ObjectiveTo investigate a suspected outbreak of healthcare-associated infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) in a geriatric emergency ward, and to provide references for the prevention and control of multidrug-resistant bacteria in a hospital in Shanghai. MethodsOn-site epidemiological investigation, combined with environmental hygiene monitoring and pulsed field gel electrophoresis (PFGE) molecular typing method, were adopted to investigate a suspected outbreak of CRKP infection in the geriatric emergency ward of a hospital from October to November 2022, aiming at finding out factors caused the outbreak before taking corresponding control measures. ResultsA total of 3 cases of healthcare-associated CRKP infection were identified, of which 2 cases were homologous to a previous case of community-associated CRKP infection. What’s more, the 2 cases lived in the same ward with the latter and with adjacent beds, but the third case was non-homologous to the community-associated infection case. A total of 46 samples were collected from the environmental surfaces and the hands of healthcare workers, of which 7 samples tested positive for CRKP and were identical to the strains from the 2 healthcare-associated infection cases and the 1 community-associated infection case, originating from the bedrails, bedside tables, surface of non-invasive ventilator, bed curtains and panels of monitoring equipment, with a detection rate of 15.22%. But none of the 11 samples from the hands of healthcare workers tested positive for CRKP. The outbreak was effectively controlled after taking specific prevention and control measures such as strengthening personnel management, intensifying environmental cleaning and disinfection and strictly enforcing hand hygiene among healthcare workers. Subsequently, no similar new cases were reported during the 14-day follow-up period. ConclusionIncomplete environmental cleaning and disinfection, as well as inadequate enforcement of hand hygiene among heatheare workers may have contributed to the suspected outbreak of CRKP in the geriatric emergency ward. Early warning and timely investigation of suspected outbreaks of multidrug-resistant bacteria are crucial for preventing and controlling such outbreaks in hospitals.

OBJECTIVE To provide a reference for standardizing the conduct of positron-emitting radiopharmaceuticals’ phase 0 clinical trials （hereinafter referred to as “phase 0 clinical trials”） and advancing the development of innovative drug by medical institutions. METHODS Initiated by the First Affiliated Hospital of Jinan University， a panel of experts consisting of pharmacy， clinical medicine and medical ethics from multiple institutions was established to investigate the current landscape， and discuss the necessary conditions， procedures， and other aspects for conducting phase 0 clinical trials in medical institutions by integrating relevant national policies， regulations and expert consensus. Finally， an agreement was reached to formulate this consensus. RESULTS & CONCLUSIONS Currently， most medical institutions have deficiencies in pharmaceutical care during the management of radiopharmaceuticals and the phase 0 clinical trials. In conjunction with the Expert Consensus on the Establishment of Nuclear Pharmacist Positions， this consensus explicitly defines the responsibilities of nuclear pharmacists in the phase 0 clinical trials on the basis of the Expert Consensus for the Application of Positron Emission Tomography Radioligands for Translational Study in the Phase 0 Clinical Trials （2020 edition）， providing a guidance for high-quality participation of nuclear pharmacists from medical institutions in China in phase 0 clinical research. Additionally， in consideration of some constraints imposed by current relevant regulations， this consensus also proposes strategic recommendations， such as encouraging medical institutions to form a consortium， leading to the establishment of dedicated bases or industrial parks， holding significant implications to strengthen institutional capacity for advancing radiopharmaceutical innovation through phase 0 clinical trials.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Objective:To explore influencing factors affecting the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy based on hematologic indexes, thus to construct and evaluate a nomogram prediction model.Methods:The clinical data of 80 patients with advanced NSCLC treated with programmed death-1 inhibitor monotherapy or combination regimen from January 2018 to June 2020 at the Affiliated Hospital of North China University of Science and Technology and Tangshan People's Hospital were retrospectively analyzed. Hematologic indexes at the baseline, the optimal remission and the progressive disease (PD) were collected separately, and independent influencing factors for patient prognosis were analyzed using