The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR /Cas9) immune system is an adaptive immune system widely distributed in bacteria and archaea. It precisely defends against invasion by exogenous phages, viruses, and plasmids through sequence-specific endogenous immune response mechanisms. As the most prominent member of this family, the CRISPR/Cas9 system has evolved into the most widely applied, flexible, and efficient technical platform in the field of genome engineering due to its exceptional genome modification capabilities. Within the CRISPR/Cas9 system, the Cas9 protein, precisely guided by a single-stranded guide RNA (gRNA), can specifically recognize target DNA sequences and induce double-strand breaks. This activates the cell’s DNA repair mechanisms, enabling gene knockout, knock-in, or modification. Demonstrating significant advantages in specificity, flexibility, and operability, CRISPR/Cas9 technology has shown immense potential in the medical field, opening new avenues for modernizing traditional Chinese medicine (TCM) research. On one hand, this technology can be used to construct precise disease models and tailor personalized treatment plans. It enables in-depth elucidation of the molecular mechanisms underlying the action targets and signaling pathways of TCM formulas and active components, thereby unraveling the scientific secrets of their complex mechanisms of action. On the other hand, it demonstrates powerful tool value in improving TCM germplasm resources, identifying and screening superior varieties, evaluating the controllability of TCM quality, and producing innovative drugs, providing technical support for the standardization and precision of TCM. Simultaneously, the high-throughput omics data generated by CRISPR technology is driving artificial intelligence (AI) to construct virtual disease models and drug prediction systems. This empowers the intelligent screening of effective TCM components, the precise prediction of potential targets, and the exploration of “reducing toxicity while enhancing efficacy” through formula combinations. This synergistic innovation between CRISPR and AI aligns perfectly with precision medicine’s urgent demand for personalized, efficient drug development, injecting new momentum into the modernization and transformation of TCM. This paper first systematically reviews and explains the developmental trajectory, structural basis, and action mechanisms of the CRISPR/Cas9 system, tracing its scientific evolution from a bacterial immune system to a gene-editing tool. It then comprehensively outlines the current state of convergence between precision medicine concepts and modernization research in TCM, analyzing the synergistic points and potential spaces for their integration. Against the backdrop of rapid precision medicine advancement, this paper emphasizes how CRISPR/Cas9 gene editing technology empowers in-depth analysis of TCM mechanisms—including specific applications in disease model construction, therapeutic target validation, and multi-target network regulation studies. It further elaborates on its multidimensional practical contributions to modernizing TCM, spanning key domains such as germplasm resource innovation, bioactive compound biosynthesis, quality standardization control, and novel TCM drug development. Finally, this paper envisions the future landscape of deep integration between CRISPR technology and AI: from data-driven intelligent drug screening to high-throughput precision discovery of effective TCM components, and further to intelligent model construction based on “reducing toxicity while enhancing efficacy” mechanisms. The synergistic convergence of these multidimensional technologies will pioneer new scientific paradigms and translational pathways for TCM modernization, propelling TCM toward leapfrogging development in the era of precision medicine.

OBJECTIVE: To explore the application value of joint detection of serum neutrophil-to-lymphocyte ratio (NLR), prostate-specific antigen (PSA) and MMP26 in differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH). METHODS: A total of 61 PCa patients (PCa group) and 63 BPH patients (BPH group) who were treated in The Affiliated Huaian Hospital of Xuzhou Medical University from May 2022 to May 2024 were retrospectively included. The relevant clinical data of all subjects were collected with the serum NLR, PSA and MMP26 levels being detected. Multivariate logistic regression analysis was used to analyze the influencing factors in differentiating PCa from BPH. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum NLR, PSA and MMP26 in differentiating PCa from BPH. RESULTS: The levels of TC and LDL-C in the PCa group were higher than those in the BPH group. And the level of HDL-C in the PCa group was lower than that in the BPH group (P<0.05). The serum levels of NLR, PSA and MMP26 in the PCa group were higher than those in the BPH group (P<0.05). The results of multivariate logistic regression analysis showed that NLR, PSA and MMP26 were risk factors for the diagnosis of PCa in patients (P<0.05). The ROC results showed that the area under the curve (AUC) of NLR, PSA MMP26 and joint diagnosis in the identification of PCa was 0.804, 0.800, 0.809 and 0.905, respectively. The comparison results of AUC showed that the joint diagnosis was superior to the single diagnosis (Z=2.262, 2.177, 2.002, P<0.05). CONCLUSION The joint detection of serum NLR, PSA and MMP26 has significant application value in the differentiation of PCa and BPH, which is expected to become an effective tool for early screening and diagnosis of PCa.
Humans ; Male ; Prostatic Hyperplasia/blood* ; Prostate-Specific Antigen/blood* ; Diagnosis, Differential ; Prostatic Neoplasms/blood* ; Retrospective Studies ; Neutrophils ; Lymphocytes ; ROC Curve ; Aged ; Middle Aged

