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 investigate the effect of 9S management combined with plan-do-check-adjust(PDCA)cycle on the incidence of nonstandard surgical instrument handover in urological endoscopic surgery in operating room and supply room.Methods A total of 760 instruments of urological endoscopic surgery used from June 2022 to December 2022 were selected as control group and received routine management.A total of 920 instruments of urological endoscopic surgery used from January 2023 to June 2023 were selected as observation group,and 9S management and PDCA cycle management mode were administrated in instrument handover.The management performance and the satisfaction of surgeons to the instrument nursing staff were compared between the two groups.Results The accuracy of instrument identification and master rate of assembly and disassembly of instruments in the observation group were significantly higher than those in the control group(P<0.05).The incidence of instrument cleaning and packaging errors in the observation group was significantly lower than that in the control group(P<0.05).The satisfaction of surgeons to the instrument nursing staff in the observation group was higher than that in the control group,but no significant difference was found(P>0.05).Conclusion The 9S management combined with PDCA cycle management solves the problem of transport and handover of urological instruments between operating room and supply room,decreases the error rates of disassembly,cleaning,assembly and packaging of instruments,improves work efficiency,reduces the probability of instrument damage,and saves costs.

BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)can release a large number of exosomes(Exos).The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified. OBJECTIVE:To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism. METHODS:Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs.The Exos were extracted by ultracentrifugation and named(BMSCs+miR-21-5p NC)-Exos and(BMSCs+miR-21-5p inhibitor)-Exos.BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes.The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection.TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats. RESULTS AND CONCLUSION:(1)The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells,the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group,indicating that miR-21-5p could target PIK3R1.(2)TUNEL test results showed that compared with(BMSCs+miR-21-5p NC)-Exos group,(BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate.Compared with the(BMSCs+miR-21-5p NC)-Exos group,after the addition of AKT inhibitor LY294002,the apoptosis rate was significantly increased.(3)The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p,in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.

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.

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 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.

[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.