Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer.

BACKGROUND: Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. METHODS: In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. RESULTS: BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. CONCLUSION: Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.

Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate. AIM: To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis. METHODS: We extracted demographic, etiological, vital sign, laboratory test, comorbidity, complication, treatment, and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU (eICU) collaborative research database (eICU-CRD). Predictor selection and model building were based on the MIMIC-IV dataset. The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors. The final predictors were included in the multivariate logistic regression model, which was used to construct a nomogram. Finally, we conducted external validation using the eICU-CRD. The area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were used to assess the efficacy of the models. RESULTS: Risk factors, including the mean respiratory rate, mean systolic blood pressure, mean heart rate, white blood cells, international normalized ratio, total bilirubin, age, invasive ventilation, vasopressor use, maximum stage of acute kidney injury, and sequential organ failure assessment score, were included in the multivariate logistic regression. The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases, respectively. The calibration curve also confirmed the predictive ability of the model, while the decision curve confirmed its clinical value. CONCLUSION: The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.

Correlation of Blood and Intestinal Mucosa miR-34a Expressions with Disease Severity in Ulcerative Colitis Patients.

BACKGROUND: miR-34a has been implicated in many autoimmune diseases and gastrointestinal diseases. However, the expression of miR-34 in ulcerative colitis (UC) patients were not fully studied. This study was performed to in-vestigate the association of blood and intestinal tissue miR-34a expression of patients with disease severity in UC patients. METHODS: Our study enrolled 82 patients with UC and 80 age- and gender- matched healthy individuals. Blood miR-34a expressions were detected using reverse transcription-polymerase chain reaction (RT-PCR). Local intestinal miR-34a, STAT3 mRNA and IL-23 mRNA expressions were also detected in the lesioned area and adjacent non-affected intestinal tissue in patients. Disease severity of UC was assessed by Mayo score. The diagnostic value of both blood and local miR-34a expression for UC patients was assessed by receiver operating characteristic (ROC) curve. RESULTS: Blood miR-34a was increased in UC patients in contrast with healthy individuals with statistical significance. In UC patients, local intestinal miR-34a expressions were markedly upregulated compared to adjacent non-affected intestinal tissue. Local intestinal miR-34a expressions were positively correlated with STAT3 mRNA and IL-23 mNRA. Both blood and local miR-34a expressions were significantly and positively related to Mayo scores. ROC curve analysis indicated that both blood and local miR-34a expressions may act as decent marker for Mayo grade. CONCLUSIONS: Blood and intestinal tissue miR-34a expressions are correlated with disease severity in UC patients. Both blood and intestinal tissue miR-34a expressions may serve as potential diagnostic and prognostic makers for UC. Therapeutic methods targeting miR-34a may act as potential ways for UC treatment.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Combined transcriptome and proteome analysis reveals MSN and ARFIP2 as biomarkers for trastuzumab resistance of breast cancer.

PURPOSE: HER2-positive breast cancer (BC) accounts for 20-30% of all BC subtypes and is linked to poor prognosis. Trastuzumab (Tz), a humanized anti-HER2 monoclonal antibody, is a first-line treatment for HER2-positive breast cancer which faces resistance challenges. This study aimed to identify the biomarkers driving trastuzumab resistance. METHODS: Differential expression analysis of genes and proteins between trastuzumab-sensitive (TS) and trastuzumab-resistant (TR) cells was conducted using RNA-seq and iTRAQ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used to study their functions. The prognostic significance and protein levels of ARFIP2 and MSN were evaluated using online tools and immunohistochemistry. Sensitivity of MSN and ARFIP2 to other therapies was assessed using public pharmacogenomics databases and the R language. RESULTS: Five genes were up-regulated, and nine genes were down-regulated in TR cells at both transcriptional and protein levels. Low ARFIP2 and high MSN expression linked to poor BC prognosis. MSN increased and ARFIP2 decreased in TR patients, correlating with shorter OS. MSN negatively impacted fulvestrant and immunotherapy sensitivity, while ARFIP2 had a positive impact. CONCLUSION: Our findings suggest that MSN and ARFIP2 could serve as promising biomarkers for predicting response to Tz, offering valuable insights for future research in the identification of diagnostic and therapeutic targets for BC patients with Tz resistance.

