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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

Bronchial asthma(asthma)is a chronic respiratory disease with complex etiology.Because of increasing application of heavy metals in human society,human exposure to heavy metals is a challenge to public health.This review summarizes recent studies to evaluate the effects and mechanisms of heavy metal exposure on asthma in chil-dren.Results of researches have showed that heavy metal exposure resulted in production of reactive oxygen species(ROS)to induce oxidative stress,enhancement of the level of inflammatory cytokines,promoting airway inflamma-tory response and airway remodeling and thus aggravating the occurrence and development of asthma.Further study on these effects may lead to the development of clinical guidance for asthma management.

Objective To investigate the association between intraoperative hypotension and post-operative acute kidney injury(AKI)in patients undergoing brain tumor resections.Methods A total of 428 patients undergoing elective craniotomy for tumor resection were selected,276 males and 152 females,aged≥18 years,BMI 15-36 kg/m2,ASA physical statusⅡ orⅢ.Based on postoperative occurrence of AKI,the patients were divided into two groups:the AKI group and the control group.This study defined three thresholds for hypotension,including MAP during surgery below 65 mmHg,60 mmHg,and 55 mmHg.Multivariate logistic regression was used to analyze the correlation between intraoperative hypotension and postoperative AKI under three thresholds.Results A total of 107 patients had postoperative AKI.The re-sults of multivariable regression analysis indicated that intraoperative MAP＜65 mmHg(OR = 1.11,95%CI 1.03-1.20,P = 0.010)and intraoperative MAP＜60 mmHg(OR = 1.12,95%CI 1.02-1.23,P = 0.017)were associated with postoperative AKI.Conclusion Intraoperative MAP＜65 mmHg or 60 mmHg is associated with postoperative AKI in patients undergoing brain tumor resection.

Objective:To establish a brain metastasis (BM) prediction model for limited-stage small cell lung cancer (LS-SCLC) patients who achieved complete response (CR) or partial response (PR) after thoracic chemoradiotherapy, and to explore the value of prophylactic cranial irradiation (PCI) in different risk groups.Methods:Clinical data of 274 patients with LS-SCLC who achieved CR/PR after thoracic chemoradiotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2021 were retrospectively analyzed, including 144 cases in the PCI group and 130 in the non-PCI group. The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. The bootstrap method, receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA) were employed to evaluate the predictive power and clinical benefits of the model. Patients were stratified into high- and low-risk groups based on risk scores. The brain metastases-free survival (BMFS), progression-free survival (PFS), extracranial progression-free survival (ePFS) and overall survival (OS) were compared between patients with and without PCI in different risk-stratified populations using the log-rank test.Results:The nomogram included five variables: systemic immune inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), pro-gastrin-releasing peptide precursor (ProGRP), neuron-specific enolase (NSE), and blood calcium. The area under the ROC curve (AUC) of the nomogram in predicting 1- and 2-year BMFS was 0.761 and 0.822. In the low-risk group, there was no significant difference in the BMFS ( P=0.374), PFS ( P=0.551), ePFS ( P=0.508) and OS ( P=0.767) between the PCI and non-PCI groups. In the high-risk group, PCI could significantly increase the BMFS ( P<0.001) and PFS ( P=0.022), while there was no significant difference in the ePFS ( P=0.963) and OS ( P=0.632). And propensity score-matching (PSM) analysis showed similar results. Conclusions:PCI does not improve OS in LS-SCLC patients regardless of high or low risk of BM. However, PCI significantly prolong the BMFS and PFS in patients at a high risk of BM.

Objective To investigate the effect of visceral fat area (VFA) on perioperative related indi-cators and short-term prognosis of patients with colorectal cancer (CRC).Methods Clinical data of 102 pa-tients who underwent laparoscopic radical surgery for CRC in the First Affiliated Hospital of Baotou Medical College from September 2020 to August 2023 were retrospectively analyzed.All patients underwent preopera-tive abdominal CT examination,and the transverse CT images at the level of the third lumbar vertebra (L3) were selected.VFA was measured using Slice-O-Matic software,and patients were divided into the high VFA group (VFA≥100 cm2) and the low VFA group (VFA<100 cm2) based on the measurement results.Clinical data,patho-logical data,surgical data,postoperative complications,and perioperative coagulation and inflammation indicators were collected.Results Compared with the low VFA group,the high VFA group had higher BMI,longer hospital stay,greater intraoperative blood loss,and fewer lymph node dissections (P<0.05).The WBC and PCT lev-els before and after surgery in the high VFA group were higher than those in the low VFA group (P<0.05). Compared with preoperative levels,WBC,C-reactive protein (CRP),PCT,plasma prothrombin time (PT), plasma fibrinogen (FIB),and international standardized ratio (INR) increased and PLT decreased in both groups after surgery,the differences were statistically significance (P<0.05);Compared with preoperative conditions,the activated partial prothrombin time (APTT) in the high VFA group and the thrombin time (TT) decreased in the low VFA group decreased after surgery,the differences were statistically significant (P<0.05).The total incidence of postoperative complications (21.2％) and the incidence of incision compli-cations (15.4％) in the high VFA group were higher than that in the low VFA group (4.0％,2.0％),the differences were statistically significant (P<0.05).Conclusion Colorectal cancer patients with high VFA during the perioperative period exhibit higher levels of inflammation indicators and poorer prognosis.

