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Jin-Jin Yang,1,2 Lei Lei,1,2 Di Qiu,1 Sai Chen,1 Li-Ka Xing,1 Jing-Wei Zhao,1 Yuan-Yuan Mao,1,2 Jian-Jun Yang1,2 1Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, People’s Republic of ChinaCorrespondence: Jian-Jun Yang, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, People’s Republic of China, Tel +8613783537619, Email yjyangjj@126.comBackground: Postoperative delirium is common in older adult patients and associated with a poor prognosis. The use of benzodiazepine was identified as an independent risk factor for delirium, but there is no randomized controlled trial regarding the relationship between remimazolam, a new ultra-short acting benzodiazepine, and postoperative delirium. We designed a randomized controlled trial to evaluate if remimazolam increases the incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery with general anesthesia.Patients and Methods: We enrolled 320 patients aged more than 60 with American Society of Anesthesiologists physical status I–III who underwent orthopedic surgery. Patients were randomized to two groups to receive intraoperative remimazolam or propofol, respectively. Our primary outcome was the incidence of delirium within 3 days after surgery. Secondary outcome was emergence quality including the incidence of emergence agitation, extubation time, and length of post-anesthesia care unit (PACU) stay. Adverse events were also recorded.Results: The incidence of postoperative delirium was 15.6% in the remimazolam group and 12.4% in the propofol group (Risk ratio, 1.26; 95% CI, 0.72 to 2.21; Risk difference, 3.2%; 95% CI, − 4.7% to 11.2%; P = 0.42). No significant differences were observed for time of delirium onset, duration of delirium, and delirium subtype between the two groups. Patients in remimazolam group had a lower incidence of hypotension after induction and consumed less vasoactive drugs intraoperatively, but had a longer postoperative extubation time and PACU stay.Conclusion: General anesthesia with remimazolam was not associated with an increased incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery.Keywords: benzodiazepines, delirium, older adults, orthopedic surgery, propofol, remimazolam

Weiya Li,1,&ast; Di Qiu,2,&ast; Han Yin,1 Yu Wang,1 Yilin Chen,3 Quanjun Liu,3 Huan Ma,1 Qingshan Geng1,3 1Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingshan Geng, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Tel +86 20 83827812, Email gengqingshan@gdph.org.cnPurpose: Patients with the comorbidity of coronary artery disease (CAD) and depression are very common and always have poor prognosis. The relationship between thyroid-stimulating hormone (TSH) levels and major cardiovascular event (MACE) in these patients is still unknown. We aimed to explore this association.Patients and Methods: We enrolled 203 CAD patients proven by coronary angiography (CAG). In the meanwhile, they were all assessed to have depression symptom by professional psycho-cardiologists. After an average follow-up of 23.7 months, patients were divided into two groups (high TSH group with TSH ≥ 1.395μIU/mL and low TSH group with TSH < 1.395μIU/mL) according to the cut-off value of baseline TSH. The impact of two different TSH groups for adverse events in CAD patients with depression was evaluated.Results: The average age of these patients was 64.9 years old. The two TSH groups had no significant difference in the comparison of other baseline data. Area under the receiver operating characteristic (ROC) curves (AUC) analysis indicated the well-discriminatory power of TSH levels for the occurrence of MACE (AUC = 0.61, 95% CI: 0.52– 0.70, P = 0.03). In the KM survival analysis, high TSH group had a higher risk of MACE (P = 0.029). After multi-factor adjustment, there still existed a higher risk of MACE in high TSH group (HR = 2.05, 95% CI: 1.08– 3.88, P = 0.028).Conclusion: In patients with the comorbidity of CAD and depression, higher TSH levels are associated with the occurrence of MACE. More researches need to be conducted to prove this association and explore whether the drug-related TSH reduction can decrease the occurrence of adverse events in the future.Keywords: thyroid-stimulating hormone, TSH, coronary artery disease, CAD, depression, MACE

