocarcinoma and paracancer adenoma (P<0.05). The positive expression of PDCD4 in P-NIMM was located in the nucleus, while the positive expression in adenocarcinoma was located in cytoplasm. The nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-NIMM than in P-LGIN, P-HGIN and adenocarcinoma (P<0.05), and the nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-LGIN, P-HGIN than in adenocarcinoma (P<0.05). The positive expression rates of LC3Ⅱ and p62 were significantly higher in adenocarcinoma than in P-NIMM and P-LGIN (P<0.05). In P-LGIN, P-HGIN and adenocarcinoma, the expression of PDCD4 was negatively correlated with the expressions of LC3Ⅱ and p62 (P<0.05). The bioinformatics analysis showed that expression of PDCD4 was significantly reduced in a variety of malignant tumors including colorectal cancer (P<0.05). Conclusions: The inhibition of apoptosis and activation of autophagy may promote the occurrence of colorectal cancer, and its mechanism may be related to the intracellular transposition of PDCD4 that inhibits cell apoptosis and enhances autophagy, and activating cellular autophagy may further accelerate the degradation of PDCD4 and thus reducing its cancer inhibiting effect.