Objective:To investigate the effects of dual vascularized tissue-engineered bone constructed by vascular bundles and endothelial progenitor cells (EPCs) on repair of large bone defects and vascular regeneration.Methods:EPCs were seeded on the demineralized bone matrix (DBM) scaffolds and cultured for 6 days. The attachment and morphology of EPCs on DBM scaffolds were observed by electron microscopy. Next, the radial artery was implanted into a vascular groove opened inside the DBM-EPCs composite scaffolds. Finally, models of a large segmental bone defect were constructed using the radii from 18 New Zealand white rabbits. The rabbits were randomly divided into 4 groups using a simple random sampling method: DBM group, DBM+EPCs group, DBM+vascular bundle group, and DBM+EPCs+vascular bundle group. The DBM group and DBM+EPCs group shared the same rabbits so that transplantations were conducted into the left and right forearms respectively; the DBM+vascular bundle group and DBM+EPCs+vascular bundle group also shared the same rabbits so that transplantations were conducted into the left and right forearms respectively. Consequently, there were 9 experimental sites in each group. X-ray examination and gross morphological observation were performed to evaluate the bone regeneration in the experimental rabbits in each group at 4, 8, and 12 weeks after surgery, and CD31 immunofluorescence staining was used to evaluate the vascular regeneration. Micro-CT was used to analyze bone tissue parameters and reconstruct the three-dimensional structures of the defects site at 12 weeks after surgery.Results:Compared with the DBM, DBM+EPCs and DBM+vascular bundle groups, the DBM+EPCs+vascular bundle group showed new bone tissue crawling on the scaffold surface at 4 weeks after surgery, almost complete healing of the bone defect area at 8 weeks, and forming of a complete and dense bone bridge and appearance of a bone marrow cavity at 12 weeks. Micro-CT data at 12 weeks after surgery showed regular arrangement of the trabeculae, significantly improved mineralization, and increased thickness of the bone cortex in the DBM+EPCs+vascular bundle group. Additionally, in the DBM+EPCs+vascular bundle group, the number of microvessels was significantly higher than that in the other groups at 4, 8, 12 weeks after surgery ( P<0.05), and the angiogenesis and bone tissue regeneration were particularly prominent at 12 weeks after surgery. The number of CD31 cells in the DBM+EPCs+vascular bundle group increased significantly more than that in the DBM, DBM+EPCs and DBM+vascular bundle groups ( P<0.05). Conclusion:As the dual vascularized tissue-engineered bone constructed by vascular bundles and EPCs can significantly promote bone tissue regeneration and angiogenesis, it may be a potential therapeutic strategy for repair of large bone defects.

Objective:To investigate the feasibility and clinical value of artificial intelligence-assisted compressed sensing (ACS) technology in accelerating MR simulation (MR-sim) for radiotherapy of nasopharyngeal carcinoma (NPC).Methods:Thirty patients with NPC scheduled to receive radical radiotherapy at Sun Yat-sen University Cancer Center were prospectively enrolled. All patients underwent head and neck MR-sim on a 3.0 T scanner, with axial T 1 weighted imaging (WI), T 2WI, contrast-enhanced T 1WI, and fat-suppressed contrast-enhanced T 1WI images acquired using both ACS and parallel imaging (PI) techniques. Paired-sample t tests or rank-sum tests were used to compare scan time, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of MR-sim images between the two techniques. A 5-point Likert scale was applied to evaluate tumor lesion visualization, lesion margin clarity, artifacts, and overall image quality, with chi-square tests used to compare subjective image quality scores between the two techniques. Tumor target volumes were delineated on MR-sim images obtained by both ACS and PI techniques after fusion with CT simulation images, and consistency was assessed using the Dice similarity coefficient (DSC). Results:For both individual sequences and overall protocols, ACS significantly reduced MR-sim acquisition time compared with PI ( P < 0.001). The total acquisition time with ACS was (378.60±17.07) s versus (694.93±17.07) s with PI, representing a 45.52% time reduction. SNR, CNR, tumor lesion identification, margin clarity, artifacts, and overall image quality scores of MR-sim images did not differ significantly between ACS and PI ( P > 0.05). Tumor target volumes delineated from ACS- and PI-based MR-sim images showed high consistency after fusion with CT simulation images ( P > 0.05), with mean DSC values of primary tumors and metastatic cervical lymph nodes approaching 1. Conclusion:Compared with conventional MR acceleration methods (PI), ACS enables faster MR-sim acquisition in NPC without compromising image quality or the accuracy of tumor target delineation.

