CircZfp644-205 inhibits osteoblast differentiation and induces apoptosis of pre-osteoblasts via sponging miR-455-3p and promoting SMAD2 expression.

BACKGROUND: Circular RNAs (circRNAs) are involved in the progression of osteoporosis; however, their impact on osteogenic differentiation has yet to be fully elucidated. In this study, we identified a novel circRNA known as circZfp644-205 and investigated its effect on osteogenic differentiation and apoptosis in osteoporosis. METHODS: CircZfp644-205, miR-445-3p, and SMAD2 levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MC3T3-E1 cells were subjected to microgravity (MG) to establish a cell model. Osteogenic differentiation was assessed using qRT-PCR, Alizarin Red S staining, alkaline phosphatase staining, and western blot. The apoptosis was evaluated using flow cytometry. The relationship between miR-445-3p and circZfp644-205 or SMAD2 was determined using bioinformatics, RNA pull-down, and luciferase reporter assay. Moreover, a hindlimb unloading mouse model was generated to investigate the role of circZfp644-205 in vivo using Micro-CT. RESULTS: CircZfp644-205 expression was up-regulated significantly in HG-treated MC3T3-E1 cells. Further in vitro studies confirmed that circZfp644-205 knockdown inhibited the osteogenic differentiation and induced apoptosis of pre-osteoblasts. CircZfp644-205 acted as a sponge for miR-455-3p, which reversed the effects of circZfp644-205 on pre-osteoblasts. Moreover, miR-455-3p directly targeted SMAD2, thus inhibiting the expression of SMAD2 to regulate cellular behaviors. Moreover, circZfp644-205 alleviated the progression of osteoporosis in mice. CONCLUSIONS: This study provides a novel circRNA that may serve as a potential therapeutic target for osteoporosis and expands our understanding of the molecular mechanism underlying the progression of osteoporosis.

Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

Introduction: The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. Methods: For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. Results and Discussion: The results obtained from in vitro experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our in vitro findings, we conducted in vivo studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise in vivo. Conclusion: In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.

Relationship Between Preoperative Nutritional Indicators and Postoperative Complications in Patients with Oesophageal Cancer: A Meta-Analysis.

Nutritional status is an essential factor in the occurrence of complications in patients with esophageal cancer. We sought to assess the relationship between malnutrition and complications using various nutritional assessment indicators. We conducted a comprehensive literature search of medical databases for articles published up to July 2023. The primary outcome indicator is the occurrence of complications, for which we combined 95% confidence intervals (CIs) and odds ratios (ORs) for postoperative complications and analyzed them using a random effects model. The analysis was carried out using STATA15.0 software. A total of 33 study groups from 22 publications with 5,675 subjects were included. Pooled results show that nutritional indicators are strongly correlated with the occurrence of postoperative complications (OR = 1.45, 95% CI: 1.30-1.62). In the subgroup analyses, comprehensive indicators and the skeletal muscle index were significantly associated with complications, whereas laboratory indicators were not associated with complications (comprehensive indicators OR = 2.68, 95% CI: 1.80-4.00; skeletal muscle index OR = 2.93, 95% CI: 1.44-5.99; laboratory indicators OR = 1.05, 95% CI: 0.96-1.16). Patients with normal body mass index and hospitalized patients were more likely to develop complications. Malnutrition is strongly associated with the development of complications. Nutritional indicators and patient characteristics influenced this relationship.

Application of TCM Rehabilitation in Joint Function Recovery After Treatment of Distal Radius Fractures: A Meta-Analysis.

