ObjectiveTaking classical herbal pair compatibility research as the entry point， this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine （TCM） formula Zhizi Houpotang， and to elucidate its antidepressant mechanism， with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 （NLRP3）/gasdermin D （GSDMD） signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group， a chronic unpredictable mild stress （CUMS） depression model group， a Zhizi Houpotang full-formula group （6 g·kg^-1·d^-1）， a Magnoliae Officinalis Cortex （MOC）-Aurantii Fructus Immaturus （AFI） herbal pair group （4.2 g·kg^-1·d^-1）， a Gardeniae Fructus （GF）-MOC herbal pair group （4.2 g·kg^-1·d^-1）， a GF-AFI herbal pair group （3.6 g·kg^-1·d^-1）， and a positive drug group （fluoxetine， 12 mg·kg^-1·d^-1）. Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 （Ibal） and the purinergic receptor P2X ligand-gated ion channel 7 （P2RX7） in the prefrontal cortex （PFC）. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of inflammatory cytokines interleukin-1β （IL-1β） and interleukin-18 （IL-18） in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 （Panx1）， P2RX7， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， GSDMD， postsynaptic density protein 95 （PSD95）， and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group， the depression model group exhibited significant depressive-like behaviors. In addition， the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased （P<0.01）， the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated （P<0.01）， and the protein expression levels of Panx1， P2RX7， NLRP3， ASC， Caspase-1， and GSDMD in the PFC were significantly upregulated （P<0.01）. In contrast， the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated （P<0.01）， and neuronal dendritic spine density was significantly reduced （P<0.01）. Compared with the model group， the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators （P<0.01）. The GF-AFI herbal pair group improved all the above indicators except P2RX7， Caspase-1， GSDMD， and PSD95 （P<0.05， P<0.01）. In contrast， the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair， GF-MOC， can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling， thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously， it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density， promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula， and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.

Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

OBJECTIVE:Neuromuscular exercise is a new comprehensive rehabilitation therapy in recent years,but its effect on knee osteoarthritis is still controversial.The purpose of this paper is to systematically evaluate the efficacy of neuromuscular exercise on knee osteoarthritis pain and function. METHODS:The randomized controlled trials addressing neuromuscular exercise in the treatment of knee osteoarthritis pain and function were retrieved from PubMed,Cochrane Library,Embase,EBSCO,CNKI,Web of Science,China Biomedical Database(CBM),VIP,and WanFang Database.The retrieval time ranged from database inception to October 2023.The neuromuscular training group(experimental group)was given neuromuscular training or neuromuscular training as the main intervention;the control group was a blank group or given conventional rehabilitation.Outcome indicators included the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,walking time,knee stability,and the maximum number of knee flexion in 30 seconds.The risk of bias was evaluated by the Cochrane Collaboration tool and the Physiotherapy Evidence Database.Meta-analysis was performed using RevMan 5.4 software. RESULTS:A total of 11 randomized controlled trials were included,and 628 samples were extracted.The results of Meta-analysis showed that the experimental group was superior to the control group in terms of WOMAC pain score[standardized mean difference(SMD)=0.38,95%confidence interval(CI):0.08-0.69,P=0.01],knee stability(SMD=0.57,95%CI:0.23-0.92,P=0.001),the maximum number of knee joint flexion in 30 seconds(SMD=0.35,95%CI:0.05-0.65,P=0.02),and WOMAC physical function score(SMD=-0.79,95%CI:-1.30 to-0.28,P=0.002).In both groups,walking speed was increased and walking ability was improved in patients with knee osteoarthritis,but there was no significant difference(walking time:SMD=-0.22,95%CI:-0.48-0.03,P=0.09). CONCLUSION:Neuromuscular exercise can effectively improve knee joint pain,enhance the stability of the knee joint,and promote functional recovery in patients with knee osteoarthritis.However,more high-quality randomized controlled trials are still needed to further confirm the research.

