Cu(II)-Loaded Polydopamine-Coated Urchin-like Titanate Microspheres as a High-Performance IMAC Adsorbent for Hemoglobin Separation.

Immobilized metal ion affinity chromatography (IMAC) adsorbents generally have excellent affinity for histidine-rich proteins. However, the leaching of metal ions from the adsorbent usually affects its adsorption performance, which greatly affects the reusable performance of the adsorbent, resulting in many limitations in practical applications. Herein, a novel IMAC adsorbent, i.e., Cu(II)-loaded polydopamine-coated urchin-like titanate microspheres (Cu-PDA-UTMS), was prepared via metal coordination to make Cu ions uniformly decorate polydopamine-coated titanate microspheres. The as-synthesized microspheres exhibit an urchin-like structure, providing more binding sites for hemoglobin. Cu-PDA-UTMS exhibit favorable selectivity for hemoglobin adsorption and have a desirable adsorption capacity towards hemoglobin up to 2704.6 mg g-1. Using 0.1% CTAB as eluent, the adsorbed hemoglobin was easily eluted with a recovery rate of 86.8%. In addition, Cu-PDA-UTMS shows good reusability up to six cycles. In the end, the adsorption properties by Cu-PDA-UTMS towards hemoglobin from human blood samples were analyzed by SDS-PAGE. The results showed that Cu-PDA-UTMS are a high-performance IMAC adsorbent for hemoglobin separation, which provides a new method for the effective separation and purification of hemoglobin from complex biological samples.

Loss of AMPK activity induces organelle dysfunction and oxidative stress during oocyte aging.

BACKGROUND: Oocyte quality is critical for the mammalian reproduction due to its necessity on fertilization and early development. During aging, the declined oocytes showing with organelle dysfunction and oxidative stress lead to infertility. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which is important for energy homeostasis for metabolism. Little is known about the potential relationship between AMPK with oocyte aging. RESULTS: In present study we reported that AMPK was related with low quality of oocytes under post ovulatory aging and the potential mechanism. We showed the altered AMPK level during aging and inhibition of AMPK activity induced mouse oocyte maturation defect. Further analysis indicated that similar with its upstream regulator PKD1, AMPK could reduce ROS level to avoid oxidative stress in oocytes, and this might be due to its regulation on mitochondria function, since loss of AMPK activity induced abnormal distribution, reduced ATP production and mtDNA copy number of mitochondria. Besides, we also found that the ER and Golgi apparatus distribution was aberrant after AMPK inhibition, and enhanced lysosome function was also observed. CONCLUSIONS: Taken together, these data indicated that AMPK is important for the organelle function to reduce oxidative stress during oocyte meiotic maturation.

Kinesin KIFC3 is essential for microtubule stability and cytokinesis in oocyte meiosis.

KIFC3 is a member of Kinesin-14 family motor proteins, which play a variety of roles such as centrosome cohesion, cytokinesis, vesicles transportation and cell proliferation in mitosis. Here, we investigated the functional roles of KIFC3 in meiosis. Our findings demonstrated that KIFC3 exhibited expression and localization at centromeres during metaphase I, followed by translocation to the midbody at telophase I throughout mouse oocyte meiosis. Disruption of KIFC3 activity resulted in defective polar body extrusion. We observed aberrant meiotic spindles and misaligned chromosomes, accompanied by the loss of kinetochore-microtubule attachment, which might be due to the failed recruitment of BubR1/Bub3. Coimmunoprecipitation data revealed that KIFC3 plays a crucial role in maintaining the acetylated tubulin level mediated by Sirt2, thereby influencing microtubule stability. Additionally, our findings demonstrated an interaction between KIFC3 and PRC1 in regulating midbody formation during telophase I, which is involved in cytokinesis regulation. Collectively, these results underscore the essential contribution of KIFC3 to spindle assembly and cytokinesis during mouse oocyte meiosis.

Increased knee torsional misalignment associated with femoral torsion is related to non-contact anterior cruciate ligament injury: a case-control study.

