ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen for both human bloodstream infections and mastitis in cows. However, little attention has been paid to the cross-host transmission of MRSA from cows to high-risk groups in China. Objective To determine the MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang, identify the antibiotic resistance profiles and molecular characteristics of the isolates, and provide scientific evidence for the formulation of targeted infection control strategies. Method A cross-sectional survey combined with laboratory pathogen analysis was conducted. From June to August 2024, large-scale dairy farms in Xinjiang region were selected as study sites. Nasal swabs (n=96) and skin swabs (n=39) were collected from workers, and bovine nasal swab samples (n=109) were collected simultaneously. All samples were subjected to MRSA isolation, cultivation, and identification, followed by antibiotic susceptibility testing to characterize resistance phenotypes. Staphylococcus aureus protein A (Spa) typing was performed to determine strain genotypes and elucidate MRSA colonization rates and molecular epidemiological patterns. Results A total of 35 MRSA strains was successfully isolated from 244 samples. The MRSA colonization rates among dairy farm workers and dairy cows were 20.83% (20/96) and 12.84% (14/109), respectively, with an overall isolation rate of 14.34% (35/244). Among the workers, the nasal colonization rate was 16.67% (16/96), and the skin colonization rate was 12.82% (5/39). One worker exhibited MRSA colonization at multiple body sites. All MRSA strains were resistant to cefoxitin (100%, 35/35). The resistance rates to erythromycin and clindamycin were 42.86% (15/35) and 34.29% (12/35), respectively. Thirteen strains showed a multidrug-resistant phenotype, whereas all strains were susceptible to vancomycin. The MRSA isolates exhibited high genetic diversity, with 13 Spa types identified, among which t441 was the most prevalent (8 strains). Both t441 and t034 types were detected in samples from both the dairy cows and their handlers. These two Spa types also carried and stably inherited specific resistance combinations, including erythromycin–clindamycin–cefoxitin and ciprofloxacin–erythromycin–clindamycin–gentamicin–cefoxitin–tetracycline, and a statistically significant association was also observed between the two resistance profiles and the bacterial types (P < 0.001). In addition, one novel Spa type strain was identified. Conclusion MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang are relatively high, with evidence of multi-site colonization. The isolates exhibit high levels of multidrug resistance and genetic diversity, indicating a potential risk of cross-host transmission.

Objectives: Osteoporosis is a silent disease with low screening rates in many developing countries. This study aimed to evaluate the feasibility of using an artificial intelligence (AI)-based system to screen osteoporosis from pelvic and hip radiographs in Vietnam. Methods: We conducted a cross-sectional study at a tertiary medical center in Central Vietnam in 2023. A total of 2000 consecutive pelvic and hip radiographs from patients aged ≥ 40 years were collected. After excluding poorquality images, 1987 radiographs were analyzed using an AI-based software designed to estimate bone mineral density (BMD) from plain radiographs and derive T-scores. Osteoporosis was defined as a T-score ≤ − 2.5. Patient characteristics, radiographic findings, and risk factors for osteoporosis were analyzed. Results: Among 1987 patients (mean age 66.4 ± 15.1 years; 41.3% men), osteoporosis was identified in 872 patients (43.9%). The prevalence increased with age and was higher in women than in men (58.7% vs 22.8%, P < 0.001). Osteoporosis was associated with femoral neck (OR = 3.8, 95% CI: 2.7–5.2) and intertrochanteric fractures (OR = 7.0, 95% CI: 4.5–11.0). Patients with lower T-scores had a higher risk of hip fractures, especially those with T-scores ≤ − 3.0 (OR = 11.5, 95% CI: 5.5–24.5). Conclusions AI-based analysis of pelvic and hip radiographs is a feasible and effective tool for osteoporosis screening in Vietnam. The prevalence of osteoporosis in this hospital-based setting was high, particularly among elderly women.AI-assisted screening may offer an accessible strategy for early detection of osteoporosis in resource-limited settings.

