BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

Objective:The toll pathway plays an essential role in the inhibition of dengue virus (DENV) replication in Aedes aegypti. Accordingly, the objective of this study was to examine the impact of microRNA on the Toll pathway regulatory genes and its influence on DENV replication in Ae. aegypti. Methods:RNAhybrid software prediction and dual-luciferase reporter gene assay were employed to study the binding relationship between dps-miR-2526-3p and Rel1 A gene. The real-time fluorescence quantitative PCR (qPCR) was used in the quantification of nuclear and cytoplasmic dps-miR-2526-3p in Wolbachia-carrying (W + ) and Wolbachia-free (W -) Ae. aegypti cells via nucleocytoplasmic separation. The miRNA up-regulation assay or miRNA silencing assay combined with virus infection assay were conducted to ascertain the impact of dps-miR-2526-3p on Rel1 A gene expression and DENV replication. Results:The result of the prediction and dual-luciferase reporter gene assay consistently demonstrated the direct binding relationship between dps-miR-2526-3p and the Rel1 A gene. The qPCR result proved the presence of dps-miR-2526-3p in the nucleus and cytoplasm of Ae. aegypti cell. Notably, the expression levels of dps-miR-2526-3p and Rel1 A gene in W + cells were significantly higher than those in W -cells. The miRNA function assay indicated that dps-miR-2526-3p could positively regulate Rel1 A gene expression. The result of viral infection assay showed that dps-miR-2526-3p exhibited a notable inhibitory effect on DENV replication. Conclusions:Ae. aegypti utilizes dps-miR-2526-3p to activate the Toll pathway via Rel1 A gene, thereby inhibiting the replication of DENV. The novel molecule with anti-DENV properties was found in this study to offer a promising approach for the development of vector control strategies aimed at prevention and control of DENV transmission.

Objective:The toll pathway plays an essential role in the inhibition of dengue virus (DENV) replication in Aedes aegypti. Accordingly, the objective of this study was to examine the impact of microRNA on the Toll pathway regulatory genes and its influence on DENV replication in Ae. aegypti. Methods:RNAhybrid software prediction and dual-luciferase reporter gene assay were employed to study the binding relationship between dps-miR-2526-3p and Rel1 A gene. The real-time fluorescence quantitative PCR (qPCR) was used in the quantification of nuclear and cytoplasmic dps-miR-2526-3p in Wolbachia-carrying (W + ) and Wolbachia-free (W -) Ae. aegypti cells via nucleocytoplasmic separation. The miRNA up-regulation assay or miRNA silencing assay combined with virus infection assay were conducted to ascertain the impact of dps-miR-2526-3p on Rel1 A gene expression and DENV replication. Results:The result of the prediction and dual-luciferase reporter gene assay consistently demonstrated the direct binding relationship between dps-miR-2526-3p and the Rel1 A gene. The qPCR result proved the presence of dps-miR-2526-3p in the nucleus and cytoplasm of Ae. aegypti cell. Notably, the expression levels of dps-miR-2526-3p and Rel1 A gene in W + cells were significantly higher than those in W -cells. The miRNA function assay indicated that dps-miR-2526-3p could positively regulate Rel1 A gene expression. The result of viral infection assay showed that dps-miR-2526-3p exhibited a notable inhibitory effect on DENV replication. Conclusions:Ae. aegypti utilizes dps-miR-2526-3p to activate the Toll pathway via Rel1 A gene, thereby inhibiting the replication of DENV. The novel molecule with anti-DENV properties was found in this study to offer a promising approach for the development of vector control strategies aimed at prevention and control of DENV transmission.