Dandan Qiu,1 Yan Zhu,1 Zhicheng Cong2 1Department of Urology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Urology, Zhejiang Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Zhicheng CongDepartment of Urology, Zhejiang Hospital, Hangzhou 310013 Zhejiang Province, People’s Republic of ChinaEmail cz111aybzz8@126.comBackground: The transcriptional regulator YAP is frequently overexpressed in human cancers, such as breast and pancreatic cancers, plays an important role in tumorigenesis and can regulate many factors affecting cancer progression. These observations encouraged us to investigate the effect of YAP expression on bladder cancer.Methods: The changes in multiple cellular functions associated with tumor progression including cell proliferation, cell migration, cell cycle, and cell apoptosis were assessed after YAP knockdown/overexpression in bladder cancer cell lines. Additionally, Western blot was developed to verify the change of proteins caused by YAP knockdown/overexpression.Results: YAP had relatively higher expression in bladder cancer tissues than in normal tissues. The proliferation and migration of bladder cancer cells were inhibited by YAP knockdown but were promoted by its overexpression. This promoting effect was accompanied by the increased activity of MAPK/ERK pathway.Conclusion: Our data established that YAP is an oncogene involved in bladder cancer and thus can be a potential target for treatment.Keywords: bladder cancer, proliferation, migration, MAPK/ERK pathway

Yongjian Yang, Dahai Qiu, Yajun Liu, Lei Chao Department of Anesthesiology, Jinan Central Hospital Affiliated to Shandong University, Ji’nan, Shandong Province 250013, People’s Republic of ChinaCorrespondence: Lei ChaoDepartment of Anesthesiology, Jinan Central Hospital Affiliated to Shandong University, No. 105 Jiefang Road, Ji’nan, Shandong Province 250013, People’s Republic of ChinaTel +86 05 318 569 5114Email leichaojncp@outlook.comPurpose: Hyaluronic acid-poly(ethylene glycol)-distearoyl phosphoethanolamine (HA-PEG-DSPE) modified and tocopheryl polyethylene glycol 1000 succinate (TPGS) contained nanostructured lipid carriers (NLCs) were prepared loading ropivacaine and dexmedetomidine to improve the topical anesthetic analgesic anesthesia efficiency.Methods: NLCs were prepared by the solvent diffusion method. The average particle size, zeta potential, release behavior, and cytotoxicity of the NLCs were tested. Ex vivo skin permeation was studied using a Franz diffusion cell mounted with depilated rat skin. Local anesthesia antinociceptive efficiency was evaluated by rat tail flick latency study in vivo.Results: NLCs have sizes of about 100 nm, with negative zeta potentials. All the NLCs formulations were found to be significantly less cytotoxic than free drugs at equivalent concentrations. The cumulative amount of drugs penetrated through rat skin from NLCs was 2.0–4.7 folds higher than that of the drugs solution. The in vivo anesthesia antinociception study displayed that NLCs showed stronger and longer anesthesia antinociceptive effect when compared with single drugs loaded NLCs and drugs solution even at a lower dosage of drugs.Conclusion: The results demonstrated that the HA modified, TPGS contained, dual drugs loaded NLCs could perform a synergistic effect and may reduce the amount of drugs, which can lower the toxicity of the system and at the meanwhile, increase the anesthesia antinociceptive efficiency.Keywords: topical anesthetic analgesic, skin penetration, hyaluronic acid, long-acting nanostructured lipid carriers, tocopheryl polyethylene glycol 1000 succinate

Fu Jin,1 Huan-Li Luo,1 Juan Zhou,2 Ya-Nan He,1 Xian-Feng Liu,1 Ming-Song Zhong,1 Han Yang,1 Chao Li,1 Qi-Cheng Li,1 Xia Huang,1 Xiu-Mei Tian,1 Da Qiu,1 Guang-Lei He,1 Li Yin,1 Ying Wang1 1Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing, People’s Republic of China; 2Forensic Identification Center, College of Criminal Investigation, Southwest University of Political Science and Law, Chongqing, People’s Republic of China Abstract: Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose–response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI. Keywords: cancer risk, radiotherapy, workflow, big data

