Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objectives:This study aimed to analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in patients with hematological diseases and to explore prognostic risk factors.Methods:This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022. The clinical features, carbapenemase test results, antimicrobial treatments, and outcomes were analyzed.Results:A total of 120 patients developed CRE BSI. Escherichia coli (58/120, 48.3%) was the most prevalent Enterobacteriaceae, followed by Klebsiella pneumoniae (52/120, 43.3%). A total of 93 CRE strains were tested for carbapenemase, of which 75 strains produced carbapenemase (metalloenzyme: 51 strains; serine enzyme: 24 strains). The 30-day mortality rate after BSI was 24.2% (29/120). Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics (7.8% vs 36.2%, P<0.001). Moreover, initiating active therapy within 24 h of BSI onset significantly reduced mortality (15.0% vs 33.3%, P=0.019). The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization (12 h: 14.5% vs 34.1%, P=0.012; 24 h: 40.8% vs 65.9%, P=0.008). Multivariate analysis revealed that septic shock ( HR=24.436, 95% CI 4.148 - 143.966, P<0.001) and pulmonary infection ( HR=9.346, 95% CI 2.718-32.140, P<0.001) were independent risk factors for death within 30 days. Appropriate therapy was initiated within 24 h ( HR=0.225, 95% CI 0.059 - 0.851, P=0.028), and treatment with the ceftazidime-avibactam-containing regimen ( HR=0.082, 95% CI 0.018-0.362, P=0.001) significantly reduced mortality. Conclusion:The prognosis of CRE BSI in patients with hematological diseases is poor. Timely, appropriate therapy and receipt of a ceftazidime-avibactam-containing regimen can improve survival and prognosis.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Objectives:This study aimed to analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in patients with hematological diseases and to explore prognostic risk factors.Methods:This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022. The clinical features, carbapenemase test results, antimicrobial treatments, and outcomes were analyzed.Results:A total of 120 patients developed CRE BSI. Escherichia coli (58/120, 48.3%) was the most prevalent Enterobacteriaceae, followed by Klebsiella pneumoniae (52/120, 43.3%). A total of 93 CRE strains were tested for carbapenemase, of which 75 strains produced carbapenemase (metalloenzyme: 51 strains; serine enzyme: 24 strains). The 30-day mortality rate after BSI was 24.2% (29/120). Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics (7.8% vs 36.2%, P<0.001). Moreover, initiating active therapy within 24 h of BSI onset significantly reduced mortality (15.0% vs 33.3%, P=0.019). The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization (12 h: 14.5% vs 34.1%, P=0.012; 24 h: 40.8% vs 65.9%, P=0.008). Multivariate analysis revealed that septic shock ( HR=24.436, 95% CI 4.148 - 143.966, P<0.001) and pulmonary infection ( HR=9.346, 95% CI 2.718-32.140, P<0.001) were independent risk factors for death within 30 days. Appropriate therapy was initiated within 24 h ( HR=0.225, 95% CI 0.059 - 0.851, P=0.028), and treatment with the ceftazidime-avibactam-containing regimen ( HR=0.082, 95% CI 0.018-0.362, P=0.001) significantly reduced mortality. Conclusion:The prognosis of CRE BSI in patients with hematological diseases is poor. Timely, appropriate therapy and receipt of a ceftazidime-avibactam-containing regimen can improve survival and prognosis.

Objective:To understand preliminarily the current status of medication safety management in pediatric medical institutions in China.Methods:Self-assessment of medication safety situation were conducted in 10 pediatric medical institutions of the Pharmacy Professional Committee of Futang Children′s Medical Development Research Center using the "optimized version of 2011 Medication Safety Self Assessment ? for Hospitals (161 assessment items)" (self-assessment criteria). The self-assessment criteria included 10 key elements, 20 core characteristics, and 161 assessment items. The self-assessment results on medication safety among participating institutions were summarized, and the percentage scores and implementation proportions of the key elements, core characteristics, and assessment items were descriptively analyzed. Results:All 10 participating medical institutions completed the questionnaires within the specified time. The results showed that the overall percentage score of medication safety self-assessment was 74.72%. The element Ⅲ (communication of medication orders and other medicines information, 83.89%) and element Ⅹ (quality process and risk management, 67.84%) were with the highest and lowest percentage scores, respectively. The element Ⅲ (66.67%) and element Ⅸ (patient education, 40.00%) were with the highest and lowest percentage of full implementation, respectively. The element Ⅸ (46.25%) and element Ⅲ (26.67%) were with the highest and lowest percentage of partial implementation, respectively. The element Ⅹ (quality process and risk management, 18.38%) and element Ⅵ (procurement, use, and monitoring maintenance of drug treatment equipment, 6.25%) were with the highest and lowest percentage of non-implementation, respectively. Among the 20 core characteristics, characteristic 10 (guaranteeing the isolation of non-pharmaceutical chemicals from patients and avoiding harm to patients due to misuse, 96.25%) and characteristic 7 (adopting measures such as developing clinical pathways and establishing standardized administration time to ensure patients receive standardized diagnosis and treatment, 57.50%) were with the highest and lowest percentage scores, respectively. The characteristic 20 (following hospital infection control measures during drug storage, formulation, preparation, and administration, 90.00%) and characteristic 17 (establishing a fair and just drug safety culture within the hospital, encouraging and advocating safe behavior, rather than punitive measures for medical personnel related to medication errors, 25.00%) were with the highest and lowest percentage of complete implementation, respectively. The characteristic 7 (55.00%) and characteristic 20 (5.00%) were with the highest and lowest percentage of partial implementation, respectively. The characteristic 17 (22.86%) and characteristic 10 (0) were the highest and lowest percentage of non-implementation, respectively.Conclusions:The 10 pediatric medical institutions participating in the self-assessment have a higher level of management in the communication of medication orders and other drug information, as well as in the storage and distribution of drugs. However, there are shortcomings in the construction of a fair culture, proactive prevention of medication risks, and improvement of information systems.

