Efficacy and safety of tranexamic acid in the treatment of gastric cancer complicated with upper gastrointestinal bleeding.

OBJECTIVE: To investigate the efficacy and safety of tranexamic acid (TXA) in preventing upper gastrointestinal (GI) bleeding in patients with gastric cancer. METHODS: The clinical data of patients with gastric cancer complicated with acute non-operative GI bleeding treated in the Fourth Hospital of Hebei Medical University from 2020 to 2022 were collected and retrospectively analyzed. The survival status of the patients was followed up by telephone. The dataset of 168 patients was divided into a control group (n=85) and a TXA group (n=83), at a 1:1 ratio. The patients in the control group were treated with esomeprazole, and the patients in the TXA group received additional TXA. The hemostatic effect, rebleeding rate, and mortality of patients were compared between the two groups. The Cox proportional hazard model was used to evaluate the overall survival of patients as well as the related risk factors. RESULTS: The success rate of hemostasis and the normal blood coagulation rate in the TXA group were significantly higher than those in the control group (P=0.003 and P=0.016). The secondary bleeding rate, thrombus formation rate and digestive tract perforation rate in the TXA group were significantly lower than those in the control group (P=0.002, P=0.003 and P=0.035). The improvement of all indicators in the TXA group was better than that in the control group (all P<0.05). For patients with gastric cancer complicated with acute GI bleeding treated with TXA, the Cox proportional hazard model identified III~IV stage, time of TXA treatment, surgical treatment after hemorrhage, and an increase of D-dimer as independent risk factors for upper GI bleeding (all P<0.05). CONCLUSION: TXA can be an effective treatment for patients with gastric cancer complicated by GI bleeding.

The success rate of cardiopulmonary resuscitation and its correlated factors in patients with emergency prehospital cardiac arrest.

To assess the initial success rate and its correlated factors on cardiopulmonary resuscitation (CPR) in emergency prehospital cardiac arrest patients. The clinical information of 429 patients with cardiac arrest who underwent prehospital CPR in the fourth hospital of Hebei Medical University from Jan 2020 to Apr 2022 were evaluated. The patients were divided into the successful group (ROSC, n = 25) and the unsuccessful group (non-ROSC, n = 404) according to whether the autonomous circulation (ROSC) was resumed. The univariate analysis was performed to evaluate the differences in age, the start time of CPR, the application of electric defibrillation, and other related data between the two groups. The multivariate analysis evaluated protective factors affecting CPR's success in prehospital cardiac arrest patients. Patients with cardiogenic causes had the highest success rate of cardiopulmonary resuscitation. The causes of traffic accidents and drowning account for a low proportion. Furthermore, the median CPR length was 25.0 min, alternating from 1.5 to 64 mi. The univariate analysis revealed that age, the start time of CPR, application of electric defibrillation, and adrenaline dosage were correlated with CPR attempts (p < 0.05). Multivariate logistic regression analysis showed that the age of patients with prehospital CA, the location of prehospital CA, etiology, bystander CPR, CPR start time, defibrillation start time, tracheal intubation time, type of rhythm before resuscitation, adrenaline dosage <5 mg, and adrenaline administration time were all the influencing factors of prehospital CPR success (p < 0.01). The factors affecting CPR's success rate in prehospital CA patients are complicated. Establishing a few procedures to diminish the incidence of these risk factors is crucial.

Effect of other venous access on cardiopulmonary resuscitation quality: A prospective, randomized, controlled trial.

This randomized controlled study aimed to prospectively evaluate the application effects of other venous access in patients undergoing cardiopulmonary resuscitation. A total of 212 patients who underwent respiratory and cardiac arrest were randomly divided into peripheral intravenous (IV) access group (IV group, n = 69), femoral vein catheterization group (FVC group, n = 72), and internal jugular vein catheterization group (IJVC group, n = 71). The puncture time, first administration time, pressure interruption time caused by the establishment of fluid pathway, endotracheal intubation time, complications, ROSC time, and ETCO2 were recorded. The time of establishing venous access was: IVIJVC>IV, P = 0.04). There was no significant difference in EtCO2 between the FVC, IV group, and IJVC group (PVC>IJVC>IV, P = 0.17). Due to catheterization, the time of suspending chest compression in the FVC group was significantly lower than in the IJVC group (5s vs. 12s). The time of establishing an artificial airway in the IV (38s) and FVC (35s) group were significantly longer than that in IJVC (52s) group. Central venous catheterization is more effective than peripheral venous catheterization in cardiopulmonary resuscitation. Moreover, femoral vein access was more effective than internal jugular vein access.