Objective:To investigate the effects of dual vascularized tissue-engineered bone constructed by vascular bundles and endothelial progenitor cells (EPCs) on repair of large bone defects and vascular regeneration.Methods:EPCs were seeded on the demineralized bone matrix (DBM) scaffolds and cultured for 6 days. The attachment and morphology of EPCs on DBM scaffolds were observed by electron microscopy. Next, the radial artery was implanted into a vascular groove opened inside the DBM-EPCs composite scaffolds. Finally, models of a large segmental bone defect were constructed using the radii from 18 New Zealand white rabbits. The rabbits were randomly divided into 4 groups using a simple random sampling method: DBM group, DBM+EPCs group, DBM+vascular bundle group, and DBM+EPCs+vascular bundle group. The DBM group and DBM+EPCs group shared the same rabbits so that transplantations were conducted into the left and right forearms respectively; the DBM+vascular bundle group and DBM+EPCs+vascular bundle group also shared the same rabbits so that transplantations were conducted into the left and right forearms respectively. Consequently, there were 9 experimental sites in each group. X-ray examination and gross morphological observation were performed to evaluate the bone regeneration in the experimental rabbits in each group at 4, 8, and 12 weeks after surgery, and CD31 immunofluorescence staining was used to evaluate the vascular regeneration. Micro-CT was used to analyze bone tissue parameters and reconstruct the three-dimensional structures of the defects site at 12 weeks after surgery.Results:Compared with the DBM, DBM+EPCs and DBM+vascular bundle groups, the DBM+EPCs+vascular bundle group showed new bone tissue crawling on the scaffold surface at 4 weeks after surgery, almost complete healing of the bone defect area at 8 weeks, and forming of a complete and dense bone bridge and appearance of a bone marrow cavity at 12 weeks. Micro-CT data at 12 weeks after surgery showed regular arrangement of the trabeculae, significantly improved mineralization, and increased thickness of the bone cortex in the DBM+EPCs+vascular bundle group. Additionally, in the DBM+EPCs+vascular bundle group, the number of microvessels was significantly higher than that in the other groups at 4, 8, 12 weeks after surgery ( P<0.05), and the angiogenesis and bone tissue regeneration were particularly prominent at 12 weeks after surgery. The number of CD31 cells in the DBM+EPCs+vascular bundle group increased significantly more than that in the DBM, DBM+EPCs and DBM+vascular bundle groups ( P<0.05). Conclusion:As the dual vascularized tissue-engineered bone constructed by vascular bundles and EPCs can significantly promote bone tissue regeneration and angiogenesis, it may be a potential therapeutic strategy for repair of large bone defects.

Objective:To investigate the feasibility and clinical value of artificial intelligence-assisted compressed sensing (ACS) technology in accelerating MR simulation (MR-sim) for radiotherapy of nasopharyngeal carcinoma (NPC).Methods:Thirty patients with NPC scheduled to receive radical radiotherapy at Sun Yat-sen University Cancer Center were prospectively enrolled. All patients underwent head and neck MR-sim on a 3.0 T scanner, with axial T 1 weighted imaging (WI), T 2WI, contrast-enhanced T 1WI, and fat-suppressed contrast-enhanced T 1WI images acquired using both ACS and parallel imaging (PI) techniques. Paired-sample t tests or rank-sum tests were used to compare scan time, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of MR-sim images between the two techniques. A 5-point Likert scale was applied to evaluate tumor lesion visualization, lesion margin clarity, artifacts, and overall image quality, with chi-square tests used to compare subjective image quality scores between the two techniques. Tumor target volumes were delineated on MR-sim images obtained by both ACS and PI techniques after fusion with CT simulation images, and consistency was assessed using the Dice similarity coefficient (DSC). Results:For both individual sequences and overall protocols, ACS significantly reduced MR-sim acquisition time compared with PI ( P < 0.001). The total acquisition time with ACS was (378.60±17.07) s versus (694.93±17.07) s with PI, representing a 45.52% time reduction. SNR, CNR, tumor lesion identification, margin clarity, artifacts, and overall image quality scores of MR-sim images did not differ significantly between ACS and PI ( P > 0.05). Tumor target volumes delineated from ACS- and PI-based MR-sim images showed high consistency after fusion with CT simulation images ( P > 0.05), with mean DSC values of primary tumors and metastatic cervical lymph nodes approaching 1. Conclusion:Compared with conventional MR acceleration methods (PI), ACS enables faster MR-sim acquisition in NPC without compromising image quality or the accuracy of tumor target delineation.