Objective: To evaluate the effect of traditional Chinese medicine (TCM) rehabilitation on the postoperative function of patients with distal radius fractures by Meta-analysis. Methods: PubMed, Embase, CNKI, Wanfang, and other databases were searched for retrospective controlled trials and prospective randomized controlled trials on the effect of traditional Chinese medicine rehabilitation on the function of patients with distal radius fractures after surgery from the establishment of the database to May 2023. Revman version 5.3 software was used to analyze the extracted and screened index data. Results: Eight studies involving 455 patients were included. Meta-analysis results showed Overall analysis showed that there was a significant difference in wrist function between the TCM rehabilitation group and the control group (MD = -12.16, 95%CI:-17.21 to -7.11, P < .00001), low heterogeneity (I2=40%, P = .17), the difference in dorsiflexion function between the TCM rehabilitation group and the control group was statistically significant (MD = -1.16, 95%CI:-2.24 to -0.08, P = .04), with high heterogeneity (I2=79%, P = .003), that there was a significant difference in grip strength between the TCM rehabilitation group and the control group at 6 weeks (MD= 0.48, 95%CI: 0.24 to 0.71, P < .0001) with low heterogeneity (I2=45%, P = .12), there was no significant difference between the TCM rehabilitation group and the control group (OR= -0.00, 95%CI: -0.08 to 0.08, P = .99), and there was no heterogeneity (I2=0%, P = .66). Conclusion: Traditional Chinese medicine rehabilitation treatment of distal radius fractures can increase the range of motion of wrist joints, reduce pain, shorten the rehabilitation time of patients, improve the quality of life, and is conducive to the standardized treatment of patients.

The optimal dosage of aspirin for preventing preeclampsia in high-risk pregnant women: A network meta-analysis of 23 randomized controlled trials.

This study aimed to assess the effectiveness and optimal dosage of aspirin in preventing preeclampsia in high-risk pregnant women. Traditional and network meta-analyses were conducted on data from 23 randomized controlled trials involving 10 547 pregnant women. The findings demonstrated that aspirin significantly reduced the incidence of preeclampsia (OR = 0.66, 95%CI [0.58, 0.75]), with the best preventive effect observed at a dosage of 80-100 mg/day (OR = 0.51, 95%CI [0.36, 0.72]). No significant differences were found in the occurrence of postpartum hemorrhage (OR = 1.03, 95%CI [0.79, 1.33]), small for gestational age (OR = 0.83, 95%CI [0.50, 1.35]), placental abruption (OR = 0.96, 95%CI [0.53, 1.73]), and intrauterine growth restriction (OR = 0.63, 95%CI [0.45, 1.86]) between women taking aspirin and those taking placebos. Different doses of aspirin showed a reduction in preeclampsia incidence, but there was no significant difference in efficacy between the dosage groups. Side effects did not significantly differ between placebo and different aspirin dosage groups. SUCRA analysis suggested that 80-100 mg/day may be the optimal dosage, prioritizing both effectiveness and minimizing side effects. Sensitivity analysis confirmed the robustness of the findings. However, improvements are needed in addressing issues like loss to follow-up, reporting bias, and publication bias. In conclusion, a dosage of 80-100 mg/day is recommended for preventing preeclampsia in high-risk pregnant women, although individual circumstances should be considered for optimizing the balance between effectiveness and safety.

Health characteristics and factors associated with transition shock in newly graduated registered nurses: a latent class analysis.

BACKGROUND: Transition shock occurs at a vulnerable time in newly graduated registered nurses' careers and has a clear impact on both newly graduated registered nurses' productivity and patient recovery outcomes. Identifying classification features of transition shock and targeting interventions to support newly graduated registered nurses is imperative. The study aimed to explore potential transition shock subgroups of newly graduated registered nurses and further explore the impact of population characteristics and two indices of health on transition shock. METHODS: A descriptive, cross-sectional design was conducted. An online questionnaire was sent via WeChat to newly graduated registered nurses who started work in 2021 at seven hospitals between August and November 2021, and 331 nurses filled out the questionnaire. Latent class analysis was used to identify the potential class of the transition shock of newly graduated registered nurses, and multinomial logistic regression analyses were used to determine the factors of potential classification. RESULTS: The study identified four classes of transition shock in newly graduated registered nurses, namely, "high transition shock", "physical fatigue-lack of knowledge", "development adaptation" and "low transition shock-worry" groups. Newly graduated registered nurses who urinated less than 4 times per day (OR = 0.051, 95% CI = 0.005-0.502) were likely to be in the "high transition shock" group. Newly graduated registered nurses who did not delay urination (OR = 4.267, 95% CI = 1.162-11.236) were more likely to belong to the "low transition shock-worry" group. Newly graduated registered nurses without sleep disturbance were more likely to be in the "physical fatigue - lack of knowledge" (OR = 3.109, 95% CI = 1.283-7.532), "development adaptation" (OR = 8.183, 95% CI = 2.447-27.066), and "low transition shock-worry" (OR = 8.749, 95% CI = 1.619-47.288) groups than in the 'high transition shock' group. CONCLUSIONS: This study highlights potential patterns of transition shock among newly graduated registered nurses. Two indices of health, namely, delayed urination and sleep disturbance, can predict the subgroups of newly graduated registered nurses with transition shock.