BACKGROUND: Altered axial biomechanics of the knee are recognized as a risk factor for non-contact anterior cruciate ligament (ACL) injury. However, the relationship of knee and segmental torsion to non-contact ACL and combined anterolateral ligament (ALL) injury is unclear. This study aims to determine the relationship of knee and segmental torsion to non-contact ACL injury and to explore their relationship with ALL injuries. METHODS: We divided 122 patients with arthroscopically confirmed non-contact ACL injuries into an ACL injury group (isolated ACL injury, 63 patients) and an ACL + ALL injury group (ACL combined with ALL injury,59 patients). Additionally, 90 normal patients with similar age, gender and body mass index (BMI) were matched as a control group. The tibial tubercle-trochlear groove (TT-TG) distance, distal femoral torsion (DFT), posterior femoral condylar torsion (PFCT) and proximal tibial torsion (PTT) were measured using magnetic resonance imaging (MRI). We assessed the differences between the groups using an independent samples t test and utilized receiver operating characteristic (ROC) curves to determine the cut-off value for the increased risk of ACL injury. RESULTS: In patients with ACL injury, the measurements of the TT-TG (11.8 ± 3.1 mm), DFT (7.7° ± 3.5°) and PFCT (3.6° ± 1.3°) were significantly higher compared to the control group (9.1 ± 2.4 mm, 6.3° ± 2.7° and 2.8° ± 1.3°, respectively; P < 0.05), but the PTT did not differ between the two groups. The TT-TG, DFT and PFCT were not significantly larger in patients combined with ALL injury. ROC curve analysis revealed ACL injury is associated with TT-TG, DFT and PFCT. CONCLUSIONS: Knee torsional alignment is associated with ACL injury, predominantly in the distal femur rather than the proximal tibia. However, its correlation with ALL injury remains unclear. These findings may help identify patients at high risk for non-contact ACL injury and inform the development of targeted prevention and treatment strategies.

Mapping the Landscape of Obesity Effects on Male Reproductive Function: A Bibliometric Study.

BACKGROUND: Due to changes in lifestyle and dietary habits, the global population with obesity is increasing gradually, resulting in a significant rise in the number of individuals having obesity. Obesity is caused by an imbalance between energy intake and consumption, leading to excessive fat accumulation, which interferes with normal human metabolism. It is also associated with cardiovascular disease, metabolic syndrome, male reproductive endocrine regulation disorders, systemic and local inflammatory reactions, excessive oxidative stress, and apoptosis. All these factors can damage the internal environment for sperm generation and maturation, resulting in male sexual dysfunction, a decline in sperm quality, and lower fertility. This study analyzes the trends and priorities of the effects of obesity on male reproductive disorders from a bibliometric perspective. METHODS: This study uses the Web of Science as the statistical source, covering all time spans. Tools like Web of Science, VOSviewer, and CiteSpace are used to analyze countries, institutions, authors, journals, and keywords in the field. Total publications, total citations, and average number of citations are selected for statistics. RESULTS: The results show that the research on the impact of obesity on male reproductive function can be roughly divided into three stages: the initial stage, the slow development stage, and the rapid development stage. Our statistical scope includes 463 highly relevant articles that we have screened. We found that the journal with the most publications in this field is Andrologia, and the institution with the highest total citations is the University of Utah. The most influential countries, institutions, and authors in this field are the United States, the University of Utah, and Carrell, Douglas. Currently, research related to the impact of obesity on male reproduction focuses mainly on three aspects: biochemistry, molecular biology, and reproductive biology. The keyword explosion results indicate that sperm, obesity, and male reproduction are at the forefront and trends of future research in this field. There has been a shift from basic biochemical and molecular research to research on molecular mechanisms relying on omics technologies. However, we have observed that the number of papers published in 2022 is lower than in 2021, indicating a growth interruption during this period. Considering that this deviation may be due to the impact of the COVID-19 pandemic, it may hinder the progress of certain experiments in 2022. In recent years, China has rapidly developed research in this field. However, the average citation rate is relatively low, indicating the need for Chinese scholars to improve the quality of their articles further. Based on our research and in the context of global obesity, men are at risk of increased infertility. Addressing this issue relies on our continued research into the mechanisms of obesity-related male reproductive disorders. Over the past forty-three years, with the contributions of scientists worldwide, research in this field has flourished. CONCLUSION: The impact of obesity on male reproductive disorders has been extensively studied. Currently, research in this field primarily focuses on male sperm function, sperm quality, and the effects or mechanisms of cells on male reproduction. Future trends in this field should concentrate on the relationship between male fertility and energy metabolism, as well as the endocrine function of adipose tissue. This study comprehensively analyzes the current research status and global trends in obesity and male reproductive disorders. We also discuss the future developments in this field, making it easier for researchers to understand its developmental history, current status, and trends, providing valuable reference for effective exploration in this area.

