Objective:To evaluate the outcomes of short-segment pedicle screw fixation after vertebroplasty augmentation using polymethylmethacrylate (PMMA) and laminectomy for stage Ⅲ Kümmell's disease with neurological symptoms.Methods:A retrospective study was conducted to analyze the clinical data of the 23 patients who had been treated at Department of Spinal Surgery, Beijing Jishuitan Hospital from January 2016 to August 2022 for single level stage Ⅲ Kümmell's disease with neurological symptoms by short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA and laminectomy. There were 9 males and 14 females, with an age of (69.7±3.8) years. The visual analogue scale (VAS) for low back pain, Oswestry disability index (ODI) for low back pain, kyphotic Cobb angle of the fixed segment, and loss of the anterior vertebral body height were compared between preoperation, 2 weeks after operation, 2 years after operation, and the last follow-up. The improvements in American Spinal Injury Association (ASIA) impairment grading at the last follow-up compared to the preoperative levels, bone graft fusion rates at the last follow-up and complications were recorded.Results:All patients were followed up for (57.4±17.7) months after operation. The VAS pain scores [(2.2±0.3) points, (1.8±0.6) points and (1.6±0.5) points], ODIs (23.9%±4.5%, 21.6%±4.5% and 19.1%±3.8%), kyphotic Cobb angles of the fixed segments (12.2°±2.7°, 12.5°±2.6° and 12.8°±2.8°) and losses of the anterior vertebral body height (20.0%±3.4%, 20.2%±3.5% and 20.3%±3.5%) at 2 weeks after operation, 2 years after operation, and the last follow-up were significantly improved compared to the pre-operative values [(7.8±0.5) points, 79.7%±5.1%, 40.2°±6.2°, and 60.4%±14.2%, respectively] ( P<0.05). However, there were no significantly differences in the above values between 2 weeks after operation, 2 years after operation and the last follow-up ( P>0.05). Of the 2 patients with grade C, the ASIA grading at the last follow-up improved to grade D in one and to grade E in the other; of the 12 patients with grade D, the ASIA grading at the last follow-up improved to grade E in 11. The complications included 2 asymptomatic cases of bone cement leakage from the upper endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the lower endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the spinal canal, and 1 case of distant vertebral compression fracture. The last follow-up showed good bone graft fusion in all patients. Conclusion:In the treatment of stage Ⅲ Kümmell's disease with neurological symptoms, short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA is a relatively minimally invasive, safe, and effective treatment, because it can alleviate back pain, improve neurological function and daily function, correct thoracolumbar kyphosis, restore vertebral height and reconstruct spinal stability without significant complications.

Primary sclerosing cholangitis(PSC)is an autoimmune disease characterized by chronic inflamma-tion and progressive fibrosis that affects both intrahepatic and extrahepatic bile ducts.Despite ongoing research,the under-lying mechanisms of PSC pathogenesis remain incompletely understood.The ductular reaction is not only a key pathologi-cal feature of PSC but also serves as a driving force in its progression.This review examines the promoting effects of the ductular reaction on PSC advancement from multiple perspectives,including the proliferation of biliary epithelial cells,in-flammation,and fibrosis.By providing theoretical insights into the pathogenesis of PSC,this review aims to facilitate the identification of novel therapeutic strategies.

Inflammatory bowel disease(IBD)is a chronic,nonspecific inflammatory condition of the intes-tine.However,its pathogenesis and molecular mechanisms remain elusive.The primary therapeutic goal for IBD is to achieve complete restoration of the intestinal mucosa.Despite various treatment strategies available in clinical practice,options to effectively promote mucosal healing remain limited.Macrophages play a pivotal role in maintaining intestinal ho-meostasis,modulating inflammatory responses,and facilitating mucosal healing.This review explores the significance and regulatory mechanisms of macrophages in intestinal mucosal healing,with particular emphasis on modulating macrophage phenotypic switching in the treatment of IBD.Furthermore,this review provides a theoretical basis for precision medicine in IBD treatment,highlighting valuable insights for more targeted therapeutic approaches.

OBJECTIVES: This study aimed to investigate the association between temporomandibular disorder (TMD) and insomnia using a two-sample Mendelian randomization (MR) approach. METHODS: Bidirectional MR analyses of two samples, TMD (n=377 277) and insomnia (n=375 359), were performed using genome-wide association study statistics published in the FinnGen database. Instrumental variables were first screened, and then inverse variance weighting (IVW) and MR-Egger were used as the main-effect assessment methods. Weighted median, weighted mode, and simple mode served as supplementary methods. We used IVW and MR-Egger to test for heterogeneity, as well as MR-Egger intercepts to assess the single nucleotide polymorphism (SNP) potential level of multiplicity effects. Sensitivity analyses were conducted based on leave-one-out to identify potentially influential SNPs. All analyses were conducted by using the two-sample MR R package and were considered statistically significant when P<0.05. RESULTS: MR analysis showed the presence of TMD on insomnia (OR=1.089, 95%CI: 1.017-1.166, P=0.014). Meanwhile, no effect of insomnia on TMD (OR=0.996, 95%CI: 0.964-1.029, P=0.816) was found. The sensitivity-analysis showed that no heterogeneity existed (P>0.05), and the presence of horizontal pleiotropy was not detected (P>0.05). Leave-one-out sensitivity analysis showed no single SNP, which may affect the causal relation. All findings indicated that the causal relationship between TMD and insomnia was not significantly affected by any individual SNP and that IV did not bias the results. CONCLUSIONS Results of MR analyses showed that TMD is a risk factor for insomnia, whereas insomnia is not a risk factor for TMD.
Humans ; Sleep Initiation and Maintenance Disorders/genetics* ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Temporomandibular Joint Disorders/complications* ; Genome-Wide Association Study

