Upregulation of IQGAP2 by EBV transactivator Rta and its influence on EBV life cycle.

Epstein-Barr virus (EBV) is a human oncogenic γ-herpesvirus that establishes persistent infection in more than 90% of the world's population. EBV has two life cycles, latency and lytic replication. Reactivation of EBV from latency to the lytic cycle is initiated and controlled by two viral immediate-early transcription factors, Zta and Rta, encoded by BZLF1 and BRLF1, respectively. In this study, we found that IQGAP2 expression was elevated in EBV-infected B cells and identified Rta as a viral gene responsible for the IQGAP2 upregulation in both B cells and nasopharyngeal carcinoma cell lines. Mechanistically, we showed that Rta increases IQGAP2 expression through direct binding to the Rta-responsive element in the IQGAP2 promoter. We also demonstrated the direct interaction between Rta and IQGAP2 as well as their colocalization in the nucleus. Functionally, we showed that the induced IQGAP2 is required for the Rta-mediated Rta promoter activation in the EBV lytic cycle progression and may influence lymphoblastoid cell line clumping morphology through regulating E-cadherin expression. IMPORTANCE Elevated levels of antibodies against EBV lytic proteins and increased EBV DNA copy numbers in the sera have been reported in patients suffering from Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, indicating that EBV lytic cycle progression may play an important role in the pathogenesis of EBV-associated diseases and highlighting the need for a more complete mechanistic understanding of the EBV lytic cycle. Rta acts as an essential transcriptional activator to induce lytic gene expression and thus trigger EBV reactivation. In this study, scaffolding protein IQGAP2 was found to be upregulated prominently following EBV infection via the direct binding of Rta to the RRE in the IQGAP2 promoter but not in response to other biological stimuli. Importantly, IQGAP2 was demonstrated to interact with Rta and promote the EBV lytic cycle progression. Suppression of IQGAP2 was also found to decrease E-cadherin expression and affect the clumping morphology of lymphoblastoid cell lines.

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with type 2 diabetes mellitus: recent findings from NHANES 2007-2018.

OBJECTIVE: This study aims to assess the relationship between NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) and Type 2 diabetes mellitus (T2DM) in US adults, using National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2018. METHODS: This study explored the connection between NHHR and T2DM by analyzing a sample reflecting the adult population of the United States (n = 10,420; NHANES 2007-2018). NHHR was characterized as the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol. T2DM was defined based on clinical guidelines. This research used multivariable logistic models to examine the connection between NHHR and T2DM. Additionally, it included subgroup and interaction analyses to assess variations among different groups. Generalized additive models, smooth curve fitting, and threshold effect analysis were also employed to analyze the data further. RESULTS: The study included 10,420 subjects, with 2160 diagnosed with T2DM and 8260 without. The weighted multivariate logistic regression model indicated an 8% higher probability of T2DM for each unit increase in NHHR (OR: 1.08, 95% CI: 1.01-1.15) after accounting for all covariates. Subgroup analysis outcomes were uniform across various categories, demonstrating a significant positive relationship between NHHR and T2DM. Interaction tests showed that the positive link between NHHR and T2DM remained consistent regardless of age, body mass index, smoking status, moderate recreational activities, hypertension, or stroke history, with all interaction P-values exceeding 0.05. However, participants' sex appeared to affect the magnitude of the connection between NHHR and T2DM (interaction P-value < 0.05). Also, a nonlinear association between NHHR and T2DM was discovered, featuring an inflection point at 1.50. CONCLUSIONS: Our study suggests that an increase in NHHR may be correlated with a heightened likelihood of developing T2DM. Consequently, NHHR could potentially serve as a marker for estimating the probability of T2DM development.