Objective To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2(T2DM)in the middle-aged and elderly populations based on the results of a Meta-analysis,and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service.Methods Cohort studies evaluating T2DM risks were identified in Chinese and English databases.The logistic model utilized Meta-combined effect values such as the odds ratio(OR)to derive β,the partial regression coefficient,of the logistic model.The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model.Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service.The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7 602 individuals who did not have T2DM at their baseline medical checkups done at the community health center.This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people.Results A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM,including age,central obesity,smoking,physical inactivity,impaired fasting glucose,a reduced level of high-density lipoprotein cholesterol(HDL-C),hypertension,body mass index(BMI),triglyceride glucose(TYG)index,and a family history of diabetes,with the OR values and 95% confidence interval(CI)being 1.04(1.03,1.05),1.55(1.29,1.88),1.36(1.11,1.66),1.26(1.07,1.49),3.93(2.94,5.24),1.14(1.06,1.23),1.47(1.34,1.61),1.11(1.05,1.18),2.15(1.75,2.62),and 1.66(1.55,1.78),respectively,and the combined β values being 0.039,0.438,0.307,0.231,1.369,0.131,0.385,0.104,0.765,and 0.507,respectively.A total of 37 studies reported the incidence rate,with the combined incidence being 0.08(0.07,0.09)and the parameter α being-2.442 for the logistic model.The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7 602 individuals who had medical checkups and were followed up for at least once.External validation results showed that the predictive model had an area under curve(AUC)of 0.794(0.771,0.816),accuracy of 74.5%,sensitivity of 71.0%,and specificity of 74.7% in the 7 602 individuals.Conclusion The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.

Objective:To investigate the effects of artesunate ( ART ) on neuronal apoptosis, inflammatory response after stroke in rats and microglia polarization.Methods:(1)Animal experiment: twenty-seven male SD rats of SPF grade were divided into sham operation group, model group and ART treatment group according to the random number table method, with 9 rats in each group.Rats in the model group and ART treatment group were used to establish a stroke model by middle cerebral artery occlusion (MCAO). And rats in the ART treatment group were intraperitoneally injected with ART (25 mg/kg) once a day for three days before modeling, while the rats in sham operation group and the model group were injected with the same amount of solvent.And 24 h after the modeling, TTC staining was used to evaluate the volume of cerebral infarction, Western blot was used to detect the expression of Bcl2 in the infarct area, penumbra and hippocampus, TUNEL method was used to detect neuronal apoptosis, and tissue immunofluorescence was used to observe the expression of tumor necrosis factor-α(TNF-α) in the penumbra region of cerebral cortex.(2)Cell experiments: microglia BV2 were cultured and divided into control group, oxygen-glucose deprivation/reoxygenation group, oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group.The levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β) and TNF-α were detected by qRT-PCR, the expressions of M2 type microglia marker protein CD206 and ARG1 were detected by Western blot, the BV2 cell medium after treatment in each of the above groups was collected as conditioned medium to culture HT22 hippocampal neuron cells and cell activity was measured by CCK8 method.GraphPad Prism 7 software was used for data analysis.One-way ANOVA was used for comparison of differences among multiple groups, and LSD was used for further two-by-two comparisons.Results:(1)Animal experiment results: TTC staining results showed that the percentage of cerebral infarction volume in the ART treatment group was smaller than that in the model group ((23.09±8.51)%, (39.63±5.71)%, t=33.93, P<0.01). The results of TUNEL staining showed that the number of apoptotic cells in the model group and ART treatment group was higher than that in the sham operation group ((638.90±177.82)cells/mm 2, (72.75±13.21) cells/mm 2, (16.16±2.73) cells/mm 2, both P<0.05), and the number of apoptotic cells in the ART treatment group was lower than that in the model group ( P<0.05). Western blot results showed that the levels of Bcl2 protein in penumbra and infarct area of the model group were both lower than those in sham group(both P<0.05). The levels of Bcl2 protein in penumbra, the hippocampus and infarcted area of the ART treatment group were significantly lower than those of the model group(all P<0.05). The results of tissue immunofluorescence showed that the fluorescence intensities of TNF-α in the model group and ART treatment group were higher than those in the sham group (all P<0.05), while the fluorescence intensity of TNF-α in the ART treatment group was lower than that in the model group ( P<0.05). (2)Cell experiment: qRT-PCR results showed that compared with the control group, the mRNA levels of IL-6, IL-1β and TNF-α (all P<0.05) in oxygen-glucose deprivation/reoxygenation group were significantly higher than those of the control group.And the mRNA levels of IL-1β, IL-6 and TNF-α in oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group were significantly lower than those of the oxygen-glucose deprivation/reoxygenation group (all P<0.05). Western blot results showed that compared with the control group, the expression of CD206 ((0.85±0.04), (1.07±0.07), P<0.05) was significantly down-regulated in the oxygen-glucose deprivation/reoxygenation group.The CD206 and ARG in oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group((1.22±0.06), (1.35±0.08)) and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group((1.24±0.14), (1.14±0.07)) were significantly higer than those of oxygen-glucose deprivation/reoxygenation group((0.85±0.04), (0.85±0.05))(all P<0.05). The results of CCK8 showed that compared with the control group, the cell viability in the oxygen-glucose deprivation/reoxygenation group was significantly decreased( P<0.05). The cell viability of the oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, the oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group, the oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group were all higher than those of oxygen-glucose deprivation/reoxygenation group(all P<0.05). Conclusion:ART reduces neuronal apoptosis after stroke, decreases the neuroinflammatory response after stroke, and promotes oxygen-glucose deprivation/reoxygenation-activated microglia BV2 polarization to the M2 type.