Nickel-Catalyzed Atroposelective C-H Alkylation Enabled by Bimetallic Catalysis with Air-Stable Heteroatom-Substituted Secondary Phosphine Oxide Preligands.

The catalytic asymmetric construction of axially chiral C-N atropisomers remains a formidable challenge due to their low rotational barriers and is largely reliant on toxic, cost-intensive, and precious metal catalysts. In sharp contrast, we herein describe the first nickel-catalyzed atroposelective C-H alkylation for the construction of C-N axially chiral compounds with the aid of a chiral heteroatom-substituted secondary phosphine oxide (HASPO)-ligated Ni-Al bimetallic catalyst. A wide range of alkenes, including terminal and internal alkenes, were well compatible with the reaction, providing a variety of benzimidazole derivatives in high yields and enantioselectivities (up to 97:3 e.r.). The key to success was the identification of novel HASPOs as highly effective chiral preligands. Mechanistic studies revealed the catalyst mode of action, and in-depth data science analysis elucidated the key features of the responsible chiral preligands in controlling the enantioselectivity.

Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways.

Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.IMPORTANCEHyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.

Tobacco Quitline Callers Who Use Cannabis and Their Likelihood of Quitting Cigarette Smoking.

INTRODUCTION: Cigarette smoking continues to decline in the U.S., but cannabis use is increasing. Many people who smoke cigarettes also use cannabis. This study examines the characteristics of persons who co-use and those who do not co-use and the likelihood of quitting cigarettes for callers to Kick It California, a large state tobacco quitline. METHODS: Data were examined from Kick It California callers from January 2020 through December 2023 (N=45,151), including those from a subgroup randomly sampled and reached for evaluation at 7 months after quitline enrollment (n=3,545). The rate of cigarette smoking cessation at 7 months after enrollment for people who co-use cannabis was compared with that for people who do not. Analyses started in 2023 and concluded in January 2024. RESULTS: More than a quarter (27.2%) of Kick It California callers co-used cannabis. They were more likely to be male, to be younger, and to have a mental health condition than those who did not. Those who co-use cannabis and those who do not have similar rates of receiving quitline counseling or using Food and Drug Administration-approved cessation aids. Controlled for effects of personal characteristics and use of smoking-cessation services, people who co-use cannabis were less likely to quit cigarette smoking 7 months after enrollment (23.2% vs 28.9%; p<0.001). Among those who co-use, 42.9% intended to quit using cannabis in the next 30 days. CONCLUSIONS: A substantial percentage of tobacco quitline callers use cannabis. Those who do co-use quit cigarette smoking at a lower rate than those who do not. Over 40% of people who co-use reported intention to quit cannabis, making tobacco quitlines a rich environment to learn about people who co-use and develop strategies for intervention.

Living in a dynamic environment: The effects of multi-ways temperature variation on embryo and newborn juveniles of a shallow-water octopus (Amphioctopus fangsiao).

Shallow waters are characterized by fluctuating environmental conditions, modulating marine life cycles and biological phenomena. Multiple variations in water temperature could affect eggs and embryos during spawning events of many marine invertebrate species, yet most of the findings on embryonic development in invertebrates come from experiments based on the constant temperature. In this study, to examine the effects of temperature variation on octopus embryos, Amphioctopus fangsiao, a common shallow-water octopus along the coast of China, was exposed to the constant temperature (18 °C, in situ temperature of the seawater in Lianyungang), ramping temperatures (from 18 to 24 °C), diel oscillating temperatures (18 °C and 20 °C for 12 h each day), and acute increasing temperatures (the temperature increased sharply from 18 °C to 24 °C at embryonic development stage XIX) for 47 days (from embryogenesis to settlement). The results demonstrated that the temperature variations accelerated the development time of A. fangsiao embryos. Temperature fluctuations could cause embryonic oxidative damage and disorder of glycolipid metabolism, thereby affecting the growth performance of embryos and the survival rate of hatchings. Through transcriptome sequencing, the mechanistic adaption of the embryo to environmental temperature variations was revealed. The pathways involved in the TCA cycle, DNA replication and repair, protein synthesis, cell signaling, and nervous system damage repair were significantly enriched, indicating that the embryo could improve heat tolerance to thermal stress by regulating gene expression. Moreover, acute warming temperatures posed the most detrimental effects on A. fangsiao embryos, which could cause embryos to hatch prematurely from the vegetal pole, further reducing the survival of hatchings. Meanwhile, the diel oscillating temperature was observed to affect the normal morphology of the embryo, resulting in embryo deformities. Thus, the constant temperature is critical for balanced growth and defense status in octopuses by maintaining metabolism homeostasis. For the first time, this study evaluates the effects of multiple temperature fluctuations on embryos of A. fangsiao, providing new insights into the physiological changes and molecular responses of cephalopod embryos following dynamic temperature stress.