Extracorporeal vs. conventional CPR for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a significant cause of mortality and morbidity worldwide. Extracorporeal cardiopulmonary resuscitation (ECPR) is a potential intervention for OHCA, but its effectiveness compared to conventional cardiopulmonary resuscitation (CCPR) needs further evaluation. METHOD: We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov for relevant studies from January 2010 to March 2023. Pooled meta-analysis was performed to investigate any potential association between ECPR and improved survival and neurological outcomes. RESULTS: This systematic review and meta-analysis included two randomized controlled trials enrolling 162 participants and 10 observational cohort studies enrolling 4507 participants. The pooled meta-analysis demonstrated that compared to CCRP, ECPR did not improve survival and neurological outcomes at 180 days following OHCA (RR: 3.39, 95% CI: 0.79 to 14.64; RR: 2.35, 95% CI: 0.97 to 5.67). While a beneficial effect of ECPR was obtained regarding 30-day survival and neurological outcomes. Furthermore, ECPR was associated with a higher risk of bleeding complications. Subgroup analysis showed that ECPR was prominently beneficial when exclusively initiated in the emergency department. Additional post-resuscitation treatments did not significantly impact the efficacy of ECPR on 180-day survival with favorable neurological outcomes. CONCLUSIONS: There is no high-quality evidence supporting the superiority of ECPR over CCPR in terms of survival and neurological outcomes in OHCA patients. However, due to the potential for bias, heterogeneity among studies, and inconsistency in practice, the non-significant results do not preclude the potential benefits of ECPR. Further high-quality research is warranted to optimize ECPR practice and provide more generalizable evidence. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/, registry number: CRD42023402211.

The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility.

BACKGROUNDS: Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. METHODS: We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. RESULTS: Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively). CONCLUSIONS: EAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).

Central venous oxygen saturation changes as a reliable predictor of the change of CI in septic shock: To explore potential influencing factors.

PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO2) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO2 (ΔScvO2) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase of cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO2 and its change before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO2 (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO2, with R2 = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO2 (R2 = 0.245, p < 0.001). ΔScvO2 had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION: ΔScvO2 served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change of CI was the sole contributing factor to the ΔScvO2. In stable hemoglobin conditions, the absolute value of ScvO2 could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.

[Difference of effective component content and key enzyme gene expression of biosynthesis in Atractylodes chinensis with different leaf shapes].

In this study, four Atractylodes chinensis(A. chinensis) with different leaf shapes, such as the split leaf, long and narrow leaf, oval leaf, and large round leaf, were used as experimental materials to establish a method for simultaneously determining atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in the rhizome of A. chinensis. The expression of key enzyme genes for biosynthesis of acetyl-CoA carboxylase(ACC), 3-hydroxy-3-methylglutaryl-CoA reductase(HMGR), and farnesyl pyrophosphate synthase(FPPS) was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR). High performance liquid chromatography(HPLC) was used to compare the difference in the content of four active components in A. chinensis with different leaf shapes, and the correlation between the content of active components and the expression of key enzyme genes in biosynthesis was discussed. The results show that there was good linearity among atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in the range of 3.30-33.00 µg·mL~(-1)(r =0.999 7), 12.04-120.40 µg·mL~(-1)(r =0.999 5), 29.16-291.60 µg·mL~(-1)(r =0.999 5), and 14.20-142.00 µg·mL~(-1)(r =0.999 5), respectively. The average recoveries were 99.77%(RSD=2.1%), 98.56%(RSD=1.2%), 103.0%(RSD=1.2%), and 100.6%(RSD=1.5%), respectively. The method was accurate and had good reproducibility, which could be used to simultaneously detect atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon. The results showed that there were significant differences in the content of four active components in A. chinensis with different leaf shapes. The content of atractylodin, atractylenolide Ⅰ, and ß-eudesmol in A. chinensis with split leaves was the highest, which were 1.341 9, 5.237 2, and 12.084 3 mg·g~(-1), respectively. The content of atractylon in A. chinensis with long and narrow leaves was the highest(5.470 1 mg·g~(-1)). The content of atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in A. chinensis with oval leaves was the lowest. The total content of the four effective components in descending order was A. chinensis with split leaves > A. chinensis with long and narrow leaves > A. chinensis with large round leaves > A. chinensis with oval leaves. The gene expression levels of key enzymes ACC, HMGR, and FPPS in A. chinensis with split leaves were the highest(P < 0.05), and the gene expression levels of key enzymes ACC and HMGR in A. chinensis with oval leaves were the lowest(P < 0.05). The gene expression level of key enzyme FPPS in A. chinensis with large round leaves was the lowest. In A. chinensis with different leaf shapes, the key enzyme gene ACC was significantly positively correlated with the polyacetylene component, namely atractylodin(P < 0.01), and the key enzyme genes HMGR and FPPS were positively correlated with the sesquiterpene components, namely atractylenolide Ⅰ, ß-eudesmol, and atractylon. In summary, the quality of A. chinensis with split leaves is the best, and the biosynthesis of atractylodin is significantly correlated with the gene expression of key enzyme ACC, which provides a theoretical basis for screening and optimizing the germplasm resources of A. chinensis and improving the quality of medicinal materials.

HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the present study, the carcinogenic potential of HOXD9 in ATC was investigated. We assessed the differential expression of HOXD9 on cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) in ATC and explored the interactions between HOXD9, microRNA-451a (miR-451a), and proteasome 20S subunit beta 8 (PSMB8). In addition, subcutaneous tumorigenesis and lung metastasis in mouse models were established to investigate the role of HOXD9 in ATC progression and metastasis in vivo. HOXD9 expression was enhanced in ATC tissues and cells. Knockdown of HOXD9 inhibited cell proliferation, migration, invasion, and EMT but increased apoptosis in ATC cells. The UCSC Genome Browser and JASPAR database identified HOXD9 as an upstream regulator of miR-451a. The direct binding of miR-451a to the untranslated region (3'-UTR) of PSMB8 was established using a luciferase experiment. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of HOXD9 interference or overexpression on ATC progression. The PI3K/AKT signaling pathway was involved in HOXD9-stimulated ATC cell proliferation and EMT. Consistent with in vitro findings, the downregulation of HOXD9 in ATC cells impeded tumor growth and lung metastasis in vivo. Our research suggests that through PI3K/AKT signaling, the HOXD9/miR-451a/PSMB8 axis may have significance in the control of cell proliferation and metastasis in ATC. Thus, HOXD9 could serve as a potential target for the diagnosis of ATC.

National incidence and mortality of hospitalized sepsis in China.

BACKGROUND: Sepsis is a leading cause of preventable death around the world. Population-based estimation of sepsis incidence is lacking in China. In this study, we aimed to estimate the population-based incidence and geographic variation of hospitalized sepsis in China. METHODS: We retrospectively identified hospitalized sepsis from the nationwide National Data Center for Medical Service (NDCMS) and the National Mortality Surveillance System (NMSS) by ICD-10 codes for the period from 2017 to 2019. In-hospital sepsis case fatality and mortality rate were calculated to extrapolate the national incidence of hospitalized sepsis. The geographic distribution of hospitalized sepsis incidence was examined using Global Moran's Index. RESULTS: We identified 9,455,279 patients with 10,682,625 implicit-coded sepsis admissions in NDCMS and 806,728 sepsis-related deaths in NMSS. We estimated that the annual standardized incidence of hospitalized sepsis was 328.25 (95% CI 315.41-341.09), 359.26 (95% CI 345.4-373.12) and 421.85 (95% CI 406.65-437.05) cases per 100,000 in 2017, 2018 and 2019, respectively. We observed 8.7% of the incidences occurred among neonates less than 1 year old, 11.7% among children aged 1-9 years, and 57.5% among elderly older than 65 years. Significant spatial autocorrelation for incidence of hospitalized sepsis was observed across China (Moran's Index 0.42, p = 0.001; 0.45, p = 0.001; 0.26, p = 0.011 for 2017, 2018, 2019, respectively). Higher number of hospital bed supply and higher disposable income per capita were significantly associated with a higher incidence of hospitalized sepsis. CONCLUSION: Our study showed a greater burden of sepsis hospitalizations than previous estimated. The geographical disparities suggested more efforts were needed in prevention of sepsis.

Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock.

BACKGROUND: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.

N6-methyladenosine methylation mediates non-coding RNAs modification in microplastic-induced cardiac injury.

Owing to their potential adverse health effects, global contamination by microplastics (MPs) has attracted increased scientific and societal concerns. However, in vivo studies on MP toxicity, along with its effects and underlying mechanisms, remain limited. We recently found that non-coding RNA (ncRNAs) contribute to MP-mediated vascular toxicity. Moreover, previous studies have identified N6-methyladenosine (m6A) modifications in ncRNAs as influencing factors in cardiovascular disease. However, whether and how m6A modifications in ncRNAs are affected by MP-induced cardiotoxicity remain unknown. Herein, we profiled differentially expressed ncRNAs and their related m6A modification profiles in MP-exposed myocardial tissue using RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq). First, we observed that MPs accumulated in different organs and upregulated apoptosis in the heart, liver, spleen, and kidney cells. Furthermore, total m6A and METTL3 levels increased in the myocardium after exposure to MPs. RNA-seq results revealed that 392 lncRNAs and 302 circRNAs were differentially expressed in MP-treated mouse myocardium compared to the control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that these altered lncRNAs and circRNAs were closely associated with endocytosis, cellular senescence, and cell cycle signaling pathways, which may cause cardiotoxicity. Furthermore, MeRIP-seq data showed different distributions and abundances of m6A modifications in lncRNAs and circRNAs. Additionally, we identified differentially m6A methylated lncRNAs and circRNAs through conjoint analysis of the two high-throughput sequencing datasets and found that both m6A modifications and the expression of circ-Arfgef2 and lncG3bp2 were upregulated after exposure to MPs. This suggests that MP-induced m6A modifications in ncRNAs are involved in cardiotoxicity. Our findings contribute to a better understanding of MP-induced cardiotoxicity and new molecular targets for treating cardiac injury.

First Report of Anthracnose on Dioscorea opposita Caused by Colletotrichum siamense in Guangdong province in China.

