Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

Objective To propose and validate a decomposition method based on half-projection reconstruction for dual-energy cone beam CT(DE CBCT),thereby providing a potentially feasible low-dose imaging solution for anatomical monitoring and dose reconstruction optimization in adaptive radiotherapy.Methods Dual-energy scans were performed on a Gammex phantom using the on-board kilovoltage CBCT system of a VitalBeam accelerator at acquisition frame rates of 15 and 7 frames per second(f/s).Images were reconstructed from the projection data,and dual-energy decomposition was applied to the 7 f/s dual-energy images to derive relative electron density(RED)and stopping power ratio(SPR)using weighted formulas and empirical functions,followed by accuracy evaluation.Additionally,the weighted CT dose index was calculated for different scanning parameters.Results Dual-energy decomposition effectively suppressed image artifacts,with RED and SPR errors remaining below 2.82%and 2.56%,respectively.Compared with the traditional dual-scan method which required high-and low-energy acquisitions,the weighted CT dose index of the half-projection DE CBCT was reduced by 11.60 mGy(a 52.90%reduction).Furthermore,it was 2.58 mGy lower than the dose of the full-projection high-energy CBCT alone(a 19.98%reduction)and only 1.31 mGy higher than that of the low-energy CBCT(a 14.52%increase).Conclusion The proposed method effectively suppresses image artifacts while maintaining high accuracy in RED and SPR under low radiation dose conditions,demonstrating its potential value for scenarios requiring frequent image guidance,such as adaptive radiotherapy.

To study the epidemiological characteristics of dengue fever(DF)cases and the molecular characteristics of local dengue virus(DENV)in Fujian from 2019 to 2022,and provide evidence for the prevention and control of DF.Statistically analyzed the demographic and epidemiological characteristics of imported and local DF cases.The locally prevalent strains from various regions and some imported strains were sequenced to analyze homology and construct phylogenetic trees by using software MEGA(version 6.0).A total of 1 661 DF cases,including 699 imported cases and 962 local cases were reported in Fujian from 2019 to 2022.The imported cases were mainly concentrated from June to October,whereas the local cases were mainly concentrated from August to October.All 10 cities in Fujian had imported cases reported,and local cases had been reported in all regions except Longyan.The male to female ratio in the imported cases(4.07∶1)was higher than that in the local cases(0.95∶1),and the median age of the imported cases(43 years old)was lower than that of the local cases(46 years old).The imported cases mainly came from Cambodia locally prevalent strains of DENV1 all belonged to genotypeⅠ,which may originate from other provinces or Southeast Asian countries such as Cambodia.The first locally prevalent cases of DENV4 were found in Putian,and the phylogenetic trees of DENV4 E gene showed that the locally prevalent strains of DENV4 in Putian were genotypeⅡ,which may originate from Singapore.They face a high risk of local DF outbreaks caused by imported DF cases,and the local epidemic areas appear a certain degree of spreading trend.It is necessary to strengthen the multi-sectoral cooperation and improve supervision systems.Timely discovery and tracing of cases to provide a basis for scientific prevention and control of DF.

