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 compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To compare the biomechanical differences among modular total sacral prosthesis, integrated total sacral prosthesis and screw-rod system for lumbosacral reconstruction after total sacrectomy by finite element analysis.Methods:Three finite element models of reconstruction after total sacrectomy were established: six-rod plus anterior column, integrated total sacral prosthesis, and modular total sacral prosthesis. A vertical load of 600 N was applied to the L 3 vertebra, and the bilateral acetabula were fixed in all degrees of freedom to restrict their movement, simulating a bipedal standing posture. The maximum stress, stress distribution on the iliac screws, stress distribution on the longitudinal rods, the shift-down displacement of the L 5 vertebra, and the stress direction on the contact surface between the prosthesis and the ilium on all implant components (including prosthesis, screws, and connecting rods) were compared. Results:Finite element analysis results show that the average maximum stress of the six-rod plus anterior column reconstruction on all implant instrumentation was 217.9±10.2 MPa, the integrated total sacral prosthesis reconstruction was 185.7±21.1 MPa, and the modular total sacral prosthesis reconstruction was 157.4±31.2 MPa. The differences were statistically significant ( F=12.357, P<0.001). Among them, the difference between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction was statistically significant ( P<0.001), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.051). The maximum stress on the iliac bone screws and longitudinal connecting rods: for the six-rod plus anterior column reconstruction, it was 157.2 MPa and 105.4 MPa respectively; for the integrated total sacral prosthesis reconstruction, it was 59.2 MPa and 97.8 MPa respectively; for the modular total sacral prosthesis reconstruction, it was 58.4 MPa and 35.6 MPa respectively. The distance of L 5 vertebral body downward displacement: for the six-rod plus anterior column reconstruction, it was 1.05±0.06 mm; for the integrated total sacral prosthesis reconstruction, it was 0.34±0.02 mm; for the modular total sacral prosthesis reconstruction, it was 0.40±0.05 mm. The difference was statistically significant ( F=357.730, P<0.001), among which the differences between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction and that between the integrated total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction were all statistically significant ( P<0.05), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.145). The stress on the iliac bone contact surface of the integrated total sacral prosthesis was 34.2° and manifested as shear force; the stress on the iliac bone contact surface of the modular total sacral prosthesis was 88.9° and manifested as compressive stress. Conclusions:This modular total sacral prosthesis exhibits lower peak stress compared with the integrated total sacral prosthesis and screw-rod system. The spinal stability of the modular total sacral prosthesis is comparable to that of the integrated total sacral prosthesis and superior to that of the screw-rod system.

Objective:To compare the biomechanical differences among modular total sacral prosthesis, integrated total sacral prosthesis and screw-rod system for lumbosacral reconstruction after total sacrectomy by finite element analysis.Methods:Three finite element models of reconstruction after total sacrectomy were established: six-rod plus anterior column, integrated total sacral prosthesis, and modular total sacral prosthesis. A vertical load of 600 N was applied to the L 3 vertebra, and the bilateral acetabula were fixed in all degrees of freedom to restrict their movement, simulating a bipedal standing posture. The maximum stress, stress distribution on the iliac screws, stress distribution on the longitudinal rods, the shift-down displacement of the L 5 vertebra, and the stress direction on the contact surface between the prosthesis and the ilium on all implant components (including prosthesis, screws, and connecting rods) were compared. Results:Finite element analysis results show that the average maximum stress of the six-rod plus anterior column reconstruction on all implant instrumentation was 217.9±10.2 MPa, the integrated total sacral prosthesis reconstruction was 185.7±21.1 MPa, and the modular total sacral prosthesis reconstruction was 157.4±31.2 MPa. The differences were statistically significant ( F=12.357, P<0.001). Among them, the difference between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction was statistically significant ( P<0.001), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.051). The maximum stress on the iliac bone screws and longitudinal connecting rods: for the six-rod plus anterior column reconstruction, it was 157.2 MPa and 105.4 MPa respectively; for the integrated total sacral prosthesis reconstruction, it was 59.2 MPa and 97.8 MPa respectively; for the modular total sacral prosthesis reconstruction, it was 58.4 MPa and 35.6 MPa respectively. The distance of L 5 vertebral body downward displacement: for the six-rod plus anterior column reconstruction, it was 1.05±0.06 mm; for the integrated total sacral prosthesis reconstruction, it was 0.34±0.02 mm; for the modular total sacral prosthesis reconstruction, it was 0.40±0.05 mm. The difference was statistically significant ( F=357.730, P<0.001), among which the differences between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction and that between the integrated total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction were all statistically significant ( P<0.05), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.145). The stress on the iliac bone contact surface of the integrated total sacral prosthesis was 34.2° and manifested as shear force; the stress on the iliac bone contact surface of the modular total sacral prosthesis was 88.9° and manifested as compressive stress. Conclusions:This modular total sacral prosthesis exhibits lower peak stress compared with the integrated total sacral prosthesis and screw-rod system. The spinal stability of the modular total sacral prosthesis is comparable to that of the integrated total sacral prosthesis and superior to that of the screw-rod system.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