Cox proportional hazards regression model. A nomogram prediction model was constructed based on the results of the multifactorial analysis, and the predictive performance of the model was evaluated by receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curves.Results:As of the follow-up cut-off date, of the 80 patients, 63 had PD, with a median overall survival (OS) of 16.9 months. Univariate analysis showed that, age ( HR=2.09, 95% CI: 1.17-3.74, P=0.013) , number of treatment lines ( HR=2.23, 95% CI: 1.21-4.12, P=0.010) , lymphocyte to monocyte ratio (LMR) at the baseline ( HR=0.75, 95% CI: 0.57-0.97, P=0.028) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) and lactate dehydrogenase (LDH) ( HR=1.01, 95% CI: 1.00-1.01, P=0.006) at the optimal remission, haemoglobin ( HR=0.97, 95% CI: 0.96-0.99, P<0.001) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) , C-reactive protein ( HR=1.01, 95% CI: 1.00-1.01, P=0.011) , albumin (ALB) ( HR=0.91, 95% CI: 0.87-0.96, P=0.001) , neutrophil to lymphocyte ratio (NLR) ( HR=1.16, 95% CI: 1.05-1.27, P=0.002) and LMR ( HR=0.62, 95% CI: 0.42-0.90, P=0.012) at the PD were all influencing factors for the prognosis of advanced NSCLC patients receiving immunotherapy. Least absolute shrinkage and selection operator regression were used to screen the variables for P<0.10 in the univariate analysis, and nine possible influencing factors were obtained, which were age, fibrinogen and LDH at the optimal remission, haemoglobin, D-dimer, C-reactive protein, LDH, ALB and LMR at the PD. Multivariate analysis of the above variables showed that, age ( HR=0.91, 95% CI: 0.86-0.97, P=0.004) , LDH ( HR=1.01, 95% CI: 1.00-1.01, P=0.013) and ALB ( HR=0.82, 95% CI: 0.67-0.99, P=0.041) at the PD were independent influencing factors for the prognosis of patients with advanced NSCLC who received immunotherapy. The area under curve of the nomogram predicting model based on the above indexes, 1- and 2-year OS rates of patients were 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.66-0.88) , respectively, and C-index was 0.71 (95% CI: 0.64-0.78) , the calibration curves showed good consistency between predicted and actual probability of occurrence. Patients in the low-risk group ( n=40) had a median OS of 29.9 months (95% CI: 22.5 months-NA) , which was significantly better than that of the high-risk group ( n=40) [13.4 months (95% CI: 11.4-23.5 months) , χ2=11.30, P<0.001]. Conclusion:Age, LDH and ALB at the PD are independent influencing factors affecting the prognosis of patients with advanced NSCLC receiving immunotherapy, and the nomogram model constructed based on the above indexes has good differentiation and calibration for predicting 1- and 2-year OS rates in advanced NSCLC patients receiving immunotherapy.

Objective:To investigate the effect of mitochondrial division of GABAergic neurons in substantia nigra pars reticulata(SNr)on motor dysfunction in mice with acute hepatic encephalopathy(AHE).Methods:AHE mice model was established by intraperitoneal injection of thioacetamide(TAA).The changes of liver lobules in AHE mice were observed by hematoxylin-eosin(HE)staining.The changes of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)and blood ammonia in AHE mice were detected by biochemical detection kit.Then,the motor function of AHE mice was observed by rod fatigue test,elevated cross maze test and open field test.Furthermore,the changes of mitochondrial area,perimeter,roundness and other morphological indicators in SNr of AHE mice were ob-served and analyzed by transmission electron microscopy.The expression of mitochondrial division and fusion related molecules in SNr of AHE mice was observed by Western Blot.Then,the expression of mitochondrial dynamic related protein 1(DRP1)in SNr of AHE mice was targeted by AAV virus.The mitochondrial membrane potential(MMP),ATP and reactive oxygen species(ROS)in SNr were detected by fluorescence enzyme marker,and the changes of motor function of mice were observed.Results:Compared with the control group,the motor function of AHE mice was signifi-cantly decreased,the mitochondrial division of SNr was significantly enhanced,and the expression of mitochondrial divi-sion related proteins was significantly increased.The MMP in SNr of AHE mice was significantly decreased,the ATP of cells was decreased,and the ROS was increased.After targeted inhibition of DRP1 expression in SNr of AHE mice,the movement was improved;further observation found that after the mitochondrial division in SNr of AHE mice was inhibi-ted,the MMP was significantly increased,the ATP of cells was increased,and the ROS was decreased,which demon-strated that the mitochondrial function was significantly improved.Conclusion:Targeted inhibition of mitochondrial di-vision of GABAergic neurons in SNr of AHE mice can improve mitochondrial morphology and function,thus alleviating their movement disorders.