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To investigate the effect of physical activity on mortality risk in patients with chronic obstructive pulmonary disease (COPD) in Sichuan Province.Methods:Based on baseline data from 2004 to 2008 from the China Kadoorie Biobank project site in Pengzhou City, Sichuan Province, a total of 8 501 COPD patients aged 30-79 years were enrolled and followed up for a long period to determine mortality outcomes. Quartiles were used to group physical activity levels. The Cox proportional hazards regression model was used to analyze the effect of physical activity level on mortality outcomes.Results:As of December 31, 2017, the cumulative follow-up of the participants totaled 85 600.58 person-years (mean follow-up duration: 10.07 years). During this period, a total of 2 000 deaths were recorded, yielding a cumulative mortality rate of 23.53%. Among these deaths, 665 were attributed to COPD, corresponding to a cumulative mortality rate of 7.82%; and 1 116 were attributed to cardiovascular and cerebrovascular disease (CVD), corresponding to a cumulative mortality rate of 13.13%. The Cox proportional hazards regression model analysis revealed that, after adjusting for confounding factors, total physical activity was associated with a reduced risk of mortality from COPD, CVD, and all causes in patients with COPD. Compared with the low-level group of total physical activity, the medium-high-level group had the lowest risk of COPD mortality, with an HR of 0.39 (95% CI: 0.30-0.49). The high-level group had the lowest risk of CVD death and all-cause death, with HRs of 0.46 (95% CI: 0.37-0.56) and 0.55 (95% CI: 0.48-0.64), respectively. The lowest risk of COPD death and CVD death was found in the medium-high level of work-based physical activity group, with HRs of 0.36 (95% CI: 0.28-0.46) and 0.43 (95% CI: 0.36-0.51), respectively; the risk of all-cause mortality was lowest in the medium-high and high-level groups, with HRs values of 0.53 (95% CI: 0.46-0.61) and 0.53 (95% CI: 0.45-0.61). The risk of COPD death was lowest in the high-level transportation physical activity group, with an HR of 0.66 (95% CI: 0.53-0.83), and the risk of CVD and all-cause death was lowest in the medium-high level group, with HRs of 0.63 (95% CI: 0.53-0.76) and 0.73 (95% CI: 0.64-0.84), respectively. The risk of COPD death and CVD death was the lowest in the high-level domestic physical activity group, with HRs of 0.66 (95% CI: 0.49-0.89) and 0.76 (95% CI: 0.61-0.95), respectively, and the risk of all-cause death was the lowest in the medium-high level group, with an HR of 0.82 (95% CI: 0.72-0.94). There is no statistical association between leisure physical activity and the risk of death from three types of diseases. Conclusions:Total physical activity, including work-based, transportation-based, and domestic physical activity, reduced the risk of COPD, CVD, and all-cause mortality in patients with COPD in Sichuan Province. The magnitude of mortality risk was influenced by the type and level of physical activity.

Objective To compare the clinical effect between laparoscopic temporary long tunneled external ventricular drainage and traditional laparoscopic ventriculoperitoneal shunt in patients with hydrocephalus after traumatic brain injury(TBI).Methods A total of 52 patients who underwent laparoscopic temporary long tunneled external ventricular drainage(external drainage group)or traditional laparoscopic ventriculoperitoneal shunt(traditional shunt group)for hydrocephalus after TBI from October 2018 to October 2021 were retrospectively analyzed.The catheterization time,remission time of intracranial hypertension,average hospital stay,therapeutic effective rate and the incidence of complications were compared between the two groups.Results The total effective rate of the external drainage group was significantly higher than that of the traditional shunt group(92.31%vs 80.77%,P＜0.05).The external drainage group had longer catheterization time and shorter remission time of intracranial hypertension and average hospital stay than the traditional shunt group.The incidence of adverse reactions such as intracranial infection,shunt obstruction and poor healing in the traditional shunt group was significantly higher than that in the external drainage group(19.23%vs 7.69%,P＜0.05).Conclusion Laparoscopic temporary long tunneled external ventricular drainage can achieve better therapeutic effect for hydrocephalus after TBI,and it is recommended in clinical treatment.

Objective To evaluate the predictive value of dose-surface histogram(DSH)for radiation proctitis(RP)in prostate cancer(PCa)patients undergoing radiotherapy.Methods This prospective randomized controlled clinical trial included 380 PCa patients who underwent image-guided radiotherapy in the First Affiliated Hospital of Hebei Northern University from January 2018 to January 2023.Patients were randomly divided into observation group(n=200)and control group(n=180).The rectal dose distribution of patients in the two groups was evaluated by using DSH and dose-volume histogram(DVH),respectively.The receiver operating characteristic(ROC)curve was utilized to evaluate the predictive value of DSH for acute RP,with DVH serving as a reference.Results The difference was not statistically significant in clinical information such as age,KPS score,and body mass index(BMI)between the observation and control groups(P＞0.05),as well as in acute RP incidence(P＞0.05).There were significant differences in S40 and V40,S50 and V50,S60 and V60,S70 and V70,and S78 and V78 between the two groups(P＜0.05).S40,S50,V40,and V50 showed low efficacy(P＜0.001)in predicting acute RP at each level,with AUC≤0.700.S60 and V60 showed moderate efficacy(P＜0.001)in predicting acute RP at each level,with AUC 0.700-0.900.S70,S78,V70 and V78 showed high efficacy(P＜0.001)in predicting acute RP at each level,with AUC＞0.900.Conclusions The predictive value of DSH for rectal toxicity in patients with PCa is basically consistent with that of DVH.It is expected to become a novel and valuable tool for evaluating radiotherapy plans in the future.