BACKGROUND:Matrigel is the best material for the culture of tumor organoids,but matrigel alone is not enough to simulate the mechanical environment of tumor growth in vitro.Although the introduction of sodium alginate material can improve the stiffness of the hydrogel based on matrigel,its mechanical properties of hydrogel are difficult to maintain stability in long-term culture.OBJECTIVE:To introduce a small amount of calcium ions into the medium of breast cancer organoids and to observe its maintenance effect on the long-term mechanical properties of the matrigel-sodium alginate hydrogel.METHODS:(1)Sodium alginate composite hydrogels with low,medium,and high stiffness were prepared by introducing different mass concentrations(0,2.5,and 5 mg/mL)of sodium alginate into the constant mass concentration(5 mg/mL)of matrigel.The mechanical properties of hydrogels were measured regularly by rheometer.(2)Human triple negative breast cancer cells MDA-MB-231 were resuspended in hydrogel pre-gels with different stiffness.After gelling,breast cancer organoid factor medium containing(or without)calcium ions was added for breast cancer organoid culture.At a set time point,rheometer was used to regularly measure the effect of calcium ion introduction on the mechanical properties of hydrogel.The morphologic changes of breast cancer organoids were observed under optical microscope.Rate of breast cancer organoids forming into pellets was calculated on day 13.After 7 days of breast cancer organoid culture,different concentrations of the chemotherapy drug docetaxel(0.1,1,10,and 100 nmol/L)were added for intervention for 6 days.Cell viability was detected and the semi-inhibitory concentration of docetaxel,IC50,was calculated.RESULTS AND CONCLUSION:(1)The introduction of sodium alginate effectively improved the mechanical strength of the composite hydrogel.(2)With the extension of breast cancer organoid culture time,the mechanical strength of hydrogels decreased.On day 13 of culture,the mechanical properties of medium and high stiffness hydrogels in the culture environment containing calcium ions were significantly higher than those in the culture environment without calcium ions(P<0.05).There was no significant change in the mechanical properties of low stiffness hydrogels in the two cultures(P>0.05).In long-term culture(13 days),breast cancer organoids changed from round to spindle shape with the decrease of hydrogel mechanical properties in the medium and high stiffness hydrogel groups.After the introduction of calcium ions,the morphology of breast cancer organoids did not change with the extension of culture time in the two groups.The introduction of calcium ions in the culture environment had no effect on the pellet formation rate of breast cancer organoids in the low stiffness hydrogel group,but could improve the pellet formation rate of breast cancer organoids in the medium and high stiffness hydrogel groups.(3)In the culture environment without calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration,and there was no significant difference in IC50 among the three hydrogel groups(P>0.05).In the culture environment containing calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration.The cell viability of breast cancer organoids in the medium and high stiffness hydrogel groups was stronger than that in the low stiffness hydrogel group,and the IC50 was higher than that in the low stiffness hydrogel group(P<0.05).(4)The results showed that the mechanical properties of the matrigel-sodium alginate hydrogel could be maintained by introducing calcium ions into the breast cancer organoid culture system.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

BACKGROUND:Matrigel is the best material for the culture of tumor organoids,but matrigel alone is not enough to simulate the mechanical environment of tumor growth in vitro.Although the introduction of sodium alginate material can improve the stiffness of the hydrogel based on matrigel,its mechanical properties of hydrogel are difficult to maintain stability in long-term culture.OBJECTIVE:To introduce a small amount of calcium ions into the medium of breast cancer organoids and to observe its maintenance effect on the long-term mechanical properties of the matrigel-sodium alginate hydrogel.METHODS:(1)Sodium alginate composite hydrogels with low,medium,and high stiffness were prepared by introducing different mass concentrations(0,2.5,and 5 mg/mL)of sodium alginate into the constant mass concentration(5 mg/mL)of matrigel.The mechanical properties of hydrogels were measured regularly by rheometer.(2)Human triple negative breast cancer cells MDA-MB-231 were resuspended in hydrogel pre-gels with different stiffness.After gelling,breast cancer organoid factor medium containing(or without)calcium ions was added for breast cancer organoid culture.At a set time point,rheometer was used to regularly measure the effect of calcium ion introduction on the mechanical properties of hydrogel.The morphologic changes of breast cancer organoids were observed under optical microscope.Rate of breast cancer organoids forming into pellets was calculated on day 13.After 7 days of breast cancer organoid culture,different concentrations of the chemotherapy drug docetaxel(0.1,1,10,and 100 nmol/L)were added for intervention for 6 days.Cell viability was detected and the semi-inhibitory concentration of docetaxel,IC50,was calculated.RESULTS AND CONCLUSION:(1)The introduction of sodium alginate effectively improved the mechanical strength of the composite hydrogel.(2)With the extension of breast cancer organoid culture time,the mechanical strength of hydrogels decreased.On day 13 of culture,the mechanical properties of medium and high stiffness hydrogels in the culture environment containing calcium ions were significantly higher than those in the culture environment without calcium ions(P<0.05).There was no significant change in the mechanical properties of low stiffness hydrogels in the two cultures(P>0.05).In long-term culture(13 days),breast cancer organoids changed from round to spindle shape with the decrease of hydrogel mechanical properties in the medium and high stiffness hydrogel groups.After the introduction of calcium ions,the morphology of breast cancer organoids did not change with the extension of culture time in the two groups.The introduction of calcium ions in the culture environment had no effect on the pellet formation rate of breast cancer organoids in the low stiffness hydrogel group,but could improve the pellet formation rate of breast cancer organoids in the medium and high stiffness hydrogel groups.(3)In the culture environment without calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration,and there was no significant difference in IC50 among the three hydrogel groups(P>0.05).In the culture environment containing calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration.The cell viability of breast cancer organoids in the medium and high stiffness hydrogel groups was stronger than that in the low stiffness hydrogel group,and the IC50 was higher than that in the low stiffness hydrogel group(P<0.05).(4)The results showed that the mechanical properties of the matrigel-sodium alginate hydrogel could be maintained by introducing calcium ions into the breast cancer organoid culture system.

