ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

Objective To explore the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with locally advanced resectable non-small cell lung cancer (NSCLC). Methods The clinical data of patients with stage ⅡA-ⅢB NSCLC who underwent surgical treatment after receiving neoadjuvant immunotherapy combined with chemotherapy or chemotherapy alone at the First People’s Hospital of Jining between April 2021 and January 2024 were retrospectively analyzed. According to the preoperative neoadjuvant regimens, the patients were divided into a combined group and a chemotherapy group, and the clinical data of the two groups were compared. Results A total of 66 patients were included, including 61 males and 5 females. There were 53 patients in the combined group with a mean age of (63.40±6.80) years, and 13 patients in the chemotherapy group with a mean age of (58.62±8.30) years. There was a statistical difference in age between the two groups (P＜0.001), while no statistical difference was observed in other baseline data (P>0.05). The major pathological response rates in the combined group and the chemotherapy group were 54.7% and 23.1%, respectively (P=0.041), and the pathological complete response rates were 39.6% and 0.0%, respectively (P=0.006). The operative time in the combined group was shorter (P=0.039). There were no statistical differences between the two groups in intraoperative blood loss, duration of postoperative tube carrying, incidence of postoperative complications, overall survival, or event-free survival (P>0.05). Conclusion Surgical treatment following neoadjuvant immunotherapy combined with chemotherapy is safe and feasible, and its long-term efficacy requires further follow-up for confirmation.

Objective To observe the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Clinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Department of Thoracic Surgery of Jining No.1 People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females with a median age of 65 years (interquartile range: 58-69). All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival and disease-free survival rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR patients compared to the non-MPR patients. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.

Objective To investigate the mechanism of autophagy induced by House dust mites(HDM)on airway epithelial tight junction through β-catenin-Snail signaling pathway.Methods Human bronchial epithelial cells(16HBE)were stimulated with HDM at different time points(0,3,6,12,24,48 h)and different concen-trations(0,40,100,200 μg/mL)to screen the appropriate stimulation concentration and stimulation time.16HBE cells were treated with oxidative stress inhibitor N-acetylcysteine(NAC),autophagy inhibitor 3-methylad-enine(3-MA),HDM,and their combinations.Cells were transfected with mCherry-EGFP-LC3B,Beclin-1-siRNA,and ATG14-siRNA lentivirus and then stimulated with NAC and HDM.Immunofluorescence was used to detect the expression levels of autophagy-related protein LC3B,tight junction-related proteins Occludin,and ZO-1 in airway epithelial cells.The level of reactive oxygen species(ROS)was detected by using DCFH-DA in each group.The protein expression levels of Occludin,ZO-1,LC3B,Beclin-1,ATG5,ATG14,P62,Snail,β-catenin and p-β-catenin were detected by Western blot method.Results Immunofluorescence results showed that compared with the control group,200 μg/mL HDM stimulation induced cellular autophagy,increased the expression level of LC3B protein,and promoted the level of ROS,all with statistical significances(all P<0.05).Compared with the HDM group,the HDM+3-MA,HDM+ATG14-si,and HDM+Beclin-1-si groupsall showed significantincreases in the expression levels of tight junction-related proteins Occludin and ZO-1(P<0.05).The HDM+NAC group demonstrated significant decreases both in the level of ROS andin the expression level of LC3B protein.Western blot results revealed that compared with HDM,3-MA and autophagy protein low-expression beads(Beclin-1-si,ATG14-si)attenuated HDM-induced cellular autophagy(P<0.05),inhibited HDM-induced upregulation of Snail and p-β-catenin expression,and improved HDM-induced decreases in Occludin and ZO-1(P<0.05).Moreover,compared with the HDM group,the NAC+HDM group exhibited significant decreases both in the conversion of LC3BⅠ to LC3BⅡ(P<0.001)in the protein levels of Snail,p-β-catenin,Beclin-1 and ATG14(P<0.01),but significant increases in the protein levels of Occludin and ZO-1(P<0.05).Conclusion HDM affects the tight connections between airway epithelial cells by inducing autophagy,which may be attributed to the β-catenin-Snail signaling pathway.

Objective:To investigate the correlation between frailty and falls among older adult residents in communities in Xinjiang Uygur Autonomous Region.Methods:This study is a prospective research. In June 2024, the 1 047 older adults (aged 65 years and older) included in the "A longitudinal cohort study of aged population in Xinjiang" (ChiCTR2400093292) were followed up. The Fried frailty phenotype was used to assess the frailty status of the participants, and general information was collected, including whether the participants had experienced falls in the past 12 months. Multivariate logistic regression analysis was performed to identify the risk factors for falls among older adults in communities in Xinjiang Uygur Autonomous Region.Results:Among the 1 047 participants, the incidence of falls among older adults was 10.2% (107/1 047). There were significant differences in frailty status and age between case and control groups (both P < 0.05). Logistic regression analysis indicated that frailty and increasing age are risk factors for falls among older adults in communities in Xinjiang Uygur Autonomous Region. The more severe the frailty, the greater the risk of falls ( χ2 = 7.57, P < 0.006, OR = 2.509, 95% CI: 1.303-4.830). Similarly, the greater the age, the greater the risk of falls ( χ2=8.94, P = 0.003, OR = 1.030, 95% CI: 1.013-1.064). Conclusions:Falls among older adults in communities in Xinjiang Uygur Autonomous Region are closely associated with frailty. It is essential to improve the assessment and screening of fall risks in frail older adults and to develop effective and appropriate fall prevention measures for this high-risk population.

Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.

Objective:To analyze the influencing factors of low fall alertness in elderly inpatients,construct a risk prediction model and validate it,providing a reference for clinical medical staff to identify elderly inpatients with low fall alertness in the early stage.Methods:A total of 605 elderly inpatients treated in Yijishan Hospital affiliated to Wannan Medical College from Oct 2023 to Mar 2024 were enrolled and randomly divided into the training group(n=423)and validation group(n=182)at a ratio of 7∶3.The patients were evaluated using a general information questionnaire,the Social Frailty Screening Tool(HALFT),the Tilburg Frailty Indicator(TFI),and the Self-Awareness of Falls in Elderly scale(SAFE).Multivariate logistic analysis was used to determine the influencing factors of low fall alertness in elderly inpatients.RStudio was used to construct a risk prediction model of low fall alertness.The discrimination,calibration,and clinical net benefit of the model were verified using the receiver operating characteristic(ROC)curves,calibration plots,and decision curve analysis(DCA).Results:Multivariate logistic analysis showed that the history of falls,monthly income,previous physical activity time,social frailty score and TFI score were independent risk factors for low fall alertness in elderly inpatients.The Hosmer-Lemeshow χ2 test showed that χ2=8.863,P=0.354,indicating good calibration of the prediction model.The area under the ROC curve of the training group and the validation group were 0.860(95%CI:0.815-0.904)and 0.937(95%CI:0.888-0.986),respectively,and the maximum Youden indices of the model was 0.576 and 0.788,respectively,indicating good discrimination of the model.The DCA decision curve showed that the model had good clinical effectiveness.Conclusion:The constructed model has a good prediction effect and can help clinical medical staff quickly and effectively screen out elderly inpatients at risk of low fall alertness.

OBJECTIVE To explore the relationship between levels of peripheral blood interleukin(IL)-6,IL-18,IL-1β,tumor necrosis factor(TNF-α),procalcitonin(PCT),C-reactive protein(CRP)and vascular cell adhesion molecule-1(VCAM-1)and disease condition and prognosis in children with Mycoplasma pneumoniae pneumonia(MPP),and to construct a prediction model.METHODS A total of 196 children with MPP admitted to Dazhou Central Hospital in Sichuan Province from Jan.2022 to Jan.2024 were selected as the MPP group and were divided into the mild group(n=124)and the severe group(n=72)according to the clinical pulmonary infection score(CPIS),and 200 healthy children who participated in physical examination in the hospital during the same period were selected as the healthy group.All 196 children with MPP received relevant treatments and were divided into a poor prognosis group(n=40)and a good prognosis group(n=156)according to their prognosis.The levels of peripheral blood IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 were measured in all the subjects,the risk factors affecting the disease condition and prognosis of children with MPP were analyzed,the prediction model was constructed,and the receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated to evaluate the predictive effect of the constructed prediction model.RESULTS Peripheral blood IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 levels in the MPP group were higher than those in the healthy group(P＜0.05).The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in peripheral blood were significantly higher in the severe group than those in the mild group(P＜0.05).IL-6(OR=1.203),IL-18(OR=1.072),IL-1β(OR=4.060),TNF-α(OR=1.264),PCT(OR=3.132),CRP(OR=1.546)and VCAM-1(OR=1.009)were risk factors for severe condition in MPP children(P＜0.05).The prediction model constructed for the devel-opment of severe illness in MPP children was as follows:Logit(P)=-67.522+0.185×IL-6+0.069×IL-18+1.401×IL-1β+0.234×TNF-α+1.142×PCT+0.436×CRP+0.009 ×VCAM-1.The AUC of the prediction model for predicting severe conditions in MPP children was 0.985.The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in peripheral blood in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).IL-6(OR=1.083,95％CI:1.024-1.145,P=0.005),TNF-α(OR=1.083,95％CI:1.002-1.172,P=0.046)and VCAM-1(OR=1.029,95％CI:1.015-1.044,P＜0.001)were risk factors for poor prognosis in MPP children.The prediction model established for poor prognosis in children with MPP was as follows:logit(P)=-31.557+0.080×IL-6+0.080×TNF-α+0.029×VCAM-1.The AUC of the prediction model for predicting poor prognosis in MPP children was 0.979.CONCLUSIONS The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in pe-ripheral blood are closely related to the severity of illness in children with MPP.The prediction model constructed on the basis of the above indicators predicts the risk of severe disease in children with MPP,and the prediction model constructed on the basis of IL-6,TNF-α and VCAM-1 predicts the risk of poor prognosis in children with MPP.

