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.].

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.

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Objective To analyze the effects of vesicoprostatic muscle(VPM)reconstruction on the early urinary control recovery and safety of patients undergoing robot-assisted radical prostatectomy(RARP).Methods A total of 128 patients who underwent RARP in our hospital during Sep.1,2021 and Aug.31,2023 were enrolled and divided into the non-reconstruction group(n=64)and reconstruction group(n=64)using random number table method.The reconstruction group received Montsouris+VPM reconstruction surgery,while the non-reconstructive group underwent Montsouris surgery only.Urinary control and perioperative data were collected with telephone interview,outpatient follow-up and inpatient records.The two groups were matched using overlap weighting and the Kaplan-Meier method was used to calculate urinary incontinence rates at 1,2 and 3 months after extubation.Early urinary control(3 months after extubation),operation time,intraoperative bleeding,positive rate of incision margin,and incidence of early postoperative complications(＜30 days)(Clavien-Dindo scale)were compared between the two groups.Results The recovery rate of urinary control at 1,2 and 3 months after extubation was significantly higher in the reconstruction group than that in the non-reconstruction group(33.9％vs.11.2％;46.7％vs.16.1％;70.6％vs.45.6％,P＜0.05),but the positive rate of resection margin was lower(16.1％vs.41.7％,P＜0.05).There were no significant differences in operation time,intraoperative bleeding and early postoperative complications between the two groups(P＞0.05).Conclusion VPM reconstruction can improve urinary control recovery in RARP patients early after extubation without increasing the risk of surgery.

Objective: Although previous studies have validated the effect of childhood trauma on depressive level, few studies have utilized the diathesis-stress theory to investigate the specific roles of perceived stress and rumination in the pathway between childhood trauma and depression in Chinese college students. This study aims to demonstrate the mediation effect of perceived stress and the moderation effect of rumination in the pathway between childhood trauma and depressive level in Chinese college students. Methods: A total of 995 Chinese college students in Guangzhou were included in this study by recruitment advertisement from October to December 2021. And they were asked to finish four self-report questionnaires, including Childhood Trauma Questionnaire-Short Form, Perceived Stress Scale, the 22-item Ruminative Response Scale, and Beck Depression Scale-II. Then the data were analyzed with Mplus 8.3. Results: Results revealed significant correlations among childhood trauma, perceived stress, rumination and depressive level. Further analyses revealed that perceived stress played a mediation role between childhood trauma and depressive level (estimate=0.09, standard error [SE]=0.02, t=5.93, 95% confidence interval [CI]=0.06–0.12), and rumination played a moderation role between childhood trauma and perceived stress (estimate=-0.17, SE=0.06, t=-2.86, 95% CI=-0.28– -0.05]) as well as between childhood trauma and depressive level (estimate=0.10, SE=0.04, t=2.74, 95% CI=0.03–0.16). Conclusion These results revealed the mediation effect of perceived stress and the moderation effect of rumination in the pathway between childhood trauma and depressive level in Chinese college students, which helped us to understand how the childhood trauma influenced the depressive level and gave us multi-dimensional indications for reducing the effect of childhood trauma on depressive level.

Objective To construct and verify a nomogram model for predicting social urinary control recovery in patients undergoing robot-assisted radical prostatectomy (RARP) immediately after extubation. Methods A retrospective analysis was conducted on the clinical data of 64 patients diagnosed with prostate cancer and treated by a single surgeon. The immediate urinary control status of the patients after removal of the catheter was evaluated, and LASSO regression was used for feature screening. Multiple Logistic regression was performed on the selected features to determine independent risk factors and establish a predictive model. And the discriminability, calibration, and clinical practicality of the model were evaluated using receiver operating curve (ROC), Hosmer Lemeshow test and calibration curve, and clinical decision curve (DCA) analysis. Results The variables in the outcome prediction model include D'Amico grading and distance of the levator muscle. The area under the ROC curve (AUC) was 0.742 (95%CI, 0.500 to 0.913, P < 0.001), indicating that the model had good discriminability. The calibration curve indicated that the model had good calibration ability. The DCA curve showed good clinical practicality. Conclusion The clinical predictive model developed inthis study can predict the recovery of immediate social urinary control in patients with RARP after surgery, which can further quantify the probability of achieving immediate social continence.