The biosafety incident response competence scale for clinical nursing staff: a development and validation study.

AIMS: This study was designed to develop a biosafety incident response competence scale and evaluate its validity and reliability among clinical nurses. DESIGN: This study employed a sequential approach, comprising four phases: (1) the establishment of a multidimensional conceptual model, (2) the preliminary selection of the items, (3) further exploration and psychometric testing of the items, (4) the application of the scale among clinical nurses. METHODS: The biosafety incident response competence conceptual model was developed through literature review and the Delphi method. A total of 1,712 clinical nurses participated in the preliminary items selection, while 1,027 clinical nurses were involved in the further psychometric testing from July 2023 to August 2023. The item analysis, exploratory factor analysis and confirmatory factor analysis were conducted to evaluate the construct validity. Reliability was measured using Cronbach's alpha, split-half reliability, and test-retest reliability, while validity analysis included content validity, structural validity, convergent validity, and discriminant validity. From September to November 2023, we conducted a survey using the established scale with a total of 4338 valid questionnaires collected. T-test and variance analysis was employed to determine potential variations in biosafety incident response competence based on participants characteristics. RESULTS: The final scale is composed of 4 factors and 29 items, including monitoring and warning abilities, nursing disposal abilities, biosafety knowledge preparedness, and infection protection abilities. The explanatory variance of the 4 factors was 75.100%. The Cronbach's alpha, split-half reliability and test-retest reliability were 0.974, 0.945 and 0.840 respectively. The Scale-level content validity index was 0.866. The Average Variance Extracted of the 4 factors was larger than 0.5, the Construct Reliability was larger than 0.7, and the Heterotrait-Monotrait ratio were less than 0.9. There were significant differences in the scores of response competence among nurses of different ages, working years, titles, positions, departments, marital status and participation in biosafety training (all P < 0.05). CONCLUSIONS: The biosafety incident response competence scale for nurses exhibits satisfactory reliability and validity, making it a valuable tool for assessing clinical nurses' abilities in responding to biosafety incidents.

Heme oxygenase-1 is an equid alphaherpesvirus 8 replication restriction host protein and suppresses viral replication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathway.

Equid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological syndromes in equines. However, no effective vaccines or therapeutic agents are available to control EqHV-8 infection. Heme oxygenase-1 (HO-1) is an antioxidant defense enzyme that displays significant cytoprotective effects against different viral infections. However, the literature on the function of HO-1 during EqHV-8 infection is little. We explored the effects of HO-1 on EqHV-8 infection and revealed its potential mechanisms. Our results demonstrated that HO-1 induced by cobalt-protoporphyrin (CoPP) or HO-1 overexpression inhibited EqHV-8 replication in susceptible cells. In contrast, HO-1 inhibitor (zinc protoporphyria) or siRNA targeting HO-1 reversed the anti-EqHV-8 activity. Furthermore, biliverdin, a metabolic product of HO-1, mediated the anti-EqHV-8 effect of HO-1 via both the protein kinase C (PKC)ß/extracellular signal-regulated kinase (ERK)1/ERK2 and nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathways. In addition, CoPP protected the mice by reducing the EqHV-8 infection in the lungs. Altogether, these results indicated that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.IMPORTANCEEqHV-8 infections have threatened continuously donkey and horse industry worldwide, which induces huge economic losses every year. However, no effective vaccination strategies or drug against EqHV-8 infection until now. Our present study found that one host protien HO-1 restrict EqHV-8 replication in vitro and in vivo. Furthermore, we demonstrate that HO-1 and its metabolite biliverdin suppress EqHV-8 relication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathways. Hence, we believe that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.