Objective:To understand preliminarily the current status of medication safety management in pediatric medical institutions in China.Methods:Self-assessment of medication safety situation were conducted in 10 pediatric medical institutions of the Pharmacy Professional Committee of Futang Children′s Medical Development Research Center using the "optimized version of 2011 Medication Safety Self Assessment ? for Hospitals (161 assessment items)" (self-assessment criteria). The self-assessment criteria included 10 key elements, 20 core characteristics, and 161 assessment items. The self-assessment results on medication safety among participating institutions were summarized, and the percentage scores and implementation proportions of the key elements, core characteristics, and assessment items were descriptively analyzed. Results:All 10 participating medical institutions completed the questionnaires within the specified time. The results showed that the overall percentage score of medication safety self-assessment was 74.72%. The element Ⅲ (communication of medication orders and other medicines information, 83.89%) and element Ⅹ (quality process and risk management, 67.84%) were with the highest and lowest percentage scores, respectively. The element Ⅲ (66.67%) and element Ⅸ (patient education, 40.00%) were with the highest and lowest percentage of full implementation, respectively. The element Ⅸ (46.25%) and element Ⅲ (26.67%) were with the highest and lowest percentage of partial implementation, respectively. The element Ⅹ (quality process and risk management, 18.38%) and element Ⅵ (procurement, use, and monitoring maintenance of drug treatment equipment, 6.25%) were with the highest and lowest percentage of non-implementation, respectively. Among the 20 core characteristics, characteristic 10 (guaranteeing the isolation of non-pharmaceutical chemicals from patients and avoiding harm to patients due to misuse, 96.25%) and characteristic 7 (adopting measures such as developing clinical pathways and establishing standardized administration time to ensure patients receive standardized diagnosis and treatment, 57.50%) were with the highest and lowest percentage scores, respectively. The characteristic 20 (following hospital infection control measures during drug storage, formulation, preparation, and administration, 90.00%) and characteristic 17 (establishing a fair and just drug safety culture within the hospital, encouraging and advocating safe behavior, rather than punitive measures for medical personnel related to medication errors, 25.00%) were with the highest and lowest percentage of complete implementation, respectively. The characteristic 7 (55.00%) and characteristic 20 (5.00%) were with the highest and lowest percentage of partial implementation, respectively. The characteristic 17 (22.86%) and characteristic 10 (0) were the highest and lowest percentage of non-implementation, respectively.Conclusions:The 10 pediatric medical institutions participating in the self-assessment have a higher level of management in the communication of medication orders and other drug information, as well as in the storage and distribution of drugs. However, there are shortcomings in the construction of a fair culture, proactive prevention of medication risks, and improvement of information systems.

Objective: To investigate the role and mechanisms of empagliflozin(EMPA) on myocardial ischemia/reperfusion(MI/R) injury. Methods : Forty male SD rats were randomly divided into Control group, MI/R group,2. 5 μmol/L EMPA combined with MI/R group(EMPA + MI/R) as well as EMPA and 10 μmol/L SIRT1 inhibitor EX527 combined with MI/R group(EMPA + EX527 + MI/R). Cardiac function, myocardial fiber morphology and infarct size were detected. The content of malonaldehyde(MDA), the activities of superoxide dismutase(SOD)and succinodehydrogenase(SDH) in myocardium were determined by ELISA. The protein expressions of Cytochrome c, Cleaved caspase-3, SOD2, gp91phoxand SIRT1 were observed by Western blot. The ROS level was detected by DHE staining. Results: Compared with Control group, MI/R group manifested the decreased cardiac function and myocardial fiber rupture. Myocardial infarction area, the expressions of Cytochrome c, Cleaved caspase-3 and gp91phox, as well as the MDA content and ROS level increased, while decreased the activities of SOD and SDH, and the expressions of SOD2 and SIRT1. Compared with MI/R group, EMPA + MI/R group improved cardiac function and inhibited myocardial fiber rupture, myocardial infarction area, the expressions of Cytochrome c and Cleaved caspase-3. The expression of gp91phox, the MDA content and ROS level were also downregulated,while the activities of SOD and SDH and the expressions of SOD2 and SIRT1 were upregulated. However, the protective effects of EMPA on MI/R heart were blocked by EX527. Conclusion EMPA alleviates MI/R injury by inhibiting mitochondrial oxidative stress and apoptosisviaactivating SIRT1.