The analysis of complete genome sequence and comparative genomics of Vibrio parahaemolyticus LF1113 in Hainan.

Vibrio parahaemolyticus is a Gram-negative, halophilic and polymorphic coccobacillus. It is world-widely distributed and has resulted in great economic losses since its first appearance. In this study, a pathogenic strain was isolated from diseased pearl gentian grouper and identified as V. parahaemolyticus based on the sequencing results of 16S rDNA gene. In order to gain a comprehensive understanding of this isolation, the whole genome sequencing was conducted. Phylogenetic analysis of the complete genomes of 16 Vibrio species showed that LF1113, ATCC17802, ATCC33787, 2210633, FORC 004, and 160807 were the most closely related. Animal experiments demonstrated that the isolated LF1113 strain was pathogenic in a fish model. This study is the first study to describe the complete genome sequence of a V. parahaemolyticus isolate, which infected pearl gentian grouper from an outbreak in a fish factory farm in Hainan. The results will expand our understanding of genetic characteristics, pathogenesis, diagnostics and disease prevention of V. parahaemolyticus, and lay the foundation for further study.

Implementation and impact of the World Health Organization integrated care for older people (ICOPE) program in China: a randomised controlled trial.

BACKGROUND: Fragmentation of services increases health and social care burden as people live longer with higher prevalence of diseases, frailty and dependency. Local evidence for implementing person-centred integrated care is urgently needed to advance practice and policies to achieve healthy ageing. OBJECTIVE: To test the feasibility and impact of World Health Organization's (WHO) Integrated Care for Older People (ICOPE) approach in China. DESIGN: A randomised controlled trial examining the feasibility of implementing ICOPE approach, evaluating its impact on health outcomes and health resource utilisation. SETTING: Primary care setting in urban and suburban communities of Chaoyang District, Beijing, China. SUBJECTS: Community-dwelling older adults screened as at-risk of functional declines and randomised into intervention (537) and control (1611) groups between September 2020 and February 2021. METHODS: A 6-month intervention program following WHO's ICOPE care pathways implemented by integrated care managers compared to standard available care. RESULTS: After 1 to 1 propensity score matching, participants in intervention and control groups (totally 938) had comparable baseline characteristics, demonstrated feasibility of implementing ICOPE with satisfaction by participants (97-99%) and providers (92-93%). All outcomes showed improvements after a 6-month intervention, while statistically significant least-squares mean differences (control-intervention) in vitality (Mini-Nutritional Assessment Short Form to measure vitality, -0.21, 95% CI, -0.40-0.02), mobility (Short Physical Performance Battery to measure mobility, -0.29, 95% CI, -0.44-0.14) and psychological health (Geriatric Depression Scale five items to measure psychological health, 0.09, 95% CI, 0.03-0.14) were observed (P < 0.05). CONCLUSIONS: It is feasible to localise and implement WHO's ICOPE approach in regions with fragmented resources such as China. Preliminary evidence supports its acceptance among key stakeholders and impact on health outcomes.

Post-Acute Care in China: Development, Challenges, and Path Forward.

