ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

AIM To establish a rapid quantitative analysis model for saponins in Paris polyphylla var.yunnanensis(PPY)by near infrared spectroscopy.METHODS The contents of polyphyllins Ⅰ,Ⅱ,Ⅶ and there total content in PPY were determined by HPLC,while spectral data within the range of 10 000 to 4 000 cm-1 were collected.A quantitative analysis model was established by combining these data with partial least squares regression(PLSR).Multivariate scatter correction(MSC)and vector normalization(SNV)were applied prior to further preprocessing the spectra with original,first-order derivative(1stD),or second-order derivative(2ndD)treatments.Lastly,the model was optimized through non-smoothing(NS),Norris Derivative filtering(Nd),and Savitzky-Golay filtering(S-G)method.Model stability was evaluated based on correlation coefficients and variance.The predicted contents of each saponin component in the validation set samples were calculated.RESULTS The contents of polyphyllins Ⅰ,Ⅱ,Ⅶ were 0.42-17.98,0.46-10.44,0.23-3.86 mg/g,respectively.The total content ranged from 2.91 to 22.1 mg/g.The optimal parameters of three saponins were achieved when selecting the MSC+2ndD+S-G pretreatment method.The corresponding ratio of line segment length to segment gap was 13∶5,15∶5,11∶5,with correlation coefficients of 0.982,0.930,0.958,respectively.The root mean square errors of calibration(RMSEC)were 0.702,0.797,0.238,and the root mean square errors of prediction(RMSEP)were 1.120,0.835,0.304,respectively.The optimal parameters for the total content were obtained when selecting the MSC+2ndD+NS pretreatment method,with a correlation coefficient of 0.970,a RMSEC of 1.090,and a RMSEP of 1.740.CONCLUSION This accurate and rapid method can be used for detection of saponin contents in P.Polyphylla.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To investigate the current situation of nuclear medicine practices, determine the number of nuclear medicine staff, conduct internal exposure monitoring and dose estimation for nuclear mecidine staff engaged in 131I treatment in Zhejiang province. Methods:A survey was conducted over all the 22 hospitals involved in 131I treatment in the province. The 131I activity in thyroid of 96 stafff in 131I treatment workplaces were measured by means of direct method. At the same time, the effective doses from internal exposure were estimated and the influencing factors were analyzed. Results:131I activity in thyroids was found to be above the detection limit for 49 staff (51.04%) in nineteen hospitals. The maximum value of 131I activity was 629.18 Bq. There was no statistically significant difference in 131I detection rate in thyroid of 131I treatment staff between different positions, different genders and different levels of hospitals ( P>0.05). Comparisons of 131I activity of thyroid of nuclear medicine staff for theatment of thyroid cancers had shown that the highest was for nurses, followed by technicians and doctors, and the lowest was for cleaning staff ( H=6.39, P<0.05). The estimated committed effective dose to the nuclear medicine staff ranged from 0.05 to 2.37 mSv, with those below 1 mSv accounting for 93.88% of the total. Logistic regression analysis showed that nursing position was the risk factor contributing to the committed effective dose ( OR=2.805, 95% CI 1.076-7.314). Conclusions:In Zhejiang province, the committed effective dose to thyroid of nuclear medicine staff from 131I internal exposure was not in excess of the dose limit. However, the staff performing iodine therapy still need to strengthen protection against internal exposure and take scientific and effective protective measures to reduce the risk of health hazards from internal exposure.

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To develop a machine learning-based risk prediction model for postoperative acute kidney injury(AKI)and a model for mortality in obese patients admitted to intensive care unit(ICU)in order to improve early warning and prognostic evaluation to support clinical decision-making.Methods Data of obese postoperative ICU patients were retrospectively retrieved from the MIMIC-Ⅳ and eICU databases for statistical analysis.Ultimately,2 520 patients(670 from MIMIC-Ⅳ and 1 850 from eICU databases)were included to build the risk prediction models for AKI and mortality.The data included demographic information,vital signs,laboratory findings,surgical types,comorbidities,and medication use.After data cleaning and preprocessing,Boruta feature selection was applied,followed by the construction of prediction models using 7 machine learning algorithms,that is,Gradient Boosting Machine(GBM),Generalized Linear Model(GLM),k-Nearest Neighbors(KNN),Na?ve Bayes(NB),Neural Network(NNET),Support Vector Machine(SVM),and XGBoost.Model performance was evaluated through cross-validation and external validation.Results In the risk prediction models of AKI,the SVM model achieved the highest AUC value of 0.80 in the testing set and 0.71 in the external validation test.For the risk prediction models of mortality,the GBM model outperformed others in the prediction,attaining an AUC value of 0.91 in the testing set.Conclusion Risk predictive models for postoperative AKI and mortality in obese ICU patients are successfully constructed,and are valuable tools for clinicians to optimize early intervention and improve clinical outcomes for the patients.