A simple and sensitive LC-MS/MS method for therapeutic drug monitoring of digoxin in children.

This short communication introduced a simple and sensitive LC-MS/MS method for therapeutic drug monitoring of digoxin in children with the lower limit of quantitation of 0.2 ng/mL based on 30 µL of plasma. The plasma sample was pretreated by one-step protein precipitation. Then the chromatographic separation was performed on a short C-18 column with a total run time of 2.4 min. The detection was achieved through multiple reaction monitoring using positive ionization mode on a triple quadrupole mass spectrometer. The linear range of digoxin in human plasma was among 0.2-6.4 ng/mL. The intra-day and inter-day accuracies of digoxin ranged from -6.0 % to 10.1 % and imprecisions were less than 8.8 %. The extraction recovery rate of digoxin in plasma samples was above 90 %. Matrix factor normalized by internal standard was within acceptance criteria. This method was fully verified and applied to determine the plasma digoxin concentrations of 43 pediatric patients. It is approved appropriate and practical for the therapeutic drug monitoring of digoxin in routine clinical laboratory practice, especially for children.

UBE2D1 and COX7C as Potential Biomarkers of Diabetes-Related Sepsis.

Patients with diabetes are physiologically frail and more likely to suffer from infections and even life-threatening sepsis. This study aimed to identify and verify potential biomarkers of diabetes-related sepsis (DRS). Datasets GSE7014, GSE57065, and GSE95233 from the Gene Expression Omnibus were used to explore diabetes- and sepsis-related differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) and functional analyses were performed to explore potential functions and pathways associated with sepsis and diabetes. Weighted gene co-expression network analysis (WGCNA) was performed to identify diabetes- and sepsis-related modules. Functional enrichment analysis was performed to determine the characteristics and pathways of key modules. Intersecting DEGs that were also present in key modules were considered as common DEGs. Protein-protein interaction (PPI) network and key genes were analyzed to screen hub genes involved in DRS development. A mouse C57 BL/6J-DRS model and a neural network prediction model were constructed to verify the relationship between hub genes and DRS. In total, 7457 diabetes-related DEGs and 2606 sepsis-related DEGs were identified. GSEA indicated that gene datasets associated with diabetes and sepsis were mainly enriched in metabolic processes linked to inflammatory responses and reactive oxygen species, respectively. WGCNA indicated that grey60 and brown modules were diabetes- and sepsis-related key modules, respectively. Functional analysis showed that grey60 module genes were mainly enriched in cell morphogenesis, heart development, and the PI3K-Akt signaling pathway, whereas genes from the brown module were mainly enriched in organelle inner membrane, mitochondrion organization, and oxidative phosphorylation. UBE2D1, IDH1, DLD, ATP5C1, COX6C, and COX7C were identified as hub genes in the PPI network. Animal DRS and neural network prediction models indicated that the expression levels of UBE2D1 and COX7C in DRS models and samples were higher than control mice. UBE2D1 and COX7C were identified as potential biomarkers of DRS. These findings may help develop treatment strategies for DRS.

An analysis of the treatment effect of two modes of oxygenation on patients with radiation pneumonia complicated by respiratory failure.