OBJECTIVES: To evaluate the evolution and challenges of China's post-acute care (PAC) system over the past 20 years and suggest actionable policy recommendations for its improvement. DESIGN: A retrospective review of policies and initiatives aimed at PAC system development, analyzed alongside unsolved challenges in light of global PAC practices, informed by literature reviews and collaborative discussion. SETTING AND PARTICIPANTS: PAC in China involves diverse settings such as general hospitals, inpatient rehabilitation centers, skilled nursing facilities, community health centers, and homes. The patients are mainly those discharged from acute hospitals with functional impairment and in need of continuous care. METHOD: An extensive search of government policy documents, statistical sources, peer-reviewed studies, and the gray literature. The research team conducted literature reviews and discussions regularly to shape the findings. RESULTS: China has strengthened its PAC system through improved rehabilitation and nursing infrastructure, establishment of tiered rehabilitation networks, and adoption of innovative payment methods. However, challenges persist, including a lack of clinical consensus, resource constraints in PAC facilities and among professionals, the need for integrated care coordination, and the unification of PAC assessment tools and payment mechanisms. CONCLUSIONS AND IMPLICATIONS: Although China has made substantial progress in its PAC system over 2 decades, continued efforts are needed to address its lingering challenges. Elevating awareness of PAC's significance and instituting policy adjustments targeting these challenges are essential for the system's optimization.

Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVE: VC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004. METHODS: The study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests. RESULTS: The maximum plasma concentration (Cmax) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to Cmax (Tmax) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of Cmax, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0-t), and AUC from zero to infinity (AUC0-∞) for VC004 between the two states were 67.18 (58.16-77.60), 103.59 (95.04-112.92) and 103.55 (95.63-112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study. CONCLUSIONS: The intake of high calorie food decreased the absorption rate and increased the Tmax of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT055528120.

Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice.

Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still poorly understood. Here, we found that in vivo, supplementation of pyrroloquinoline quinone (PQQ) efficaciously ameliorated the abnormal lipid metabolism and testicular spermatogenic function from high-fat-diet (HFD)-induced obese mice. Moreover, the transcriptome analysis of the liver and testicular showed that PQQ supplementation not only inhibited the high expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9) but also weakened the NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis, which both played a negative role in T synthesis of Leydig Cells (LCs). Eventually, the function and the pyroptosis of LCs cultured with palmitic acid in vitro were simultaneously benefited by suppressing the expression of NLRP3 or PCSK9 respectively, as well the parallel effects of PQQ were affirmed. Collectively, our data revealed that PQQ supplementation is a feasible approach to protect T synthesis from PCSK9-NLRP3 crosstalk-induced LCs' pyroptosis in obese men.

Toxicity of the Mycotoxin Deoxynivalenol on Early Cleavage of Mouse Embryos by Fluorescence Intensity Analysis.

Deoxynivalenol is a mycotoxin, produced by Fusarium from contaminated corn, wheat, and other grains, that induces multiple effects in humans and animals, including cytotoxic, genotoxic, immunotoxic, and carcinogenic effects. Recent studies show that deoxynivalenol also affects the reproductive system of mammals, including oocyte quality. However, the effects of deoxynivalenol on early embryonic development have not been reported. In this study, fluorescence intensity analysis was used to show that deoxynivalenol disrupted the first cleavage of the zygote. The high deoxynivalenol dose disturbed the movement of the pronucleus after fertilization, while the low deoxynivalenol dose caused aberrant spindle morphology during the metaphase of the first cleavage. Further analysis showed that the reactive oxygen species level increased in the deoxynivalenol-exposed two-cell embryos, indicating oxidative stress. Moreover, deoxynivalenol caused DNA damage in the embryos, as positive γH2A.X signals were detected in the nucleus. These events led to the early apoptosis of mouse embryos, which was confirmed by autophagy. Taken together, our study provides evidence for the toxicity of deoxynivalenol during early embryonic development in the mouse model.

Therapeutic drug monitoring of immune checkpoint inhibitors: based on their pharmacokinetic properties and biomarkers.

As a new means of oncology treatment, immune checkpoint inhibitors (ICIs) can improve survival rates in patients with resistant or refractory tumors. However, there are obvious inter-individual differences in the unsatisfactory response rate, drug resistance rate and the occurrence of immune-related adverse events (irAE). These questions have sparked interest in researchers looking for a way to screen sensitive populations and predict efficacy and safety. Therapeutic drug monitoring (TDM) is a way to ensure the safety and effectiveness of medication by measuring the concentration of drugs in body fluids and adjusting the medication regimen. It has the potential to be an adjunctive means of predicting the safety and efficacy of ICIs treatment. In this review, the author outlined the pharmacokinetic (PK) characteristics of ICIs in patients. The feasibility and limitations of TDM of ICIs were discussed by summarizing the relationships between the pharmacokinetic parameters and the efficacy, toxicity and biomarkers.

