Objective:To investigate the miRNA-mRNA regulatory network in a rat model of Tourette syndrome(TS)using transcriptomic technology and to screen key signaling pathways and potential traditional Chinese medicine(TCM)candidates for intervention.Methods:A TS rat model was established using iminodipropionitrile(IDPN).RNA sequencing was performed to identify differentially expressed miRNAs and mRNAs in the brain tissues of TS rats.Bioinformatics analysis was applied to construct interaction networks,and network pharmacology was further employed to screen potential TCM compounds.Results:After 7 days of IDPN modeling,the model group exhibited motor and stereotypical behavioral changes,with behavioral scores greater than 3 points.Hema toxylin-eosin(HE)staining revealed irregular neuronal nuclear morphology,uneven chromatin distribution,nuclear pyknosis,and increased glial cell density.KEGG enrichment analysis identified key pathways:calcium signaling pathway,neuroactive ligand-receptor interaction,p53 signaling pathway,ECM-receptor interaction,and TGF-β signaling pathway.miR-125a-3p,miR-106-3p,and miR-760-3p were identified as pivotal miRNAs.Potential TCM candidates included Ajuga decumbens,Acanthopanax bark,Codonopsis pilosula,Stephania japonica,Os Draconis,Notopterygium root,Siraitia grosvenorii,Zanthoxylum nitidum root,Morinda officinalis,and Corydalis yanhusuo.Conclusion:The miRNAs miR-106-3p,miR-125a-3p,and miR-760-3p may mediate TS pathogenesis by altering critical signaling networks,including the calcium signaling pathway,neuroactive ligand-receptor interaction,and ECM-receptor interaction pathways,leading to neuroimmune inflammation and dopaminergic system dysregulation.TCM compounds such as Corydalis yanhusuo and Ajuga decumbens may exert therapeutic effects through multi-component synergistic regulation of these miRNAs and downstream pathways.

Objective By comparing the prevalence and mortality of dementia among rural people in Xi'an in 1997 and 2014 to clarify the epidemiological changes of dementia among rural people in the city over 17 years.Methods In 1997 and 2014,people aged 55 and above in villages in Xi'an were selected by random cluster sampling method,and face-to-face questionnaire survey was conducted by combining centralized and home visits.Dementia and its subtypes were diagnosed by"the three-step method";the changes of dementia prevalence and mortality were compared between the two surveys.Results The prevalence of dementia among rural residents aged 55 and above in Xi'an was 3.49％in 1997,with age-gender standardized prevalence of 2.08％.In 2014,the prevalence of dementia was 4.25％,with age-gender standardized prevalence of 2.78％.Over the 17 years,the prevalence of dementia increased by 1.79 times(OR=1.79,95％CI:1.20-2.65,P=0.004),with a 1.9-fold increase in females and a 1.67-fold increase in males.The mortality of dementia patients was 61.76‰ and age-gender standardized mortality was 60.20‰ in 1997,while the mortality was 35.71‰ and age-gender standardized mortality was 34.18‰ in 2014.The mortality of dementia decreased by 33％over the 17 years(HR=0.33,95％CI:0.15-0.74,P=0.007).Conclusion The prevalence of dementia in rural areas of Xi'an increased significantly over the 17 years,but the mortality rate decreased,and this trend was more obvious in women.

Objective:To investigate the effects of combination therapy with aqueous extract of corn silk(CS)and training on exercise capacity and glycolipid metabolism in mice with metabolic syndrome(MS).Methods:In this study,db/db mice were used as the animal model of MS.The mice were administered aqueous extract of CS via gavage and subjected to different intensities of training for 12 weeks(3 months).The specific experimental design was as follows:24 db/db mice were randomly divided into four groups on average:negative control group(NC),aqueous extract of CS group(CS),aqueous extract of CS+moderate-intensity training group(CS+MT),and CS aqueous extract of CS+high-intensity training group(CS+HT).The maximum running speed,forelimb grip strength,body weight and fasting blood glucose of mice were measured before and after treatment.After the intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted to assess glucose metabolism,while serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels were measured to evaluate lipid metabolism.Results:After 3 months of intervention,there were significant differences in the maximum running speed and forelimb grip strength among the four groups(P＜0.05).The maximum running speed and forelimb grip strength of CS group,CS+MT group and CS+HT group were higher than those of NC group(P＜0.05).The CS+MT group exhibited higher forelimb grip strength,and the CS+HT group showed higher maximum running speed and forelimb grip strength compared to the CS group(P＜0.05),while no significant difference was found between the CS+MT and CS+HT groups(P＞0.05).Significant differences in body weight were observed among the four groups after 3 months of intervention(P＜0.05).Specifically,the CS+MT and CS+HT groups exhibited significantly lower body weight compared to both the NC and CS groups(P＜0.05),with the CS+MT group having the lowest body weight(P＜0.05).Fasting blood glucose levels also differed significantly among the groups after 2 and 3 months of intervention(P＜0.05).The CS,CS+MT,and CS+HT groups had lower fasting blood glucose levels compared to the NC group(P＜0.05),with the CS+MT and CS+HT groups showing the lowest levels(P＜0.05).No significant difference was found between the CS+MT and CS+HT groups(P＞0.05).After 3 months of intervention,significant differences in the area under the curve(AUC)of OGTT and ITT were observed among the four groups(P＜0.05).The AUC of OGTT and ITT were significantly lower in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT and CS+HT groups exhibited the lowest AUC values for both OGTT and ITT(P＜0.05),with the CS+MT group showing the lowest AUC for OGTT(P＜0.05).Significant differences in serum lipid levels were observed among the four groups after 3 months of intervention(P＜0.05).TG,TC,and LDL-C levels were significantly lower,while HDL-C levels were higher in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT group had the lowest TG levels and the highest HDL-C levels compared to the CS+HT group(P＜0.05),with no significant differences in TC and LDL-C levels between these two groups(P＞0.05).Conclusion:Aqueous extract of CS combined with different intensity training can significantly improve the exercise capacity and glycolipid metabolism of MS mice and reduce body weight,especially CS combined with MT treatment is more effective in improving lipid metabolism.In addition,when combined with HT,aqueous extract of CS can also play an auxiliary role in reducing the side effects of high-intensity exercise and improving the therapeutic effect.

