Objective: To investigate the reciprocal causal relationships between periodontitis and hepatobiliary diseases through Mendelian randomization (MR) analyses, to provide evidence for joint prevention and clinical decision-making in patients with concurrent periodontitis and hepatobiliary diseases. Methods: Single nucleotide polymorphisms (SNPs) were extracted from the largest genome-wide association study on periodontitis (17 353 cases, 28 210 controls) and hepatobiliary diseases within the European ancestry and used as instrumental variables (IVs). The strength of the associations was examined by calculating the F-statistic. The SNPs significantly associated with the outcome were removed by scanning on Phenoscanner platform. Bidirectional causal associations between periodontitis and hepatobiliary diseases were estimated using inverse variance weighted (IVW), MR-Egger, and Weighted Median methods. The robustness of the findings was further verified through additional sensitive MR approaches, including Cochran’s Q statistic （IVW）, Rucker’s Q statistic （MR-Egger）, MR-PRESSO and Leave-one-out analysis. Further MR analyses, utilizing other available genome-wide association studies (GWAS) on hepatobiliary diseases, were conducted to validate the results. Results: The IVW method found that periodontitis had a causal impact on acalculous cholecystitis (odds ratio = 1.277, 95% CI 1.097-1.485, P=0.002), implying an increased risk of acalculous cholecystitis associated with periodontitis, while the MR-Egger regression and Weighted Median failed to observe significant causal effects of periodontitis on acalculous cholecystitis. However, no bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer were observed using IVW, MR-Egger regression and Weighted Median. The bidirectional causal relationships were deemed unlikely to be influenced by horizontal pleiotropy. Further, the validation analysis based on alternative GWAS data suggested parallel results. Conclusions The MR analyses suggest that periodontitis may elevate the risk of acalculous cholecystitis. Further investigations, including clinical studies and mechanistic explorations, are warranted to validate these findings. However, the MR analyses do not support bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer.

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective:To investigate the detection rate of nonalcoholic fatty liver disease(NAFLD)and its influencing factors among residents in western Chongqing of China during physical examination.Methods:Based on the clinical diagnostic criteria and ultra-sound examination results of NAFLD,the individuals who underwent physical examination in a grade A tertiary hospital in Western Chongqing from January 1,2020 to November 30,2023 were enrolled as subjects.The methods such as the t-test,the chi-square test,and the multivariate logistic regression analysis were used to clarify the detection rate of NAFLD and its influencing factors among the individuals undergoing physical examination.Results:The detection rate of NAFLD was 23.64%(12 872/54 067)among the individu-als undergoing physical examination.The detection rate of NAFLD in male individuals was significantly higher than that in female indi-viduals(39.22%vs.15.91%,χ2=2 197.112,P<0.001).The individuals in the age group of 50-59 years had the highest NAFLD detec-tion rate of 33.18%,and before the age of 60 years,the detection rate of NAFLD increased with age,while after the age of 60 years,the detection rate of NAFLD decreased with age(χ2=367.554,P<0.001),indicating the detection of NAFLD in younger populations in western Chongqing.The individuals with a body mass index in-dicative of overweight and obesity had a significantly higher detec-tion rate of NAFLD than those with a body mass index indicative of emaciation and normal weight(39.39%/71.40%vs.0.23%/9.68%,χ2=7 644.383,P<0.001).The multivariate logistic regression analy-sis showed that sex,age,body mass index,fasting blood glucose(FBG),systolic blood pressure(SBP),diastolic blood pressure(DBP),triglyceride(TG),uric acid(UA),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were risk factors for the detection rate of NAFLD in individuals undergoing physical examination(P<0.05),while total cholesterol(TC)was not a risk factor for the detection rate of NAFLD.Conclusion:The detection rate of NAFLD is 23.64%among the individuals aged 18 years or above who undergo physical examination in Western Chongqing,and there is a relatively high incidence rate of NAFLD in the age group of 50-59 years.Male individuals and overweight or obese individuals are at a high risk of NAFLD.FBG,SBP,DBP,TG,UA,HDL-C,and LDL-C are risk factors for NAFLD,while TC is not a risk factor for NAFLD.

OBJECTIVE To analyze the results of speech-evoked auditory brainstem response(s-ABR)tests in patients with presbycusis and explore the mechanisms of speech coding in these patients.METHODS Thirty patients with presbycusis(presbycusis group),30 elderly individuals with normal hearing(elderly normal group),and 30 young adults with normal hearing(young control group)were recruited.The s-ABR was elicited using a 40 ms duration complex speech stimulus/da/,and the characteristics of s-ABR were analyzed in each group.RESULTS The latencies of waves V and A in the presbycusis group were significantly prolonged compared to both the elderly normal group and the young control group(P<0.05).However,there was no statistically significant difference in the latencies of waves between the elderly normal group and the young control group(P>0.05).The amplitude of wave A and the slope of the V-A complex wave in the presbycusis group were significantly lower than those in the young control group(P<0.05),while no statistically significant differences were observed in the amplitudes of other waves.CONCLUSION The characteristics of s-ABR in patients with presbycusis suggest that these patients have poor synchronization in response to stimulus timing and deficiencies in coding high-frequency and rapidly changing auditory information,which may be one of the mechanisms underlying the decline in speech abilities in patients with presbycusis.