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice.

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment. Davunetide, an active fragment of the activity-dependent neuroprotective protein (ADNP), has been implicated in social and cognitive protection. However, the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood. In this study, ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice. The neuropathological basis was also explored using Golgi staining, morphological analysis, western blotting, electrophysiological analysis, and behavioral analysis. Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane. In adulthood, anterior cingulate cortex (ACC) neurons exposed to sevoflurane exhibited a decrease in dendrite number, total dendrite length, and spine density. Furthermore, the expression levels of Homer, PSD95, synaptophysin, and vglut2 were significantly reduced in the sevoflurane group. Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). Notably, davunetide significantly ameliorated the synaptic defects, social behavior deficits, and cognitive impairments induced by sevoflurane. Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca 2+ activity via the Wnt/ß-catenin signaling, resulting in decreased expression of synaptic proteins. Suppression of Wnt signaling was restored in the davunetide-treated group. Thus, ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics. This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis.

BACKGROUND: Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA. METHODS: TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan-Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2. RESULTS: Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC50 values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups. CONCLUSIONS: Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA.

Integrated analysis identified the role of three family members of ARHGAP in pancreatic adenocarcinoma.

The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues. Survival curve was drawn by Kaplan-Meier. ARHGAPs were integrated analyzed by GEPIA2, TIMER, UCLCAN, cBioPortal and R language. Protein level and prognostic value were evaluated via IHC staining or survival analysis. We totally identify 18 differentially expressed (DE) ARHGAPs in PAAD. Among the 18 DE genes, 8 were positively correlated with tumor grade; abnorrmal expression of 5 was positively correlated with copy number variation; expression of 4 was positively correlated with promoter hypomethylation. Multivariate Cox regression identified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors of PAAD. The function of ARHGAPs was mainly related to GTPase activity and signaling, axon guidance, proteoglycans in cancer and focal adhesion. Expression of 7 ARHGAPs was strongly correlated with immune infiltration. Immunohistochemistry showed increased protein levels of ARHGAP5, ARHGAP11A, and ARHGAP12 in PAAD tissues. Survival analysis confirmed a negative correlation between ARHGAP5, ARHGAP11A, and ARHGAP12 expression and patient prognosis. Multivariate Cox regression proved ARHGAP5, ARHGAP11A, and ARHGAP12 could serve as independent prognostic indicators for PAAD. Finally, this study verified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors in PAAD, suggesting their significance for the diagnosis and treatment of PAAD.

Precise lymph node biopsy for endometrial cancer confined to the uterus: Analysis of 43 clinical cases.

OBJECTIVE: To explore a precise association between tumor location and lymph node (LN) biopsy algorithm in uterine confined endometrial cancer (EC). MATERIALS AND METHODS: Patients with EC treated in the Department of Obstetrics and Gynecology, South Branch of Fujian Provincial Hospital were included in this observational retrospective study. Based on the procedure of treatment, patients were separated to stage I (2015.07-2019.09) and stage II (2019.09-2021.9). In each stage, patients were separated to high and low-risk group by the predicted results. Patients in the high-risk group received systematic lymphadenectomy in stage I and sentinel lymph node (SLN) dissection in stage II. The efficiency of lymph node metastasis (LNM) detection rates was compared between stage I and stage II cases. Precise lymph node biopsy algorithm was also constructed based on the outcomes of stage II. RESULTS: Overall, 43 patients, 28 in stage I and 15 in stage II, were included in the study. No recurrence or death cases had been found within follow-up terms. Based on the difference in the detection efficiency of LNM (p > 0.05), there was no difference between two stages. Thus, systematic lymphadenectomy and SLN biopsy provided similar success rates. The location of tumor site was also important for deciding whether pelvic or para-aortic SLN should be sampled for LNM. CONCLUSIONS: Precise SLN biopsy for EC confined to the uterus showed comparable LNM detection rate as systematic lymphadenectomy. EC location may be used to determine whether pelvic or para-aortic SLN sampling should be conducted for treatment.

