ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective::There is limited evidence regarding the choice of P2Y 12 receptor inhibitors as a component of dual antiplatelet therapy in patients with left main (LM) disease undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate long-term clinical outcomes of ticagrelor- vs. clopidogrel-based dual antiplatelet therapy strategy in acute coronary syndrome (ACS) patients undergoing LM PCI. Methods::This is a post-hoc analysis from a prospective, single-center, real-world PCI registry. A total of 1,163 patients discharged post-ACS who underwent LM PCI and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, including cardiac death, myocardial infarction, or stroke. Secondary outcomes included all-cause death and Bleeding Academic Research Consortium types 2, 3, and 5, and types 3 and 5 bleeding. Propensity score matching was used to adjust for bias due to confounders between the 2 groups.Results::The ticagrelor and clopidogrel groups comprised 529 (45.49%) and 634 (54.51%) patients, respectively. During the follow-up period, the rate of ischemic events was significantly lower with ticagrelor than with clopidogrel before (1.32% (7/529) vs. 3.63% (23/634), P = 0.013,6) and after propensity score matching (1.41% (6/425) vs. 4.00% (17/425), P = 0.020,1). The rates of all-cause death, Bleeding Academic Research Consortium-defined type 2, 3, and 5 bleeding, and type 3 and 5 bleeding were similar between the ticagrelor group and clopidogrel group before or after propensity score matching adjustment (all P > 0.05). Conclusion::Among patients with ACS undergoing LM PCI, ticagrelor use was associated with ischemic events benefit without excessive risk of bleeding at 12 months compared with clopidogrel.

Objective::There is limited evidence regarding the choice of P2Y 12 receptor inhibitors as a component of dual antiplatelet therapy in patients with left main (LM) disease undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate long-term clinical outcomes of ticagrelor- vs. clopidogrel-based dual antiplatelet therapy strategy in acute coronary syndrome (ACS) patients undergoing LM PCI. Methods::This is a post-hoc analysis from a prospective, single-center, real-world PCI registry. A total of 1,163 patients discharged post-ACS who underwent LM PCI and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, including cardiac death, myocardial infarction, or stroke. Secondary outcomes included all-cause death and Bleeding Academic Research Consortium types 2, 3, and 5, and types 3 and 5 bleeding. Propensity score matching was used to adjust for bias due to confounders between the 2 groups.Results::The ticagrelor and clopidogrel groups comprised 529 (45.49%) and 634 (54.51%) patients, respectively. During the follow-up period, the rate of ischemic events was significantly lower with ticagrelor than with clopidogrel before (1.32% (7/529) vs. 3.63% (23/634), P = 0.013,6) and after propensity score matching (1.41% (6/425) vs. 4.00% (17/425), P = 0.020,1). The rates of all-cause death, Bleeding Academic Research Consortium-defined type 2, 3, and 5 bleeding, and type 3 and 5 bleeding were similar between the ticagrelor group and clopidogrel group before or after propensity score matching adjustment (all P > 0.05). Conclusion::Among patients with ACS undergoing LM PCI, ticagrelor use was associated with ischemic events benefit without excessive risk of bleeding at 12 months compared with clopidogrel.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Objective: To evaluate the long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases. Methods: CREDIT Ⅱ trial was a prospective, multicenter, randomized, controlled study, conducted at 15 Chinese cardiac centres from November 2013 to December 2014. In this analysis, eligible patients for coronary stenting (n=419) were randomized to receive either the EXCEL2 stent (n=208) or the EXCEL stent (n=211). The primary endpoint was target lesion failure (TLF) at 3 years after PCI defined as a composite endpoints of cardiac death, target vessel myocardial infarction (TVMI), or clinically indicated target lesion revascularization (CI-TLR). Secondary endpoints included patient-oriented composite endpoint (PoCE) including all-cause death, all MI, or any revascularization at 3 years and independent components, and stent thrombosis according to Academic Research Consortium′s (ARC) definition. Results: Among 419 enrolled patients, 413 (98.6%) patients completed 3-year clinical follow-up. Compared with the EXCEL group, 3-year TLF (5.4%(11/204) vs. 11.5% (24/209), P=0.025) and PoCE (9.8% (20/204) vs. 20.1% (42/209), P=0.003) were significantly lower in the EXCEL2 group. The cumulative event rate of CI-TLR (2.0% (4/204) vs. 5.7% (12/209), P=0.042) and any revascularization (4.9% (10/204) vs. 14.4% (30/209), P=0.001) were statistically lower in the EXCEL2 group than in the EXCEL group. There were no significant difference between two groups in terms of all-cause death and all MI. Rates of stent thrombosis were low without significant difference between the two groups (EXCEL2 vs. EXCEL, 1.0% (2/204) vs. 2.9% (6/209), P=0.285). Conclusion 3-year clinical follow-up results demonstrate that EXCEL2 stents are effective and safe in treating CAD patients with de novo coronary lesions.

