Proteins are fundamental carriers as the structural elements and biochemically active entities responsible for catalysis, transport, and regulation. These functions are depending on the protein folding into precise three-dimensional structures, interacting with ligands, and conformational changes. This article reviews the recent progress of nanopores in single-molecule protein sensing, involving the identification of polypeptides and proteins, the conformation changes of protein folding, the molecular structure responsible to the pH of solutions, the molecular interactions, and protein sequencing. These studies provide clues to understand life activities and facilitate the early diagnosis of diseases and design of drugs for precise treatment.
Nanopores ; Proteins/chemistry* ; Biosensing Techniques/methods* ; Protein Folding ; Humans

[Objective]To understand the current status of human immunodeficiency virus(HIV),Treponema palli-dum(TP),hepatitis C virus(HCV)and hepatitis B virus(HBV)infections among patients undergoing screening tests in a specialized cancer hospital in South China,and to analyze the completion of further testing for confirmation,so as to pro-vide a reference for management of common infectious diseases and prevention of nosocomial infections.[Methods]We ana-lyzed the positive rates of HIV antigen/antibody combination assay(HIV-comb),TP antibody(anti-TP),HCV antibody(anti-HCV)and hepatitis B surface antigen(HBsAg)among the outpatients and inpatients who underwent the screening tests in 2022.Then we examined the percentage of those patients with seropositivity for further confirmation.[Results]In patients who underwent the screening tests,the positive rate,percentage of patients for further confirmation test and over-all prevalence for HIV-comb were were 0.07%,100%and 0.06%,respectively;for Anti-PT 1.99%,100%and 0.51%,respectively.Positive rate of anti-HCV was 0.90%and 26.61%of patients completed further HCV RNA quantitative as-say,in 26.44%of whom,HCV RNA levels were above the detection limit.Positive rate of HBsAg was 21.06%and 54.40%of patients completed further HBV DNA quantitative assay,in 51.60%of whom,HBV DNA levels were above the detec-tion limit.As for the nucleic acid testing among the suspected hepatitis patients,we found smaller coverage in outpatients than in inpatients and larger coverage in liver cancer patients than in other patients.[Conclusions]Compared with general population,patients in this specialized cancer hospital had similar infection levels of HIV and syphilis,and 100%of them completed further confirmation testing.Hepatitis C and hepatitis B infections were at a relatively high level,but which could not accurately reflect the level of virus replication due to insufficient coverage of nucleic acid testing.Specialized can-cer hospitals should prompt medical staff to attach more importance to screening and further confirmation of common infec-tious diseases among tumor patients.While offering anti-cancer treatment,hospitals should also actively refer the con-firmed cases with infectious diseases to designated or general hospitals for a better outcome and quality of medical services.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective:To understand the epidemiological characteristics of fatal drowning in children in Zhejiang Province in 2022, analyze factors such as the swimming ability of children, the caregiver behavior at drowning site, types of first aid personnel and methods of first aid of unintentional fatal drowning and provide evidence for targeted intervention.Methods:Using the "Survey Form of Fatal Drowning Case in Children" designed by National Center for Chronic and Non-communicable Disease Control and Prevention of the China CDC, we collected case information of children aged 0-17 years who died due to drowning in Zhejiang in 2022 from medical history/death investigation records, telephone interviews, and home visits.Results:A total of 341 fatal drowning cases in children occurred in Zhejiang in 2022 and 330 cases were investigated (96.77%). The male to female of the cases was 2.33∶1, most cases were aged 15-17 years and 0-4 years, and 54.24% of fatal drowning cases occurred in children from other provinces. In the drowning cases, 83.33% were unintentional ones, and the proportion of intentional fatal drowning cases in children increased with age. Fatal drowning cases mainly occurred in open natural water bodies and public water storage facilities. More fatal drowning cases occurred in open natural water bodies in older children, while more fatal drowning cases occurred in public water storage facilities in younger children. In 275 children who died due to unintentional drowning, 73.09% could not swim, and only 1.09% were fully supervised by adults within an arm's length. First aid personnel, mainly medical staffs, bystanders and adult caregivers, were present for 47.63% fatal drowning cases. The proportion of the cases who had cardiopulmonary resuscitation as the first aid within 5 minutes was 2.18%.Conclusions:Drowning poses a serious threat to children's lives and there are differences in reasons and locations of fatal drowning in children in different age groups in Zhejiang Province in 2022. It is necessary to conduct to interventions to improve children's swimming skills, strengthen effective adult care and conduct health education about field first aid of drowning to reduce the incidence of drowning and related deaths in children.