Contamination Status and Acute Dietary Exposure Assessment of Paralytic Shellfish Toxins in Shellfish in the Dalian Area of the Yellow-Bohai Sea, China.

The Yellow-Bohai Sea is an important semi-enclosed continental shelf marginal seas with an intensive aquaculture industry in China. The current study analyzed the contamination status and the time variations of paralytic shellfish toxins (PSTs) in shellfish between 2019 and 2020 from the Yellow-Bohai Sea in the Dalian area and estimated the acute health risks to consumers in China. A total of 199 shellfish samples (including 34 Pacific oysters, 25 Mediterranean blue mussels, 34 Manila clams, 36 bay scallops, 34 veined rapa whelks and 36 bloody clams) were analyzed from four representative aquaculture zones around the Yellow-Bohai Sea in Dalian. Among the samples, scallops and blood clams were the shellfish species with the highest detection rate of PSTs (94.4%), and the highest level of PSTs was detected in scallops with 3953.5 µg STX.2HCl eq./kg (µg STX.2HCL equivalents per kg shellfish tissue), followed by blood clams with 993.4 µg STX.2HCl eq./kg. The contents of PSTs in shellfish showed a time variation trend, and autumn was the season of concern for PST contamination in Dalian. For general Chinese consumers, the probability of acute health risks to shellfish consumers from dietary exposure to PSTs was around 13%. For typical consumers in coastal areas of China, especially those with higher shellfish intake, there was an acute health risk associated with exposure to PSTs through shellfish consumption during the occurrence of harmful algal blooms. It is suggested that the government continue to strengthen the monitoring of the source of PSTs and the monitoring of harmful algal blooms and give reasonable advice on shellfish consumption for consumers in coastal areas, such as not eating scallop viscera.

Development and validation of the Convalescence Symptom Assessment Scale for EsophageCtomy patients.

AIM: A specific, valid and reliable measure is much needed to dynamically assess the recovery of symptoms in oesophagectomy patients. This study describes developing and validating the Convalescent Symptom Assessment Scale for oesophagectomy patients (CSAS_EC). DESIGN: An instrument development and cross-sectional validation study was conducted. METHODS: This study consists of two components: instrument development and psychometric tests. In instrument development, the literature review, qualitative interviews, Delphi method expert consultation and face validation were used to develop and refine scale content. In psychometric tests, the clinical test version scale was used to conduct a cross-sectional in the thoracic surgery department from 17 June to 20 November 2022. The Classical Test Theory and Multidimensional Item Response Theory (MIRT) analyses examined psychometric properties. RESULTS: In instrument development, literature review (n = 20), qualitative interviews (n = 21), expert consultation (n = 12) and pre-survey (n = 15) led to the development of the clinical test version scale. In psychometric tests, a total of 331 participants were enrolled. Confirmatory factor analysis and MIRT analysis verified that a model with 28 items in four dimensions was good. The four dimensions were early recovery symptoms, late recovery symptoms, persistent present symptoms and psychosocial symptoms. The Cronbach's α is 0.827. The validity and reliability were demonstrated to be acceptable. CONCLUSIONS: The CSAS_EC scale can be used as a tool to evaluate the recovery status of oesophagectomy patients.

Universal screening and treatment towards the elimination of chronic hepatitis C in China: an economic evaluation.