Objective To investigate the diagnostic value of CT plain scanning for isolated superior mesenteric artery dissection(ISMAD).Methods This study retrospectively investigated CT plain images of the superior mesenteric artery(SMA)in 45 patients with ISM AD and 45 patients without ISMAD.The imaging manifestations of ISMAD were analyzed,and the sensitivity and specificity of these manifestations were analyzed using receiver operating characteristic(ROC)curve.Results There were statistically significant differences in both the trunk diameter and standardized trunk diameter of the SMA between the two groups(P＜0.001,P=0.001).Additionally,the area under the curve(AUC)for the SMA trunk diameter in diagnosing ISMAD was determined to be 0.988,with a statistically significant P-value of less than 0.001.Furthermore,when the diameter of the SMA trunk reached 8.20 mm,the diagnostic sensitivity was 97.8％and the specificity was 93.3％.The AUC for the standardized diameter of the SMA trunk was determined to be 0.976.Additionally,when the standardized diameter of the SMA trunk reached 70.33％,the diagnostic sensitivity was 95.6％and the specificity was 82.2％.There was no statistically significant difference observed in the luminal CT value and standardized CT value of the SMA between the two groups(P＞0.05).Additionally,the presence of the"crescent sign"and peritubular fat blurring in the SMA demonstrated some level of diagnostic significance.Conclusion CT scanning has the capability to identify the enlarged diameter of the SMA trunk,as well as plain the"crescent sign"and related manifestations.This finding holds significant value in diagnosing ISMAD.Furthermore,it provides the basis for the necessity of subsequent computed tomography angiography(CTA)examinations.

Noise-induced hearing loss(NIHL)is a public health problem that requires immediate attention.Nearly one-third of hearing loss can be attributed to noise exposure.However,the molecular mechanism of NIHL is complex,and there is currently no specific drug available for preventing and treating NIHL.Therefore,it is particu-larly important to establish standardized preclinical research models of NIHL and identify molecular targets for treat-ment so as to carry out the prevention and drug treatment of NIHL effectively.In this article,we summarized the research methods and pharmacological treatment studies on NIHL to provide references for the prevention and treat-ment of NIHL.

Objective:To explore the role and relationship between oxidative stress and immune infiltration in idiopathic pul-monary fibrosis(IPF),and to predict the relevant therapeutic herbal medicines and active ingredients.Methods:GSE10667 gene expression profiles were downloaded from GEO database to obtain differential expression genes,differential expression of oxidative stress genes(DEOSGs)were identified in combination with oxidative stress genes.GSEA was used to evaluate the pathways and biologi-cal processes in IPF,and GO,KEGG and PPI network analysis were performed on DEOSGs.Candidate central genes were derived from PPI results and CytoHubba,and GSE110147 was validated as an independent group to identify central genes;in addition,the immune microenvironment of samples was evaluated using CIBERSORTF,and correlation between central gene levels and relative proportion of immune cells was explored;finally,therapeutic herbal medicines and components were predicted by central genes,and mole-cular docking verification was carried out.Results:A total of 51 DEOSGs,four central genes(ICAM-1,APOE,MMP-1,TGF-β2)were obtained;DEOSGs were mainly related to oxidative stress,immune response,etc;four central gene levels were closely correlated with 8 relative proportions of immune cells;therapeutic herbal medicines included 4 flavors such as Huangqi and Chuanxiong,and the active ingredients included 8 kinds of β-carotene,etc,the molecular docking results were stable.Conclusion:Oxidative stress and immune firing are exist in IPF,and oxidative stress may be recognized by immune cells or directly activate immune cells.

Objective:To observe the intervention mechanism of phlegm-stasis co-treatment for the JNK signaling pathway in the myocardium of diabetes rats.Methods:Totally 50 male SD rats of SPF grade were selected. Diabetes model was established by single intraperitoneal injection of 55 mg/kg streptozotocin (STZ) solution. After continued feeding for 3 weeks, the rats were divided into normal group, model group, alachloramine group, blood stasis removing group, phlegm removing group and phlegm-blood stasis co-treatment group according to random number table method, with 6 rats in each group. Xiaoxianxiong Decoction (4.05 g/kg), Xuefu Zhuyu Decoction (7.02 g/kg), Didang Xianxiong Decoction (8.10 g/kg) were administered to the stomach respectively in the phlegm removing group, the blood stasis removing group and the phlegm-blood stasis co-treatment group. Alachloramine (3 mg/kg) was administered to the stomach by gavage in the alachloramine group. After 8 weeks, HE staining was used to observe the morphological changes of myocardial tissue in diabetic rats. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium in rats. The expression of JNK1 protein was determined by immunohistochemistry. JNK1 mRNA, IRS1 mRNA and NLRP3 expression levels were detected by Real-time PCR. Western blot was used to detect the protein expressions of IRS-1, p-Akt and NLRP3.Results:The myocardial cells in the model group were disorganized, with hypertrophy, blurred texture, inflammatory infiltration of interstitium, increased collagen fibers, and focal necrosis. All treatment groups could improve fibrosis, inflammatory infiltration and reduce myocardial collagen deposition in different degrees. Compared with the model group, the mRNA and protein expressions of JNK1 and NLRP3 bodies decreased ( P<0.01), the IRS-1 mRNA and protein increased ( P<0.01), and p-Akt protein expression increased ( P<0.01). Conclusions:The phlegm and stasis co-treatment can effectively improve the cardiomyopathy of diabetes rats, and the effect is better than the phlegm-resolving method or the stasis resolving method alone. The mechanism may be related to the inhibition of JNK signaling pathway activation, reduce the expressions of JNK1 and NLRP3, and increase the IRS-1 and Akt.