Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

OBJECTIVE: To explore whether the effect of low-frequency pulsed electromagnetic fields (PEMFs) in promoting osteoblast mineralization and maturation is related to the primary cilia, polycystin2 (PC2) and sAC/PKA/CREB signaling pathway. METHODS: We detected the expression levels of PC2, sAC, PKA, CREB and their phosphorylated proteins in primary rat calvarial osteoblasts exposed to 50 Hz 0.6 mT PEMFs for 0, 5, 15, 30, 60, 90, and 120 min. We blocked PC2 function with amiloride hydrochloride and detected the changes in the activity of sAC/PKA/CREB signal pathway and the mineralization and maturation of the osteoblasts. These examinations were repeated in the osteoblasts after specific knockdown of PC2 via RNA interference and were the co-localization of PC2, sAC, PKA, CREB and their phosphorylated proteins with the primary cilia were using immunofluorescence staining. The expressions of PC2 and the signaling proteins of sAC/PKA/CREB pathway were detected after inhibition of primary ciliation by RNA interference. RESULTS: The expression levels of PC2, sAC, p-PKA and p- CREB were significantly increased in the osteoblasts after exposure to PEMFs for different time lengths (P < 0.01). Blocking PC2 function or PC2 knockdown in the osteoblasts resulted in failure of sAC/PKA/CREB signaling pathway activation and arrest of osteoblast mineralization and maturation. PC2, sAC, p-PKA and p-CREB were localized to the entire primary cilia or its roots, but PKA and CREB were not detected in the primary cilia. After interference of the primary cilia, PEMFs exposure no longer caused increase of PC2 expression and failed to activate the sAC/PKA/CREB signaling pathway or promote osteoblast mineralization and maturation. CONCLUSION PC2, located on the surface of the primary cilia of osteoblasts, can perceive and transmit the physical signals from PEMFs and promote the mineralization and maturation of osteoblasts by activating the PC2/ sAC/PKA/CREB signaling pathway.
Animals ; Cell Differentiation ; Electromagnetic Fields ; Osteoblasts ; Osteogenesis/genetics* ; Rats ; Signal Transduction

ObjectiveTo investigate the perioperative safety and complications of radical cystectomy （RC）. MethodsThe clinicopathological indexes， postoperative complications and prognosis of patients who underwent RC at Sun Yat-sen University Cancer Centre from January 2001 to August 2020 were retrospectively collected and analyzed. Among them， patients from 2011 to 2020 were further analyzed and compared according to the open surgery group （ORC）， laparoscopic group （LRC） and robot-assisted laparoscopic group （RARC）. Independent sample t test， Chi-square test， K-M survival curve and other statistical methods were used to describe the complications and prognosis of patients， and Logistic regression was used to analyze the influencing factors of complications of RC. ResultsAmong the 1041 patients who underwent RC surgery from 2001 to 2020， the median age was 63 （55-69） years. In terms of the gender ratio， men were the majority at 86 percent. Compared with that of the first 10 years， the complication rate of the second 10 years decreased significantly （37.4% vs. 26.7%）. Complications of 667 patients who underwent RC surgery were analyzed from 2010 to 2020， with a median follow-up of 34 months. A total of 415 patients were enrolled in the ORC group， 161 in the LRC group， and 91 in the RARC group. Ileal conduit （659 cases， 63.3%） accounted for the highest proportion of all urinary diversion methods， while orthotopic neobladder accounted for the second （343 cases， 32.9%）. The incidence of all grade complications was 30.5%， and the most common complication was urinary complications. The incidence of total complications and grade ≥3 complications in the ORC group was higher than that in the LRC and RARC groups （Total complications： ORC， 30.8%； LRC，21.1%， RARC，24.2%； P=0.047； Grade ≥3 complications： ORC， 14.7%； LRC，9.3%； RARC，6.6%； P=0.043）. ConclusionsWith the improvement of surgical techniques and experience， the incidence of recent postoperative complications after radical resection of bladder cancer in our center has decreased. Compared with open surgery， minimally invasive surgery has some advantages in reducing the complication rate.