Inflammatory bowel disease(IBD)is a chronic,nonspecific inflammatory condition of the intes-tine.However,its pathogenesis and molecular mechanisms remain elusive.The primary therapeutic goal for IBD is to achieve complete restoration of the intestinal mucosa.Despite various treatment strategies available in clinical practice,options to effectively promote mucosal healing remain limited.Macrophages play a pivotal role in maintaining intestinal ho-meostasis,modulating inflammatory responses,and facilitating mucosal healing.This review explores the significance and regulatory mechanisms of macrophages in intestinal mucosal healing,with particular emphasis on modulating macrophage phenotypic switching in the treatment of IBD.Furthermore,this review provides a theoretical basis for precision medicine in IBD treatment,highlighting valuable insights for more targeted therapeutic approaches.

Objective:To evaluate the outcomes of short-segment pedicle screw fixation after vertebroplasty augmentation using polymethylmethacrylate (PMMA) and laminectomy for stage Ⅲ Kümmell's disease with neurological symptoms.Methods:A retrospective study was conducted to analyze the clinical data of the 23 patients who had been treated at Department of Spinal Surgery, Beijing Jishuitan Hospital from January 2016 to August 2022 for single level stage Ⅲ Kümmell's disease with neurological symptoms by short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA and laminectomy. There were 9 males and 14 females, with an age of (69.7±3.8) years. The visual analogue scale (VAS) for low back pain, Oswestry disability index (ODI) for low back pain, kyphotic Cobb angle of the fixed segment, and loss of the anterior vertebral body height were compared between preoperation, 2 weeks after operation, 2 years after operation, and the last follow-up. The improvements in American Spinal Injury Association (ASIA) impairment grading at the last follow-up compared to the preoperative levels, bone graft fusion rates at the last follow-up and complications were recorded.Results:All patients were followed up for (57.4±17.7) months after operation. The VAS pain scores [(2.2±0.3) points, (1.8±0.6) points and (1.6±0.5) points], ODIs (23.9%±4.5%, 21.6%±4.5% and 19.1%±3.8%), kyphotic Cobb angles of the fixed segments (12.2°±2.7°, 12.5°±2.6° and 12.8°±2.8°) and losses of the anterior vertebral body height (20.0%±3.4%, 20.2%±3.5% and 20.3%±3.5%) at 2 weeks after operation, 2 years after operation, and the last follow-up were significantly improved compared to the pre-operative values [(7.8±0.5) points, 79.7%±5.1%, 40.2°±6.2°, and 60.4%±14.2%, respectively] ( P<0.05). However, there were no significantly differences in the above values between 2 weeks after operation, 2 years after operation and the last follow-up ( P>0.05). Of the 2 patients with grade C, the ASIA grading at the last follow-up improved to grade D in one and to grade E in the other; of the 12 patients with grade D, the ASIA grading at the last follow-up improved to grade E in 11. The complications included 2 asymptomatic cases of bone cement leakage from the upper endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the lower endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the spinal canal, and 1 case of distant vertebral compression fracture. The last follow-up showed good bone graft fusion in all patients. Conclusion:In the treatment of stage Ⅲ Kümmell's disease with neurological symptoms, short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA is a relatively minimally invasive, safe, and effective treatment, because it can alleviate back pain, improve neurological function and daily function, correct thoracolumbar kyphosis, restore vertebral height and reconstruct spinal stability without significant complications.

Primary sclerosing cholangitis(PSC)is an autoimmune disease characterized by chronic inflamma-tion and progressive fibrosis that affects both intrahepatic and extrahepatic bile ducts.Despite ongoing research,the under-lying mechanisms of PSC pathogenesis remain incompletely understood.The ductular reaction is not only a key pathologi-cal feature of PSC but also serves as a driving force in its progression.This review examines the promoting effects of the ductular reaction on PSC advancement from multiple perspectives,including the proliferation of biliary epithelial cells,in-flammation,and fibrosis.By providing theoretical insights into the pathogenesis of PSC,this review aims to facilitate the identification of novel therapeutic strategies.