Humans ; Uric Acid ; Cross-Sectional Studies ; Spondylarthritis/diagnostic imaging* ; C-Reactive Protein ; Spondylitis, Ankylosing

Objective:To explore the effect of postoperative delirium risk management in elderly patients with hip fragility fracture based on failure mode and effect analysis (FMEA) theory, and to provide a basis for reducing the incidence of postoperative delirium.Methods:A total of 50 patients admitted to the First Affiliated Hospital of Sun Yat-sen University due to hip fragility fractures from January to December 2019 were selected as the control group, and 50 patients admitted to the First Affiliated Hospital of Sun Yat-sen University for hip fragility fractures from January to December 2020 were selected as the observation group. The control group received routine care, and the observation group implemented risk control intervention measures based on FMEA theory on the basis of the control group. The risk priority number (RPN) value, incidence of delirium, duration of delirium, pain score, satisfaction, and average length of hospital stay were compared between the two groups of patients in each link of failure risk.Results:The RPN values of each link failure risk of the observation group were 100.80 ± 13.39, 103.96 ± 9.96, 103.76 ± 8.04, delirium duration was (36.33 ± 9.07) min, pain scores were 1.86 ± 0.76, 4.16 ± 1.17, average length of stay was (8.98 ± 4.64) days, and incidence of delirium was 6.0% (3/50), the RPN values of each link failure risk of the control group were 274.10 ± 8.48, 291.00 ± 10.10, 287.78 ± 11.64, delirium duration (78.70 ± 20.10) min, pain scores 2.26 ± 1.02, 4.74 ± 1.19, average length of stay was (11.50 ± 7.66) days, and incidence of delirium was 22.0% (11/50). The differences between two groups showed significant differences ( t values were 1.99-93.24, χ2=4.07, P<0.05). The patient satisfaction score of the observation group was 99.36 ± 1.01, which was higher than that of the control group 89.63 ± 2.62, and the difference was statistically significant ( t=24.50, P<0.05). Conclusions:The perioperative implementation of postoperative delirium risk management model based on FMEA theory in elderly patients with hip fractures can reduce the incidence of postoperative delirium, relieve pain, shorten hospital stay, and improve satisfaction degree. It is worthy of clinical promotion.

Cholecystic adenomyosis is a common benign lesion of the biliary system. Recently, cholecystic adenomyosis has been diagnosed to harbour an incidental gallbladder cancer (IGBC) on intraoperative or postoperative pathological examinations. In this article, we reviewed 586 patients who were treated at Zhongshan Hospital, Fudan University with a preoperative diagnosis of cholecystic adenomyosis, and found 5 patients with IGBC diagnosed by pathological examinations. We described the clinical characteristics, imaging features and pathological findings of these 5 cases. We further reviewed the relevant medical literatures to provide a comprehensive view on IGBC of adenomyosis origin.

Objectives:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) and identify the risk factors for death.Methods:The clinical data of 60 patients undergoing ECPR admitted to our hospital and Hangzhou First People's Hospital from September 2014 to September 2019 were retrospectively analyzed. The patients were divided into the survival group and the death group. The clinical data of the two groups were compared to explore the risk factors related to death. COX regression analysis was used to identify the risk factors for death.Results:Sixty patients undergoing ECPR were included in our study, of them, 16 (26.7%) cases were out-of-hospital cardiac arrest (OHCA) and 44 (73.3%) cases were in-hospital cardiac arrest (IHCA). The mortality of OHCA patients was higher than that of IHCA patients (87.5% vs. 56.89%, P < 0.05), and the duration from CPR to ECMO installation in the death group was longer than that in the survival group [(105.4±105.1) min vs. (53.0±28.5) min, P < 0.05]. Compared with the survival group, patients in the death group had higher troponin and glutamic oxalacetic transaminase and lower PH and lactate ( P < 0.05). The median survival time of the 60 patients was 42 days. Out-of-hospital cardiac arrest, high SOFA score before ECMO, high-dose norepinephrine, pulmonary infection during ECMO support and long ECMO support time were independent predictors of patients’ death. Conclusions:Risk factors associated with patients’ death undergoing ECPR are out-of-hospital cardiac arrest, high SOFA score before ECMO, high-dose norepinephrine, long duration from CPR to ECMO installation, pulmonary infection during ECMO support and long ECMO support time.