Objective To investigate the effect of miR-373-3p in diabetic retinopathy(DR),as well as the underlying mechanisms.Methods Serum samples from 35 DR patients and 35 non-DR patients visiting Tianjin Fifth Central Hospital from February 2021 to February 2022 were collected,and expression levels of miR-373-3p and vascular endothelial growth factor A(VEGFA)mRNA were detected using quantitative reverse transcription polymerase chain reaction(qRT-PCR).An in vitro DR model was constructed using high glucose(HG)-treated human retinal microvascular endothelial cells(HRMEC).HRMECs were divided into control group(5 mmol/L glucose and 25 mmol/L mannitol treatment),HG group(30 mmol/L glucose treatment),HG+miR-373-3p mimic-negative control(miR-con)group(30 mmol/L glucose treatment after transfection with miR-con),HG+miR-373-3p mimic group(30 mmol/L glucose treatment after transfection with miR-373-3p),HG+miR-373-3p+vector group(30 mmol/L glucose treatment after co-transfection with miR-373-3p and vector),and HG+miR-373-3p+vascular endothelial growth factor A(VEGFA)group(30 mmol/L glucose treatment after co-transfection with miR-373-3p and VEGFA).The expression levels of miR-373-3p,VEGFA mRNA and protein were analyzed by qRT-PCR and Western blotting.CCK-8,immunofluorescence,Transwell assay,angiogenesis assay,and Western blotting were used to evaluate HRMEC proliferation,migration and angiogenesis abilities.The relationship between miR-373-3p and VEGFA was determined by dual luciferase reporter assay.Results Compared with non-DR patients,DR patients exhibited significantly lower expression levels of miR-373-3p(P＜0.05)and higher expression levels of VEGFA mRNA(P＜0.05)in serum.Compared with control group,HG group showed decreased expression of miR-373-3p(P＜0.05),increased expressions of the mRNA and protein of VEGFA(P＜0.05),higher cell viability,proliferation rate,proliferating cell nuclear antigen(PCNA)and Cylin D1 protein,and numbers of migrating cells and angiogenesis ability(P＜0.05)in HRMECs.Compared with HG+miR-con group,HG+miR-373-3p group showed increased expression of miR-373-3p(P＜0.05),decreased expressions of VEGFA(P＜0.05),lower cell viability,proliferation rate,PCNA and Cylin D1 protein(P＜0.05),and lower numbers of migrating cells and angiogenesis ability(P＜0.05)in HRMECs.Compared with HG+miR-373-3p+vector group,HG+miR-373-3p+VEGFA group showed increased expression of VEGFA(P＜0.05),higher cell viability,proliferation rate,PCNA and Cylin D1 protein,and numbers of migrating cells and angiogenesis ability(P＜0.05)in HRMECs.The results of dual luciferase reporter assay showed decreased enzymatic activity of luciferase after cotransfection of miR-373-3p and VEGFA sequence(P＜0.05).Conclusion MiR-373-3p is lowly expressed in the serum of DR patients,and its potential mechanism may involve targeting VEGFA to inhibit HG-induced HRMEC dysfunction.

Objective To investigate the effect of farrerol on pyroptosis induced by hydrogen peroxide(H2O2)in lens epithelial cells through regulating JAK2/STAT3 signaling pathway.Methods Thirty-six neonatal SD rats were randomly divided into normal group,cataract group(20 μmol/kg sodium selenite),farrerol low dose,medium dose and high dose groups(10,20,40 mg/kg farrerol)and positive control group(benzyda lysine eye drops).Lens turbidity was observed by slit-lamp and scored,and pathological changes of lens were observed by HE staining.Human lens epithelial cells were cultured and divided into control group,model group,low concentration farrerol group(20 mg/L),high concentration farrerol group(40 mg/L),high concentration farrerol+R08191 group(40 mg/L+10 μmol/L),except the control group,other groups were induced by H2O2.The cell activity was detected by CCK-8 method;the concentrations of interleukin(IL-1 β)and IL-18 in cell culture medium were measured by ELISA;inverted phase contrast microscope was used to observe the cell scorch in each group;The expression of N-terminal fragment of GSDMD(GSDMD-N)protein was detected by immunofluorescent staining;the content of reactive ozygen species(ROS)was measured by flow cytometry;the expressions of latent heat protein(NLRP3),apoptosis-associate speck-like protein containing a CARD(ASC),Caspase-1,GSDMD-N,JAK2/STAT3 pathway proteins were detected by Western blotting.Results In cataract rats,the lens epithelial cells were disorderly and loosely arranged,the lens fibrosis/liquefaction,and the lens turbidity score increased(P＜0.05).Compared with the cataract group,the lens damage and the lens turbidity score decreased in the low,medium and farrerol high dose group and the positive control group(P＜0.05),and the effect of the farrerol high dose group was the best,which was basically consistent with the positive control group.The cells in the control group were closely connected and arranged in order,without scorched cells;in the model group,the cells were swollen and had typical charring characteristics of bubble like protrusion;Compared with the model group,the cell bubble protrusion in the low concentration farrerol group and the high concentration farrerol group was alleviated;Compared with the high concentration farrerol group,the cell bubble protrusion in the high concentration farrerol+R08191 group was aggravated.Compared with the control group,the cell survival rate in model group was decreased,the levels of IL-18 and IL-1 β in supernatant,the number of GSDMD-N positive cells,the level of ROS,the expression of NLPR3,ASC,Caspase-1,GSDMD-N protein,p-JAK2/JAK2,p-STAT3/STAT3 were increased(P＜0.05);Compared with the model group,the cell survival rate in the low concentration farrerol group and the high concentration farrerol group was increased,the levels of IL-18 and IL-1β in supernatant,the number of GSDMD-N positive cells,the level of ROS,the expression of NLPR3,ASC,Caspase-1,GSDMD-N protein,p-JAK2/JAK2,p-STAT3/STAT3 were decreased(P＜0.05);compared with the high concentration farrerol group,the cell survival rate in the high concentration farrerol+R08191 group was decreased,the levels of IL-18 and IL-1 β in supernatant,the number of GSDMD-N positive cells,the level of ROS,the expression of NLPR3,ASC,Caspase-1,GSDMD-N protein,p-JAK2/JAK2,p-STAT3/STAT3 signaling were increased(P＜0.05).Conclusion Farrerol may inhibit H2O2-induced pyroptosis of lens epithelial cells by inhibiting JAK2/STAT3 signaling pathway.