Aim To explore the effect of FTO on adria-mycin resistance in triple-negative breast cancer through the Wnt/β-catenin signaling pathway and to reveal the underlying mechanism.Methods The MDA-MB-231/ADR drug-resistant cell line was constructed using a method of gradually increasing adriamycin concentra-tion with intermittent induction.The half-inhibitory concentration(IC50)of adriamycin for MDA-MB-231 and MDA-MB-231/ADR cells and the expression of FTO were compared.After knocking down FTO in MDA-MB-231/ADR cells,CCK-8,qRT-PCR,colony formation assay,transwell,flow cytometry,and Western blot were used to assess the changes in the IC50 of adri-amycin,cell proliferation,migration,invasion,apopto-sis,and the expression of related proteins.Results FTO was highly expressed in MDA-MB-231/ADR cells.After FTO knockdown,the IC50 value of adriamy-cin in MDA-MB-231/ADR cells decreased,and the a-bilities of proliferation,migration and invasion were weakened.In the FTO knockdown group,the expres-sion levels of Bax,cleaved-caspase3,GSK-3 β proteins and the apoptosis rate significantly increased,while the expression levels of Bcl-2,Wnt5a,β-catenin,c-myc,cyclin D1,and P-gp proteins decreased.Conclusion FTO may inhibit the apoptosis of MDA-MB-231/ADR cells through the Wnt/β-catenin signaling pathway,al-ter P-gp expression,and thereby enhance the resistance of MDA-MB-231/ADR cells to adriamycin.

