Objective To investigate the role and regulatory mechanism of LINC00657 in the progression of cervical cancer. Methods Bioinformatics analysis predicted potential binding sites between LINC00657 and miR-30a-5p and between miR-30a-5p and Skp2. These sites were verified by using RNA immunoprecipitation and dual-luciferase reporter experiments. LINC00657, miR-30a-5p, and Skp2 mRNA expression levels in cervical cancer tissues and cell lines were assessed by utilizing RT-qPCR. Western blot analysis was employed to examine the protein levels of Skp2 in cells and subcutaneous xenograft tumor models in nude mice. Immunohistochemistry was applied to analyze Skp2 expression in animal tissues. The cellular processes of cervical cancer cell lines were evaluated through CCK-8, scratch, and Transwell assays. Results LINC00657 and Skp2 presented binding sites for miR-30a-5p. In cervical cancer, LINC00657 and Skp2 showed high expression levels (P<0.05), whereas miR-30a-5p displayed low expression (P<0.05). Functional experiments demonstrated that linc00657 upregulates Skp2 expression, a process that is dependent on its sequestration of miR-30a-5p. Conclusion LINC00657 promoted the malignant progression of cervical cancer by upregulating Skp2 expression through specifically sequestering miR-30a-5p, thereby relieving its inhibitory effect on the target gene Skp2.

ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Background: Sex-based differences often influence the therapeutic efficacy and safety of medications. Semen Cuscutae is a traditional tonic botanical drug with sex-specific characteristics, traditionally indicated for conditions such as impotence (exclusive to males) and restless fetus (exclusive to pregnant females). However, most existing studies have focused on a single sex. Objective: To evaluate the sex-specific biological effects of Semen Cuscutae in rats and explore its molecular mechanisms, with the aim of uncovering its pharmacological characteristics through a multiomics approach. Methods: A traditional aqueous extract of Semen Cuscutae (SCA) was used as the experimental material. Forty adult Sprague-Dawley rats (equal numbers of males and females) were randomly divided into 4 groups: male control, male SCA treatment (240 mg/kg), female control, and female SCA treatment (240 mg/kg), with 10 rats in each group. The biological effects were comprehensively evaluated using a combination of open field test, biochemical analyses, proteomics, and gut microbiota profiling. Results: As a tonic botanical drug, SCA appeared to directly affect the mental and behavioral state of rats. It significantly altered the time spent by rats in the center area during the open field test, showing a sex-dependent reversal of behaviors. Proteomic analysis of brain tissue identified 624 differentially expressed proteins across the groups, with 10 key differentially expressed proteins related to sex differences, including fibroblast growth factor receptor 3, transcription elongation factor A protein-like 1, 40S ribosomal protein S25, neural cell adhesion molecule, and anion exchange protein 2 (SLC4A2). Enrichment analysis revealed that in male rats, SCA upregulated proteins involved in biological processes such as ribosome function and energy derivation, supporting protein synthesis and enhancing energy supply, showing an overall gain effect. In contrast, in female rats, SCA downregulated proteins associated with processes such as positive regulation of target of rapamycin (TOR) signaling and vesicle transport, suggesting suppression of neuronal signaling and material transport, indicative of a shift toward a more restrained physiological state. Furthermore, SCA reduced gut microbiota diversity in female rats but increased it in males, including the abundance of Akkermansia, which may serve as a crucial mediator. Conclusion: Overall, the biological effects of SCA differ significantly between male and female rats, with evidence suggesting greater health benefits in males. These findings help elucidate the scientific basis of its traditional applications and provide guidance for the precise application of SCA as a functional health food.