Objective:To explore the association of different obesity measurement indexes on serum C-reactive protein (CRP) in Chinese adult women.Methods:The data were obtained from baseline and follow-up surveys of the urban Breast Cancer Screening Program in Shuangliu District, Chengdu. A total of 441 adult women were included in the study. A questionnaire survey, physical examination, and laboratory testing were conducted on the subjects. Multivariate logistic regression model, two-level mixed effects logistic regression model, and restricted cubic spline method were used to investigate the linear and nonlinear correlation between different obesity measurement indexes and serum CRP in adult women.Results:For every 1 unit increase in BMI, waist circumference (WC), and adiposity, the risk of elevated serum CRP or exacerbation of chronic low-grade inflammation in adult women increased by 16.5%, 5.0%, and 11.1% ( P<0.05), respectively. Both BMI and adiposity were nonlinear correlated with serum CRP. Using BMI=24.0 kg/m 2 as the reference point, serum CRP level increased with the increase of BMI when BMI >24.0 kg/m 2. Using adiposity=30% as the reference point, serum CRP level increased with the increase of adiposity when adiposity >30%. Conclusions:Overall, obesity reflected by BMI had the strongest association with serum CRP in adult women, followed by body fat content reflected by adiposity, and central obesity reflected by WC had the weakest association with CRP. Adult women with BMI >24.0 kg/m 2 or adiposity >30% are at high risk for obesity-related inflammatory manifestations.

【Objective】 In this study， reactive oxygen species （ROS） scavenger N-acetyl-L-cysteine （NAC） was used to explore the inhibitory effect and mechanism of artesunate （ART） on pancreatic carcinoma （PC） cells. 【Methods】 Different concentrations of ART interfered with 3 PC cell lines CFPAC-1， Capan-2 and BxPC3. Cell viability was measured by CCK8； cell migration ability was measured by Transwell method， and the expressions of migration-related proteins E-cadherin， N-cadherin and Vimentin were measured by Western blotting. ROS probe DCFH-DA was used to measure intracellular ROS； LC3 cell immunofluorescence （IF） was used to detect the formation of intracellular autophagosomes. After adding NAC or autophagy inhibitor 3-MA， the cell viability was tested again by CCK8， and the expressions of p-AMPK/ AMPK， p-mTOR/mTOR， p62 and LC3Ⅱ/Ⅰ were detected by Western blotting. 【Results】 ART inhibited the growth of CFPAC-1 and Capan-2 in a time- and dose-dependent manner. After treatment of CFPAC-1 and Capan-2 cells with 200 μmol/L of ART for 48 h， the expression of E-cadherin was upregulated， while N-cadherin and Vimentin were downregulated， and the cell migration ability was significantly reduced. ART significantly upregulated intracellular ROS level and promoted the formation of autophagosomes. NAC could reduce the inhibitory effect of ART on CFPAC-1 and Capan-2 cells， upregulate p-AMPK/AMPK， P62 and LC3Ⅱ/Ⅰ， downregulate the expression of p-mTOR/mTOR， and intensify autophagy. 3-MA could not reverse the inhibitory effect of ART on PC cells. 【Conclusion】 ART is dependent on ROS， but not on autophagy， in exerting an anti-pancreatic carcinoma effect. NAC attenuates the inhibitory effect of ART on PC cells by activating protective autophagy through AMPK/mTOR signaling pathway.