BACKGROUND:Emodin has a variety of pharmacological activities such as anti-inflammatory,anti-viral and anti-oxidative stress,and also has a certain protective effect on sepsis-induced myocardial injury,but its mechanism of action is still unclear.OBJECTIVE:To investigate whether emodin can improve myocardial injury in septic mice by promoting autophagy.METHODS:Thirty-two male Kunming mice were divided into sham operation group(n=4),sham operation+emodin group(n=4),model group(n=8),model+emodin group(n=8),and emodin+3-methyladenine group(n=8).The myocardial injury model of septic mice was constructed by cecal ligation and puncture.3-methyladenine(10 mg/kg)was injected intraperitoneally 1 hour before modeling.Emodin(20 mg/kg)was injected intraperitoneally 30 minutes before modeling,and the other groups were injected with the same amount of normal saline at the same time point.Blood and myocardial samples were collected from all mice 24 hours after surgery.ELISA was used to detect the levels of brain natriuretic peptide and cardiac troponin Ⅰ in serum.Western blot assay was used to detect the protein expression of LC3B,Beclin-1,and p62 in myocardial tissue.Hematoxylin-eosin staining was used to observe the pathological changes in myocardial tissue.Ultrasound was used to evaluate the cardiac function of mice.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,there was no significant difference in the levels of serum brain natriuretic peptide,cardiac troponin Ⅰ,and the protein expression of myocardial autophagy proteins LC3Ⅱ/LC3Ⅰ and p62 in the sham operation+emodin group(P＞0.05).(2)Compared with the sham operation+emodin group,the levels of serum brain natriuretic peptide and cardiac troponin I were significantly increased in the model group(P＜0.05).Compared with the model group,the levels of serum brain natriuretic peptide and cardiac troponin I were decreased in the model+emodin group(P＜0.05).(3)Compared with the model group,the expression of LC3Ⅱ/LC3Ⅰ and Beclin-1 protein was increased and the expression of p62 protein was decreased in the myocardial tissue of the model+emodin group(P＜0.05).Compared with the model+emodin group,the expression of LC3Ⅱ/LC3Ⅰ and Beclin-1 protein decreased and the expression of p62 protein increased in the emodin+3-methyladenine group(P＜0.05).(4)The myocardial fibers in the sham operation group were normal,the myocardial fibers in the model group were disordered with a large number of inflammatory cell infiltration,the myocardial fibers in the model+emodin group were slightly disordered,and some vacuolar changes were observed.The myocardial fibers were disordered,and more inflammatory cell infiltration was observed in the emodin+3-methyladenine group.(5)Compared with the sham operation group,the left ventricular short axis shortening rate and left ventricular ejection fraction were decreased in the model group(P＜0.05).Compared with the model group,the left ventricular short axis shortening rate and left ventricular ejection fraction were increased in the model+emodin group(P＜0.05).Compared with the model+emodin group,the left ventricular ejection fraction of emodin+3-methyladenine group was decreased(P＜0.05),and the left ventricular short axis shortening rate was reduced but not statistically significant(P＞0.05).(6)The above results indicate that emodin pretreatment can improve myocardial injury and myocardial dysfunction in septic mice by promoting autophagy.

Objective To investigate the relationship between interventricular septal dimensions(IVSd)and urinary albumin/creatinine ratio(UACR)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 757 patients with T2DM hospitalized in the Department of Endocrinology of Gansu Provincial People's Hospital from March 2021 to April 2024 were enrolled in this study.All the patients were divided into T2DM patients without proteinuria(n=388),microproteinuria group(Mic,n=260)and macroproteinuria group(Mac,n=109)according to the UACR levels.General clinical data and biochemical indexes were collected from all the patients.Color Doppler echocardiography was used to record left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),IVSd,left ventricular posterior wall dimensions(LVPWd),and left atrial diameter(LAD).Pearson correlation analysis was conducted to analyze the correlation between IVSd,LVPWd and related indicators of renal function.Logistic regression analysis was conducted to analyze the influencing factors for T2DM patients with proteinuria.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of the DM duration and IVSd in patients with T2DM and proteinuria.Results The DM duration,SBP,FIns,HbA1c,Scr,24 hUTP,UACR,UAER,IVSd,LVPWd were increased successively(P<0.05),while LVEF and eGFR were decreased successively(P<0.05)in T2DM,Mic,Mac group.Age was higher in Mic group than in T2DM group(P<0.05).DBP and FPG were higher in Mac group than in T2DM and Mic group(P<0.05).Pearson correlation analysis showed that IVSd and LVPWd were positively correlated with 24 hUTP,UACR,UAER and Scr(P<0.05),and negatively correlated with eGFR(P<0.05).Logistic regression analysis indicated that the DM duration and IVSd were significant influencing factors for proteinuria in patients with T2DM.ROC curve showed that the area under ROC curve of IVSd was 0.620,with sensitivity 43.3%and specificity 76.8%,respeictively.Conclusions The DM duration and IVSd are influencing factors for UACR in patients with T2DM.The risk of proteinuria in T2DM patients increases with rising IVSd.