OBJECTIVES: China has the largest number of hepatitis C virus (HCV) infection in the world, but current levels of diagnosis and treatment are low. The objective of this study was to assess the cost-effectiveness of various universal HCV screening and treatment strategies in China and inform decisions on health policy. STUDY DESIGN: A cost-effectiveness analytical study. METHODS: We developed a Markov model to investigate cost-effectiveness of different HCV screening and treatment strategies in China. We simulated several screening scenarios for Chinese people aged 18-70 years. We estimated incremental cost-effectiveness ratios (ICERs) of different intervention scenarios compared with status quo. RESULTS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups (Scenario S5) was the most cost-effective strategy (ICER: USD $11,667.71/quality-adjusted life-year [QALY] gained), which resulted in great reduction in HCV-related diseases and deaths, with a 67.11% reduction in cases of chronic HCV. Universal HCV screening and treatment implementation remains a cost-effective strategy when delayed until 2025 (ICER: USD $17,093.69/QALY), yet the delayed strategy is less effective in reducing HCV-related deaths. CONCLUSIONS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups is the most cost-effective strategy and has lead to a significant reduction in both HCV morbidity and mortality in China, which would essentially eliminate HCV as a public threat.

Evaluation of the effectiveness of promoted psychological resilience intervention for oesophageal cancer patients in rural China: A randomized controlled study.

PURPOSE: The objective of this randomized controlled trial was to examine the effectiveness of promoted resilience intervention to facilitate resilience, self-efficacy, coping mode, and social support for oesophageal cancer patients in rural China. METHODS: A two-arm, parallel design, single-blinded, randomized controlled trial was conducted in a comprehensive tertiary hospital in Anhui from August 2021 to September 2022. A total of 82 oesophageal cancer patients were assigned to two groups via blocked randomization. The intervention group (n = 41) received the Promoted Psychological Resilience Intervention based on survivors' experiences and the control group (n = 41) received routine care. Study data were collected using the sociodemographic information, Connor-Davidson Resilience Scale, Strategies Used by People to Promote Health, Medical Coping Modes Questionnaire, and Perceived Social Support Scale. RESULTS: The groups were well-balanced at baseline. Post-intervention and three months after intervention, the resilience, self-efficacy, acceptance-resignation, and social support were all significantly different in the intervention and control groups (p < 0.05 for each). The main effect of group, time, and the interaction between group and time was statistically significant in the scores of resilience, self-efficacy, acceptance-resignation, and social support, except for the factor of self-determination and friends support (p < 0.05 for each). CONCLUSIONS: This study demonstrated that an intervention program based on the experiences of long-term oesophageal cancer survivors can promote patients' resilience.

6-Gingerol ameliorates alveolar hypercoagulation and fibrinolytic inhibition in LPS-provoked ARDS via RUNX1/NF-κB signaling pathway.

BACKGROUND: Alveolar hypercoagulation and fibrinolytic inhibition play a central role in refractory hypoxemia in acute respiratory distress syndrome (ARDS), but it lacks effective drugs for prevention and treatment of this pathophysiology. Our previous experiment confirmed that RUNX1 promoted alveolar hypercoagulation and fibrinolytic inhibition through NF-κB pathway. Other studies demonstrated that 6-gingerol regulated inflammation and metabolism by inhibiting the NF-κB signaling pathway. We assume that 6-gingerol would ameliorate alveolar hypercoagulation and fibrinolytic inhibition via RUNX1/ NF-κB pathway in LPS-induced ARDS. METHODS: Rat ARDS model was replicated through LPS inhalation. Before LPS inhalation, the rats were intraperitoneally treated with different doses of 6-gingerol or the same volume of normal saline (NS) for 12 h, and then intratracheal inhalation of LPS for 24 h. In cell experiment, alveolar epithelial cell type II (AECII) was treated with 6-gingerol for 6 h and then with LPS for another 24 h. RUNX1 gene was down-regulated both in pulmonary tissue and in cells. Tissue factor (TF), plasminogen Activator Inhibitor 1(PAI-1) and thrombin were determined by Wester-blot (WB), qPCR or by enzyme-linked immunosorbent (ELISA). Lung injury score, pulmonary edema and pulmonary collagen III in rat were assessed. NF-κB pathway were also observed in vivo and in vitro. The direct binding capability of 6-gingerol to RUNX1 was confirmed by using Drug Affinity Responsive Target Stability test (DARTS). RESULTS: 6-gingerol dose-dependently attenuated LPS-induced lung injury and pulmonary edema. LPS administration caused excessive TF and PAI-1 expression both in pulmonary tissue and in AECII cell and a large amount of TF, PAI-1 and thrombin in bronchial alveolar lavage fluid (BALF), which all were effectively decreased by 6-gingerol treatment in a dose-dependent manner. The high collagen Ⅲ level in lung tissue provoked by LPS was significantly abated by 6-gingerol. 6-gingerol was seen to dramatically inhibit the LPS-stimulated activation of NF-κB pathway, indicated by decreases of p-p65/total p65, p-IKKß/total IKKß, and also to suppress the RUNX1 expression. RUNX1 gene knock down or RUNX1 inhibitor Ro5-3335 significantly enhanced the efficacies of 6-gingerol in vivo and in vitro, but RUNX1 over expression remarkably impaired the effects of 6-gingerol on TF, PAI-1 and on NF-κB pathway. DARTS result showed that 6-gingerol directly bond to RUNX1 molecules. CONCLUSIONS: Our experimental data demonstrated that 6-gingerol ameliorates alveolar hypercoagulation and fibrinolytic inhibition via RUNX1/NF-κB pathway in LPS-induced ARDS. 6-gingerol is expected to be an effective drug in ARDS.

