Purpose: Although the medical decision-making process can be overwhelming for some surrogates, there is a lack of understanding regarding their experiences. The objectives of this study were to examine the decision self-efficacy and decisional conflict experienced by surrogates in intensive care units (ICUs) when faced with the decision of whether to reintubate patients with respiratory failure after a planned extubation. In addition, predictors and mediators influencing these decision-making processes were identified. Methods: This study utilized a cross-sectional design to investigate the decision-making processes of 174 surrogates who were faced with the decision of whether to reintubate patients with respiratory failure after a planned extubation in the internal ICU of a medical center between August 2021 and February 2022. Structured questionnaires were administered to collect data on the surrogates' background information, decision self-efficacy, decisional conflict, and positive and negative affect. The patients’ background information was also collected. Univariate and multivariate analyses were performed to model the data. Results: The mean decision self-efficacy score of the surrogates was 82.41 points, and 20.7% surrogates had decisional conflict scores exceeding 37.5 points, suggesting that they faced challenges in the decision-making process. Surrogates' employment status and negative affect significantly predicted their decision self-efficacy. In addition, patients' activities of daily living prior to hospitalization and the decision self-efficacy of the surrogate significantly predicted surrogate decisional conflict. The impact of surrogates’ negative affect on decisional conflict was fully mediated by decision self-efficacy. Conclusions Surrogate decision self-efficacy mediates the relationship between negative affect and decisional conflict. Providing clinical care interventions that focus on enhancing surrogate self-efficacy and reducing negative affect can help alleviate decisional conflict in this population.

Coronary vasospasm is a rare diagnosis resulting in sudden arrhythmic cardiac arrest. We report a case of a healthy, non-smoking elderly woman resuscitated from arrhythmic cardiac arrest. She had persistent spontaneous coronary vasospasm, leading to right ventricular myocardial injury and failure, and shock. She responded quickly to intravenous normal saline bolus infusion, but had irreversible neurological sequelae. Additionally, she had atrial fibrillation preceding ischemic ventricular fibrillation, a rare finding in coronary vasospasm-related cardiac arrest. We suggest immediate coronary angiography of patients in sudden arrhythmic cardiac arrest with acute right ventricular failure for a prompt, accurate diagnosis and appropriate management of the coronary vasospasm.
Aged ; Coronary Angiography ; Coronary Vasospasm ; diagnosis ; diagnostic imaging ; Death, Sudden, Cardiac ; pathology ; Electrocardiography ; Female ; Humans

mTOR (mammalian target of rapamycin) is the center for cellular activities. It controls many cell activities via inhibiting apoptosis and promoting cell growth. Rheb can activate mTOR signaling pathway and participate in genesis and development of multiple cancers. This study was purposed to explore the underlying role of Rheb in human myeloid leukemia by using the myeloid leukemia cell lines. Two myeloid leukemia cell lines HL-60 and K562 overexpressing Rheb were established with retrovirus containing Rheb. The mRNA and protein expressions of Rheb were determined by Real-Time PCR and Western blot respectively. Cell proliferation rate was examined by CCK-8 assay and apoptosis rate was analyzed using Annexin V and 7-AAD double-staining. The results showed that Rheb was overexpressed in both HL-60 and K562 cell lines. The Rheb overexpression cell lines were successfully established. It is found that overexpression of Rheb could promote cell growth. Furthermore, the overexpression of Rheb could accelerate cells entering into G2/M phase (P < 0.01), while did not affect the apoptosis. It is concluded that Rheb overexpression promotes myeloid leukemia cell proliferation through accelerating cell cycle progression.
Cell Cycle ; Cell Proliferation ; HL-60 Cells ; Humans ; K562 Cells ; Monomeric GTP-Binding Proteins ; metabolism ; Neuropeptides ; metabolism ; Ras Homolog Enriched in Brain Protein ; Signal Transduction

OBJECTIVETo explore the intervention effect of the auricular stimulator in the cavum concha for diabetes.

METHODSForty-five cases were treated with auricular simulator in the cavum concha for 30 min, once daily for consecutive 3 months. The changes of the fasting plasma glucose (FBG), blood glucose load after 2-hour 75 g oral glucose tolerance test (P2 BG)and glycosylated hemoglobin (HbA1c) were compared before and after treatment.

RESULTSThe level of the HbA1c was obviously decreased (P < 0.05, P < 0.01), and there were also statistically significant differences in FBG and P2 BG after the treatment (P < 0.05, P < 0.01).

CONCLUSIONWith the auricular stimulator, the stimulation in the cavum concha is benefit for the improvement of HbA1c of the diabetes.