Context. Heat stress is an increasing concern for the Australian dairy industry. Aims. This study aimed to evaluate the effect of temperature-humidity index (THI) on rumination time (RT), milk yield and quality, and milking frequency in a pasture-based voluntary-movement automatic milking system (AMS). Methods. Data were collected from the University of Melbourne Dookie College AMS farm for 3 years (June 2016 to March 2019). Daily RT was collected through the transponder collar (Qwes-HR, Lely). Climatic data (maximumambient temperature and relative humidity) were obtained fromthe Dookie Meteorological station to calculate daily maximumTHI (THImax). Key results. Daily milk yield increased with a rising THImax to 65, then declined after THImax 65. Milking frequency was highest at THImax 90, followed by a steady decline afterwards. Rumination time was maximum at mid-range THImax and declined for high and low values. Conclusions. The findings of this study clearly indicated that under pasture-based voluntary-movement AMS, high THI resulted in a drop in the milk yield, milking frequency and RT. Implications. With the provision of automation of data collection from AMS, further study with mathematical modelling describing the daily patterns and thresholds in conjunction with the different heat stress levels can be useful for assessing animal welfare and to mitigate heat stress and seek alternative management strategies. [ABSTRACT FROM AUTHOR]

A retroreflector array, composed of a cluster of small retroreflectors, is experimentally studied for application to a Michelson-type interferometer system in the fusion plasma experiment. Such a new-type reflector has the potential to be a vital and effective tool at a spatially limited location, such as on the vacuum chamber wall of plasma experimental devices. To investigate the effect of retroreflector array on the reflected beam properties, a tabletop experiment is performed with the retroreflector array composed of 4 mm corner-cube retroreflectors and with a 320-GHz (λ ∼ 0.937 mm) submillimeter wave source. An imaging camera is utilized to measure the submillimeter wave beam profile and is scanned perpendicularly to the beam propagation direction if necessary. The experimental result exhibits a diffraction effect on the reflected beam, resulting in the emergence of discrete peaks on the reflected beam profile, as predicted in the past numerical study; however, the most reflected beam power converges on the one reflected into the incident direction, resulting from a property as a retroreflector. Furthermore, the dependence of the reflected beam on the incident beam angle is characterized while fixing the detector position, and the retroreflection beam intensity is found to vary due to the diffraction effect. Such an undesired variation of beam intensity induced by the diffraction can be suppressed with a focusing lens placed in front of the detector in the practical application to an interferometer. [ABSTRACT FROM AUTHOR]

Abstract The diagnosis of early prostate cancer depends on the accurate segmentation of prostate regions in magnetic resonance imaging (MRI). However, this segmentation task is challenging due to the particularities of prostate MR images themselves and the limitations of existing methods. To address these issues, we propose a U-shaped encoder-decoder network MM-UNet based on Mamba and CNN for prostate segmentation in MR images. Specifically, we first proposed an adaptive feature fusion module based on channel attention guidance to achieve effective fusion between adjacent hierarchical features and suppress the interference of background noise. Secondly, we propose a global context-aware module based on Mamba, which has strong long-range modeling capabilities and linear complexity, to capture global context information in images. Finally, we propose a multi-scale anisotropic convolution module based on the principle of parallel multi-scale anisotropic convolution blocks and 3D convolution decomposition. Experimental results on two public prostate MR image segmentation datasets demonstrate that the proposed method outperforms competing models in terms of prostate segmentation performance and achieves state-of-the-art performance. In future work, we intend to enhance the model's robustness and extend its applicability to additional medical image segmentation tasks.