This study systematically retrieved the clinical studies in the treatment of idiopathic pulmonary fibrosis(IPF) with traditional Chinese medicine(TCM) and employed evidence mapping to summarize the overall research status and deficiencies of TCM in treating IPF. CNKI, VIP, SinoMed, Wanfang, PubMed, Web of Science, Cochrane Library, and EMbase were searched for the relevant studies published from inception to February 20, 2024. The distribution characteristics of the evidence were analyzed and presented through charts combined with words. A total of 323 studies were included, including 295 randomized controlled trials(RCTs) and 28 Meta-analysis. The number of publications in this field rose with fluctuations, yet the proportion of core papers was low, and the research lacked the attention of foreign researchers. There were scant cross-regional collaboration between researchers and insufficient attention from relevant departments. The included RCT generally had low quality, with small sample sizes, short treatment courses, and insufficient attention to acute exacerbation and complications of IPF. In addition, few studies employed TCM alone, and the TCM syndromes remained to be standardized. A considerable number of outcome indicators were involved in the publications, while the majority of them failed to emphasize the disparity between primary and secondary outcome indicators. There were diverse reference standards for the comprehensive indicators among the outcome indicators, and insufficient attention was paid to long-term prognosis and health economic indicators. The included Meta-analysis concluded that TCM had potential clinical efficacy in treating IPF. However, the methodological credibility grading and the GRADE grading results of outcome indicators were low. The results suggested that TCM demonstrated certain advantages in the treatment of IPF, while the quality of the included studies was not high. In the future, clinical research protocols should be standardized and registered. Multicenter, large-sample, and follow-up clinical studies should be conducted. The research reports should refer to relevant reporting standards to improve the quality and generate high-level evidence, thus providing a reference for the clinical application of TCM in the treatment of IPF.
Humans ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

Objective: To understand the situation of neglect of preschool children in the urban area of Xi an under the background of multi child policy, so as to provide a reference for making effective prevention. Methods: In Novmber 2022, according to the multi stage stratified cluster sampling principle, 2 450 parents of children aged 3-6 years were randomly selected from 7 urban areas of Xi an to participate in the questionnaire survey. A questionnaire survey was conducted using the "Neglect Evaluation Norms of 3-6 Years Old (Preschool) Children in Urban Areas of China". SPSS 18.0 software was used for statistical description, Chi square test and variance analysis. Results: The total neglect rate of preschool children in the urban area of Xi an was 29.0% and the total neglect score was (37.58±8.44). There was no statistical difference in the neglect status of children in different grade groups ( χ 2/ F =1.61, 2.98, P >0.05). The neglect score of boys was higher than girls ( t =2.45, P <0.05). There was no statistical difference in the neglect rate and neglect score of boys and girls in other levels ( P >0.05); except for the significant difference in the neglect degree of medical treatment, education and safety ( t =2.01, 2.28, 2.02, P <0.05). The rate and score of neglect in multi-child families were higher than only-child families ( χ 2/ t = 13.68, -4.54, P <0.05). There were significant differences in the rate and degree of neglect of children with different birth order, which were "third and fourth-born>second-born>first-born" ( χ 2/ F = 10.84 , 2.79, P <0.05). The neglect rate and score of "single parent family" were significantly higher than that of "nuclear family" and "three-generation family" ( χ 2/ F =4.78, 2.79, P <0.05). Conclusion The neglect situation of preschool children in urban area of Xi an is still serious, especially in multi-child families. It should actively explore the risk factors and formulate effective intervention measures.

Background::Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.Methods::In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg -1·h -1, which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg -1·h -1, whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg -1·h -1, which could be adjusted to 0.30-4.00 mg·kg -1·h -1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration. Results::Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar. Conclusions::ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.Trial registration::ClinicalTrials.gov, NCT04147416.