ObjectiveTo analyze the epidemiological characteristics of 21 respiratory pathogens in influenza-like illness (ILI) cases in Jing’an District, Shanghai in 2024, and to provide a scientific basis for the prevention and control of respiratory infectious diseases. MethodsData of1 907 ILI cases at four sentinel hospitals in Jing’an District were collected from January to December 2024. Nasopharyngeal swab samples were collected and tested for 21 respiratory pathogens using polymerase chain reaction (PCR) methods. Chi-square test and Cochran-Armitage trend test were used for data analyses. ResultsAmong the 1 907 ILI cases, 1 340 were tested positive (70.27%), including 1 160 (60.83%) virus-positive cases, 424 (22.23%) bacteria-positive cases , and 86 (4.51%) positive cases of other pathogens (fungi, mycoplasma, and chlamydia). The top five viruses by detection rate were: influenza virus (14.84%), SARS-CoV-2 (14.47%), rhinovirus (12.69%), adenovirus (7.08%), and parainfluenza virus (6.71%). The top two bacteria by detection rate were Streptococcus pneumoniae (14.47%) and Haemophilus influenzae (10.33%). Among other pathogens (fungi, mycoplasma, and chlamydia), Mycoplasma pneumoniae showed the highest detection rate (4.30%). In terms of age distribution, statistically significant differences were observed in the detection rates of SARS-CoV-2, Legionella, and Klebsiella pneumoniae (P<0.05), with the highest rates found in individuals aged 65 years and above. Statistically significant differences were also found in the detection rates of rhinovirus, adenovirus, enterovirus, common coronavirus, respiratory syncytial virus, bocavirus, parainfluenza virus, human metapenu-movirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae among different age groups (P<0.05), all showing the highest detection rates in the 0‒<15 years age group. In terms of seasonal distribution, SARS-CoV-2, adenovirus, parainfluenza virus, enterovirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae showed epidemic peaks in summer; rhinovirus, common coronavirus, bocavirus, and Klebsiella pneumoniae had higher detection rates in autumn. Influenza virus exhibited a peak incidence during winter, while human metapenu-movirus peaked in winter and spring. Significant differences in co-infection detection rates were observed among age groups, with the rate in children aged 0‒<15 years (34.81%) being the highest. The co-infection detection rate was higher in males than in females (P=0.019). Both the single-pathogen detection rate and the co-infection detection rate (P<0.001) varied significantly across seasons: the single-pathogen detection rate was highest in winter (62.06%), while the co-infection detection rate peaked in summer (31.20%) and was lowest in winter (14.52%). ConclusionBased on detection rates, the main pathogens in the ILI population of Jing’an District, Shanghai, 2024 were influenza virus, SARS-CoV-2, rhinovirus, adenovirus, parainfluenza virus, common coronavirus, enterovirus, Human metapenu-movirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. Pathogen detection rates varied by age and season. Coinfection rates were much higher in children than in adults, higher in males than in females, and peaked in summer while being lowest in winter.

Objective To analyze the correlations between the thoracic electrical impedance tomography(EIT)-derived parameters global inhomogeneity(GI),center of ventilation(COV),regional ventilation delay(RVD),and atelectasis in hospitalized patients,and to explore their effectiveness in evaluating atelectasis.Methods The clinical data of 140 hospitalized patients monitored by thoracic EIT between Sep.2024 and Jan.2025 were retrospectively analyzed.Patients were assigned to 2 groups based on chest computed tomography confirmation of atelectasis within the preceding short-term period during EIT monitoring:non-atelectasis group or atelectasis group.The algorithm software designed with MATLAB was used to acquire GI and COV.RVD was obtained through analysis with the Dr?ger EIT Data Analysis Tool 6.3 software,and patients'general data were concurrently documented.Comparative analysis of EIT-derived parameters between groups was conducted.Multivariate logistic regression analysis was employed to investigate the correlations of GI,COV,and RVD with atelectasis,while receiver operating characteristic curve analysis was performed to assess the efficacy of EIT-derived parameters in evaluating atelectasis.Results A total of 140 patients were enrolled,with 19(13.6%)cases presenting atelectasis.Compared to the non-atelectasis group,the atelectasis group demonstrated significantly higher proportions of male patients and cardiovascular disease and thoracic surgery(non-pulmonary)histories,lower body mass index(BMI),and alongside elevated GI and RVD values with reduced COV(all P＜0.05).Multivariate logistic regression analysis revealed that GI,COV,and RVD maintained independent associations with atelectasis after adjusting for age,gender,BMI,pleural effusion,and emphysema(odds ratio[OR]=1.39,95%confidence interval[CI]1.20-1.67;OR=0.85,95%CI 0.75-0.96;OR=1.22,95%CI 1.09-1.39;all P＜0.05).The area under curve(AUC)values of GI,COV,and RVD for evaluating atelectasis in hospitalized patients were 0.82,0.80,and 0.82,respectively(while RVD demonstrated a higher AUC,its clinical applicability was influenced by respiratory patterns).Conclusion Thoracic EIT-derived parameters GI and COV demonstrate significant correlations with atelectasis and may serve as valuable indicators for evaluating atelectasis in hospitalized patients.