A new 320 GHz solid-state source interferometer is installed in the Heliotron J helical device to explore the physics of high-density plasmas (ne > 2–3 × 1019 m−3, typically) realized with advanced fueling techniques. This interferometry system is of the Michelson type and is based on the heterodyne principle, with two independent solid-state sources that can deliver an output power of up to 50 mW. A high time resolution measurement of <1 µs can be derived by tuning the frequency of one source in the frequency range of 312–324 GHz on the new system, which can realize the fluctuation measurement. We successfully measured the line-averaged electron density in high-density plasma experiments. The measured density agreed well with a microwave interferometer measurement using a different viewing chord, demonstrating that the new system can be used for routine diagnostics of electron density in Heliotron J. [ABSTRACT FROM AUTHOR]

The aim of the study was to explore the relationship between species diversity of understory ferns and plant biomass in high-nitrogen habitats in China. Four species Cyrtogonellum fraxinellum, Pteris nipponica, Humata griffithiana and Pteris fauriei were chosen to set up three species richness (1, 2 and 4 species) and a total of 11 species combinations at two nitrogen habitats (control and 10 g N m2 yr-1 ). Plant biomass and soil physical and chemical properties were determined. The study had the following results: (1) Species richness had no significant effect on plant biomass under both nitrogen habitats. (2) Under both nitrogen habitats, species combination had a significant effect on plant biomass. (3) The presence of P. nipponica and P. fauriei significantly increased the plant biomass, and the presence of C. fraxinellum significantly reduced the plant biomass under two nitrogen habitats. (4) Nitrogen addition significantly increased soil nitrogen content, but plant species diversity had no significant effect on soil physical and chemical properties. (5) There was a significantly negative correlation between plant biomass (aboveground, underground, and total) and soil phosphorus content; there was also a significantly negative correlation between plant underground biomass and soil pH. Assembling specific species combinations can improve plant biomass and promote ecological restoration under high nitrogen habitat. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that growth factors are crucial in regenerative endodontic therapy. To achieve the desired effects, the systematic administration of supraphysiologic concentrations of exogenous growth factors is commonly performed, but this is usually associated with high costs, technique, and safety issues. Here, we describe a novel biomaterial that can manipulate endogenous growth factors without the need for adding exogenous growth factors. Transforming growth factor β1 binding peptide (TGFp) was grafted onto the surface of a neutral pH phytic acid–derived bioactive glass (PSC) to synthesize modified bioactive glass (PSC-TGFp). Fourier transform infrared spectroscopy and thermogravimetric analysis results demonstrated that the TGFp was successfully grafted to the surface of the PSC. Scanning electron microscopy and x-ray diffraction showed that PSC-TGFp possessed good in vitro bioactivity. After soaking in simulated body fluid for 24 h, hydroxyapatite formed on the surface of PSC-TGFp. Enzyme-linked immunosorbent assay showed that PSC-TGFp could capture endogenous transforming growth factor β1 from dentin matrix–extracted proteins (DMEP) and release it slowly over 21 d. Cytologic experiments revealed that PSC-TGFp after adsorbing DMEP could enhance the adhesion, migration, viability, and odontogenic differentiation of stem cells from apical papilla. The results highlight that PSC-TGFp may be a promising biomaterial to manipulate endogenous growth factors for regenerative endodontic therapy in the future. [ABSTRACT FROM AUTHOR]