BACKGROUND: Stereotactic radiotherapy (SBRT) is widely used in the treatment of thoracic cancer. OBJECTIVE: To evaluate the efficacy of a non-rebreather mask (NRBM) and high-flow nasal cannula (HFNC) in patients with radiation pneumonia complicated with respiratory failure. METHODS: This was a single-center randomized controlled study. Patients admitted to the EICU of the Fourth Hospital of Hebei Medical University were selected and divided into NRBM and HFNC group. Arterial blood gas analysis, tidal volume, respiratory rates and the cases of patients receiving invasive assisted ventilation were collected at 0, 4, 8, 12, 24, 48, and 72 h after admission. RESULTS: (1) The PaO2/FiO2, respiratory rates, and tidal volume between the two groups at 0, 4, 8, 12, 24, 48, and 72 h were different, with F values of 258.177, 294.121, and 134.372, all P< 0.01. These indicators were different under two modes of oxygenation, with F values of 40.671, 168.742, and 55.353, all P< 0.01, also varied with time, with an F value of 7.480, 9.115, and 12.165, all P< 0.01. (2) The incidence of trachea intubation within 72 h between HFNC and NRBM groups (23 [37.1%] vs. 34 [54.0%], P< 0.05). The transition time to mechanical ventilation in the HFNC and NRBM groups (55.3 ± 3.2 h vs. 45.9 ± 3.6 h, P< 0.05). (3) The risk of intubation in patients with an APACHE-II score > 23 was 2.557 times than score ⩽ 23, and the risk of intubation in the NRBM group was 1.948 times more than the HFNC group (P< 0.05). CONCLUSION: Compared with the NRBM, HFNC can improve the oxygenation state of patients with radiation pneumonia complicated with respiratory failure in a short time, and reduce the incidence of trachea intubation within 72 h.

Retraction: Analysis of risk factors and countermeasures of sepsis-associated encephalopathy.

The paper entitled "Analysis of risk factors and countermeasures of sepsis-associated encephalopathy" by YU et al., which was published online on October 15, 2021, has been withdrawn by the Publisher upon request by the authors. Their recent studies found that some data used in this paper could not be replicated in their latest studies and, as a result, they now have doubts about the accuracy of the published results.

Relationship between built environments and risks of ischemic stroke based on meteorological factors: A case study of Wuhan's main urban area.

Ischemic stroke is one of the most common causes of death worldwide, and uncomfortable meteorological and built environments may increase its risk. Residents in different built environments are exposed to different risks of ischemic stroke in cold and hot weather. By using the data from 3547 patients hospitalized, a distributed lag non-linear model was established to compare the differences in the risk of ischemic stroke in urban areas with respect to different Building Height, Building Density, Normalized Differential Vegetation Index, and Distance to Water under the meteorological condition. The results showed that lower Building Height is related to the negative cold effects in winter, and higher Building Height is related to increased risks at high temperatures. Built environments with Building Heights of 10-15 m in hot weather and above 15 m in cold weather have low risks. Higher Building Density was found to be associated with reduced negative cold effects; however, the negative hot effects increased in summer. Built environments with a Building Density of more than 0.3 showed low risks, regardless of the weather conditions. Increasing NDVI seemed to mitigate negative effects in uncomfortable weather, and built environments with higher NDVI were found to be associated with lower risks of ischemic stroke. Built environments with shorter Distance to Water seemed to pose higher risks in summer, and longer Distance to Water was correlated with higher risks in winter. Built environments with Distance to Water in the range of 0.65-2.30 km showed low risks. The research results could have some implications for urban planners to form reasonable built environments under certain meteorological factors which can be beneficial for the mitigation of incidence of ischemic stroke.

Screening and Identification of Potential Peripheral Blood Biomarkers for Alzheimer's Disease Based on Bioinformatics Analysis.

BACKGROUND Alzheimer's disease (AD) is the leading cause of dementia worldwide; however, the molecular mechanisms underlying its pathogenesis remain unclear. The present study aimed to discover some potential peripheral blood biomarkers for early detection of patients with AD. MATERIAL AND METHODS Publicly available AD datasets - GSE18309 and GSE97760 - were obtained from the Gene Expression Omnibus database, and limma package from Bioconductor was employed to search for differently expressed genes (DEGs). Weighted correlation network analysis was performed to identify DEGs with highly synergistic changes, and functional annotation of DEGs was performed using gene set enrichment analysis and Metascape. STRING and Cytoscape were used to construct protein-protein interaction networks and analyze the most significant hub genes. Thereafter, the Comparative Toxicogenomics Database (CTD) was used to identify hub genes associated with AD pathology, and Connectivity Map was used to screen small molecule drugs for AD. Finally, hub genes coupled with corresponding predicted miRNAs involved in AD were assessed via TargetScan, and functional annotation of predicted miRNAs was performed using DIANA database. RESULTS Our analyses revealed 5042 DEGs; based on functional analyses, these DEGs were mainly associated with oligosaccharide lipid intermediate biosynthetic process, cyclin binding, signaling pathways regulating pluripotency of ubiquitin mediated proteolysis, and extracellular matrix-receptor interaction. UBB, UBA52, SRC, MMP9, VWF, GP6, and PF4 were identified as the hub genes. The CTD showed that these hub genes are closely related with AD or cognition impairment. CONCLUSIONS The identified hub genes and corresponding miRNAs might be useful as potential peripheral blood biomarkers of AD.