OBJE CTIVE To establish the finger prints for Yinhuang solution for inhalation and determine the contents of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid simultaneously. METHODS Using baicalin as reference ，the fingerprints of Yinhuang solution for inhalation were established by high performance liquid chromatography （HPLC）. Relative correction factors of neochlorogenic acid and cryptochlorogenic acid were calculated by slope correction method ，using chlorogenic acid as reference ；the contents of them were calculated according to relative correction factor. The results of quantitative analysis of multi-components by single marker （QAMS）were compared with those of external standard method （ESM）. RESULTS There were 18 common peaks in the fingerprints of 10 batches of Yinhuang solution for inhalation ，and their similarities with reference fingerprint were higher than 0.90. A total of 7 common peaks were identified as baicalin ，neochlorogenic acid ，chlorogenic acid ， cryptochlorogenic acid ，isochlorogenic acid B ，3，5-di-O-caffeoylquinic acid and 4，5-di-O-caffeoylquinic acid. The linear range of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid were 0.025 0-1.247 4 μg（r＝0.999 7），0.039 3-1.178 7 μg（r＝ 0.999 9），0.031 6-1.184 1 μg（r＝0.999 9），respectively. RSDs of precision ，reproducibility and stability tests （48 h）were all lower than 1.0％. The average recoveries were 93.92％（RSD＝1.32％ ，n＝6），94.46％（RSD＝1.45％，n＝6），93.93％（RSD＝ 1.57％，n＝6）. Relative correction factors of neochlorogenic acid and cryptochlorogenic acid were 1.068 and 1.233. The contents of neochlorogenic acid and cryptochlorogenic acid determined by QAMS method were 0.301 8-0.386 3 and 0.262 5-0.362 5 mg/mL， respectively. The contents of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid by ESM were 0.302 6-0.387 2， 0.231 0- 0.334 0，0.261 6-0.361 3 mg/mL，respectively. The deviations of the content determination results of the two methods（except for chlorogenic acid ）were both not higher than 0.20％. CONCLUSIONS Established HPLC fingerprints are stable and feasible. Established QAMS method is accurate and rapid. HPLC fingerprint combined with QAMS can be used for the quality control for Yinhuang solution for inhalation ．

Objective:To observe and compare the therapeutic effects of glucosamine sulfate (GS) and diacerein (DCN) on adult Kashin-Beck disease (KBD).Methods:A clinical randomized controlled trial was conducted in the historical severe KBD areas Fanrong Township, Fulu Town, Long'anqiao Town, Lianghe Town, Shaowen Township of Heilongjiang Province, and 240 patients were selected according to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), then divided into GS and DCN groups (gender, age, and KBD condition balanced) via the random number table method, with 120 patients in each group. Followed up once a month to investigate the patient's medication and clinical symptoms, and distributed drugs for the next stage. Fasting blood samples and urine samples were collected before, during, and at the end of treatment (0, 90, and 180 days). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β level and urine pyridinol (PYD) level. Visual analog scale (VAS) scores, evaluation of affected joints, self-evaluated efficacy, and evaluation of adverse reactions were carried out through questionnaires. Joint dysfunction scores and medications efficacy determination were performed according to the "Judgment of Kaschin-Beck Disease Treatment Effect" (WS/T 79-2011).Results:Expression of cytokines related to cartilage metabolism: after 180 days of treatment, serum IL-1β levels, urine PYD levels in GS group and urine PYD levels in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.332, - 5.420, - 5.204, P < 0.05). VAS scores: after 90 days of treatment, the pain, stiffness scores of patients in GS group and the pain, stiffness, and function scores in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.612, - 2.359, - 3.637, - 2.881, - 2.238, P < 0.05); after 180 days of treatment, the pain, stiffness and function scores of patients in GS and DCN groups were significantly lower than those of the same group at 0 day of treatment ( Z = - 6.738, - 9.530, - 7.781, - 5.428, - 3.761, - 3.587, P < 0.01). Evaluation of affected joints: after 90 and 180 days of treatment, except for pain of weather changes in DCN group, the scores of symptomatic joints in the two groups were lower than those at 0 day of treatment ( P < 0.05). Efficacy self-evaluation: after 180 days of treatment, the self-evaluated efficacy ratio of DCN group was higher than that of GS group and the same group after 90 days of treatment (χ 2 = 4.165, 4.022, P < 0.05). Evaluation of adverse reactions: after 90 and 180 days of treatment, the main adverse reactions of patients in GS and DCN groups were gastrointestinal symptoms. Joint dysfunction scores: after 90 days of treatment, the sum of the effective rate and the markedly effective rate of GS group was higher than that of DCN group (χ 2 = 4.993 , P < 0.05); while after the 180 days of treatment, there was no significant difference between the two groups (χ 2 = 0.417 , P > 0.05). Conclusions:Both GS and DCN have a certain therapeutic effect on adult KBD and can improve clinical symptoms. The GS takes effect quickly, and long-term use can protect cartilage from inflammatory factors to a certain extent.