AIM:This study aims to investigate whether a specific synbiotic,consisting of Bifidobacterium longum subspecies BB536 and fructooligosaccharides,can inhibit colon tumorigenesis by modulating gut flora composi-tion.METHODS:Six-week-old male ApcMin/+mice were randomly divided into control group and synbiotic-treated group,with 8 mice in each group.The mice in synbiotic-treated group received daily gavage of 1×109 CFU/kg of Bifidobacterium longum BB536 and 2 g/kg of fructooligosaccharides,while those in control group were gavaged with sterile water for 10 weeks.The number and size of colon tumors were assessed and compared between the 2 groups.Colon tissue sections were evaluated using hematoxylin-eosin staining,Alcian blue staining,and immunohistochemistry assays.The bacterial compo-sition in the colon was analyzed via 16S rDNA sequencing,and differentially expressed genes were examined through tran-scriptome sequencing and RT-qPCR.RESULTS:The synbiotic treatment significantly enhanced bacterial diversity and increased the relative abundance of Bifidobacterium in the colon(P<0.01).Additionally,the number and size of colon tu-mors were both significantly reduced in the synbiotic-treated mice(P<0.01),along with decreased expression of Ki-67(P<0.01).Concurrently,the number of goblet cells and the expression of epithelial tight junction proteins(ZO-1 and occlu-din)were up-regulated(P<0.05).CONCLUSION:Supplementation with this synbiotic effectively modulated gut flora composition and suppressed colon tumorigenesis in ApcMin/+mice.

The nursing experience of buttonhole cannulation for an autogenous arteriovenous fistula with an Eluvia drug-eluting stent in a patient undergoing maintenance hemodialysis was summarized.Key nursing points included:developing a scientific and rational buttonhole cannulation plan for the autogenous arteriovenous fistula stent based on its characteristics post-stent implantation;conducting preoperative ultrasonic evaluations of the arteriovenous fistula and stent;establishing and maintaining a buttonhole tunnel at the stent site;regularly monitoring and following up on the cannulation site and the condition of the autogenous arteriovenous fistula;strengthening the observation and prevention of potential complications.Through rigorous and standardized assessments,procedures,and nursing care,the patient maintained good autogenous arteriovenous fistula function without stent-related complications such as fracture,stenosis,or infection over a 14-month follow-up period.

AIM:This study aims to investigate whether a specific synbiotic,consisting of Bifidobacterium longum subspecies BB536 and fructooligosaccharides,can inhibit colon tumorigenesis by modulating gut flora composi-tion.METHODS:Six-week-old male ApcMin/+mice were randomly divided into control group and synbiotic-treated group,with 8 mice in each group.The mice in synbiotic-treated group received daily gavage of 1×109 CFU/kg of Bifidobacterium longum BB536 and 2 g/kg of fructooligosaccharides,while those in control group were gavaged with sterile water for 10 weeks.The number and size of colon tumors were assessed and compared between the 2 groups.Colon tissue sections were evaluated using hematoxylin-eosin staining,Alcian blue staining,and immunohistochemistry assays.The bacterial compo-sition in the colon was analyzed via 16S rDNA sequencing,and differentially expressed genes were examined through tran-scriptome sequencing and RT-qPCR.RESULTS:The synbiotic treatment significantly enhanced bacterial diversity and increased the relative abundance of Bifidobacterium in the colon(P<0.01).Additionally,the number and size of colon tu-mors were both significantly reduced in the synbiotic-treated mice(P<0.01),along with decreased expression of Ki-67(P<0.01).Concurrently,the number of goblet cells and the expression of epithelial tight junction proteins(ZO-1 and occlu-din)were up-regulated(P<0.05).CONCLUSION:Supplementation with this synbiotic effectively modulated gut flora composition and suppressed colon tumorigenesis in ApcMin/+mice.

The nursing experience of buttonhole cannulation for an autogenous arteriovenous fistula with an Eluvia drug-eluting stent in a patient undergoing maintenance hemodialysis was summarized.Key nursing points included:developing a scientific and rational buttonhole cannulation plan for the autogenous arteriovenous fistula stent based on its characteristics post-stent implantation;conducting preoperative ultrasonic evaluations of the arteriovenous fistula and stent;establishing and maintaining a buttonhole tunnel at the stent site;regularly monitoring and following up on the cannulation site and the condition of the autogenous arteriovenous fistula;strengthening the observation and prevention of potential complications.Through rigorous and standardized assessments,procedures,and nursing care,the patient maintained good autogenous arteriovenous fistula function without stent-related complications such as fracture,stenosis,or infection over a 14-month follow-up period.