Luteolin and its analog luteolin-7-methylether from Leonurus japonicus Houtt suppress aromatase-mediated estrogen biosynthesis to alleviate polycystic ovary syndrome by the inhibition of tumor progression locus 2.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt (L. japonicus, Chinese motherwort), known as Yi Mu Cao which means "good for women", has long been widely used in China and other Asian countries to alleviate gynecological disorders, often characterized by estrogen dysregulation. It has been used for the treatment of polycystic ovary syndrome (PCOS), a common endocrine disorder in women but the underlying mechanism remains unknown. AIM OF THE STUDY: The present study was designed to investigate the effect and mechanism of flavonoid luteolin and its analog luteolin-7-methylether contained in L. japonicus on aromatase, a rate-limiting enzyme that catalyzes the conversion of androgens to estrogens and a drug target to induce ovulation in PCOS patients. MATERIALS AND METHODS: Estrogen biosynthesis in human ovarian granulosa cells was examined using ELISA. Western blots were used to explore the signaling pathways in the regulation of aromatase expression. Transcriptomic analysis was conducted to elucidate the potential mechanisms of action of compounds. Finally, animal models were used to assess the therapeutic potential of these compounds in PCOS. RESULTS: Luteolin potently inhibited estrogen biosynthesis in human ovarian granulosa cells stimulated by follicle-stimulating hormone. This effect was achieved by decreasing cAMP response element-binding protein (CREB)-mediated expression of aromatase. Mechanistically, luteolin and luteolin-7-methylether targeted tumor progression locus 2 (TPL2) to suppress mitogen-activated protein kinase 3/6 (MKK3/6)-p38 MAPK-CREB pathway signaling. Transcriptional analysis showed that these compounds regulated the expression of different genes, with the MAPK signaling pathway being the most significantly affected. Furthermore, luteolin and luteolin-7-methylether effectively alleviated the symptoms of PCOS in mice. CONCLUSIONS: This study demonstrates a previously unrecognized role of TPL2 in estrogen biosynthesis and suggests that luteolin and luteolin-7-methylether have potential as novel therapeutic agents for the treatment of PCOS. The results provide a foundation for further development of these compounds as effective and safe therapies for women with PCOS.

Niche convergence and biogeographic history shape elevational tree community assembly in a subtropical mountain forest.

Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.

Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

High-performance flexible p-type Ce-filled Fe3CoSb12 skutterudite thin film for medium-to-high-temperature applications.

P-type Fe3CoSb12-based skutterudite thin films are successfully fabricated, exhibiting high thermoelectric performance, stability, and flexibility at medium-to-high temperatures, based on preparing custom target materials and employing advanced pulsed laser deposition techniques to address the bonding challenge between the thin films and high-temperature flexible polyimide substrates. Through the optimization of fabrication processing and nominal doping concentration of Ce, the thin films show a power factor of >100 µW m-1 K-2 and a ZT close to 0.6 at 653 K. After >2000 bending cycle tests at a radius of 4 mm, only a 6 % change in resistivity can be observed. Additionally, the assembled p-type Fe3CoSb12-based flexible device exhibits a power density of 135.7 µW cm-2 under a temperature difference of 100 K with the hot side at 623 K. This work fills a gap in the realization of flexible thermoelectric devices in the medium-to-high-temperature range and holds significant practical application value.

Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19.

BACKGROUND: Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells (ADSCs) are an effective therapeutic approach for managing coronavirus disease 2019 (COVID-19); however, further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors (TFs) and cytokine release in peripheral blood mononuclear cells (PBMCs). AIM: To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer (CRC) patients with severe COVID-19 (CRC+ patients). METHODS: PBMCs from CRC+ patients (PBMCs-C+) and age-matched CRC patients (PBMCs-C) were stimulated and cultured in the presence/absence of ADSCs. The mRNA levels of T-box TF TBX21 (T-bet), GATA binding protein 3 (GATA-3), RAR-related orphan receptor C (RORC), and forkhead box P3 (FoxP3) in the PBMCs were determined by reverse transcriptase-polymerase chain reaction. Culture supernatants were evaluated for levels of interferon gamma (IFN-γ), interleukin 4 (IL-4), IL-17A, and transforming growth factor beta 1 (TGF-ß1) using an enzyme-linked immunosorbent assay. RESULTS: Compared with PBMCs-C, PBMCs-C+ exhibited higher mRNA levels of T-bet and RORC, and increased levels of IFN-γ and IL-17A. Additionally, a significant decrease in FoxP3 mRNA and TGF-ß1, as well as an increase in T-bet/GATA-3, RORC/FoxP3, IFN-γ/IL-4, and IL-17A/TGF-ß1 ratios were observed in PBMCs-C+. Furthermore, ADSCs significantly induced a functional regulatory T cell (Treg) subset, as evidenced by an increase in FoxP3 mRNA and TGF-ß1 release levels. This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC, release of IFN-γ and IL-17A, and T-bet/GATA-3, RORC/FoxP3, IFN-γ/IL-4, and IL-17A/TGF-ß1 ratios, compared with the PBMCs-C+alone. CONCLUSION: The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+, favoring Treg responses. Thus, ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.