Background/Aims: Colorectal cancer (CRC) patients often exhibit peritoneal metastasis, which negatively impacts their prognosis. CD31 and D2-40 have recently been suggested to be predictors of breast cancer prognosis, but their role in colorectal peritoneal metastasis (CRPM) remains unknown. Methods: The expression profiles of CD31 and D2-40 were analyzed in CRC patients with or without CRPM and in CRC cell lines with increasing metastatic potential. Overexpression and short hairpin RNA knockdown assays were performed in CRC cells, and the effects of these alterations on epithelial-mesenchymal transition (EMT) in vitro, growth of xenograft tumors in vivo, and peritoneal metastasis potential in a mouse model of CRPM were examined. Results: The expressions of CD31 and D2-40 were upregulated in CRC tumor tissues and was elevated further in tumor tissues from patients with CRPM. CD31 and D2-40 expression levels exhibited increasing trends parallel to the EMT potential of CRC cells. CD31 and D2-40 are essential for CRC cell EMT in vitro as well as for xenograft tumor growth and peritoneal metastasis in vivo. Conclusions CD31 and D2-40 contribute to CRPM by promoting EMT and may serve as prognostic markers and therapeutic targets for CRC, particularly in patients with peritoneal metastasis.

Objective:To compare the treatment effect of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) patients in the prophylactic distal perfusion catheter (DPC) and the non-prophylactic DPC.Methods:A prospective randomized controlled trial (RCT) was conducted. Patients who received VA-ECMO treatment were reviewed at Affiliated Jinhua Hospital, Zhejiang University School of Medicine from January 2019 to June 2020 were divided into two groups, the prophylactic DPC group (DPC placed immediately after the patient VA-ECMO) and the non-prophylactic DPC group (the DPC was placed after the early limb ischemic signs by using evaluation of the lower extremity perfusion assessment table). Comparing the differences of clinical data of two group patients. Pearson correlation analysis was used to analyze the correlation between peak velocity of dorsalis pedis artery and peak velocity of posterior tibial artery and transcutaneous oxygen partial pressure (TcPO 2). Results:A total of 62 patients were included in the analysis, with 31 cases in prophylactic DPC group and another 31 cases in non-prophylactic DPC group. There were no significant differences in sex, age, body mass index (BMI), smoking index, underlying disease, catheterization site, recovery time before on machine, extracorporeal membrane oxygenation (ECMO) operation time, mechanical ventilation time, length of stay in intensive care unit (ICU), mortality rate in hospital, and acute physiology and chronic health evaluationⅡ(APACHEⅡ) between the preventive DPC group and the non-preventive DPC group. There was no significant difference in ECMO indications, ECMO intubation location and pipeline type. The bleeding in the non-prophylactic DPC group was lower than that in the non-prophylactic DPC group [6.5% (2/31) vs. 29.0% (9/31), P < 0.05]. There were no significant differences in limb complications such as cyanosis, necrosis, amputation, compartment syndrome, arterial thrombosis, vascular reconstruction and repair, pseudoaneurysm, limb ischemic or limb infection. During the ECMO operation, except the blood stream infection in the non-prophylactic DPC group was lower than that in the non-prophylactic DPC group [3.2%(1/31) vs. 19.4% (6/31), P < 0.05], there was no other statistical difference in complications between the two groups. The peak velocity of dorsalis pedis artery in the preventive DPC group was significantly higher than that of the non-preventive DPC group (cm/s: 19.30±10.85 vs. 17.85±8.55, P < 0.05), and the peak velocity of posterior tibial artery was significantly lower than that of the non-preventive DPC group (cm/s: 19.90±10.94 vs. 21.58±9.77, P < 0.05). Pearson correlation analysis showed that the peak velocity of dorsalis pedis artery and peak velocity of posterior tibial artery of the preventive DPC group and the non-preventive DPC group were positively correlated with TcPO 2 ( r values were 0.747, 0.856, 0.850, 0.813, respectively, and P values were all 0.000). Conclusions:For patients with VA-ECMO treatment, the incidence of blood stream infection and bleeding during ECMO operation in non-prophylactic DPC implantation patients is lower than that of prophylactic DPC implantation patients. TcPO 2 is positively correlated with peak velocity of posterior tibial artery and dorsal foot artery in the cannulated limb. In patients with VA-ECMO undergoing femoral artery and vein puncture, in addition to judging the blood supply of lower limbs according to symptoms and signs, ultrasound and TcPO 2 monitoring can also be used as effective monitoring methods.