Yam is the world's fourth most important tuber crop, after cassava, potato, and sweet potato in the world, the cultivation area of yam from the Food and Agriculture Organization of the United Nations Statistics Division database (FAOSTAT) is about 8,831,037 ha in 2020. Chinese yam (Dioscorea opposita Thunb.) is an economically important root crop throughout China due to its high economic and medicinal value. South China including Guangdong and Guangxi provinces is one of the important production districts of Chinese yam with economic value. A disease affecting the leaves was observed on yam leaves in August 2021 with an incidence of 20 to 90% in Guangdong and Guangxi provinces. Symptoms start as pinpoint lesions on yam leaves which enlarged to oval spots and large irregular spots. The spots were brown and surrounded by a chlorotic halo with sunken cavities, which are typical symptoms of anthracnose. To identify the causal agent, 9 symptomatic leaves from 3 different districts were collected in Guangdong and Guangxi provinces. Leaf samples were disinfested with 1% NaOCl for 3 min, and cultured on potato dextrose agar (PDA) at 28 °C for 3 days week. 9 single-spore isolates were recovered from each PDA medium. Colonies on PDA were grayish white with bright orange conidial spore masses. Fungal mycelia were hyaline, septate, and branched. Conidia were born on a long conidiogenous cell, straight, hyaline and cylindrical with rounded ends, 5.3 to 6.8×15.2 to 21.3µm (n = 50). Appressoria were dark, smooth-walled, oval in shape. The isolates were morphologically identified as Colletotrichum sp. (Weir et al. 2012). 3 strains were used for the pathogenicity test, 5 plants at creeping stage were inoculated with each isolate separately and 3-5 leaves of each plant were inoculated. Fresh wounds were made with a sterile needle on the healthy surface of yam leaves and each leaf was covered with a piece of cotton drenched with conidial suspension (106 conidia/mL) from each isolate. Control seedlings were inoculated identically except sterile water was used. Inoculated plants were placed in a moisturizing light incubator at 25℃ and 80% humidity under a 12-h light/dark cycle for 7 days and examined daily to monitor disease symptom development. Small round brown spots were observed at the inoculation sites 3 days after the inoculation and eventually became large brown lesions. No symptoms wre observed in the water-inoculated plants. A Colletotrichum sp. strain based on morphology was reisolated from inoculated leaves, fulfilling Koch's postulates. For molecular identification, the direct colony PCR method (Lu et al. 2012) was used to amplify the internal transcribed spacer (ITS) region of ribosomal DNA, calmodulin (Cal), tubulin (Tub) and Apmat loci of three isolates using primer pairs of ITS4/ITS5, CL1C/CL2C, T1/T2 and AM-F/AM-R (Sharma et al. 2015). A phylogenetic tree derived from a maximum likelihood analysis of a concatenated alignment of ITS, Cal, Tub and ApMAT sequences was created. The accession numbers of the three isolates YamZJCS, YamSXCS and YamYLCS used in this study were OP128056-OP128058 for ITS, OP128059-OP128061 for ApMAT，OP128062-OP128064 for Cal and OP128065-OP128067 for Tub. The sequences of the 3 isolates were aligned with related species of Colletotrichum (Sharma et al. 2015). Analyses based on concatenated data sets of 4 genes showed that the sequences had high levels of identity to that of the C. siamense strains. According to both morphological and sequence analyses, the pathogen was identified as C. siamense. There were reports of anthracnose on yam caused by Colletotrichum sp. in Guangxi (Zhu et al. 2007), Hainan (Lin et al. 2018) and Jiangsu (Han et al. 2020) provinces in China. To our knowledge, this is the first report of anthracnose on D. opposita caused by C. siamense in Guangdong province in China.

Anxiety, pain intensity, and decision regret of living liver donors during postoperative period.

AIM: The aim of this study was to explore and examine the relationship between anxiety, acute pain intensity, and decision regret of living liver donors in the postoperative stage. METHODS: This is a prospective correlational study. Data were collected consecutively for one year (from September 2017 to September 2018) at a medical center in northern Taiwan. Information about anxiety and acute pain intensity was collected preoperatively and on postoperative day (POD) 3 and POD 7. Satisfaction with pain management and decision regret was inquired about on POD 7. RESULTS: Data of 57 consecutive living liver donors (56.1 % male, mean age 34.12 ± 9.92 years) were analyzed. Living liver donors experienced moderate anxiety and acute pain levels in the postoperative period. The mean score of decision regret was 12.63 (range 0-60), indicating a low level of regret. The acute pain intensity decreased significantly between POD 3 and POD 7 (p < .001); however, the anxiety level slightly increased (p = .031). Older and married living liver donors had higher anxiety levels. The satisfaction level of pain management was negatively correlated with the POD 7 acute pain intensity (r = -0.26, p = .049) and decision regret (r = -0.37, p = .005), but it was positively correlated with POD 7 anxiety (r = 0.38, p = .004). CONCLUSIONS: The postoperative period was hard for living liver donors as they would experience moderate acute pain and anxiety. Although the decision regret was low, the satisfaction level of pain management would negatively affect it. Therefore, the effectiveness of pain management and anxiety management should be continually ensured in the postoperative period.

Factors associated with the intention to engage in care planning among persons with mild cognitive impairment and dementia.

This study examined factors associated with the intention to engage in advance care planning among persons with cognitive impairment. This cross-sectional study recruited 116 persons with cognitive impairment by convenience sampling from two teaching hospitals in Northern Taiwan from November 1, 2018, to December 31, 2020. Fewer than 50% of the participants intended to engage in advance care planning, and less than 10% signed the living will for hospice and palliative care. Multivariate linear regression determined factors influencing advance care planning intention included education level, a proxy signed do-not-resuscitate document, belief that family members would provide a signed do-not-resuscitate at their end-of-life, and necessity of explaining future care in advance. It is recommended to popularize advance care planning education and ensure the rights of persons with cognitive impairment to enable them to fully participate in their own care plans through family-centered advance care planning.

Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody JS016 in Hospitalized Chinese Patients with COVID-19: a Phase 2/3, Multicenter, Randomized, Open-Label, Controlled Trial.

Recombinant human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody JS016 showed neutralizing and therapeutic effects in preclinical studies. The clinical efficacy and safety of the therapy needed to be evaluated. In this phase 2/3, multicenter, randomized, open-label, controlled trial, hospitalized patients with moderate or severe coronavirus disease 2019 (COVID-19) were randomly assigned in a 1:1 ratio to receive standard care or standard care plus a single intravenous infusion of JS016. The primary outcome was a six-level ordinal scale of clinical status on day 28 since randomization. Secondary outcomes include adverse events, 28-day mortality, ventilator-free days within 28 days, length of hospital stay, and negative conversion rate of SARS-CoV-2 nucleic acid on day 14. A total of 199 patients were randomized, and 197 (99 in the JS016 group and 98 in the control group) were analyzed. Most patients, 95 (96%) in the JS016 group and 97 (99%) in the control group were in the best category on day 28 since randomization. The odds ratio of being in a better clinical status was 0.31 (95% confidence interval [CI], 0.03 to 3.19; P = 0.33). Few adverse events occurred in both groups (3% in the JS016 group and 1% in the control group, respectively; P = 0.34). SARS-CoV-2 neutralizing antibody JS016 did not show clinical efficacy among hospitalized Chinese patients with moderate to severe COVID-19 disease. Further studies are needed to assess the efficacy of the neutralizing antibody to prevent disease deterioration and its benefits among groups of patients specified by disease course and severity. (This study has been registered at ClinicalTrials.gov under identifier NCT04931238.).

The impact of symptom distress on health-related quality of life in liver cancer patients receiving arterial chemoembolization: the mediating role of hope.

BACKGROUND: Trans-hepatic arterial chemoembolization (TACE) is a treatment option for liver cancer patients. It can prolong patients' survival but can also cause symptom distress. Symptom distress (SDs) can directly impact quality of life (QOL) and may indirectly influence QOL by lessening hope. In this study, we wanted to explore the mediating effect of hope on the relationship between SDs and QOL among patients with liver cancer receiving TACE. METHODS: A cross-sectional study was conducted from December 20, 2017, to August 6, 2018, at a gastroenterology ward of a medical center. The participants were 92 liver cancer patients (69.6% male, mean age 67.8) who were admitted for TACE treatment. Information on SDs, hope, and QOL was collected by questionnaire on discharge day. Hayes' PROCESS model was used to test the mediating effect of hope on the relationship between SDs and QOL. RESULTS: The mean score and standard deviation (SD) of SDs, hope, and QOL were 32.08 (SD = 6.22), 27.09 (SD = 3.51), and 55.16 (SD = 17.33), respectively. SDs negatively impacts quality of life. The total effect of SDs on QOL was - 1.41 (95% confidence interval [CI]: - 1.96, - 0.86). The indirect effect via the mediation of hope was - 0.95 (95% CI: - 1.7, - 0.45). Hope partially mediated the effect of SDs on QOL. CONCLUSION: SDs after TACE is vital; it directly reduces a patient's overall QOL and can indirectly hinder it by reducing the patient's hope. In addition to symptom management, interventions that help patients maintain their hope are key to improving QOL among patients receiving TACE.

Association of annual hospital septic shock case volume and hospital mortality.