Objective:To investigate the efficacy and safety of chemotherapy combined with inetetamab and pyrotinib (triplet therapy group), and capecitabine combined with pyrotinib (doublet therapy group) in second-line treatment for HER2-positive metastatic breast cancer patients who have failed on trastuzumab.Methods:A retrospective analysis was conducted on 30 HER2-positive metastatic breast cancer patients who underwent second-line treatment with a regimen of chemotherapy plus inetetamab and pyrotinib at Fujian Provincial Tumor Hospital between Jan. 1, 2020 and Dec. 31, 2023, and on 28 HER2-positive metastatic breast cancer patients treated with capecitabine plus pyrotinib during the same period. The study analyzed the differences in ORR (objective response rate), CBR (clinical benefit rate), PFS (progression free survival), and OS (overall survival) between the two groups and documented any adverse reactions observed during treatment.Results:The three-drug group exhibited a higher ORR rate than the two-drug group (60.0% vs. 39.2%, P>0.05), and a higher CBR rate (83.3% vs. 57.1%, P<0.05). Univariate analysis and multivariate Logistic regression analysis showed that group (three drug group compared to two drug group) was the only independent prognostic factor affecting median PFS in patients ( P<0.05). The median PFS of the three drug group was higher than that of the two drug group (19 months vs. 11 months, P<0.05), but by the end of follow-up, neither group had reached the median OS ( P>0.05) .The three-drug group and the two-drug group demonstrated 1-year OS rates of 85% and 85%, 2-year OS rates of 74% and 63%, and 3-year OS rates of 56% and 52%, respectively. The most frequent hematological toxicities in the three-drug group were leukopenia, neutropenia, and anemia, with diarrhea being the most common non-hematological toxicity. No significant differences were observed in adverse reaction profiles between the two groups ( P>0.05) . Conclusion:In the second-line treatment of HER2 positive metastatic breast cancer, chemotherapy + inetetamab + pyrotinib significantly prolonged the median PFS and increased the CBR compared with the current domestic standard capecitabine + pyrotinib regimen, and did not increase the incidence of adverse reactions, demonstrating higher efficacy and safety.

Objective:To investigate the role and related mechanisms of the LiaSR two-component system in acid tolerance and biofilm formation abilities of Streptococcus mutans (Sm) 593. Methods:The growth curves of various Sm strains in pH=5.5 brian heart infusion (BHI) medium were analyzed. And colony forming unit (CFU) was also performed to evaluate the acid tolerance of Sm. Laurdan probe, H +-K +adenosine triphosphate (ATP)ase activity analysis kit, proton permeability assay and real-time fluorescence quantitative PCR (RT-qPCR) were conducted to detect the acid tolerant mechanisms of LiaSR two-component system in Sm. Crystal violet staining, CFU, SYTOX probe and anthrone-sulfuric method were used to analyze the properties and structures of the Sm biofilms. RT-qPCR was conducted to detect the expression levels of underlying regulated genes. Results:The growth of mutants in acidic BHI were inhibited ( P<0.05). The acid tolerance of mutants significantly decreased compared to the wild-type strain ( P<0.05). In mutants, the activity of H +-ATPase (917.06±59.53 and 469.53±47.65) were elevated by 7.22-folds and 3.70-folds compared to the wild-type strain (127.00±50.71) ( P<0.001, P<0.001) and the encoded gene atpD (3.39±0.21 and 1.94±0.17) were also elevated by 3.39-folds and 1.94-folds compared to the wild-type strain (1.00±0.15) ( P<0.001, P=0.001). The Laurdan generalized polarization of mutants (0.18±0.04 and 0.18±0.05) increased significantly compared to the wild-type strain (0.08±0.05) ( P=0.006, P=0.003) and the expression levels of fabM gene were decreased in mutants (0.52±0.11 and 0.57±0.05) by 1/2 ( P=0.014, P=0.022). In liaR deletion mutant, the reduced terminal pH (4.76±0.01) can also be observed ( P<0.001). The total amount of the biofilms of three Sm didn't show significant differences ( P>0.05). But the number of viable bacteria of mutants′ biofilms were decreased [Sm 593: (12.00±2.80)×10 7 CFU/ml; Sm ΔliaS: (2.95±1.13)×10 7 CFU/ml; Sm ΔliaR: (7.25±1.60)×10 7 CFU/ml] ( P=0.001, P=0.024). The extracellular DNA were increased by 18.00-folds and 6.50-folds in mutants′ biofilms (128.73±15.65 and 46.38±5.52) compared to the wild-type strain (7.16±3.62) ( P<0.001, P=0.003). Water-soluble exopolysaccharides could be found up-regulated in liaS deletion mutant [(138.73±10.12) μg/ml] ( P=0.003) along with the expression level of gtfC gene (1.65±0.39) ( P=0.014). The expression level of gtfD were elevated by 47.43-folds and 16.90-folds in mutants ( P<0.001, P=0.010). Conclusions:The LiaSR two-component system can promote the expression of fabM gene and increase the fluidity of Sm which contributes to acid tolerance. The LiaR can also decrease the proton permeability and restrict the entrance of H +. The LiaSR two-component system can negatively regulate the production of the extracellular matrix in Sm biofilm.