Objective:To develop and evaluate the efficacy and safety of a three-dimensional (3D) digestive endoscope for gastric endoscopic submucosal dissection (ESD) through animal experiments.Methods:Two Dutch pigs were utilized from the Zhengzhou University Animal Experiment Center for the study. ESD procedures were performed by two senior endoscopists, one using 3D glasses and the other utilizing a 3D high-definition head display. The success of ESD was assessed based on predefined criteria, including completion of surgical steps, complete detachment of the presumptive lesion, and effective bleeding control during and after the surgery. The number of successful procedures and incidences of perforation were recorded. The stereoscopic experience of the endoscopists, including both the primary endoscopist and the assistant, was also evaluated. Furthermore, the assessment encompassed any reported symptoms of eye discomfort, such as eye fatigue, ocular pain, and blurred vision. Additionally, the confidence level of the endoscopists in the mechanical aspects of the operation, as well as encountered issues during the endoscopic procedures, were documented.Results:Two ESD were successful and no perforation occurred. Feedback from endoscopists suggested that 3D digestive endoscopy offered clear images with enhanced three-dimensionality during surgery, clear sense of distance and layering, allowing for a precise judgment of bleeding points, which surpassed 2D capabilities. No eye discomfort was experienced by endoscopists or assistants during or after the procedures. While endoscopists exhibited high confidence in 3D digestive endoscopy, they noted issues with image blurring when the camera was positioned less than 10 mm from the gastrointestinal tract wall.Conclusion:Preliminary results show that 3D digestive endoscopes can provide excellent stereo imaging, improved positioning accuracy, and safety during live animal stomach ESD procedures, without significantly increasing endoscopists' eye discomfort. Nevertheless, efforts are needed to address image blurring concerns when the camera is close to the gastrointestinal tract wall.

Objective:To analyze the symmetry of different reference planes in the surgical simulation design of patients with protrusive jaw deformity with high and low eyes.Methods:Fifteen patients with partial jaw deformity were selected from January 2019 to June 2020, including 3 males and 12 females, aged 18-26 years, with average 23.78 years. Inclusion criteria were that the patients, aged more than 18 years, were diagnosed as protrusive jaw deformity with maxillary occlusal plane tilt and high and low eyes by clinical and imaging analysis. Three different 3D reference plane systems were established by different modeling methods. The distance between the landmarks of soft and hard tissues and the median sagittal plane was measured. The symmetry of skull was qualitatively analyzed by mirror image technique. The difference of three reference planes in surgical simulation symmetry of patients with protrusion jaw and high and low eyes was evaluated by one-way ANOVA.Results:Qualitative analysis showed that in the three measurement planes, the symmetry of the third reference plane was the best, and the symmetry of the second and the first was poor. Quantitative analysis showed that in measurement index of hard tissue, there was statistical difference between the distance of each landmark in the reference plane established by Method 3 and Method 1, Method 2 [(1.65±1.19) mm; (3.37±1.58) mm; (3.26±2.36) mm, P<0.05], but there was no statistical difference between Method 1 and Method 2 (P > 0.05). The measurement result of soft tissue was consistent with that of hard tissue, and the distance of each landmark in Method 3 from the median sagittal plane was very small, and the mean error was less than 0.5 mm, which was consistent with the clinical results. Conclusions:Digital model surgery technology can assist orthognathic surgeons in the design and prediction of surgical scheme, especially for patients with special partial jaw deformity.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