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Background and aims:Studies indicate that the gut microbiota and its metabolites are involved in the progression of cardiovascular diseases,and enterohepatic circulation plays an important role in this progression.This study aims to identify potential probiotics for the treatment of unstable angina(UA)and elucidate their mechanisms of action.Methods:Initially,the gut microbiota from patients with UA and control was analyzed.To directly assess the effects of Bifidobacterium supplementation,10 patients with UA were enrolled and administered Bifidobacterium(630 mg per intake twice a day for 1 month).The fecal metagenome,serum trimethyl-amine N-oxide(TMAO)levels,and other laboratory parameters were evaluated before and after Bifido-bacterium supplementation.Results:After supplementing with Bifidobacterium for 1 month,there were statistically significant dif-ferences(P＜0.05)in TMAO,aspartate aminotransferase,total cholesterol,and low-density lipoprotein compared to before.Additionally,the abundance of Bifidobacterium longum increased significantly,although the overall abundance of Bifidobacterium did not reach statistical significance.The gut micro-biota,metabolites,and gut-liver axis are involved in the progression of UA,and potential mechanisms should be further studied.Conclusions:Metagenomic analysis demonstrated a reduced abundance of Bifidobacterium in patients with UA.Supplementation with Bifidobacterium restored gut dysbiosis and decreased circulating TMAO levels in patients with UA.This study provides evidence that Bifidobacterium may exert cardiovascular-protective effects through the gut-liver-heart axis.

ObjectiveTo improve the efficacy of Astragalus membranaceus (Fisch.) Bunge (A. membranaceus, Huang Qi), and to further develop and utilize it, fermentation technology was applied to the stem and leaf of A. membranaceus to enhance its immune function.MethodsIn this study, we fermented A. membranaceus stem and leaf (ASL) with probiotics and investigated its immune function. Firstly, we screened suitable strains for ASL fermentation and optimized the fermentation process. Secondly, we determined the antioxidant capacity of fermented ASL and its effect on inflammation in mouse monocyte-macrophage cell. Finally, the immunocompromised mice were treated with fermented ASL to investigate the changes in their immune ability.ResultsAmong the 10 selected probiotics, Lactobacillus plantarum was the most suitable strain for ASL fermentation. After optimization of the fermentation process, the content of saponins in fermented ASL was significantly increased. The fermented ASL exhibited strong anti-inflammatory and antioxidant activities in vitro. The in vivo immune efficacy improved by promoting the development of the spleen and thymus, as well as raising the immunoglobulin M, tumor necrosis factor-α, and interleukin-1β levels of in the serum.ConclusionThis study contributes to developing the non-medicinal parts of A. membranaceus, expands its medicinal resources, highlights the potential of fermentation technology to enhance these parts, and provides a reference for further development. Based on this approach, we can promote using non-medicinal parts of herbal medicines, minimize drug waste, and offer a reference for developing non-medicinal components in Chinese herbal medicines.

Objective: To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis. Methods: Human hepatoma cell lines PLC/PRF/5 and Huh_7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating agent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh_7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK_8 kit. The cell death induced by ES + Cu2 + was detected by flow cytometry and the changes of ES + Cu2 + after pretreatment with copper chelating agent ATTM. The expression of Cuproptosis related proteins ATPase copper transporting beta (ATP7B) ,ferredoxin 1 (FDX1) , dihydrolipoamide s_acetyltransferase(DLAT) and superoxide dismutase 1 (SOD1) were detected by Western blot. The effect of ES + Cu2 + on cell proliferation and the reverse effect after ATTM pretreatment was detected by cell scratch assay. Results: The toxicity of ES + Cu2 + to human hepatocellular carcinoma cell lines PLC/PRF/5 and Huh_7 was significantly dose_dependent (P < 0. 05) . Compared with the control group , the combined application of ES and Cu2 + had a more significant inhibitory effect on hepatocellular carcinoma cells than ES or Cu2 + alone (P < 0. 05) , and copper chelating agent ATTM could reverse the inhibitory effect of ES + Cu2 + on hepatocellular carcinoma cells (P < 0. 05) . Flow cytometry results showed that compared with the control group , the proportion of cell death in PLC/PRF/5 and Huh_7 cells treated with ES + Cu2 + increased , while the proportion of cell death decreased after ATTM intervention (P < 0. 05) . The results of cell scratch test showed that the migration ability of PLC/PRF/5 and Huh_7 cells was decreased after ES + Cu2 + treatment , however, the addition of ATTM reversed the inhibitory effect of ES + Cu2 + on cell migration (P < 0. 05) . Compared with the control group , the expression levels of copper death related proteins ATP7B , FDX1 , DLAT and SOD1 decreased after ES + Cu2 + treatment , but the addition of ATTM reversed the expression trend of these proteins (P < 0. 05) . Conclusion The combination of ES and Cu2 + can effectively inhibit the proliferation and migration of PLC/PRF/5 and Huh_7 of hepatocellular carcinoma cells , and induce Cuproptosis , which provides a new strategy for the treatment of hepatocellular carcinoma.