ObjectiveTo investigate the efficacy and safety of Shuganning injection in the treatment of liver injury by observing the clinical outcome of patients with liver injury after treatment with Shuganning injection and comparing it with reduced glutathione （GSH）. MethodsThis study was conducted among 175 patients with liver injury who attended 6 hospitals in China （Beijing YouAn Hospital， Capital Medical University； Nanyang First People’s Hospital； The Second Affiliated Hospital of Xi’an Jiaotong University； The Fifth Medical Center of Chinese PLA General Hospital； The Third Hospital of Hebei Medical University； The Affiliated Hospital of Guizhou Medical University） from April 25， 2019 to February 28， 2022. The patients were divided into experimental group （89 patients treated with Shuganning injection） and control group （86 patients treated with GSH）， and the course of treatment was 4 weeks for both groups. Related indicators were recorded before treatment， after treatment， and after drug withdrawal for 8 weeks， including liver function parameters， blood biochemical parameters， blood lipids， coagulation profiles， liver fibrosis markers， traditional Chinese medicine （TCM） syndrome score， and ultrasound findings， as well as adverse events during treatment. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Wilcoxon signed-rank test was used for comparison of observation indicators before treatment， at week 4 of treatment， and after drug withdrawal for 8 weeks. When the efficacy evaluation of TCM syndromes was used as the outcome， a pooled analysis was performed for the effective cases and the markedly effective cases， and a Logistic regression model was used to calculate the odds ratio （OR） and its 95%CI. ResultsAfter 4 weeks of treatment with Shuganning injection， the patients showed significant reductions in TCM syndrome score （P<0.001） and the levels of aspartate aminotransferase， alanine aminotransferase， total bilirubin， and direct bilirubin （all P<0.001） and a significant increase in the level of albumin （P=0.002）， and these significant improvements persisted after drug withdrawal for 8 weeks. Furthermore， compared with the control group， the experimental group had a significantly higher proportion of patients assessed as effective or markedly effective cases （48.31% vs 32.56%， P=0.033）. Compared with the control group， the experimental group had a significantly greater change in TCM syndrome score at weeks 1-4 of treatment and after drug withdrawal for 8 weeks （P<0.05）. At week 4 of treatment， the experimental group had a significantly greater reduction in alanine aminotransferase than the control group （P<0.05）， and at week 8 after drug withdrawal， the experimental group had a significantly greater reduction in alanine aminotransferase and aspartate aminotransferase than the control group （all P<0.05）. One patient in the experimental group （1.12%） experienced an adverse event， which was determined to be associated with the progression of viral hepatitis. ConclusionShuganning injection can effectively improve liver injury， with good long-term efficacy and a low incidence rate of adverse reactions.

Objective:To investigate the factors influencing early recurrence for patients with initially unresectable hepatocellular carcinoma (HCC) who underwent salvage liver resection (SLR) following transcatheter arterial chemoembolization-based downstaging treatment, and construct a predictive model to evaluate its predicting performance.Methods:The retrospective cohort study was constructed. The clinicopathological data of 305 patients with initially unresectable HCC who were admitted to 4 medical centers in China, including the Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) et al, from January 2019 to December 2021 were collected. There were 286 males and 19 females, aged (48.7±10.4)years. A total of 133 patients who were admitted from January 2019 to December 2020 were set as the training cohort, and the other 172 patients who were admitted from January to December 2021 were set as the validation cohort. Observation indicators: (1) postoperative recurrence-free survival in HCC patients; (2) analysis of factors influencing postoperative early recurrence in HCC patients; (3) construction and validation of the predictive model. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regre-ssion model. The Kaplan-Meier method was used to calculate survival. The Log-rank test was used for survival analysis. The predicting performance of the model was evaluated using the concordance index (C-index) and the area under curve (AUC) of time-dependent receiver operating characteristic (ROC) curve, and the accuracy of the model was validated using the calibration curve. The total net gain of the model was evaluated using the decision curve. Results:(1) Postoperative recurrence-free survival in HCC patients. The recurrence-free survival time of 133 HCC patients in the training cohort was 10.0(range, 1.5-24.0)months, with 1-, 2-year recurrence-free survival rate of 47.3% and 36.8%. The recurrence-free survival time of 172 HCC patients in the validation cohort was 11.0(range, 1.0-24.0)months, with 1-, 2-year recurrence-free survival rate of 51.7% and 37.2%. There was no significant difference in recurrence-free survival between patients in the training cohort and the validation cohort ( χ2=0.075, P>0.05). (2) Analysis of factors influencing postoperative early recur-rence in HCC patients. Results of multivariate analysis showed that tumor burden prior to down-staging treatment, grade of albumin-bilirubin (ALBI) score prior to SLR, alpha-fetoprotein (AFP) half-life prior to SLR, and tumor response prior to SLR were independent factors influencing early recurrence in HCC patients after surgery [ hazard ratio=3.212, 2.526, 2.304, 1.575, 95% confidence interal ( CI) as 1.262-8.175, 1.324-4.818, 1.477-3.595, 1.138-2.180, P<0.05]. (3) Construction and validation of the predictive model. A nomogram predictive model for postoperative early recurrence was constructed base on the results of multivariate analysis. The C-index of predictive model was 0.786 for the training cohort and 0.734 for the validation cohort. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the training cohort were 0.890 (95% CI as 0.836-0.944), 0.895 (95% CI as 0.842-0.947), and 0.887 (95% CI as 0.831-0.942), respectively. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the validation cohort were 0.845 (95% CI as 0.781-0.909], 0.888 (95% CI as 0.826-0.950), and 0.919 (95% CI as 0.870-0.968), respectively. Results of calibration curve showed high consistency between the predicted results of nomogram predictive model and actual outcomes. Results of decision curve showed the nomogram predictive model with a good total net gain at a threshold of 0.10-0.50. Conclusions:Tumor burden prior to downstaging treatment, grade of ALBI score prior to SLR, AFP half-life prior to SLR, and tumor response prior to SLR are independent factors influencing early recurrence in initially unresectable HCC patients undergoing SLR following downstaging treatment. The nomogram predictive model based on these factors can effectively evaluate the prognosis of this patient population.

Objective To explore the relationship between blood pressure at baseline and significant decline in cognitive function after 4 years in middle-aged and elderly people in rural Xi'an,and the potential effect of age on the relationship.Methods Data were collected from a cohort of middle-aged and elderly people with cognitive impairment in rural Xi'an,Shaanxi Province.The cohort consisted of people aged≥40 years from a village in Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.Blood pressure parameters studied included hypertension and high systolic blood pressure(≥140 mmHg vs.＜140 mmHg),and high diastolic blood pressure(≥90 mmHg vs.＜90 mmHg).The Mini-Mental State Examination(MMSE)was used to assess the whole cognitive function,and the decline of MMSE score ≥4 points in 4 years was defined as significant decline of cognitive function.Multivariate Logistic regression was used to analyze the relationship between blood pressure and cognitive function at baseline.Subgroup analysis was used to study the effect of age(＜65 vs.≥65 years)on the relationship.Results We recruited a total of 1 350 subjects in the analysis,including 235 subjects(17.4％)with baseline age ≥65 years and 533 male subjects(39.5％);671 subjects(49.7％)had hypertension,with systolic blood pressure of(131.71±17.79)mmHg;840 subjects(62.2％)had high systolic blood pressure,with diastolic blood pressure of(82.18±10.56)mmHg;395(29.3％)had high diastolic blood pressure.During the 4-year follow-up,56 cases(4.2％)met the criteria for significant decline of cognitive function.We did not find significant association of hypertension and high systolic blood pressure with cognitive decline in the general population,＜65-year-old subgroup,or ≥ 65-year-old subgroup.The incidence of significant cognitive decline was not statistically significant in the total population(3.6％vs.5.6％,P=0.092),the ≥65-year-old subgroup(7.5％vs.8.2％,P=0.855),the normal diastolic blood pressure group,or the high diastolic blood pressure group.However,in the subgroup＜65 years,the incidence of cognitive decline was higher in the high diastolic blood pressure group than in the normal diastolic blood pressure group(2.7％vs.5.1％,P=0.043).Multivariate analysis showed that high diastolic blood pressure was not found to be associated with significant cognitive decline in the total population(OR=1.744,95％CI:0.953-3.192,P=0.071),the subgroup of ≥65 years old(OR=0.858,95％CI:0.221-3.338,P=0.825),or the subgroup of ≥65 years old.In the＜65 age group,high diastolic blood pressure was significantly associated with cognitive decline(OR=2.051,95％CI:1.005-4.186,P=0.048).Conclusion High diastolic blood pressure is associated with 4-year cognitive decline in people aged 40-65 years,but not in those aged ≥65.No association is found between hypertension or high systolic blood pressure and significant cognitive decline.