Acupuncture, Ear ; Adult ; Aged ; Diabetes Mellitus ; metabolism ; therapy ; Female ; Glucose ; metabolism ; Glycated Hemoglobin A ; metabolism ; Humans ; Male ; Middle Aged

The study was aimed to generate monoclonal antibodies (mAbs) against homo sapiens UDP-glucose pyrophosphorylase 2 (UGP2). Normal human liver tissues homogenized, and cytosolic proteins isolated by centrifugation were used to immunize BALB/c mice to generate mAbs by hybridoma technique. The mAbs were identified by ELISA, Western blot, and immunohistochemistry assay. The antibody specificity was confirmed by Uni-ZAP expression library screening. The results indicated that one hybridoma BAD062 secreting specific mAb against UGP2 was established. The Ig subclass of this mAb was IgG(2b) (kappa), and it could be used in ELISA, Western blot, immunohistochemistry assay. The antigen recognized by BAD062 mAb was localized in the hepatocyte cytoplasm, with molecular weight of 56 kD in the cytosolic proteins of human liver tissue. The BAD062 mAb was further confirmed by immunoscreening of Uni-ZAP XR liver cDNA expression library. It is concluded that a hybridoma cell line stably secretes specific mAb against UGP2. This mAb reacted with UGP2 in ELISA, Western blot, immunohistochemistry assay, and would be very useful for the UGP2 studies.
Animals ; Antibodies, Monoclonal ; analysis ; biosynthesis ; Antibody Specificity ; Base Sequence ; Humans ; Hybridomas ; secretion ; Liver ; metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; UTP-Glucose-1-Phosphate Uridylyltransferase ; immunology

Objective: To analyze the gene mutation spectrum, clinical features, and the factors of disease progression and prognosis in patients with essential thrombocytosis (ET) . Methods: A retrospective analysis was conducted on 178 newly diagnosed ET patients admitted from February 1st, 2009 to November 1st, 2018. Results: Of the 178 patients, 89 were male and 89 female, and the median diagnosis age was 49.5 (3-86) years old. JAK2V617F, CALR and MPL mutations frequencies were 16.45% (1.67%-43.90%) , 40.00% (10.00%-49.15%) and 25.10% (25.00%-40.00%) , respectively. Compared with patients with CALR mutations, patients with JAK2V617F mutation had higher diagnosis age (P=0.035) , higher white blood cell count (P=0.040) , higher hemoglobin concentration (P=0.001) , and lower platelet count (P=0.002) , respectively. Of them, 47 patients (27.01%) developed thrombotic events before diagnosis, and 3 ones (1.72%) experienced thrombotic events after diagnosis. Multivariate analysis revealed age >60 years (P=0.013, OR=4.595, 95%CI 1.382-15.282) and cardiovascular risk factors (CVF) (P<0.001, OR=8.873, 95%CI 2.921-26.955) as risk factors for thrombotic events, CALR mutation (P=0.032, OR=0.126, 95%CI 0.019-0.838) as a protective factor for thrombotic events. Age >60 years (P=0.042, OR=4.045, 95%CI 1.053-15.534) was found to be a risk factor for the overall survival (OS) of ET patients. OS of age ≤60 years and age>60 years were calculated by Kaplan-Meier analysis to be (115.231±1.899) months and (83.291±4.991) months (χ²=6.406, P=0.011) , respectively. Conclusion Age>60 years and CVF were risk factors for thrombotic event. CALR mutation was a protective factor for thrombotic event. Age >60 years was a risk factor for OS in ET patients.

Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET). Antibiotics is hard to work in advanced anthrax infections, because injuries and deaths of the infected are mainly caused by lethal toxin (LT). Thus, the therapeutic neutralizing antibody is the most effective treatment of anthrax. Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs) for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the treatment of inhalational anthrax. Once B. anthracis was artificially reconstructed or PA had mutations within recognized neutralization epitopes, anti-PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important supplement for anthrax treatment. Most of the anti-LF antibodies are murine or chimeric antibodies. By contrast, fully human MAbs can avoid the high immunogenicity of murine antibodies. First, we used LF to immunize the transgenic mice and used fluorescent cell sorting to get antigen-specific memory B cells from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7 and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice, fluorescent cell sorting and single-cell PCR methods, this study shows new ideas and methods for the rapid screening of fully human monoclonal antibodies.