Remifentanil versus Fentanyl for Analgesia in Mechanically Ventilated Patients: A Multicenter, Prospective, Randomized, Double-Blind, Parallel-Group Clinical Trial.

Purpose: Fentanyl is approved for use in many countries as an analgesic for patients requiring mechanical ventilation. However, it redistributes and accumulates easily in the plasma because of its long half-life. Remifentanil is a short context-sensitive half-life analgesic with a lower risk of redistribution and accumulation. Materials and methods: We conducted a multicenter, randomized, double-blind, non-inferiority trial. Critically ill patients requiring mechanical ventilation were randomly allocated to receive an infusion of either remifentanil or fentanyl for up to 72 h. The primary outcome was the analgesic success rate. A 95% confidence interval lower boundary greater than -8% for the difference between the groups was considered to indicate non-inferiority between the drugs. Results: A total of 137 patients received remifentanil (69) or fentanyl (68). Remifentanil's non-inferiority to fentanyl concerning its analgesic success rate was established (difference, 5.97%; 95% confidence interval: -3.99% to 16.35%). Mechanical ventilation duration, extubation duration, successful extubation, intensive care unit discharge, intensive care unit length of stay, and adverse events did not differ significantly between the two groups. Conclusions: Remifentanil was non-inferior to fentanyl regarding the analgesic success rate in critically ill patients requiring mechanical ventilation.

Aflatoxin B1 impairs porcine oocyte quality via disturbing intracellular membrane system and ATP production.

Aflatoxin is the most common type of mycotoxins in contaminated corn, peanuts and rice, which affects the livestock and ultimately endangers human health. Aflatoxin is reported to have carcinogenicity, mutation, growth retardation, immunosuppression and reproductive toxicity. In present study we reported the causes for the declined porcine oocyte quality under aflatoxin exposure. We set up an in vitro exposure model and showed that aflatoxin B1 disturbed cumulus cell expansion and oocyte polar body extrusion. We found that aflatoxin B1 exposure disrupted ER distribution and elevated the expression of GRP78, indicating the occurrence of ER stress, and the increased calcium storage also confirmed this. Besides, the structure of cis-Golgi apparatus, another intracellular membrane system was also affected, showing with decreased GM130 expression. The oocytes under aflatoxin B1 exposure showed aberrant lysosome accumulation and higher LAMP2 expression, a marker for lysosome membrane protection, and this might be due to the aberrant mitochondria function with low ATP production and the increase of apoptosis, since we found that BAX expression increased, and ribosomal protein which is also an apoptosis-related factor RPS3 decreased. Taken together, our study revealed that aflatoxin B1 impairs intracellular membrane system ER, Golgi apparatus, lysosome and mitochondria function to affect porcine oocyte maturation quality.

Genome-wide identification of Brassicaceae histone modification genes and their responses to abiotic stresses in allotetraploid rapeseed.