AIM:This study aimed to identify the key active components and signaling pathways in the tradi-tional Chinese medicine Fructus Aurantii that contribute to the prevention and treatment of cardiac hypertrophy,along with experimental validation.METHODS:H9C2 cardiomyocytes were pretreated with nobiletin(NOB)for 1 h and then ex-posed to 100 nmol/L angiotensin Ⅱ(Ang Ⅱ)for 24 h.RT-qPCR was used to quantify the mRNA expression of hypertrophy-related genes,including atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and myosin heavy chain 7(MYH7).Immunofluorescence staining was employed to assess the surface area of cardiomyocytes.Additionally,a kit was utilized to measure levels of pyroptosis-related factors such as lactate dehydrogenase(LDH),interleukin-1β(IL-1β),IL-18 and caspase-1,while Western blot was performed to evaluate the expression of gasdermin D and caspase-1.RESULTS:Network pharmacology analyses indicated that NOB is the key active component in Fructus Aurantii that regu-lates cardiac hypertrophy,potentially through the pyroptosis pathway.Further molecular biology experiments confirmed that NOB inhibits Ang Ⅱ-induced cardiac hypertrophy and pyroptosis.Furthermore,the involvement of the pyroptosis pathway was highlighted in the protective effects of NOB against cardiac hypertrophy.CONCLUSION:The active compo-nent NOB in the traditional Chinese medicine Fructus Aurantii alleviates cardiac hypertrophy by inhibiting pyroptosis.

Objective To establish the content determination method of Zhihuoding granules(ZHDG)by the anti-inflammatory active ingredients and fingerprint.Methods The inflammatory model of BEAS-2B cells was established by LPS(10 μg·mL-1)stimulation for 24 h,and the level of TNF-α in the supernatant was detected by enzyme-linked immunosorbent assay(ELISA).Using the reverse high-performance liquid chromatography(RP-HPLC)of 7 batch ZHDG fingerprint;HPLC was used to determine the content of geniposide and baicalin in granules.Results Compared with LPS Group,ZHDG,prim-O-glucosylcimifugin,5-O-methylvisammioside,baicalin,geniposide,and total polysaccharide extract all significantly decreased TNF-αlevels in BEAS-2B cells induced by LPS(P＜0.05).Fingerprint spectra of 7 batches of ZHDG were established,with a similarity of 1.000 to the reference.A total of 15 peaks were calibrated,and 7 chromatographic peaks were identified.Gardenin and baicalin were selected as the index components of ZHDG for evaluation.The established method was rapid and accurate.Conclusion The method for the determination of baicalin and geniposide in ZHDG are exclusive,accurate,and effective,providing reference for the quality control and clinical application of ZHDG.