Crosstalk between ACE2 and PLGF regulates vascular permeability during acute lung injury.

Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI), through antagonizing hydrolyzing angiotensin II (AngII) and the ALI-induced apoptosis of pulmonary endothelial cells. Nevertheless, the effects of ACE2 on vessel permeability and its relationship with placental growth factor (PLGF) remain ill-defined. In the current study, we examined the relationship between ACE2 and PLGF in ALI model in mice. We used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of PLGF in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5 µg/kg Visudyne. PLGF pump or soluble Flt-1 (sFlt-1) pump was given to augment or suppress PLGF effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine. We found that ACE2 treatment did not alter PLGF levels in lung, but antagonized the effects of PLGF on increases of lung vessel permeability. Ectogenic PLGF abolished the antagonizing effects of ACE2 on the vessel permeability against PLGF. On the other hand, suppression of PLGF signaling mimicked the effects of ACE2 on the vessel permeability against PLGF. The suppression of vessel permeability resulted in improvement of lung function after ALI. Thus, ACE2 may antagonize the PLGF-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI.

[Comparison of the effect of fluid resuscitation as guided either by lactate clearance rate or by central venous oxygen saturation in patients with sepsis].

OBJECTIVE: To compare the efficacy of fluid resuscitation as guided by lactate clearance rate (LCR) and central venous oxygen saturation (ScvO2) in patients with sepsis. METHODS: A prospective randomized control study was conducted. Fifty patients diagnosed with severe sepsis or septic shock from January 2011 to February 2012 in department of critical care medicine of Fourth Hospital of Hebei Medical University were enrolled in the study. The patients were randomly divided into two groups according to the sequence (each n=25): ScvO2 group and LCR group. After ICU admission, the patients were treated symptomatically timely, and fluid resuscitation was started as early as possible according to Surviving Sepsis Campaign guidance for management of severe sepsis and septic shock 2008. Central venous pressure (CVP)≥8 mm Hg (1 mm Hg=0.133 kPa), mean arterial pressure (MAP)≥65 mm Hg and ScvO2≥0.70 served as goal values to accomplish the fluid resuscitation therapy in ScvO2 group, while CVP≥8 mm Hg, MAP≥65 mm Hg, LCR≥10% served as goal value to accomplish the fluid resuscitation therapy in LCR group. The general condition and clinical characteristics on arrival in ICU, changes in CVP, MAP, ScvO2, lactate level and/or LCR before (0 hour) and 3, 6, 72 hours after the start of fluid resuscitation and the other related conditions during the therapy were recorded. RESULTS: There was no significant difference in general data or clinical characteristics before the start of therapy, occurrence of organ dysfunction, or treatment measures during different time periods after start of fluid resuscitation. Compared with the condition immediately before fluid resuscitation, at 3 hours after start of fluid resuscitation, CVP were improved in LCR and ScvO2 groups (8.58±1.17 mm Hg vs. 6.33±1.21 mm Hg, 9.08±2.43 mm Hg vs. 5.33±0.98 mm Hg, both P<0.05); at 6 hours after start of fluid resuscitation, heart rate (HR) and respiratory rate (RR) were lowered in LCR and ScvO2 groups (HR: 96±18 bpm vs. 127±13 bpm, 98±13 bpm vs. 116±19 bpm, RR: 23±3 times/min vs. 33±9 times/min, 24±5 times/min vs. 35±6 times/min, all P<0.05), oxygenation index (PaO2/FiO2) was increased in LCR and ScvO2 groups (179±41 mm Hg vs. 86±21 mm Hg, 202±33 mm Hg vs. 95±17 mm Hg, both P<0.05), and there was no significant difference in MAP in both groups. There was no significant difference in all indexes between two groups. In LCR group, 3 hours after start of fluid resuscitation, lactate level was significantly decreased (2.81±0.18 mmol/L vs. 3.43±1.31 mmol/L, P<0.05). Compared with the value 3 hours after start of fluid resuscitation, LCR was significantly improved at 6 hours and 72 hours after start of fluid resuscitation in LCR group [(42.69±8.75)%, (48.87±9.69)% vs. (20.32±4.58)%, both P<0.05]. Compared with that immediately before fluid resuscitation, ScvO2 was significant improved in ScvO2 group at 3 hours after start of fluid resuscitation (0.65±0.04 vs. 0.53±0.06, P<0.05). There was no significant difference in success rate of fluid resuscitation comparing that of 6 hours and that of 72 hours [6 hours: 72% (18/25) vs. 64% (16/25), χ(2)=0.368, P=0.762; 72 hours: 88% (22/25) vs. 88% (22/25) ,χ(2)=0.000, P=1.000], length of ICU stay (8±3 days vs. 10±4 days, t=0.533, P=0.874), length of hospital stay (29±11 days vs. 35±16 days, t=0.692, P=0.531), improvement rate [84% (21/25) vs. 76%(19/25), χ(2)=0.500, P=0.480] or 28-day mortality [20% (5/25) vs. 28% (7/25), χ(2)=0.439, P=0.742] between LCR and ScvO2 groups. CONCLUSIONS: Both LCR and ScvO2 can be taken as the index in confirming the endpoint of fluid resuscitation for patients with severe sepsis and septic shock. Fluid resuscitation therapy under the guidance of LCR is accurate and reliable in patients with severe sepsis and septic shock.