Background Bacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. Objective To understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. Methods Three subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO₂), fine particulate matter (PM_2.5), and inhalable particulate matter (PM₁₀) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min⁻¹, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO₂ concentration and total bacterial count. Results The pass rates were 100.0% for airborne total bacteria count, PM_2.5, and PM₁₀ in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO₂, but 0% for humidity. The overall median (P₂₅, P₇₅) total bacteria count was 177 (138,262) CFU·m⁻³. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P<0.05). A total of 874 strains and 82 species were identified by automatic microbial mass spectrometry. The results of identification were all over 9 points, and the predominant bacteria in the air were Micrococcus luteus (52.2%) and Staphylococcus hominis (9.8%). Three pathogens, Acinetobacter baumannii (0.3%), Corynebacterium striatum (0.1%), and Staphylococcus epidermidis bacilli (2.2%) were detected in 23 samples (2.6%), and the associated locations were mainly distributed in train compartments during evening rush hours. Conclusion The total bacteria count in indoor air varies by monitoring sites of subway stations and time periods, and there is a risk of opportunistic bacterial infection. Attention should be paid to cleaning and disinfection during peak passenger flow hours in all areas.

Objective:To standardize the management of auditory hallucination symptoms in inpatients with mental illness and develop an expert consensus on the management of auditory hallucinations in hospitalized psychiatric patients.Methods:From March 2023 to July 2023, the Mental Health Committee of the Chinese Nursing Association focused on the key issues in the management of auditory hallucinations symptoms in inpatients with mental illness, based on clinical practice, using literature analysis combined with the work experience of mental health experts, and formed the first draft of the expert consensus on the management of auditory hallucinations in inpatients with mental illness (hereinafter referred to as the consensus). Through 3 rounds of expert consultation and 3 rounds of expert demonstration meeting, the draft was adjusted, revised, and improved.Results:37 experts were included in the Delphi expert consultation, 1 male and 36 females with 39-67(51.48 ± 6.61) years old. The positive coefficients of experts in 3 rounds of Delphi expert consultations were all 100%, and the degrees of expert authority were 0.924, 0.938 and 0.949, respectively. The average importance value of each item was higher than 4.00, the variation coefficient of each item was less than 0.25. The Kendall harmony coefficient of the experts were 0.179, 0.195 and 0.198, respectively (all P<0.05). There were 15, 12, 12 experts in the first, seeond, third rounds of expert demonstration meeting. Finally, a consensus was reached on the recommendation of 4 parts, included auditory hallucination assessment, management format, symptom management implementation, and precautions. Conclusions:The consensus covers all parts of the management of auditory hallucination symptoms in hospitalized patients with mental disorders, which is practical and scientific. It is helpful to guide mental health professionals to standardize the management of auditory hallucination symptoms, improve the quality of nursing and ensure the safety of patients.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective:To explore the effect of clinical conventional fractionated dose radiation on the expression levels of immunogenic cell death (ICD) related proteins in patients with nasopharyngeal carcinoma (NPC).Methods:A total of 38 newly-treated NPC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from November 2020 to December 2021 were enrolled, all of whom received induction chemotherapy and concurrent chemoradiotherapy, and another 20 healthy volunteers were selected as controls for a prospective study. The contents of ICD related proteins, namely calreticulin (CRT), high mobility group box 1 protein (HMGB-1) and heat shock protein 70 (HSP70) and the proportion of dendritic cell (DC) in the peripheral blood of patients were detected before treatment, after induction chemotherapy and after concurrent chemoradiotherapy, respectively. The correlation between the above indicators, general clinical data and short-term efficacy was analyzed by statistical methods such as t-test and analysis of variance (ANOVA). Results:The levels of HSP70 and HMGB-1 in peripheral blood of NPC patients before treatment were higher than those of healthy controls (both P<0.05). After concurrent chemoradiotherapy, the content of CRT was significantly higher than that before treatment ( P<0.05), whereas the difference before and after induction chemotherapy and the difference before and after concurrent chemoradiotherapy were not significantly correlated with the short-term efficacy of NPC patients. HSP70 level was significantly decreased after concurrent chemoradiotherapy ( P<0.001). There were no significant differences in the content of HMGB-1 after induction chemotherapy and concurrent chemoradiotherapy (both P>0.05). Conclusion:NPC patients receiving TPF regimen (docetaxel+cisplatin+fluorouracil) for induction chemotherapy and sequential cisplatin concurrent chemotherapy may induce ICD in NPC cells, and CRT has potential value in reflecting the clinical efficacy of NPC.