Objective:To investigate the effect of local anesthesia in patients with a PI-RADS score of 5 and ECOG score ≥2 for prostate puncture.Methods:Retrospective analysis of case data of 33 patients admitted to the Subei People's Hospital for prostate puncture from April 2020 to April 2022. Age (82.5±3.6) years. There were 18 cases with hypertensive disease, 8 cases with diabetes mellitus, and 6 cases with both diabetes mellitus and hypertensive disease. Body mass index (25.2±3.5) kg/m 2. prostate-specific antigen (PSA)(131.5±69.7) ng/ml. prostate volume (38.5±21.4) ml. all patients had a PI-RADS score of 5 on multiparametric magnetic resonance (mpMRI) and an Eastern Cooperative Oncology Group (ECOG) score ≥2. All 33 cases in this group underwent trans-perineal targeted prostate puncture using local anesthesia at the tip of the prostate. The visual analog score (VAS) and visual numeric score (VNS) were applied by the same surgeon to assess the patient's pain level and satisfaction at the time of puncture (VAS-1 and VNS-1) and 30 min after puncture (VAS-2 and VNS-2), and to record the duration of the procedure and the occurrence of postoperative complications. Results:In this group of 33 cases, the VAS-1 score was (1.9±0.3) and the VAS-2 score was (0.1±0.2); the VNS-1 score was (2.9±0.2) and the VNS-2 score was (3.9±0.1). Postoperative pathological results indicated that one of the 33 patients had a negative puncture result (pathology report indicating interstitial inflammation), while the rest of the patients had a positive puncture pathology report (puncture pathology report indicating prostate cancer), with a positive rate of 97%. One case of postoperative carnal haematuria occurred, which gradually improved after the patient was advised to drink water and take alpha-blockers. No perineal hematoma occurred, and all patients did not suffer complications such as urinary tract infection, urinary retention, azoospermia, vagal reaction, and infectious shock.Conclusion:In patients with a PI-RADS score of 5 and ECOG score ≥2, the use of single-hole local anesthesia for performing trans-perineal targeted puncture biopsy has the advantages of good paroxysmal pain and high safety.

Objective:To investigate the factors affecting the effect of periprostatic nerve block (PNB), establish a prediction model of pain degree, and verify the prediction efficiency.Methods:The clinical data of 314 patients who underwent transperineal prostate biopsy in our hospital from June 2022 to January 2023 were retrospectively analyzed. The median age was 71 (65, 76) years, the median prostate-specific antigen (PSA) was 14.6 (10.70, 24.65) ng/ml, and the median puncture needle number was 21 (19, 23) needles, median prostate volume 45.86 (31.52, 67.96) ml, median body mass index (BMI)24.02(22.97, 25.33)kg/m 2, including 109 patients with a history of diabetes, 90 patients with a history of surgery, and 57 patients with a history of severe trauma. The patients were divided into mild pain group (1-3 points), moderate pain group (4-6 points) and severe pain group (7-10 points) according to the intraoperative visual analogue scale (VAS). According to the clinical characteristics, the factors affecting the effect of PNB were analyzed by univariate analysis and multiple ordered logistic regression method. R language was used to construct a nomogram model for predicting PNB effect, receiver operating characteristic (ROC) curve and calibration curve were drawn, and Hosmer-Lemeshow test was carried out to verify the prediction efficiency of the model. Results:The results of univariate analysis showed that 171 patients in the mild pain group had a median age of 71 (65, 75) years, a median PSA14.5 (9.6, 24.6) ng/ml, a median number of puncture needles of 20 (18, 22), and a median prostate volume of 34.94 (26.36, 45.12) ml, median BMI24.17(23.14, 25.79)kg/m 2, including 74 patients with a history of diabetes, 51 patients with a history of surgery, and 40 patients with a history of severe trauma; There were 110 patients in the moderate pain group, the median age was 71 (65, 76) years, the median PSA14.8 (11.03, 24.27) ng/ml, the median number of puncture needles was 23 (20, 24) needles, median prostatic volume 63.24 (49.14, 78.72) ml, median BMI23.91(22.58, 24.88)kg/m 2, including 26 patients with a history of diabetes, 29 patients with a history of surgery, and 10 patients with a history of severe trauma; In the severe pain group, 33 patients had a median age of 73 (67, 78) years, a median PSA14.6 (10.85, 34.80) ng/ml, and a median puncture needle number of 23 (22.5, 24) needles, median prostate volume 70.64 (61.50, 104.51) ml, median BMI24.32(23.00, 26.06)kg/m 2, including 9 patients with a history of diabetes, 10 patients with a history of surgery, and 7 patients with a history of severe trauma. The results of univariate analysis showed that the number of puncture needles ( P<0.01), prostate volume ( P<0.01), history of diabetes ( P=0.002) and history of major trauma ( P= 0.009) were the factors affecting the effect of PNB. Multiple logistic regression analysis showed that puncture needle number ( P=0.009), prostate volume ( P<0.01) and diabetes history ( P=0.041) were independent risk factors for PNB effect. The area under ROC curve (AUC) of the moderate and above pain prediction model was 0.872, P<0.01; the area under ROC curve of the severe pain prediction model was 0.817, P<0.01; the result of Hosmer-Lemeshow test of the moderate and above pain prediction model was χ2=5.001, P=0.757. The results of the severe pain prediction model were χ2=4.452 and P=0.814. The calibration curve was established, which showed that the prediction probability of pain degree was in good agreement with the actual risk. Conclusions:The number of puncture needles, prostate volume and history of diabetes are the risk factors affecting the effect of PNB. The prediction model of PNB effect based on this model can be used to predict the pain degree of patients undergoing prostate biopsy after PNB.