Bone age assessment has always been one of the key issues and difficulties in forensic science. With the gradual development of machine learning in many industries, it has been widely introduced to imageology, genomics, oncology, pathology, surgery and other medical research fields in recent years. The reason why the above research fields can be closely combined with machine learning, is because the research subjects of the above branches of medicine belong to the computer vision category. Machine learning provides unique advantages for computer vision research and has made breakthroughs in medical image recognition. Based on the advantages of machine learning in image recognition, it was combined with bone age assessment research, in order to construct a recognition model suitable for forensic skeletal images. This paper reviews the research progress in bone age assessment made by scholars at home and abroad using machine learning technology in recent years.
Age Determination by Skeleton ; Humans ; Machine Learning

Objective To compare the performance of three deep-learning models （VGG19, Inception-V3 and Inception-ResNet-V2） in automatic bone age assessment based on pelvic X-ray radiographs. Methods A total of 962 pelvic X ray radiographs taken from adolescents （481 males, 481 females） aged from 11.0 to 21.0 years in five provinces and cities of China were collected, preprocessed and used as objects of study. Eighty percent of these X ray radiographs were divided into training set and validation set with random sampling method and used for model fitting and hyper-parameters adjustment. Twenty percent were used as test sets, to evaluate the ability of model generalization. The performances of the three models were assessed by comparing the root mean square error （RMSE）, mean absolute error （MAE） and Bland-Altman plots between the model estimates and the chronological ages. Results The mean RMSE and MAE between bone age estimates of the VGG19 model and the chronological ages were 1.29 and 1.02 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-V3 model and the chronological ages were 1.17 and 0.82 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-ResNet-V2 model and the chronological ages were 1.11 and 0.84 years, respectively. The Bland-Altman plots showed that the mean value of differences between bone age estimates of Inception-ResNet-V2 model and the chronological ages was the lowest. Conclusion In the automatic bone age assessment of adolescent pelvis, the Inception-ResNet-V2 model performs the best while the Inception-V3 model achieves a similar accuracy as VGG19 model.
Adolescent ; Adult ; Age Determination by Skeleton ; Child ; China ; Female ; Humans ; Male ; Pelvis ; Radiography ; Young Adult

OBJECTIVE: To study the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF, the Chinese Medicine) on hippocampal neuron apoptosis in diabetes mellitus complicated with depression (DD). METHODS: The primary cultured hippocampal neurons were treated with high glucose (150 mmol/L) and corticosterone (200 micromol/L) to establish the cell model of DD in vitro. The cultured hippocampal neurons were randomly divided into five groups: blank serum group, normal group, Zuogui Jiangtang Jieyu recipe drug-containing serum group, positive drug (metformin + fluoxetine) drug-containing serum group and model group (three compound holes in each group). The model group and the normal group were given the same amount of culture medium, and the other groups were given the corresponding serum with 10% volume fraction for 18 hours. Hoechst staining, high content cell imaging and RT-PCR were used to detect the apoptosis of hippocampal neurons and the expressions of apoptosis-related ETS-like 1 transcription factor(ELK-1), C-Jun N-terminal kinase(JNK) and c-Fos proteins and genes. RESULTS: Compared with the blank group, the apoptotic number of hippocampal neurons in the model group was increased significantly, and the expression levels of ELK-1, JNK and c-Fos were increased significantly (P＜0.05). Compared with the model group, the local bright spots of hippocampal neurons in the Zuogui Jiangtang Jieyu recipe-containing serum group and the positive drug-containing serum group were decreased significantly, and the number of apoptotic cells was decreased significantly. The expressions of JNK, c-fos protein and mRNA were down-regulated significantly (P＜ 0.05), and the neural network and dendritic junction were improved significantly. CONCLUSION Zuo Gui Jiang Tang Jie Yu Formula can reverse the expressions of ELK-1, JNK and c-Fos signals in hippocampal neurons under DD environment and play an anti-apoptotic effect.
Animals ; Apoptosis ; drug effects ; Depression ; drug therapy ; Diabetes Complications ; drug therapy ; Diabetes Mellitus ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; drug effects ; MAP Kinase Kinase 4 ; drug effects ; Neurons ; Proto-Oncogene Proteins c-fos ; drug effects ; Random Allocation ; Rats ; ets-Domain Protein Elk-1 ; drug effects