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 relationship between baseline serum lipid levels and cognitive decline after a 4-year follow-up in a cohort of middle-aged and elderly people in rural Xi'an.Methods The data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an,Shaanxi Province.The cohort selected the population ≥40 years old in two villages of Huyi District,Xi'an,as the research subjects.The baseline survey was completed from October 2014 to March 2015,and two follow-up visits were conducted in 2016 and 2018.The Mini-Mental State Examination(MMSE)was applied to assess the overall cognitive function.The MMSE score dropping between the 2014 and 2018(△MMSE)≥2 points were defined as cognitive decline.Baseline lipid levels[total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-c),low-density lipoprotein cholesterol(LDL-c)]were converted into three classification data based on 25％quantile and 75％quantile[Q1(≤25％)vs.Q2-Q3(25％-75％)vs.Q4(≥75％)],and using the Q2-Q3 group as the reference group.The relationship between serum lipid levels and cognitive decline at baseline was analyzed by multivariate Logistic regression.Interaction effect analysis and subgroup analysis were made to investigate the interaction effect of age(＜65 years vs.≥65 years)on the relationship between serum lipid and cognitive decline.Results There were 1 349 participants with complete baseline data,and 235(17.42％)were ≥65 years old at baseline;230 cases(17.05％)had cognitive decline.No significant association was found between TC,TG,LDL-c,HDL-c and cognitive decline in subgroups＜65 years of age.In the subgroup ≥65 years of age,the Q1(≤4.37 mmol/L)group of TC was not significantly associated with the risk of cognitive decline compared with the Q2-Q3(4.37-5.61 mmol/L)group of TC,but the Q,(≥5.61 mmol/L)group of TC was significantly associated withan increased risk of cognitive decline(OR=2.519,95％CI:1.217-5.214,P=0.013).Age had an interactive effect on the relationship between the Q4 group of TC and cognitive decline(OR=2.202,95％CI:1.111-4.363,P=0.024).Compared with the Q2-Q3(1.03-2.01 mmol/L)group of TG,the Q,(≤ 1.03 mmol/L)group of TG was associated with a lower risk of cognitive decline(OR=0.318,95％CI:0.120-0.838,P=0.020).Age had an interactive effect on the relationship between the Q1 group of TG and cognitive decline(OR=0.344,95％CI:0.132-0.896,P=0.029).However,there was no significant correlation between the Q4(≥2.01 mmol/L)group of TG and the risk of cognitive decline.Compared with the Q2-Q3(2.70-3.81 mmol/L)group of LDL-c,the Q1(≤ 2.70 mmol/L)group of LDL-c was not significantly associated with the risk of cognitive decline,but the Q4(≥3.81 mmol/L)group of LDL-c had significant association with an increased risk of cognitive decline(OR=2.367,95％CI:1.143-4.900,P=0.020).Age had an interactive effect on the relationship between the Q4 group of LDL-c and cognitive decline(OR=2.237,95％CI:1.134-4.415,P=0.020).No significant association was found between HDL-c and cognitive decline.Conclusion No significant association was found between HDL-c and cognitive decline at baseline.The relationship of TC,TG and LDL-c with cognitive decline was affected by age.Only in participants over 65 years old,the risk of cognitive decline was higher in those with high baseline levels of TC and LDL-c.Those with low baseline serum TG levels had a lower risk of cognitive decline.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.