Objective:This study constructed a mouse model carrying the human SNCA gene with E46K and A53T double mutations through transgenic technology,providing a suitable experimental animal model for drug screening,safety evaluation,pathogenesis research of Parkinson's disease,and studies on neurodegenerative diseases associated with abnormal α-synuclein aggregation.Methods:Using transgenic techniques,we introduced the human SNCA gene with the E46K and A53T mutations into the C57BL/6J mouse genome.These mutations are associated with familial PD and are known to promote α-Synuclein aggregation and neurotoxicity.The resulting B6-hSNCA E46K/A53T transgenic mice were systematically evaluated through behavioral tests to assess motor dysfunction,immunohistochemistry to characterize α-Synuclein pathology,and Western blotting to quantify molecular changes.Additionally,the therapeutic potential of glial cell line-derived neurotrophic factor(GDNF)delivered via adeno-associated virus(AAV)was assessed.Results:The B6-hSNCA E46KA53T double-mutant mice exhibitα-Synuclein aggregation in brain regions such as the cortex,brainstem,and cerebellum starting from 1-months-old.Phosphorylated α-Synuclein protein at serine 129 is detected in regions including the cortex and hippocampus.By 2-months-old,these mice begin to show significant declines in limb strength and motor coordination,as evidenced by grip strength and rotarod tests,displaying motor impairments reminiscent of Parkinson's disease.From 3-months-old,high-performance liquid chromatography(HPLC)reveals a reduction in dopamine and its metabolites in the striatum.Following treatment with AAV-GDNF injection,the mice demonstrate partial improvement in motor behaviors,as observed in rotarod and grip strength behavioral tests.Conclusion:The B6-hSNCA E46KA53T double-mutant mouse model effectively simulates the onset and progression of Parkinson's disease,demonstrating high clinical relevance.This model not only serves as a valuable tool for investigating the pathogenesis of Parkinson's disease but also provides a critical experimental platform for screening and safety evaluation of drugs targeting abnormal α-Synuclein aggregation.It holds significant potential for advancing the development of early diagnostic methods and targeted therapeutic strategies for Parkinson's disease.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.

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.

Objective:To explore the protective effect and mechanism of Rougan Tongluo Decoction on ischemic stroke induced motor disorder rats based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Cysteinyl aspartate specific proteinase 1(Caspase-1)pathway.Methods:Establishing a rat model of ischemic stroke with motor disorders using the modified suture method.The rats were randomly divided into model control group,Rougan Tongluo Decoction low,medium and high dose groups and butylphthalide soft capsule group,with 10 rats in each group,Another 10 rats were selected as sham surgery group.After 28 days of administration,the neurological function of rats in each group was evaluated by the Zea-Longa scoring method;The forelimb grasping force of rats in each group was detected by grip tester;The coordination ability of rats was evaluated by rat-mouse rotarod instrument;The expression of NLRP3,GSDMD,Caspase-1 protein and Interleukin-1β(IL-1β)was detected by immunohistochemistry.Results:The NLRP3,Caspase-1,GSDMD protein and IL-1β expression Zea-Longa score in the cerebral cortex of the model control group were significantly higher than those in sham surgery group,the forelimb grasping force was lower than that in sham surgery group,and the latency period for turning the baton was shorter than that in sham surgery group(P＜0.05).The Zeba-Longa score,NLRP3,Caspase-1,GSDMD protein and IL-1 β expression in the cerebral cortex the butylphthalide soft capsule group,low dose,medium dose,high dose Rougan Tongluo decoction group were lower than those in model control group,the forelimb grasping force was higher than that in model control group,and the latency period for turning the baton was longer than that in model control group(P＜0.05).Conclusion:Rougan Tongluo Decoction may alleviate inflammatory response by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to improve neurological function and motor ability in ischemic stroke induced motor disorder rats.

Objective To explore the differences in coronary-based and lesion-based fat attenuation index(FAI)in patients with coronary artery disease(CAD)across different risk stratifications,and to compare the diagnostic efficiency of coronary-based and lesion-based FAI in stable CAD patients with myocardial ischemia.Methods The patients with CAD,who underwent preoperative coronary CT angiography(CCTA)and invasive coronary angiography(ICA)with coronary fractional flow reserve(FFR)measurement between Apr 2019 and Oct 2022 in Zhongshan Hospital,Fudan University,were retrospectively collected.There were 57 cases of acute coronary syndrome(ACS)patients and 206 cases of stable CAD patients included following inclusion criteria.The coronary-based and lesion-based FAI were measured,and the differences in these indices were recorded and analyzed among ACS patients,ischemic and non-ischemic groups of stable CAD patients(FFR=0.8 as the threshold).ROC curves were utilized to assess the diagnostic efficiency of coronary-based and lesion-based FAI for myocardial ischemia in stable CAD patients.Results The coronary-based FAI and lesion-based FAI in ACS patients were significantly higher than those in stable CAD patients[coronary-based FAI:(-72.40±6.83)HU vs.(-76.82±9.01)HU,P<0.001;lesion-based FAI:(-65.65±4.79)HU vs.(-77.48±8.64)HU,P<0.001].Among stable CAD patients,the lesion-based FAI in the ischemic group was significantly higher than that in the non-ischemic group[(-69.28±5.65)HU vs.(-80.10±7.75)HU,P<0.001].The diagnostic efficiency of lesion-based FAI for predicting myocardial ischemia in stable CAD patients was superior to coronary-based FAI(AUC:0.892 vs.0.525,Z=9.803,P<0.001).Conclusion Coronary-based and lesion-based FAI tended to be higher in ACS patients than in stable CAD patients,suggesting a potential for stratifying CAD patients with different risks.Lesion-based FAI showed some promise in evaluating myocardial ischemia among stable CAD patients.