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

Background Environmental noise pollution is serious, and there are few studies on the effects of long-term noise exposure during sleep on cognitive function and possible biological clock mechanism. Objective To explore the cognitive impairment induced by noise exposure during sleep in mice and possible biological clock mechanism, and to provide a theoretical basis for the protection against noise exposure. Methods Twenty male C57BL/6J mice were randomly divided into a control group and a noise-exposed group, 10 mice in each group. The noise-exposed group was exposed to sleep-period noise using a noise generator for 12 h (08:00–20:00) per day for a total of 30 d. The calibrated noise intensity was set at 90 dB. No intervention was imposed on the control group. At the end of the noise exposure, cognitive function of mice was examined using the new object recognition experiment and the open field test, and the hippocampal tissue damage of mice were evaluated by Nissl staining, ionized calcium binding adaptor molecule 1 (Iba1) immunofluorescence staining, and real-time fluorescence quantitative PCR for inflammatory factors and biological clock genes. Oxidative stress indicators in the hippocampus of mice were also detected by assay kit. Results After noise exposure during sleep period, the results of new object recognition experiment showed that the discrimination index of mice in the noise-exposed group was 0.06±0.04, which was significantly lower than that of the control group (0.65±0.13) (P<0.05). The results of open field test showed that the central activity distance of the noise-exposed group was (242.20±176.10) mm, which was significantly lower than that of the control group, (1548.00±790.30) mm (P < 0.05), and the central activity time of the noise-exposed group was (0.87±0.64) s, which was significantly lower than that of the control group, (6.00±2.86) s (P < 0.05). The Nissl staining results showed that compared with the control group, neurons in the hippocampus of the noise-exposed mice were shrunken, deeply stained, disorganized, and loosely connected. The immunofluorescence results showed that microglia in the hippocampus of the noise-exposed mice were activated and the expression of Iba1 was significantly increased compared with those of the control group (P<0.05). The real-time PCR results of showed that the mRNA levels of the biological clock genes Clock, Per2, and Rev-erbα were significantly increased compared with those of the control group (P<0.05), and the mRNA level of Per1 was significantly decreased compared with that of the control group (P<0.05); and the mRNA levels of IL-18, IL-6, iNOS, and NLRP3 in the hippocampal tissues of mice were significantly increased compared with those of the control group (P<0.05). The results of oxidative stress evaluation showed that compared with the control group, reduced glutathione content was significantly reduced in the noise-exposed group (P<0.001). Conclusion Noise exposure during sleep period can lead to the destabilization of biological clock genes in hippocampal tissues and trigger hippocampal neuroinflammation, which can lead to the activation of microglia and cause cognitive impairment in mice.

BACKGROUND:Prevention of fractures after stroke is very important,and there are currently no models to predict the occurrence of hip fractures after stroke. OBJECTIVE:To investigate the risk factors leading to hip fracture in stroke patients and to establish a risk prediction model to visualize this risk. METHODS:A total of 439 stroke patients were selected from the Affiliated Hospital of Xuzhou Medical University from June 2014 to June 2017,including 107 males and 332 females,with a mean age of(71.38±9.74)years.They were divided into fracture group(n=35)and non-fracture group(n=404)according to the presence or absence of hip fracture.Univariate and multivariate analyses were used to determine the risk factors for hip fracture after stroke.The data were randomly divided into training set(70%)and test set(30%).Nomogram predicting the risk of hip fracture occurrence was created based on the results of the multifactor analysis,and performance was evaluated using receiver operating characteristic curve,calibration curves,and decision curve analysis.A web calculator was created to facilitate a more convenient interactive experience for clinicians. RESULTS AND CONCLUSION:(1)Univariate analysis showed significant differences between the two groups in the number of falls,smoking,hypertension,glucocorticoids,number of strokes,Mini-Mental State Examination,visual acuity level,National Institute of Health Stroke Scale,Berg Balance Scale,and Stop Walking When Talking scale scores(P<0.05).(2)Multivariate analysis showed that number of falls[OR=17.104,95%CI(3.727-78.489),P=0.000],National Institute of Health Stroke Scale[OR=1.565,95%CI(1.193-2.052),P=0.001],Stop Walking When Talking[OR=12.080,95%CI(2.398-60.851),P=0.003]were independent risk factors positively associated with new hip fractures.Bone mineral density[OR=0.155,95%CI(0.044-0.546),P=0.012]and Berg Balance Scale[OR=0.840,95%CI(0.739-0.954),P=0.007]were negatively associated with new hip fractures after stroke.(3)The AUC values of nomogram were 0.956 and 0.907 in the training and test sets,respectively,and the calibration curves showed a high agreement between predicted and actual status with an area under the decision curve of 0.038 and 0.030,respectively.(4)These findings conclude that the number of falls,low bone mineral density,low Berg Balance Scale score,high National Institute of Health Stroke Scale score,and positive Stop Walking When Talking are risk factors for hip fracture after stroke.Based on this,a nomogram with high accuracy was developed and a web calculator(https://stroke.shinyapps.io/DynNomapp/)was created.