BACKGROUND: The burden of sepsis remains high in China. The relationship between case volume and hospital mortality among patients with septic shock, the most severe complication of sepsis, is unknown in China. METHODS: In this retrospective cohort study, we analyzed surveillance data from a national quality improvement program in intensive care units (ICUs) in China in 2020. Association between septic shock case volume and hospital mortality was analyzed using multivariate linear regression and restricted cubic splines. RESULTS: We enrolled a total of 134,046 septic shock cases in ICUs from 1902 hospitals in China during 2020. In this septic shock cohort, the median septic shock volume per hospital was 33 cases (interquartile range 14-76 cases), 41.4% were female, and more than half of the patients were over 61 years old, with average hospital mortality of 21.2%. An increase in case volume was associated with improved survival among septic shock cases. In the linear regression model, the highest quartile of septic shock volume was associated with lower hospital mortality compared with the lowest quartile (ß - 0.86; 95% CI - 0.98, - 0.74; p < 0.001). Similar differences were found in hospitals of respective geographic locations and hospital levels. With case volume modeled as a continuous variable in a restricted cubic spline, a lower volume threshold of 40 cases before which a substantial reduction of the hospital mortality rate was observed. CONCLUSIONS: The findings suggest that hospitals with higher septic shock case volume have lower hospital mortality in China. Further research is needed to explain the mechanism of this volume-outcome relationship.

Mediating effect of self-efficacy on the relationship between social support and self-management behaviors among patients with knee osteoarthritis: a cross-sectional study.

BACKGROUND: Good self-management behaviors in patients with knee osteoarthritis can improve disease awareness, treatment effectiveness, quality of life, and reduce medical costs. However, there is a paucity of studies focusing on patients with knee osteoarthritis. Therefore, the purpose of this study was to explore the mediating effect of self-efficacy on aspects of social support and self-management behaviors in this population. METHODS: This study employed a cross-sectional design and convenience sampling to survey patients with knee osteoarthritis in an outpatient department of a regional hospital in northern Taiwan from February 22, 2021, to April 15, 2021. The inclusion criteria for patients were (1) those diagnosed by a physician with knee osteoarthritis and (2) who could communicate in Chinese or Taiwanese. Participants were asked to complete a demographic questionnaire, the Arthritis Self-Efficacy Scale (ASE), the Inventory of Socially Supportive Behavior (including enacted support and perceived social support), and the Arthritis Self-Management Assessment Tool (ASMAT). In addition, the Kellgren-Lawrence Grading Scale was obtained from a chart review. Data were analyzed with descriptive statistics, t-test, one-way analysis of variance, Pearson product-moment correlation, and mediation analysis. RESULTS: A total of 140 patients met the inclusion criteria. The mean age of participants was 70.21 ± 10.84years; most (73.6%) were female. The mean total score of the ASMAT was 64.27 ± 14.84. Scores for the ASE, enacted support, and perceived social support were significantly positively correlated with ASMAT (all p < .001). The standardized coefficient for total effect and direct effect of perceived social support on ASMAT was 0.899 (p < .001) and 0.754 (p < .05), respectively. After introducing the ASE into the model, the indirect effect was 0.145 (p < .05), which indicated that ASE had a partial mediating effect on the relationship between perceived social support and ASMAT. CONCLUSION: Our findings might suggest that perceived social support indirectly affected ASMAT through ASE. Therefore, interventions designed to increase self-efficacy and social support could enhance self-management behaviors for patients with knee osteoarthritis.

Cross-cultural validation of the Chinese version of the EmPHasis-10 questionnaire in connective tissue disease patients with pulmonary arterial hypertension and its relationship with risk stratification.