BACKGROUND: Histone modification is an important epigenetic regulatory mechanism and essential for stress adaptation in plants. However, systematic analysis of histone modification genes (HMs) in Brassicaceae species is lacking, and their roles in response to abiotic stress have not yet been identified. RESULTS: In this study, we identified 102 AtHMs, 280 BnaHMs, 251 BcHMs, 251 BjHMs, 144 BnHMs, 155 BoHMs, 137 BrHMs, 122 CrHMs, and 356 CsHMs in nine Brassicaceae species, respectively. Their chromosomal locations, protein/gene structures, phylogenetic trees, and syntenies were determined. Specific domains were identified in several Brassicaceae HMs, indicating an association with diverse functions. Syntenic analysis showed that the expansion of Brassicaceae HMs may be due to segmental and whole-genome duplications. Nine key BnaHMs in allotetraploid rapeseed may be responsible for ammonium, salt, boron, cadmium, nitrate, and potassium stress based on co-expression network analysis. According to weighted gene co-expression network analysis (WGCNA), 12 BnaHMs were associated with stress adaptation. Among the above genes, BnaPRMT11 simultaneously responded to four different stresses based on differential expression analysis, while BnaSDG46, BnaHDT10, and BnaHDA1 participated in five stresses. BnaSDG46 was also involved in four different stresses based on WGCNA, while BnaSDG10 and BnaJMJ58 were differentially expressed in response to six different stresses. In summary, six candidate genes for stress resistance (BnaPRMT11, BnaSDG46, BnaSDG10, BnaJMJ58, BnaHDT10, and BnaHDA1) were identified. CONCLUSIONS: Taken together, these findings help clarify the biological roles of Brassicaceae HMs. The identified candidate genes provide an important reference for the potential development of stress-tolerant oilseed plants.

Thioredoxin1 Binding Metastasis-Associated Lung Adenocarcinoma Transcript 1 Attenuates Inflammation and Apoptosis after Intracerebral Hemorrhage.

Post-transcriptional regulation and RNA-binding proteins (RBPs) play vital roles in the occurrence of secondary injury after intracerebral hemorrhage (ICH). Therefore, we identified RBPs distinctively expressed after ICH by screening and determined thioredoxin1 (Txn1) as one of the most distinctive RBPs. We employed an ICH model and in vitro experiments to investigate the role of Txn1 in ICH. Firstly, we found that Txn1 was mainly expressed in microglia and neurons in the central nervous system, and its expression was significantly reduced in perihematomal tissue. Additionally, adeno-associated virus (AAV) carrying Txn1 was injected into the ICH rat model. Our results showed that overexpression of Txn1 reduced secondary injury and improved outcome in the ICH rat model. Moreover, to understand the therapeutic mechanism of Txn1 after ICH, we performed RNA immunoprecipitation combined with high-throughput sequencing. The results showed that Txn1 binds to inflammation- and apoptosis-related mRNAs and affects gene expression through RNA splicing and translation. Finally, RNA pull-down assays and in vitro experiments confirmed that Txn1 binds to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), leading to reduced inflammation and apoptosis. Our study suggests that Txn1 is a potential therapeutic target for alleviating ICH-induced brain injury.

Analysis of preoperative influential factors and construction of a predictive nomogram of difficult thyroidectomy.

OBJECTIVE: To explore the preoperative influential factors of difficult thyroidectomy and establish a preoperative nomogram for predicting the difficulty of thyroidectomy. METHODS: A total of 753 patients who underwent total thyroidectomy with central lymph node dissection between January 2018 and December 2021 were retrospectively enrolled in this study and randomly divided into training and validation groups at a ratio of 8:2. In both subgroups, the patients were divided into difficult thyroidectomy and nondifficult thyroidectomy groups based on the operation time. Patient age, sex, body mass index (BMI), thyroid ultrasound, thyroid function, preoperative fine needle aspiration (FNA), postoperative complications and other data were collected. Logistic regression analysis was performed to identify the predictors of difficult thyroidectomy, and a nomogram predicting surgical difficulty was created. RESULTS: Multivariate logistic regression analysis demonstrated that male sex (OR = 2.138, 95% CI 1.055-4.336, p = 0.035), age (OR = 0.954, 95% CI 0.932-0.976, p < 0.001), BMI (OR = 1.233, 95% CI 1.106-1.375, p < 0.001), thyroid volume (OR = 1.177, 95% CI 1.104-1.254, p < 0.001) and TPO-Ab (OR = 1.001, 95% CI 1.001-1.002, p = 0.001) were independent risk factors for difficult thyroidectomy. The nomogram model incorporating the above predictors performed well in both the training and validation sets. A higher postoperative complication rate was found in the difficult thyroidectomy group than in the nondifficult thyroidectomy group. CONCLUSION: This study identified independent risk factors for difficult thyroidectomy and created a predictive nomogram for difficult thyroidectomy. This nomogram may help to objectively and individually predict surgical difficulty before surgery and provide optimal treatment.