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective:To investigate the risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrilla-tion(AF)after percutaneous left atrial appendage closure(LAAC)combined with radiofrequency ablation(RFA).Meth-ods:A total of 199 elderly AF patients who admitted in Department of Cardiology,Yuhuangding Hospital between Jan 1st,2019 and Aug 17th,2023 and underwent LAAC combined RFA were enrolled.The patients were divided into case group(n=78)and control group(n=121)according to presence of atrial arrhythmia and/or cerebral infarction(CI)within one year after operation.Baseline clinical data,laboratory indexes and color Doppler ultrasound indexes were compared be-tween the two groups,and multivariate Logistic regression was used to analyze the risk factors for postoperative atrial ar-rhythmia and/or CI.Receiver operating characteristic(ROC)curve was constructed to analyze the predictive efficacy of risk factors for atrial arrhythmia and/or CI after operation.Results:Univariate analysis indicated that compared with pa-tients in control group,those in case group had significant higher proportions of preoperative persistent atrial fibrillation(52.60％ vs.37.20％),old myocardial infarction(OMI)(11.50％vs.1.70％)and left atrial diameter(LAD)[(45.47±6.90)mm vs.(43.34±6.64)mm](P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated history of OMI(OR=8.736,95％CI 1.772～43.069,P=0.008)and LAD(OR=1.053,95％CI 1.006～1.102,P=0.027)were independent risk factors of adverse outcomes in elderly AF patients after LAAC+RFA.ROC analysis indicated that predic-tive efficacy of combined detection of OMI and LAD(AUC=0.663,95％CI 0.593～0.728)for adverse outcomes within 1 year in elderly AF patients after LAAC+RFA was significantly better than those of OMI(AUC=0.549,95％CI 0.477～0.620)and LAD(AUC=0.602,95％CI 0.531～0.671)alone(Z=3.045,2.312,P=0.002,0.021).Conclusion:His-tory of old myocardial infarction and left atrial diameter are independent risk factors for atrial arrhythmia and/or cerebral infarction within 1 year after percutaneous left atrial appendage closure combined with radiofrequency ablation in elderly patients with atrial fibrillation,and the combination has good predictive performance.

Objective:To investigate the risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrilla-tion(AF)after percutaneous left atrial appendage closure(LAAC)combined with radiofrequency ablation(RFA).Meth-ods:A total of 199 elderly AF patients who admitted in Department of Cardiology,Yuhuangding Hospital between Jan 1st,2019 and Aug 17th,2023 and underwent LAAC combined RFA were enrolled.The patients were divided into case group(n=78)and control group(n=121)according to presence of atrial arrhythmia and/or cerebral infarction(CI)within one year after operation.Baseline clinical data,laboratory indexes and color Doppler ultrasound indexes were compared be-tween the two groups,and multivariate Logistic regression was used to analyze the risk factors for postoperative atrial ar-rhythmia and/or CI.Receiver operating characteristic(ROC)curve was constructed to analyze the predictive efficacy of risk factors for atrial arrhythmia and/or CI after operation.Results:Univariate analysis indicated that compared with pa-tients in control group,those in case group had significant higher proportions of preoperative persistent atrial fibrillation(52.60％ vs.37.20％),old myocardial infarction(OMI)(11.50％vs.1.70％)and left atrial diameter(LAD)[(45.47±6.90)mm vs.(43.34±6.64)mm](P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated history of OMI(OR=8.736,95％CI 1.772～43.069,P=0.008)and LAD(OR=1.053,95％CI 1.006～1.102,P=0.027)were independent risk factors of adverse outcomes in elderly AF patients after LAAC+RFA.ROC analysis indicated that predic-tive efficacy of combined detection of OMI and LAD(AUC=0.663,95％CI 0.593～0.728)for adverse outcomes within 1 year in elderly AF patients after LAAC+RFA was significantly better than those of OMI(AUC=0.549,95％CI 0.477～0.620)and LAD(AUC=0.602,95％CI 0.531～0.671)alone(Z=3.045,2.312,P=0.002,0.021).Conclusion:His-tory of old myocardial infarction and left atrial diameter are independent risk factors for atrial arrhythmia and/or cerebral infarction within 1 year after percutaneous left atrial appendage closure combined with radiofrequency ablation in elderly patients with atrial fibrillation,and the combination has good predictive performance.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Due to the poor ionization efficiency and the weak mass spectrometry(MS)intensity of weakly polar substances,direct analysis using the traditional electrospray ionization mass spectrometry(ESI-MS)is a big challenge.In this study,a novel rapid on-site detection method of four prohibited sex hormones in cosmetics was proposed using online derivatization strategy coupled with a miniature mass spectrometer.The target substances in the samples were extracted by a custom-made polyaniline/multi-walled carbon nanotube solid-phase microextraction(SPME)probe.The stirring speed was 200 r/min,the extraction temperature was 40℃,and the extraction time was 2 min.A pulled dual-channel θ borosilicate glass capillary emitter was used as the nano-ESI ion source.The SPME probe was inserted into the channel containing methanol in theθborosilicate glass capillary.When the spray voltage was applied,the four sex hormones were desorbed and formed spray microdroplets,which then collided with the hydroxylamine microdroplets generated from the other channel.The microdroplets of reaction product entered into the miniature mass spectrometer for direct analysis.The limits of detection(LOD)and limits of quantification(LOQ)for the four sex hormones were 10-20 ng/mL and 20-50 ng/mL,respectively.The recoveries were from 84.6%to 107.8%with the relative standard deviations(RSD)from 4.1%to 11.6%.Compared to detection without derivatization,the MS signals of the four target substances were increased by 3 to 15 times.This method was simple,rapid,highly efficient and sensitive,and suitable for on-site rapid analysis of weakly polar sex hormones in cosmetics.