BackgroundChatGPT is a natural language processing model developed by OpenAI, which can be iteratively updated and optimized to accommodate the changing and complex requirements of human verbal communication. ObjectiveThe study aimed to evaluate ChatGPT’s accuracy in answering orthopedics-related multiple-choice questions (MCQs) and assess its short-term effects as a learning aid through a randomized controlled trial. In addition, long-term effects on student performance in other subjects were measured using final examination results. MethodsWe first evaluated ChatGPT’s accuracy in answering MCQs pertaining to orthopedics across various question formats. Then, 129 undergraduate medical students participated in a randomized controlled study in which the ChatGPT group used ChatGPT as a learning tool, while the control group was prohibited from using artificial intelligence software to support learning. Following a 2-week intervention, the 2 groups’ understanding of orthopedics was assessed by an orthopedics test, and variations in the 2 groups’ performance in other disciplines were noted through a follow-up at the end of the semester. ResultsChatGPT-4.0 answered 1051 orthopedics-related MCQs with a 70.60% (742/1051) accuracy rate, including 71.8% (237/330) accuracy for A1 MCQs, 73.7% (330/448) accuracy for A2 MCQs, 70.2% (92/131) accuracy for A3/4 MCQs, and 58.5% (83/142) accuracy for case analysis MCQs. As of April 7, 2023, a total of 129 individuals participated in the experiment. However, 19 individuals withdrew from the experiment at various phases; thus, as of July 1, 2023, a total of 110 individuals accomplished the trial and completed all follow-up work. After we intervened in the learning style of the students in the short term, the ChatGPT group answered more questions correctly than the control group (ChatGPT group: mean 141.20, SD 26.68; control group: mean 130.80, SD 25.56; P=.04) in the orthopedics test, particularly on A1 (ChatGPT group: mean 46.57, SD 8.52; control group: mean 42.18, SD 9.43; P=.01), A2 (ChatGPT group: mean 60.59, SD 10.58; control group: mean 56.66, SD 9.91; P=.047), and A3/4 MCQs (ChatGPT group: mean 19.57, SD 5.48; control group: mean 16.46, SD 4.58; P=.002). At the end of the semester, we found that the ChatGPT group performed better on final examinations in surgery (ChatGPT group: mean 76.54, SD 9.79; control group: mean 72.54, SD 8.11; P=.02) and obstetrics and gynecology (ChatGPT group: mean 75.98, SD 8.94; control group: mean 72.54, SD 8.66; P=.04) than the control group. ConclusionsChatGPT answers orthopedics-related MCQs accurately, and students using it excel in both short-term and long-term assessments. Our findings strongly support ChatGPT’s integration into medical education, enhancing contemporary instructional methods. Trial RegistrationChinese Clinical Trial Registry Chictr2300071774; https://www.chictr.org.cn/hvshowproject.html ?id=225740&v=1.0

BackgroundOsteoporosis (OP) associated with aging exerts substantial clinical and fiscal strains on societal structures. An increasing number of research studies have suggested a bidirectional relationship between circulating inflammatory markers (CIMs) and OP. However, observational studies are susceptible to perturbations in confounding variables. In contrast, Mendelian randomization (MR) offers a robust methodological framework to circumvent such confounders, facilitating a more accurate assessment of causality. Our study aimed to evaluate the causal relationships between CIMs and OP, identifying new approaches and strategies for the prevention, diagnosis and treatment of OP.MethodsWe analyzed publicly available GWAS summary statistics to investigate the causal relationships between CIMs and OP. Causal estimates were calculated via a systematic analytical framework, including bidirectional MR analysis and Bayesian colocalization analysis.ResultsGenetically determined levels of CXCL11 (OR = 0.91, 95% CI = 0.85–0.98, P = 0.008, PFDR = 0.119), IL-18 (OR = 0.88, 95% CI = 0.83–0.94, P = 8.66×10–5, PFDR = 0.008), and LIF (OR = 0.86, 95% CI = 0.76–0.96, P = 0.008, PFDR = 0.119) were linked to a reduced risk of OP. Conversely, higher levels of ARTN (OR = 1.11, 95% CI = 1.02–1.20, P = 0.012, PFDR = 0.119) and IFNG (OR = 1.16, 95% CI = 1.03–1.30, P = 0.013, PFDR = 0.119) were associated with an increased risk of OP. Bayesian colocalization analysis revealed no evidence of shared causal variants.ConclusionDespite finding no overall association between CIMs and OP, five CIMs demonstrated a potentially significant association with OP. These findings could pave the way for future mechanistic studies aimed at discovering new treatments for this disease. Additionally, we are the first to suggest a unidirectional causal relationship between ARTN and OP. This novel insight introduces new avenues for research into diagnostic and therapeutic strategies for OP.