Objective To evaluate the long?term efficacy of a second generation biodegradable polymer sirolimus?eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases. Methods CREDITⅡtrial was a prospective, multicenter, randomized, controlled study, conducted at 15 Chinese cardiac centres from November 2013 to December 2014. In this analysis, eligible patients for coronary stenting (n=419) were randomized to receive either the EXCEL2 stent (n=208) or the EXCEL stent (n=211). The primary endpoint was target lesion failure (TLF) at 3 years after PCI defined as a composite endpoints of cardiac death, target vessel myocardial infarction (TVMI), or clinically indicated target lesion revascularization (CI?TLR). Secondary endpoints included patient?oriented composite endpoint (PoCE) including all?cause death, all MI, or any revascularization at 3 years and independent components, and stent thrombosis according to Academic Research Consortium＇s (ARC) definition. Results Among 419 enrolled patients, 413 (98.6%) patients completed 3?year clinical follow?up. Compared with the EXCEL group, 3?year TLF (5.4%(11/204) vs. 11.5% (24/209), P=0.025) and PoCE (9.8% (20/204) vs. 20.1% (42/209), P=0.003) were significantly lower in the EXCEL2 group. The cumulative event rate of CI?TLR (2.0% (4/204) vs. 5.7% (12/209), P=0.042) and any revascularization (4.9% (10/204) vs. 14.4% (30/209), P=0.001) were statistically lower in the EXCEL2 group than in the EXCEL group. There were no significant difference between two groups in terms of all?cause death and all MI. Rates of stent thrombosis were low without significant difference between the two groups (EXCEL2 vs. EXCEL, 1.0% (2/204) vs. 2.9% (6/209), P=0.285). Conclusion 3?year clinical follow?up results demonstrate that EXCEL2 stents are effective and safe in treating CAD patients with de novo coronary lesions.

Objective To investigate the effect of human urinary kallidinogenase (HUK) on cerebral ischemia reperfusion injury in mice.Methods One hundred and ten male ICR mice were randomly divided into sham operation,control and HUK groups.A cerebral ischemia-reperfusion model was induced by transient middle cerebral artery occlusion.The infarct volume was detected by triphenyltetrazolium chloride staining.Bcl-2,Bax,and caspase-3 expression levels in the ischemic cortex were detected by Western blot.Bcl-2 and Bax positive cells in the hippocampal CA1 area on the ischemic side were detected using Immunohistochemical staining.Apoptotic cells in the ischemic cortex were detected by TUNEL staining.Results No infarction and neurological deficits were found in the sham operation group.At 24 h after ischemia-reperfusion,the infarction voltne (P ＜0.01) and neurological deficit score (P =0.02) in the HUK group were significantly lower than those in the control group;at 72 h after ischemia-reperfusion,the infarction volume (P ＜ 0.01) and neurologic deficit score (P =0.03) in the HUK group were also significantly lower than those in the control group.Westem blot analysis showed that the expression level of Bcl-2 in the ischemic cortex in the HUK group was significantly higher than that in the control group (P ＜ 0.001),and the expression levels of caspase-3 (P ＜ 0.001) and Bax (P ＜ 0.001) in the cerebral cortex in the HUK group were significantly lower than those in the control group.No apoptotic cells were found in the sham operation group.The number of apoptotic cells in hippocampal CA1 area (P ＜ 0.01) and the number of Bax positive cells (P ＜0.01) in the HUK group were significantly less than those in the control group,while the number of Bcl-2 positive cells was significantly more in the control group (P ＜ 0.01).Conclusions HUK has a certain protective effect on ischemia-reperfusion injury in mice,its mechanism may be associated with the upregulation of Bcl-2 protein expression and downregulation of caspase-3 and Bax protein expression,thus inhibiting cell apoptosis.