Objective To investigate the role and molecular mechanism of Sirt1 in renal injury in diabetic mice under acute inflammatory state.Methods Forty SPF grade C57BL/6J male mice,8 weeks old,weighing 20-25 g were selected.The mice were divided into five groups by random number table meth-od:control group(group C),diabetic group(group D),lipopolysaccharide(LPS)+diabetic group(group L),LPS+diabetic+Sirt1 blocker EX527 group(group E),and LPS+diabetic+Sirt1 agonist ginkgoflavone sapogenins group(group G),8 mice in each group.After successful preparation of the diabet-ic mouse model,group L was injected intraperitoneally with LPS 10 mg/kg.Group E was injected intraper-itoneally with EX527 5 mg/kg(dissolved in DMSO 0.2 ml)1 hour before giving LPS treatment to diabetic mice.Group G was injected intraperitoneally with 200 mg/kg of ginkgoflavone sapogenins(dissolved in DMSO 0.2 ml)1 hour before LPS treatment was given to diabetic mice,groups C and D underwent an in-traperitoneal injection of 2％DMSO 0.15 ml at the same time point.24-hours urine volume was collected and 24-hours urinary protein concentration was determined,and blood was taken from the posterior eyes to detect serum Scr and BUN concentrations.After kidney tissues were removed,IL-1βand IL-18 concentra-tions were measured by ELISA,nitrate reductase assay for nitric oxide(NO)content in kidney,iron ion an-tioxidant capacity assay for total antioxidant capacity(T-AOC),qPCR and Western blot assay for Sirtl,caspase-1,NLRP3,and ASC mRNA expression and protein content.The acetylated FoxO3a protein content was detected by immunoprecipitation,the reactive oxygen species(ROS)content was calculated by di-hydroethidium staining,the pyroptosis rate was calculated by immunofluorescence double staining,HE stai-ning was performed,and the pathological results were observed under light microscope.Results Compared with group C,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,con-centrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,ROS content and pyroptosis rate were significantly increased,T-AOC activity was signifi-cantly decreased in groups D,L,E,and G(P＜0.05).Compared with group D,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1 β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,ROS content and pyroptosis rate were significantly increased,T-AOC activity was significantly decreased in groups L,E,and G(P＜0.05).Compared with group L,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein content,ROS content,and pyroptosis rate were significantly increased,T-AOC activity,Sirt1 mRNA expression and protein content,and FoxO3a mRNA expression were significantly decreased in group E(P＜0.05),24-hours urine volume,urine pro-tein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein con-tent,ROS content and pyroptosis rate were significantly decreased,T-AOC activity,Sirt1 mRNA expression and protein content were significantly increased in group G(P＜0.05).Compared with group E,24-hours urine volume,urinary protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein content,ROS content,and pyroptosis rate were significantly decreased,T-AOC activity,Sirt1 mRNA expression and protein content were significantly increased in group G(P＜0.05).Conclusion In diabetic mice under acute inflammatory state,elevated Sirt1 reduces kidney injury by de-creasing acetylated FoxO3a protein content,reduced urine volume,urine protein concentration,serum Scr and BUN concentration,inflammatory factor concentrations and apoptosis levels in renal tissue,and attenua-ted oxidative stress and inflammation levels.

As the development of radiotherapy, the plan making that depends on CT image information and staff skills limits its further development. Whereas virtual reality (VR) based on computer technology is a simulation system for human-machine interaction in 3D environment. VR can provide 3D information on the radiotherapy environment, patient anatomy, isodose distribution, etc. VR has been used to guide patient positioning, automatic collision detection of non-coplanar treatment plans, holographic imaging system to optimize radiotherapy plans, teaching and training, and patient publicity and education. The purpose is to improve the quality of radiotherapy on a safe and effective basis, and provide practical tools for radiotherapy technical training, teaching and publicity education.