Background:Despite the growing epidemic of heart failure (HF),there is limited data available to systematically compare non-cardiac comorbidities in the young-old,old-old,and oldest-old patients hospitalized for HF.The precise differences will add valuable information for better management of HF in elderly patients.Methods:A total of 1053 patients aged 65 years or older hospitalized with HF were included in this study.Patients were compared among three age groups:(1) young-old:65 to 74 years,(2) old-old:75 to 84 years,and (3) oldest-old:≥85 years.Clinical details of presentation,comorbidities,and prescribed medications were recorded.Results:The mean age was 76.7 years and 12.7％ were 85 years or older.Most elderly patients with HF (97.5％) had at least one of the non-cardiac comorbidities.The patterns of common non-cardiac comorbidities were different between the young-old and oldestold group.The three most common non-cardiac comorbidities were anemia (53.6％),hyperlipidemia (45.9％),and diabetes (42.4％) in the young-old group,while anemia (73.1％),infection (58.2％),and chronic kidney disease (44.0％) in the oldest-old group.Polypharmacy was observed in 93.0％ elderly patients with HF.Additionally,29.2％ patients were diagnosed with infection,and 67.0％ patients were prescribed antibiotics.However,60.4％ patients were diagnosed with anemia with only 8.9％ of them receiving iron repletion.Conclusions:Non-cardiac comorbidities are nearly universal in three groups but obviously differ by age,and inappropriate medications are very common in elderly patients with HF.Further treatment strategies should be focused on providing optimal medications for age-specific non-cardiac conditions.

Objective To study the content of monoamine neurotransmitters and neurotrophic factor in the hippocampus, amygdala and prefrontal cortex in anxious depression rats, and explore the possible pathogenesis.Methods 60 SD rats were randomly divided into normal group, vehicle group, anxiety group, depression group, and anxious depression group, 12 rats in each group.Chronic restraint stress combined with corticosterone injection was used to establish anxiety and depression model, the modeling time was 21 d.After modeling, elevated plus maze test, open field test, and forced swimming test were used to evaluate the anxiety and depression-like behavior, HPLC-ECD was used to detect the content of 5-HT, NE, and DA in the hippocampus, amygdala, and prefrontal cortex of rats.Western-blotting was used to detect the expression of BDNF and NT-3 in rats.Results Rats in anxious depression model group were comparable to the anxiety group in time and frequency entering open arm time, and number of locomotor activity in open field, and it had a significant difference when compared with the control and depression groups (P<0.01 or P<0.05).Immobile time in anxious depression model rats was increased significantly when compared with the control and anxiety groups (P<0.01).Meanwhile, compared with the control group, 5-HT in hippocampus and 5-HT, NE in amygdala or prefrontal cortex were significantly decreased in the depressive rats with anxiety (P<0.01 or P<0.05).Moreover, the content of BDNF and NT-3 was significantly decreased in each brain regions compared with the control group (P<0.01 or P<0.05), and BDNF levels were obviously decreased compared with the anxiety group (P<0.05).Conclusions Rats of anxious depression have significant anxiety and depression-like behaviors.Its mechanism may be associated with the down-regulation of monoamine neurotransmitters and neurotrophic factors BDNF and NT-3 in hippocampus, amygdala, and prefrontal cortex region.