Depression is one of the leading causes of disability,and it usually begins during adolescence.It is well known that depression often leads to academic failure,poor peer relationships,behavioral problems,conflict with family and social relationships,and even suicide in adolescents.It is very urgent to take active and effective prevention and treatment for adolescent depression.Diffusion tensor imaging can evaluate white matter microstructure and build structural brain networks.In addition,it can be used to analyze the correlation between white matter abnormalities and clinical symptoms,age,gender and other clinical variables in adolescent depression.In recent years,diffusion tensor imaging studies on adolescent depression have shown that the abnormal microstructure of several white matter fiber tracts such as the corpus callosum,cingulate tract and uncinate tract,as well as the damaged neural circuits of the prefrontal striatum and prefrontal limbic system have been confirmed in adolescent depression,which is closely related to memory,emotion management,reward and cognitive processing.The results are consistent with findings in adult depression.This article will briefly review the principle of diffusion tensor imaging,data processing methods and its application in adolescent depression,aiming to provide new ideas for future research.

Objective:To construct a prediction model for peripherally inserted central catheter-related upper extremity deep vein thrombosis (PICC-UEDVT) in patients with traumatic brain injury (TBI) and validate its effectiveness.Methods:A case-control study was conducted on the clinical data of 222 TBI patients admitted to Xiangya Hospital of Central South University from January 2019 to December 2021, including 171 males and 51 females, aged 18-86 years [54.5(46.0, 65.0)years]. Glasgow coma scale (GCS) motor score was 4.0(3.0, 5.0)points on the day of catheterization. A total of 82 patients (36.9%) had PICC-UEDVT. The patients were randomly divided with a ratio of 7∶3 into training set ( n=156, including 58 with PICC-UEDVT) and validation set ( n=66, including 24 with PICC-UEDVT) using R programming language. The baseline data of general information, intravenous medication, catheterization, and laboratory indices were compared between the training set and the validation set. Lasso regression analysis was employed to identify those variables, with the diagnosis of PICC-UEDVT as the outcome variable. Variables with non-zero regression coefficients were included in a multifactorial Logistic regression model and independent variables were selected based on the Akaike Information Criterion (AIC) of R programming language. The regression equation was constructed, based on which, the predictive nomogram model was constructed for PICC-UEDVT in TBI patients. Receiver operating characteristic (ROC) curves for the training set and validation set were plotted and the discriminability of the model was assessed. The calibration of the model was evaluated using the Hosmer-Lemeshow (H-L) goodness-of-fit test and calibration curves and the clinical practicality of the model was assessed with decision curve analysis (DCA). Results:The baseline analysis of both the training set and the validation set demonstrated a well-balanced sample distribution. Through Lasso regression analysis, 5 prediction variables were identified: GCS motor score on the day of catheterization, Caprini score on the day of catheterization, use of glucocorticoids, tip position of the catheter, and D-dimer (D-D) level before catheterization. The multivariate Logistic regression analysis revealed that the Caprini score on the day of catheterization ( OR=1.20, 95% CI 1.08, 1.33), use of glucocorticoids ( OR=3.13, 95% CI 0.99, 10.46), and D-D level before catheterization ( OR=1.16, 95% CI 1.07, 1.33) were independent risk factors for PICC-UEDVT in TBI patients. The regression equation was developed as: Logit [ P/(1- P)]=-2.56+0.18×"Caprini score on the day of catheterization"+1.14×"use of glucocorticoids"+0.15×"D-D level before catheterization". In the prediction model which was constructed based on the equation, the AUC values for the training set and validation set were 0.73 (95% CI 0.65, 0.81) and 0.77 (95% CI 0.65, 0.87) respectively. The H-L goodness-of-fit test indicated χ2=3.28, P=0.950 for the training set and χ2=13.05, P=0.160 for the validation set. Calibration curves for both sets demonstrated alignment between the actual and predicted probabilities of PICC-UEDVT in TBI patients. DCA results showed that the net benefit rate of patients was optimal when the threshold probability ranged from 15% to 72% for the training set and from 10% to 81% for the validation set. Conclusion:The prediction model based on the Caprini score on the day of catheterization, use of glucocorticoids, and D-D level before catheterization demonstrates good predictive accuracy, calibration and clinical practicality in predicting PICC-UEDVT in TBI patients.

Objective:To investigate alterations in the glymphatic system of spinocerebellar ataxia type 3 (SCA3) patients based on quantitative MRI, and its association with genetic information and motor dysfunction.Methods:The study was a cross-sectional study. This prospective study recruited 39 confirmed SCA3 patients (SCA3 group) and 40 matched healthy controls (HC group) who were seen at the Southwest Hospital of Army Medical University from May 2017 to June 2023. All subjects underwent cranial MRI scanning. Clinical assessments were conducted on all participants using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). The automatic segmentation and volume measurement of the choroid plexus based on Freesurfer 6.0; the perivascular interstitial space (PVS) was automatically segmented based on the deep-learning model VB-Net, and the volume of the PVS in each brain region was quantified after manual correction. Independent samples t-test and Mann-Whitney U-test were used to analyze the changes in the class lymphatic system in the SCA3 group and the HC group. Pearson partial correlation analysis was used to explore the relationship between CAG repeats, the glymphatic system, and motor dysfunction. Results:The standardized choroid plexus volume in the SCA3 group was (1.24±0.36)×10 3 mm 3, and that in the HC group was (0.96±0.34)×10 3 mm 3, with a statistically significant difference ( t=4.01, P<0.001). PVS volumes in the frontal lobe, temporal lobe, parietal lobe, basal ganglia, cerebellum, thalamus, and brainstem regions in the SCA3 group were significantly higher than those of HC group ( P<0.05). Partial correlation analysis revealed that CAG repeats in SCA3 group were positively correlated with SARA, ICARS, and basal ganglia PVS volumes ( r=0.65, 0.58, 0.29; P=0.001, 0.001, 0.042). Cerebellar and temporal lobe PVS volumes were positively correlated with SARA ( r=0.59, 0.47; P=0.001, 0.003), and positively correlated with ICARS scores ( r=0.61, 0.40; P=0.001, 0.011). Choroid plexus volume was positively correlated with cerebellar and basal ganglia PVS volumes ( r=0.41, 0.31; P=0.009, 0.043). Conclusions:The glymphatic system of SCA3 patients have significant alteration and have association with CAG repeats and motor dysfunction.