Dexmedetomidine use during orthotopic liver transplantation surgery on early allograft dysfunction: A randomized controlled trial.

BACKGROUND: Previous studies have shown a protective effect of dexmedetomidine use in kidney transplantation. In contrast, it is not known whether intraoperative administration of dexmedetomidine can reduce early allograft dysfunction incidence following liver transplantation. OBJECTIVE: To investigate the effect of dexmedetomidine use during surgery on early allograft dysfunction following orthotopic liver transplantation (OLT). STUDY DESIGN: This is a single-center, double-blinded, placebo-controlled randomized clinical trial. 330 adult patients undergoing orthotopic liver transplantation were enrolled from Jan 14th, 2019 to May 22nd, 2022. Patients received dexmedetomidine or normal saline during surgery. 1 year follow-ups were recorded. METHODS: Patients were randomized to two groups receiving either dexmedetomidine or normal saline intraoperatively. For patients in the dexmedetomidine group, a loading dose (1 µg/kg over 10 min) of dexmedetomidine was given after induction of anesthesia followed by a continuous infusion (0.5 µg/kg /h) until the end of surgery. For patients in the normal saline group, an equal volume loading dose of 0.9% saline was given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. The primary outcome was early allograft dysfunction. Secondary outcomes included primary graft non-function, acute kidney injury and acute lung injury/ acute respiratory distress syndrome. RESULTS: Of 330 patients included in the intention-to-treat analysis, 165 were in the dexmedetomidine group (mean [SD] age, 49 [10] years; 117 [70.9%] men), and 165 were in the normal saline group (mean SD age, 49 [9] years; 118 [74%] men). 39 (24.4%) patients in the dexmedetomidine group and 31 (19.4%) in normal saline group developed early allograft dysfunction and the difference was statistically insignificant (P=0.28). Secondary outcomes including primary graft non-function and acute kidney injury was similar between the two groups. CONCLUSION: Intraoperative administration of dexmedetomidine did not reduce early allograft dysfunction rate after orthotopic liver transplantation.

Boosting thermoelectric performance of single-walled carbon nanotubes-based films through rational triple treatments.

Single-walled carbon nanotubes (SWCNTs)-based thermoelectric materials, valued for their flexibility, lightweight, and cost-effectiveness, show promise for wearable thermoelectric devices. However, their thermoelectric performance requires significant enhancement for practical applications. To achieve this goal, in this work, we introduce rational "triple treatments" to improve the overall performance of flexible SWCNT-based films, achieving a high power factor of 20.29 µW cm-1 K-2 at room temperature. Ultrasonic dispersion enhances the conductivity, NaBH4 treatment reduces defects and enhances the Seebeck coefficient, and cold pressing significantly densifies the SWCNT films while preserving the high Seebeck coefficient. Also, bending tests confirm structural stability and exceptional flexibility, and a six-legged flexible device demonstrates a maximum power density of 2996 µW cm-2 at a 40 K temperature difference, showing great application potential. This advancement positions SWCNT films as promising flexible thermoelectric materials, providing insights into high-performance carbon-based thermoelectrics.

Analysis of the influencing factors of the scientific fitness literacy of nurses in the context of exercise and medicine integration.