Objective To study the effects of Zuogui Jiangtang Jieyu Prescription(ZJJP) on the anti-depression effects in diabetes mellitus rats with depression,and the regulation function on Ras-ERK1/2-CREB signaling.Methods The animal model of diabetes mellitus with depression was established by successively feeding with high fat diet,streptozotocin injection on the tail and chronic unpredictable stress.Model rats were randomly divided into 5 groups:model group,control group(0.18 g · kg-1metformin hydrochloride + 1.8 mg · kg-1 fluoxetine),experimental-L,-M,-H groups (ZJJP:20.52,10.26,5.13 g · kg-1),normal rats were in normal group.The rats were administered with drugs for 4 weeks.The depression-like behavior was evaluated by Open-field test.The learning and memory function was estimated by Morris water maze.The expression of mall GTP-binding protein (Ras),extracellular signal-regulated kinase 1/2 (ERK1/2),phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2),cAMP responsive element binding protein (CREB),phospho-cAMP responsive element binding protein (p-CREB) proteins were tested by Western-blotting.Results After dosing,the number of activities in normal group,model group and experimental-H group were 47.50 ± 15.81,7.50 ± 5.24,21.88 ± 14.47.Compared with the control group,the activities in model group were significantly reduce(P ＜ 0.01),and compared with the model group,experimental-H group could significantly improve(P ＜0.05).The regression line of escape latency in normal group,model group and experimental-H group were y =66.88-10.76x,y =63.56-5.964x,y =67.75-9.51x.Compared with the normal group,the model group was significantly decreased (P ＜0.05),and compared with the model group,the escape latency in experimental-H group was significantly incresasd (P ＜ 0.05).The exploration time of this three groups were (36.63 ± 13.39),(22.25 ±5.42),(30.75 ±7.92) s.Compared with the normal group,model group was statistically lower(P ＜0.05),and compared with the model group,experimental-H group could significantly improve(P ＜0.05).The expression of protein Ras in normal group,model group and experimental-H group were 0.70 ± 0.06,0.08 ± 0.03,0.52 ± 0.08,the ratio of (p-ERK1) to ERK1 in the three groups were 0.62 ±0.10,0.20 ±0.03,0.41 ±0.02,the ratio of p-ERK2 to ERK2 in the three groups were 0.40 ± 0.09,0.29±0.09,0.32 ± 0.10,the ratio of p-CREB to CREB in the three groups were 0.60 ± 0.10,0.10 ± 0.02,0.46 ± 0.08.Compared with the normal group,the expression of Ras,the rates of p-ERK1/2/ERK1/2 and p-CREB/CREB were decreased in model group(P ＜ 0.01).Compared with the model group,experimental-H group could significantly increased the Ras expression and up the rate of p-ERK1/ERK1 and p-CREB/CREB (P ＜ 0.01).But experinental-L,experimental-M groups could significantly increased the rate of p-ERK1/ERK1 (P ＜ 0.01,P ＜ 0.05).Conclusion The anti-depression function of ZJJP might be correlated with the regulation of ERK signaling pathway and activation of transcription enhancer factor CREB.

Patient safety education is conducive to medical students' cognition on patient safety and to improvement of medical quality and safety. Developing patient safety education for medical students is more and more widely recognized by World Health Organization and countries all over the world. However, in China, patient safety courses aiming at medical students are relatively few, and there are few reports about the effect of patient safety courses. This paper explored the influence of patient safety curriculum on medical students' attitude to and knowledge of patient safety. The patient safety curriculum was carried out for 2011-grade undergraduates of Tongji Medical College, Huazhong University of Science and Technology. The students participated in the class according to free choice. After the curriculum, the information of gender, major, attended course, attitude toward patient safety, and knowledge of laws and regulations of the 2011-grade undergraduates were collected. After rejecting invalid questionnaires, the number of undergraduates that participated in the survey was 112 (61 students did not take part in the curriculum; 51 took part in). Chi-square test was applied to analyze patient safety education's influence on medical students' attitude to patient safety and their knowledge mastery situation. The influence of patient safety education on the attitude of medical students to patient safety was not significant, but that on their knowledge of patient safety was remarkable. No matter male or female, as compared with medical students who had not accepted patient safety education, they both had a better acquisition of knowledge after having this education (for male students: 95% CI, 4.556-106.238, P<0.001; for female students: 95% CI, 3.183-33.238, P<0.001). Students majoring in Western Medicine had a relatively better mastery of knowledge of patient safety after receiving patient safety education (95% CI, 6.267-76.271, P<0.001). Short-term patient safety education cannot change medical students' stereotyped cognition on matters related to patient safety, but it can effectively enhance their knowledge of laws and regulations of patient safety.
Adult ; China ; epidemiology ; Curriculum ; Education, Medical ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Patient Safety ; Students, Medical ; Surveys and Questionnaires