[Changes in adrenal cortex function and protective effect of dexamethasone in septic rats during early phases].

OBJECTIVE: To affirm the presence of relative adrenal insufficiency (RAI) in the early phases of sepsis and its probable mechanisms, and to study the optimal time for glucocorticoid replacement therapy. METHODS: A total of 260 healthy male Wistar rats were randomized into five groups (each group n=52), including normal control group, sham operation group, cecal ligation and puncture (CLP) group, dexamethasone prevention group (with 10 mg/kg dexamethasone injection into the abdominal cavity before CLP) and dexamethasone treatment group (with 10 mg/kg dexamethasone injection into the abdominal cavity 7 hours after CLP). Each group was subdivided into five subgroups according to five time points: 2, 4, 6, 8 and 12 hours. Adrenocorticotrophic hormone (ACTH) test was conducted at 8 hours and 12 hours, and before and after 30 minutes of ACTH administration, the cortisol content in serum was determined with radioimmunoassay (RIA) and the expressions of Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha) mRNA in adrenal glands were detected with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Ultrastructure of adrenal cortex was observed with transmission electron microscope. The survival rats was recorded in all groups. RESULTS: (1) The levels of cortisol in CLP group, dexamethasone prevention group and dexamethasone treatment group were respectively higher than those of normal control and sham operation groups (all P<0.05). But there was no marked change in the levels of cortisol between pre-and post-ACTH in rats with sepsis in the early phases. (2)The expressions of TLR4, TNF-alpha mRNA in adrenal both were significantly increased in CLP group, and they were higher than those in sham operation group (P<0.05 or P<0.01). The expressions of TLR4, TNF-alpha mRNA in dexamethasone prevention group and treatment group were significantly lower than those in CLP group, and those in the dexamethasone prevention group were lower than those in sham operation group. (3)In the groups of CLP, dexamethasone prevention and treatment, ultrastructure changes were observed in the adrenal, especially in CLP group. (4)The survival rate of the dexamethasone prevention and treatment groups at 12 hours were higher than that of CLP group (76.92%, 40.00% vs. 33.33%, P<0.01 and P<0.05). The survival rate of dexamethasone prevention group was higher than that of dexamethasone treatment group (P<0.05). CONCLUSION: (1)RAI occurs during the early stage of sepsis. (2)The expressions of TLR4, TNF-alpha mRNA in adrenal and changes in corticoadrenal ultrastructure participates in the pathogenesis of RAI in the early stage of sepsis in rat. (3) Dexamethasone therapy could effectively increase the survival rate and improve outcome through down-regulating the expression changes in TLR4, TNF-alpha mRNA and alleviating changes in ultrastructure of adrenal glands. Early administration of dexamethasone may give good result in the treatment of sepsis.