Objective:To investigate the effects of navigation bronchoscopy and artificial intelligence in the standardized training of residents on basic bronchoscopy skills, with the goal of enhancing their practical abilities.Methods:We selected 26 trainees (14 on standardized training of residents and 12 on standardized training of specialists) who participated in the basic navigational bronchoscopy skills and technique training (NBSTAT) at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2023 to January 2024. The training was structured around a modular curriculum with navigation as the core design concept, consisting of five modules: lesion identification, precise localization, route planning, navigation operation, and real-time error correction. Theoretical teaching and skill practice were combined. The skill proficiency of the trainees was assessed using the Ruijin Hospital bronchoscopy simulation training system and the electromagnetic navigation bronchoscopy system. SPSS 26.0 was used to perform the t-test and Wilcoxon rank-sum test for comparisons. Results:After the training, the trainees as a whole showed significant improvements in practicing the skills, with the simulated operation time was reduced from (125.08±48.16) seconds to (77.69±24.75) seconds, the number of errors decreased from 1 to 0, the total score increased from (60.77±15.01) to (75.19±17.63), and the navigation operation time was reduced from 3 (3, 4) minutes to 2 (2, 3) minutes (all P<0.05). There were no significant differences in these assessment items between resident trainees and specialist trainees. The satisfaction rate of the trainees with the training reached 100.00%. Conclusions:The curriculum is effective in basic bronchoscopy skill training, remarkably enhancing the bronchoscopy skills of resident and specialist physicians, which is a useful approach for physicians to cope with the continuous development of diagnostic and therapeutic techniques for pulmonary diseases.

Objective:The emergence of polymyxin-resistant Klebsiella pneumoniae(KPN)in clinical settings necessitates an analysis of its antibiotic resistance characteristics,epidemiological features,and risk factors for its development.This study aims to provide insights for the prevention and control of polymyxin-resistant KPN infections. Methods:Thirty clinical isolates of polymyxin-resistant KPN were collected from the Third Xiangya Hospital of Central South University.Their antibiotic resistance profiles were analyzed.The presence of carbapenemase KPC,OXA-48,VIM,IMP,and NDM was detected using colloidal gold immunochromatography.Hypervirulent KPN was initially screened using the string test.Biofilm formation capacity was assessed using crystal violet staining.Combination drug susceptibility tests(polymyxin B with meropenem,tigecycline,cefoperazone/sulbactam)were conducted using the checkerboard method.Polymyxin-related resistance genes were detected by PCR.Multi-locus sequence typing(MLST)was performed for genotyping and phylogenetic tree construction.The study also involved collecting data from carbapenem-resistant(CR)-KPN polymyxin-resistant strains(23 strains,experimental group)and CR-KPN polymyxin-sensitive strains(57 strains,control group)to analyze potential risk factors for polymyxin-resistant KPN infection through univariate analysis and multivariate Logistic regression.The induction of resistance by continuous exposure to polymyxin B and colistin E was also tested. Results:Among the 30 polymyxin-resistant KPN isolates,28 were CR-KPN,all producing KPC enzyme.Four isolates were positive in the string test.Most isolates showed strong biofilm formation capabilities.Combination therapy showed additive or synergistic effects.All isolates carried the pmrA and phoP genes,while no mcr-1 or mcr-2 genes were detected.MLST results indicated that ST11 was the predominant type.The phylogenetic tree suggested that polymyxin-resistant KPN had not caused a hospital outbreak in the institution.The use of two or more different classes of antibiotics and the use of polymyxin were identified as independent risk factors for the development of polymyxin-resistant strains.Continuous use of polymyxin induced drug resistance. Conclusion:Polymyxin-resistant KPN is resistant to nearly all commonly used antibiotics,making polymyxin-based combination therapy a viable option.No plasmid-mediated polymyxin-resistant KPN has been isolated in the hospital.Polymyxin can induce resistance in KPN,highlighting the need for rational antibiotic use in clinical settings to delay the emergence of resistance.