Reward enhances resilience to chronic social defeat stress in mice: Neural ECs and mGluR5 mechanism via neuroprotection in VTA and DRN.

Introduction: Stress often leads to emotional disorders such as depression. The reward might render this effect through the enhancement of stress resilience. However, the effect of reward on stress resilience under different intensities of stress needs more evidence, and its potential neural mechanism has been poorly revealed. It has been reported that the endogenous cannabinoid system (ECs) and downstream metabolic glutamate receptor 5 (mGluR5) are closely related to stress and reward, which might be the potential cerebral mechanism between reward and stress resilience, but there is a lack of direct evidence. This study aims to observe the effect of reward on stress resilience under different intensities of stress and further explore potential cerebral mechanisms underlying this effect. Methods: Using the chronic social defeat stress model, we applied reward (accompanied by a female mouse) under different intensities of stress in mice during the modeling process. The impact of reward on stress resilience and the potential cerebral mechanism were observed after modeling through behavioral tests and biomolecules. Results: The results showed that stronger stress led to higher degrees of depression-like behavior. Reward reduced depression-like behavior and enhanced stress resilience (all p-value <0.05) (more social interaction in the social test, less immobility time in the forced swimming test, etc.), with a stronger effect under the large stress. Furthermore, the mRNA expression levels of CB1 and mGluR5, the protein expression level of mGluR5, and the expression level of 2-AG (2-arachidonoylglycerol) in both ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) were significantly upregulated by reward after modeling (all p-value <0.05). However, the protein expression of CB1 in VTA and DRN and the expression of AEA (anandamide) in VTA did not differ significantly between groups. Intraperitoneal injection of a CB1 agonist (URB-597) during social defeat stress significantly reduced depression-like behavior compared with a CB1 inhibitor (AM251) (all p-value <0.05). Interestingly, in DRN, the expression of AEA in the stress group was lower than that of the control group, with or without reward (all p-value <0.05). Discussion: These findings demonstrate that combined social and sexual reward has a positive effect on stress resilience during chronic social defeat stress, potentially by influencing the ECs and mGluR5 in VTA and DRN.

Patient healthcare experiences of cancer hospitals in China: A multilevel modeling analysis based on a national survey.

Importance: Patient satisfaction is a crucial indicator for assessing quality of care in healthcare settings. However, patient satisfaction benchmark for cancer hospitals in China is not established. Objective: To examine patient satisfaction levels in tertiary cancer hospitals in China, and inter-hospital variations after case-mix adjustment. Design: A nationwide cross-sectional hospital performance survey conducted from January to March 2021. Settings: At 30 tertiary cancer hospitals in China. Participants: A total of 4,847 adult inpatients consecutively recruited at 30 tertiary cancer hospitals were included. Exposures: Patient characteristics included demographic characteristics (sex, age, education, and annual family income), clinical characteristics (cancer type, cancer stage, self-reported health status, and length of stay), and actual respondents of questionnaire. Main outcomes and measures: Patient satisfaction was measured using 23 items covering five aspects, administrative process, hospital environment, medical care, symptom management, and overall satisfaction. Responses to each item were recorded using a 5-point Likert scale. Patient satisfaction level for each aspect was described at individual and hospital levels. Using multilevel logistic regression, patient characteristics associated with patient satisfaction were examined as case-mix adjusters and inter-hospital variation were determined. Results: The satisfaction rates for symptom management, administrative process, hospital environment, overall satisfaction, and medical care aspects were 74.56, 81.70, 84.18, 84.26, and 90.86% with a cut-off value of 4, respectively. Significant predictors of patient satisfaction included sex, age, cancer type, cancer stage, self-reported health status, and actual respondent (representative or patient) (all P < 0.05). The ranking of the hospitals' performance in satisfaction was altered after the case-mix adjustment was made. But even after the adjustment, significant variation in satisfaction among hospitals remained. Conclusions and relevance: This study pointed to symptom management as a special area, to which a keen attention should be paid by policymakers and hospital administrators. Significant variation in satisfaction among hospitals remained, implying that future studies should examine major factors affecting the variation. In review, target interventions are needed in low-performing hospitals.