Objective To investigate the serum levels of miR-488 and miR-654 in patients with diabetes nephropathy(DN)and their relationship with the severity and prognosis of the disease.Methods 92 DN patients who received treatment at Ya'an People's Hospital from January 2022 to January 2024(DN group)and 60 healthy controls(healthy group)were selected.The correlation between serum miR-488 and miR-654 was analyzed with pearson.The chi-square test was used to analyze the relationship between serum miR-488 and miR-654 expression levels,clinical pathological features,and degree of renal injury.ROC was used to predict the prognosis of DN patients Results Compared with healthy individuals,the expression level of serum miR-488(1.71±0.40 vs 1.08±0.15)was increased in DN patients,while the expression level of miR-654(0.66±0.19 vs 0.94±0.22)was reduced,and the differences were statistically significant(t=11.666,8.340,all P<0.05).In DN patients with diabetes≥10 years,24h urinary protein≥3 g/L,serum creatinine(Scr)≥150 μmol/L,glomerular filtration rate<60 ml/min/1.73m2,and blood urea nitrogen(BUN)≥7.5 mmol/L,the proportions of high expression of serum miR-488 and low expression of miR-654 were higher than the proportions of low expression of serum miR-488 and high expression of miR-654,and the differences were statistically significant(χ2=5.283～25.234;4.356～8.587,all P<0.05).Pearson analyze the correlation between serum miR-488 and miR-654 in the DN group were negatively correlated(r=-0.405),serum miR-488 was positively correlated with 24h urinary protein,Scr and BUN(r=0.376,0.435,0.406)and negatively correlated with glomerular filtration rate(r=-0.382).Serum miR-654 was negatively correlated with 24-hour urine protein,Scr and BUN(r=-0.418,-0.367,-0.425)and positively correlated with glomerular filtration rate(r=0.374).The proportions of high expression of miR-488 and low expression of miR-654 in DN patients with glomerular grade IV,2 points of interstitial inflammation,and 3 points of interstitial fibrosis and tubular atrophy(IFTA)were higher than proportions of low expression of miR-488 and high expression of miR-654,and the differences was statistically significant(χ2=7.916～20.669,8.432～13.258,all P<0.05).Compared with the poor prognosis group,the serum miR-488 expression level in the good prognosis group was obviously reduced(1.57±0.29 vs 1.89±0.17),while the miR-654 expression level was obviously increased(0.78±0.21 vs 0.51±0.19),and the differences were statisticolly significant(t=6.202,6.369,all P<0.05).The sensitivity of serum miR-488,miR-654 and their combination for prog-nosis of DN patients were 87.50%,80.00%and 90.00%,respectively.The specificity were 84.62%,86.54%and 82.69%,respec-tively.The AUC(95%CI)were 0.838(0.748～0.927),0.824(0.731～0.916)and 0.906(0.846～0.966),respectively,the joint prediction of the two was better than their individual predictions(Z=2.225,2.033,P=0.026,0.042).Conclusion The lower the degree of renal injury in DN patients,the lower the serum miR-488,and the higher the serum miR-654,serum miR-488 and miR-654 can be used to predict the condition and prognosis of DN patients,and combined prediction is better than individual predic-tion.