Objective:To explore the diagnostic efficacy of monocyte chemotactic protein-1(MCP-1)and creatine kinase isoenzyme(CK-MB)for chronic heart failure(CHF)and their association with New York Heart Associa-tion(NYHA)class.Methods:A total of 300 patients suspected of CHF who underwent physical examination in the Second People's Hospital of Hefei between January 2020 and August 2021 were analyzed.After 3-month follow-up,a total of 150 patients were diagnosed with CHF.According to NYHA cardiac function classification,CHF pa-tients were divided into class Ⅱ group(n=45),class Ⅲ group(n=45)and class Ⅳ group(n=60).MCP-1 and CK-MB levels were compared among above groups.Receiver operating characteristic(ROC)curve was used to an-alyze the diagnostic efficacy of each index and their combination for CHF and their association with NYHA class were analyzed using Spearman correlation analysis.Results:Compared to those without CHF,patients with CHF had significant higher levels of MCP-1[96.01(86.21,124.28)ng/ml vs.25.38(22.79,28.72)ng/ml,P＜0.001]and CK-MB[46.26(32.74,59.72)U/L vs.19.09(18.61,19.87)U/L,P＜0.001].ROC curve showed that a combination of MCP-1 and CK-MB had a significant higher area under the ROC curve(AUC)(0.947,95％CI 0.915～0.969)than MCP-1(0.797,95％CI 0.747～0.841)or CK-MB(0.855,95％CI 0.810～0.893)alone(Z=4.543,3.170,P＜0.001 all).Compared to those in the class Ⅱ group,those in the class Ⅲgroup and class Ⅳ group had significant higher MCP-1[94.57(91.18,96.92)ng/ml vs.125.27(123.20,128.24)ng/ml vs.68.38(27.55,86.38)ng/ml]and CK-MB[48.04(45.66,51.47)U/L vs.61.01(58.81,62.96)U/L vs.31.75(25.08,33.57)U/L],and those of class Ⅳ group were significantly higher than those of class Ⅲ group(P＜0.001 all).Spearman correlation analysis indicated that the levels of MCP-1 and CK-MB were significant positively correlated with NYHA class in CHF patients(r=0.712,0.878,P＜0.001 both).Con-clusion:MCP-1 and CK-MB were abnormally elevated in CHF patients.Serum levels of MCP-1 and CK-MB are significantly correlated with NYHA class.The combination had high diagnostic efficacy for CHF.

Objective:To explore the diagnostic efficacy of monocyte chemotactic protein-1(MCP-1)and creatine kinase isoenzyme(CK-MB)for chronic heart failure(CHF)and their association with New York Heart Associa-tion(NYHA)class.Methods:A total of 300 patients suspected of CHF who underwent physical examination in the Second People's Hospital of Hefei between January 2020 and August 2021 were analyzed.After 3-month follow-up,a total of 150 patients were diagnosed with CHF.According to NYHA cardiac function classification,CHF pa-tients were divided into class Ⅱ group(n=45),class Ⅲ group(n=45)and class Ⅳ group(n=60).MCP-1 and CK-MB levels were compared among above groups.Receiver operating characteristic(ROC)curve was used to an-alyze the diagnostic efficacy of each index and their combination for CHF and their association with NYHA class were analyzed using Spearman correlation analysis.Results:Compared to those without CHF,patients with CHF had significant higher levels of MCP-1[96.01(86.21,124.28)ng/ml vs.25.38(22.79,28.72)ng/ml,P＜0.001]and CK-MB[46.26(32.74,59.72)U/L vs.19.09(18.61,19.87)U/L,P＜0.001].ROC curve showed that a combination of MCP-1 and CK-MB had a significant higher area under the ROC curve(AUC)(0.947,95％CI 0.915～0.969)than MCP-1(0.797,95％CI 0.747～0.841)or CK-MB(0.855,95％CI 0.810～0.893)alone(Z=4.543,3.170,P＜0.001 all).Compared to those in the class Ⅱ group,those in the class Ⅲgroup and class Ⅳ group had significant higher MCP-1[94.57(91.18,96.92)ng/ml vs.125.27(123.20,128.24)ng/ml vs.68.38(27.55,86.38)ng/ml]and CK-MB[48.04(45.66,51.47)U/L vs.61.01(58.81,62.96)U/L vs.31.75(25.08,33.57)U/L],and those of class Ⅳ group were significantly higher than those of class Ⅲ group(P＜0.001 all).Spearman correlation analysis indicated that the levels of MCP-1 and CK-MB were significant positively correlated with NYHA class in CHF patients(r=0.712,0.878,P＜0.001 both).Con-clusion:MCP-1 and CK-MB were abnormally elevated in CHF patients.Serum levels of MCP-1 and CK-MB are significantly correlated with NYHA class.The combination had high diagnostic efficacy for CHF.