Association between serum sodium and 28-day mortality in sepsis patients: A secondary data analysis from three large critical illness cohorts.

OBJECTIVE: The present study was designed to explore the association between serum sodium and mortality in patients with sepsis by using a large sample, multicenter MIMIC-IV database. METHODS: We extracted the data of 34 925 sepsis patients from the retrospective cohort mimicIV database. After adjusting the confounders, we explored the independent effects of serum sodium on 28-day mortality. RESULTS: A nonlinear relationship existed between serum sodium and 28-day mortality, of which a negative association was found between serum sodium and 28-day mortality (odds ratio: 0.95, 95% CI: 0.94, 0.96, p = 0.0001) when serum sodium was in 102 mmol/L to 138 mmol/L, but a positive correlation appeared when sodium climbed to the range of 140-179 mmol/L (odds ratio: 1.04, 95% CI: 1.03-1.06, p = 0.0001). CONCLUSIONS: Both lower and higher serum sodium levels are associated with an increased risk of death in sepsis patients.

Unveiling facial kinship: The BioKinVis dataset for facial kinship verification and genetic association studies.

Facial image-based kinship verification represents a burgeoning frontier within the realms of computer vision and biomedicine. Recent genome-wide association studies have underscored the heritability of human facial morphology, revealing its predictability based on genetic information. These revelations form a robust foundation for advancing facial image-based kinship verification. Despite strides in computer vision, there remains a discernible gap between the biomedical and computer vision domains. Notably, the absence of family photo datasets established through biological paternity testing methods poses a significant challenge. This study addresses this gap by introducing the biological kinship visualization dataset, encompassing 5773 individuals from 2412 families with biologically confirmed kinship. Our analysis delves into the distribution and influencing factors of facial similarity among parent-child pairs, probing the potential association between forensic short tandem repeat polymorphisms and facial similarity. Additionally, we have developed a machine learning model for facial image-based kinship verification, achieving an accuracy of 0.80 in the dataset. To facilitate further exploration, we have established an online tool and database, accessible at http://120.55.161.230:88/.

Pathogenicity and host cytokines response of EqHV-8 infection in C57BL/6J mice.

Equid herpesvirus type 8 (EqHV-8) is known to cause abortion, respiratory signs, and viral encephalitis in equines. EqHV-8 has been reported to cause serious economic losses in large-scale donkey farms in China. However, little is known about the viral replication and immune reaction in the brains and lungs of EqHV-8-induced C57BL/6J mice. We determined the pathogenicity and immune status in a mice model. The C57BL/6J mice were infected with the EqHV-8 donkey/Shandong/10/2021 strain, and the clinical signs and body weights were evaluated every day. In addition, viremia, virus loads, and the expression of pro-inflammatory cytokines in mice brains and lungs were assessed at 1, 3, 5, and 7 days post infection (dpi). Our results demonstrated that mice in the EqHV-8 infected group displayed body weight loss, dyspnea signs, and viremia. The expression of interleukin (IL)-1ß, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 mRNA was increased in the brains and lungs of EqHV-8-infected mice than that in control group at 5 dpi and 7 dpi, and IL-12a expression was increased at 7 dpi. These data indicated that EqHV-8 elicited a strong cytokines response, caused neurogenic disease and respiratory signs in C57BL/6J mice, thus revealing the pathogenicity of EqHV-8.