BACKGROUNDS: The EmPHasis-10 questionnaire is a disease-specific quality of life (QoL) measurement in patients with pulmonary hypertension. We report the results of cross-cultural validation of the Chinese version of the EmPHasis-10 and its relationship with risk stratification in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). METHODS: The Emphasis-10 was administered to 75 CTD-PAH patients along with the 36-item Medical Outcomes Study Short Form Survey (SF-36) and EuroQol five dimensions questionnaire (EQ-5D). The diagnosis of PAH was confirmed by right heart catheterization. Demographic and clinical data were obtained. Multivariable logistic regression was conducted based on the low risk profile assessed by a 4-strata risk assessment model (COMPERA 2.0) at follow-up. RESULTS: Date from 75 patients with CTD-PAH were analysed. The EmPHasis-10 demonstrated satisfactory reliability (Cronbach α = 0.95) and convergent validity showed by the significant relationship with WHO Functional Class (P = 0.003), SF-36 (P < 0.001) and EQ-5D (P = 0.002). EmPHasis-10 was significantly associated with achieving the low risk profile at 12 months of follow-up (Odds ratio: 0.928, P = 0.029) after adjusting for WHO Functional Class. CONCLUSION: EmPHasis-10 has acceptable reliability and validity in CTD-PAH patients and may serve as an additional parameter in risk stratification.

Diversity of hemodynamic types in connective tissue disease associated pulmonary hypertension: more than a subgroup of pulmonary arterial hypertension.

OBJECTIVE: Connective tissue disease associated pulmonary hypertension (CTD-PH) is classified as a subgroup of WHO group 1 PH, also called pulmonary arterial hypertension (PAH). However, not all CTD-PH fit hemodynamic definition of PAH. This study investigates the diversity of hemodynamic types of CTD-PH, their differences in clinical characteristics and outcomes. METHOD: We performed a retrospective cohort study. CTD-PH patients were enrolled and divided into WHO group1 PH, WHO group 2 PH and hyperdynamic PH (mPAP > 20 mmHg, PVR < 3WU, PAWP < 15 mmHg) according to hemodynamics obtained by right heart catheterization. Patients with severe lung diseases, heart failure with reduced ejection fraction, pulmonary embolism, and hepatic cirrhosis were excluded. Baseline characteristics, autoantibodies, cardiac function, echocardiogram parameters, hemodynamics and survival rates were compared. RESULT: A total of 202 CTD-PH patients were included, 138 in WHO group 1 PH, 33 in WHO group 2 PH and 31 in hyperdynamic PH. We found hyperdynamic PH is less severe, presenting lower NT-proBNP level, better WHO function class, lower mPAP and PVR, higher cardiac output, and less cardiac remodeling. Incidence of anti-RNP was significantly lower in patients with elevated PAWP. Short-term survival was worse in WHO group 2 PH, yet 5-year survival rates didn't differ between groups. CONCLUSION: Considering diversity in hemodynamic types, CTD-PH is more than a subgroup of PAH. Different types of CTD-PH present different clinical phenotypes and outcome. Phenotyping PH in CTD-PH patients is important.

Dynamic prediction of life-threatening events for patients in intensive care unit.

BACKGROUND: Early prediction of patients' deterioration is helpful in early intervention for patients at greater risk of deterioration in Intensive Care Unit (ICU). This study aims to apply machine learning approaches to heterogeneous clinical data for predicting life-threatening events of patients in ICU. METHODS: We collected clinical data from a total of 3151 patients admitted to the Medical Intensive Care Unit of Peking Union Medical College Hospital in China from January 1st, 2014, to October 1st, 2019. After excluding the patients who were under 18 years old or stayed less than 24 h at the ICU, a total of 2170 patients were enrolled in this study. Multiple machine learning approaches were utilized to predict life-threatening events (i.e., death) in seven 24-h windows (day 1 to day 7) and their performance was compared. RESULTS: Light Gradient Boosting Machine showed the best performance. We found that life-threatening events during the short-term windows can be better predicted than those in the medium-term windows. For example, death in 24 h can be predicted with an Area Under Curve of 0.905. Features like infusion pump related fluid input were highly related to life-threatening events. Furthermore, the prediction power of static features such as age and cardio-pulmonary function increased with the extended prediction window. CONCLUSION: This study demonstrates that the integration of machine learning approaches and large-scale high-quality clinical data in ICU could accurately predict life-threatening events for ICU patients for early intervention.