Objective:To explore and screen the immunophenotypic characteristics of acute promyelocytic leukemia (APL) by multiparameter flow cytometry (MFC).Methods:A retrospective and descriptive study. A total of 130 acute myeloid leukemia (AML) patients who registrated in Hebei Yanda Lu Daopei Hospital were studied, among which there were 44 classical APL (cAPL), 24 microgranular variant of APL (APLv) and 62 non-APL patients (including NPM1 mut AML and AML with KMT2A rearrangement). MFC immunotyping was used to analyze and compare the median expression intensity (MEI) of side scatter (SSC), along with the ratio of the MEI on leukemic cells with those on lymphocytes (T/L MEIR), the median fluorescence intensity (MDFI) of CD34, myeloperoxidase (MPO), CD64 and CD9 on leukemic cells, as well as the ratios of these MDFIs on leukemic cells with those on lymphocytes (T/L MDFIR). Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficiency of the multiparameters model for distinguishing cAPL and non-APL, APLv and non-APL. Results:The MEI and T/L MEIR of SSC in the cAPL group were higher than those in the APLv and non-APL groups ( P<0.05), and these two parameters in APLv group were higher than those in the non-APL group, respectively ( P<0.05). The MDFIs of CD34 in cAPL and APLv groups were higher than those in the non-APL group ( P<0.05), and the T/L MDFIR of CD34 was higher in APLv group than non-APL group ( P<0.05). The MDFIs of MPO and CD9, as well as the T/L MDFIRs in cAPL and APLv groups were both higher than those in the non-APL group, respectively ( P<0.05). The MDFI and T/L MDFIR of CD64 in the cAPL group were higher than those in non-APL group, respectively ( P<0.05). ROC curve results showed that the area under the curve (AUC) of MEI of SSC, the MDFI of CD64 and CD9, as well as the T/L MEIR of SSC and T/L MDFIR of CD9 were 0.932, 0.816, 0.893, 0.960 and 0.894 for diagnosing cAPL, respectively, and the AUC of these parameters were 0.725, 0.737, 0.791, 0.729 and 0.736 for diagnosis APLv, respectively ( P<0.05). Conclusion:MFC method can analyze and screen the immunophenotypic characteristics of APL for differential diagnosis of cAPL, APLv and non-APL patients.

Objective:To investigate the efficacy and safety of chemotherapy combined with inetetamab and pyrotinib (triplet therapy group), and capecitabine combined with pyrotinib (doublet therapy group) in second-line treatment for HER2-positive metastatic breast cancer patients who have failed on trastuzumab.Methods:A retrospective analysis was conducted on 30 HER2-positive metastatic breast cancer patients who underwent second-line treatment with a regimen of chemotherapy plus inetetamab and pyrotinib at Fujian Provincial Tumor Hospital between Jan. 1, 2020 and Dec. 31, 2023, and on 28 HER2-positive metastatic breast cancer patients treated with capecitabine plus pyrotinib during the same period. The study analyzed the differences in ORR (objective response rate), CBR (clinical benefit rate), PFS (progression free survival), and OS (overall survival) between the two groups and documented any adverse reactions observed during treatment.Results:The three-drug group exhibited a higher ORR rate than the two-drug group (60.0% vs. 39.2%, P>0.05), and a higher CBR rate (83.3% vs. 57.1%, P<0.05). Univariate analysis and multivariate Logistic regression analysis showed that group (three drug group compared to two drug group) was the only independent prognostic factor affecting median PFS in patients ( P<0.05). The median PFS of the three drug group was higher than that of the two drug group (19 months vs. 11 months, P<0.05), but by the end of follow-up, neither group had reached the median OS ( P>0.05) .The three-drug group and the two-drug group demonstrated 1-year OS rates of 85% and 85%, 2-year OS rates of 74% and 63%, and 3-year OS rates of 56% and 52%, respectively. The most frequent hematological toxicities in the three-drug group were leukopenia, neutropenia, and anemia, with diarrhea being the most common non-hematological toxicity. No significant differences were observed in adverse reaction profiles between the two groups ( P>0.05) . Conclusion:In the second-line treatment of HER2 positive metastatic breast cancer, chemotherapy + inetetamab + pyrotinib significantly prolonged the median PFS and increased the CBR compared with the current domestic standard capecitabine + pyrotinib regimen, and did not increase the incidence of adverse reactions, demonstrating higher efficacy and safety.