Gatifloxacin (GFX) is a kind of chiral fluoroquinolones compound due to the methyl group at the C-3 position of the piperazine ring[1]. Although the enantiomers of GFX show similar levels of antimicrobial activity and pharmacokinetics[2], the other biological activities (i.e., toxicity or enantioselective recognition to various receptors in vivo) of GFX enantiomers have not yet been studied. With this in mind, we developed a rapid and cost-effective high performance liquid chromatographic (HPLC) separation procedure for GFX enantiomers with a pre-column esterification strategy. With significant enhancement of drug solubility and optimization for chromatographic conditions, the proposed method was scaled up to preparative HPLC to obtain optical active S-(-)- and R-(+)-GFX. The antibacterial activities of GFX enantiomers after preparative separation were further verified by measuring the Minimum Inhibitory Concentration (MIC) values against Escherichia coli ATCC 25922. In addition, the binding selectivity of GFX enantiomers to protein receptor were evaluated by antibody using enzyme-linked immunosorbent assay (ELISA) for the first time.
Anti-Bacterial Agents ; chemistry ; pharmacology ; Escherichia coli ; drug effects ; Esterification ; Fluoroquinolones ; chemistry ; pharmacology ; Microbial Sensitivity Tests ; Molecular Structure ; Structure-Activity Relationship

OBJECTIVETo investigate the clinical characteristics and long-term outcome of Chinese young patients (≤40 years) with essential thrombocythemia(ET), and to develop a thrombosis predicting model specific for young patients with ET, so as to provide a new evidence for risk stratification and treatment.

METHODSMedical records of 125 Chinese young patients with newly diagnosed of ET were retrospectively analyzed.

RESULTSThe median age at diagnosis was 32 (18-40) years old, with 37 males and 88 females. During follow-up, 18 patients (14.4%) experienced major thrombotic events. JAK2 V617F (HR=8.895, P=0.001), history of thrombosis (HR=8.001, P<0.001) and WBC≥12.0×10/L (HR=5.225, P=0.002) were independent risk factors for thrombosis. The incidence of thrombosis and risk factors in young patients were different from that in general ET population, so a thrombosis predicting model specific for young patients with ET was developed. In this model, JAK2 V617F (score 2), history of thrombosis (score 2) and WBC≥12.0×10/L (score 1) were used to divide the patients into low risk (score 0), intermediate risk (score 1-2) and high risk (score≥3) groups. These 3 groups exhibited significantly different thrombosis-free survival (&chi;=32.223, P<0.001). Antiplatelet treatment could prevent the occurrence of thrombosis (HR=0.081, P<0.001), while cytoreductive agents significantly decreased the risk of thrombosis only in intermediate and high risk groups (14.3% vs 36.4%, &chi;=4.416, P=0.036). Seven patients (5.6%) evolved to myelofibrosis, and one of them finally progressed in to acute leukemia. The only risk factor for evolution was WBC≥15.0×10/L (&chi;=5.434, P=0.020). Neither antiplatelet treatment nor cytoreductive agents could prevent disease progression.

CONCLUSIONThe incidence of thrombosis and risk factors in young patients with ET are different from that in general ET population. The thrombosis-predicting model specific for young patients with ET is useful for guiding therapeutic decisions.

BACKGROUNDEssential thrombocythemia is a subgroup of myeloproliferative neoplasms. Previous studies identified mutations of JAK2, CALR, and MPL that are closely related with the pathogenesis of myeloproliferative neoplasms. All these mutations contribute to the hyperactivation of JAK2/STAT pathway. However, a small proportion of essential thrombocythemia patients does not display such mutations. The pathogenesis of "triple-negative" form of essential thrombocythemia remains unknown.

OBJECTIVETo investigate the clinical characteristics of triple-negative essential thrombocythemia and related mutation genes.

METHODSTo identify the mutations associated with triple-negative essential thrombocythemia, next-generation sequencing was used to conduct targeted sequencing of 360 genes in samples from 68 patients.

RESULTSAt least one missense mutation was detected in all the patients and all the detected genes. After screening the data, it was observed that 10 genes with the 10 highest mutation were follows: FLT3, SH2B3, ASXL1, ADAMTS1, TET2, TP53, EGFR, CUX1, GATA2, and MPL.When only rare genes (i.e., with a frequency in Asian populations lower than 5%, as estimated by the 1000 Genomes Project) were analyzed, the most frequently mutated genes in the patients were TET2 (33.82%), SH2B3(29.41%), and ASXL1 (23.53%). Our study identified some mutations that did not previously reported. Although all these mutations need further validation, high incidence rates may indicate relevance of the respective mutations to essential thrombocythemia pathogenesis. Some of the detected mutations have been previously reported; these mutations were also found in a large proportion of our subjects.

CONCLUSIONwhole-exon sequencing can provide a higher level of accuracy for gene mutation analysis and assist in identifying mutations that contribute to illustrate the pathogenesis of essential thrombocythemia.

Calreticulin ; DNA Mutational Analysis ; Humans ; Janus Kinase 2 ; Mutation ; Myeloproliferative Disorders ; Receptors, Thrombopoietin ; Thrombocythemia, Essential