OBJECTIVE: The present study aims to explore the influencing factors of the scientific fitness literacy of nurses and provide a strategic basis for literacy improvement. METHODS: A questionnaire on the influencing factors of scientific fitness literacy of nurses was designed by the group conducting the present study; the questionnaire was based on the socioecology model and the questionnaire preparation method. The general data questionnaire and the questionnaire on the influencing factors of scientific fitness literacy of nurses were adopted to investigate nurses in tertiary hospitals in order to analyze and discuss the influencing factors of their scientific fitness literacy. RESULTS: (1) The questionnaire on the influencing factors of the scientific fitness literacy of nurses comprised five dimensions and 36 items. The overall item-content validity index was 0.833-1.000, the scale-content validity index was 0.974, and the overall Cronbach's α coefficient was 0.955; (2) the results of the pairwise Pearson correlation analysis showed that all five dimensions were positively correlated with the scientific fitness literacy of nurses; and (3) the results of the multiple linear regression analysis revealed that five dimensions, as well as the existence of exercise habits in daily life, had a significant impact on the scientific fitness literacy of nurses (P < 0.001). CONCLUSION: The factors influencing the scientific fitness literacy of nurses involved all levels of the socioecological system. The methods of improving the awareness of the scientific fitness of nurses and providing opportunities for scientific fitness activities via the hospital played a critical role in literacy improvement. However, the lack of professional guidance and an atmosphere promoting scientific fitness might hinder literacy improvement.

Survival outcome and optimal candidates of primary tumor resection for patients with metastatic medullary thyroid cancer.

CONTEXT: Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. OBJECTIVE: The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. MATERIALS AND METHODS: Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. RESULTS: A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (OS) (p = 0.007) and cancer-specific survival (CSS) (p = 0.0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality (OM) and cancer-specific mortality (CSM) (all p < 0.05). When analyzing different metastatic patterns, PTR significantly lowered the risk of OM and CSM for patients with bone, lung, liver, or distant lymph node (DLN) involvement (all p < 0.05). Additionally, among patients with one or two metastases, those undergoing surgical resection were significantly associated with favorable OS (p = 0.008) and CSS (p = 0.0247). CONCLUSIONS: PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

Designer Receptor Exclusively Activated by Designer Drug (DREADD)-Mediated Activation of the Periaqueductal Gray Restores Nociceptive Descending Inhibition After Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) patients frequently experience chronic pain that can enhance their suffering and significantly impair rehabilitative efforts. Clinical studies suggest that damage to the periaqueductal gray matter (PAG) following TBI, a principal center involved in endogenous pain control, may underlie the development of chronic pain. We hypothesized that TBI would diminish the usual pain control functions of the PAG, but that directly stimulating this center using a chemogenetic approach would restore descending pain modulation. We used a well-characterized lateral fluid percussion model (1.3 ± 0.1 atm) of TBI in male rats (n = 271) and measured hindpaw mechanical nociceptive withdrawal thresholds using von Frey filaments. To investigate the role of the PAG in pain both before and after TBI, we activated the neurons of the PAG using a Designer Receptor Exclusively Activated by Designer Drug (DREADD) viral construct. Immunohistochemical analysis of brain tissue was used to assess the location and confirm the appropriate expression of the viral constructs in the PAG. Activation of the PAG DREADD using clozapine N-oxide (CNO) caused hindpaw analgesia that could be blocked using opioid receptor antagonist, naloxone, in uninjured but not TBI rats. Due to the importance of descending serotonergic signaling in modulating nociception, we ablated spinal serotonin signaling using 5,7-DHT. This treatment strongly reduced CNO-mediated anti-nociceptive effects in TBI but not uninjured rats. To define the serotonergic receptor(s) required for the CNO-stimulated effects in TBI rats, we administered 5-HT7 (SB-269970) and 5-HT1A (WAY-100635) receptor antagonists but observed no effects. The selective 5-HT2A receptor antagonist ketanserin, however, blocked CNO's effects in the DREADD expressing TBI but not DREADD expressing sham TBI animals. Blockade of alpha-1 adrenergic receptors with prazosin also had no effect after TBI. Descending pain control originating in the PAG is mediated through opioid receptors in uninjured rats. TBI, however, fundamentally alters the descending nociceptive control circuitry such that serotonergic influences predominate, and those are mediated by the 5-HT2A receptor. These results provide further evidence that the PAG is a key target for anti-nociception after TBI.