Objective:To evaluate the relationship between spinal cord cytoplasmic activation/proliferation-associated protein-1 (Caprin-1)-mediated expression of calmodulin-dependent protein kinase Ⅱ alpha(CaMKⅡα) and pain perception in mice.Methods:Nestin CreERT2 mice and Caprin-1 flox/flox mice were hybridized to obtain Nestin CreERT2; Caprin-1 flox/flox homozygous mice. The mice were divided into 2 groups ( n=5 each) using a random number table method: Nestin CreERT2; Caprin-1 flox/floxsolventcontrol group (SC group) and Caprin-1 gene knockout group (KO group). Tamoxifen 100 mg/kg was intraperitoneally injected for 5 consecutive days to generate inducible knockout of the Caprin-1 gene in KO group. The mechanical paw withdrawal threshold was measured at day 1 before and day 5 after the end of administration. Then the mice were sacrificed, and L 4-6 segments of the spinal cord were removed for determination of the expression of Caprin-1 and CaMKⅡα protein and mRNA (by Western blot or real-time quantitative polymerase chain reaction) and co-expression of Caprin-1 with CaMKⅡα (by immunofluorescent double staining). Results:Compared with SC group, the mechanical paw withdrawal threshold was significantly increased at 5 days after the end of tamoxifen administration, the expression of Caprin-1 and CaMKⅡα protein and mRNA was down-regulated ( P<0.05), and the co-localization expression of Caprin-1 and CaMKⅡα in the spinal dorsal horn was down-regulated in KO group. Conclusions:Caprin-1 is involved in the development of pain perception by promoting CaMKⅡα expression.

Objective:This study aims to analyze the counts (per kilogram of body weight) or percentages of transplanted lymphocyte subgroups in children with non-infectious pulmonary complications (NIPC) and air-leak syndrome (ALS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explore its significance in the progression of lung complications after transplantation.Methods:The patients with NIPC and ALS after allo-HSCT from January 2013 to December 2019 in Hebei Yanda Ludaopei Hospital were retrospectively studied and the influencing factors in the progress of NIPC after HSCT were statistically analyzed.Results:Of the 2026 children who received HSCT treatment, 59 patients (34 males and 25 females) developed NIPC, the probability was 2.9% (59/2 026), and the probability of combined ALS was 1.4% (28/206). The differences in the comparison between NIPC progressed to ALS group (ALS group) and failed to progress to ALS group (non-ALS group) in the patient′s age( P=0.028), disease condition before transplantation( P=0.022), NIPC onset time( P=0.004) were significant. The P values of the percentage of NKT-like cells in the bone marrow ( P=0.008) or peripheral stem cells ( P=0.003) accounted for the lymphocytes. CD4+CD25+dim cells in bone marrow ( P=0.029) or peripheral stem cells ( P=0.036) accounted for the CD4+lymphocytes and the ratio of CD4/CD8 in bone marrow( P=0.004) or peripheral stem cells ( P=0.020) were less than 0.05, which meant the differences in patients′ refusion cells were significant. In the binary logistic regression model, the percentage of bone marrow NKT-like cells to lymphocytes, the ratio of bone marrow CD4+/CD8+and the percentage of peripheral stem NK cells to lymphocytes were important risk factors for the progression of NIPC to ALS. The rest factors were excluded from the model (AUC=0.918, P<0.05). Conclusion:During allo-HSCT transplantation, a high proportion of NKT-like cell and NK cell levels, and a high CD4+/CD8+ratio in the infusion of donors with high immune tolerance have an important correlation with the progression of the NIPC.