Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

Objective:To compare the short-term efficacy between femoral neck system (FNS) and cannulated compression screws (CCS) in the treatment of femoral neck fractures in young and middle-aged patients.Methods:A retrospective study was performed of the 29 young and middle-aged patients with femoral neck fracture who had been treated with FNS at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2020 to December 2020. A control group of another 29 patients with femoral neck fracture was selected who had been treated with CCS but matched in gender, age, and body mass index. In the CCS group, there were 14 males and 15 females with an age of (48.2±12.3) years; in the FNS group, there were 14 males and 15 females with an age of (48.2±12.0) years. The fracture reduction quality, operation time, intraoperative blood loss, and femoral neck shortening, hip joint function, Barthel index and health survey 12-item short form (SF-12) score at the last follow-up and complications during follow-up were compared between the 2 groups.Results:No significant difference was found in the preoperative general data or follow-up time between the 2 groups, showing comparability ( P>0.05). The intraoperative blood loss in the CCS group [20 (10, 50) mL] was significantly less than that in the FNS group [50 (20, 50) mL], and the femoral neck shortening at the last follow-up in the CCS group (grade 1 in 5 cases; grade 2 in 18 cases and grade 3 in 6 cases) was significantly worse than that in the FNS group (grade 1 in 21 cases, grade 2 in 6 cases and grade 3 in 2 cases) ( P<0.05). No significant difference was found regarding fracture reduction quality, operation time, complications during follow-up, or Merle D'Aubigne Postel score, Barthel index or SF-12 score at the last follow-up ( P>0.05). Conclusions:In the treatment of femoral neck fractures in young and middle-aged patients, both FNS and CCS are good options for internal fixation. However, FNS can reduce the severity of femoral neck shortening and maintain the length of femoral neck better than CCS.

In this study, a polyethylene glycol and dodecaldehyde modified bovine serum albumin (PEG-DSA) was developed, and its feasibility as a new high-efficiency micellar carrier for dasatinib (DAS) was explored.Circular dichroism, 1H NMR, elemental analysis, FT-IR and other methods were used to characterize the material structure and the single factor method was used to optimize the process of PEG-DSA/DAS micelles and non-PEGylated control micelles DSA/DAS.The results indicated that the optimal formulation was obtained with a mass ratio of 4∶1 between PEG-DSA and DAS, with average particle size of (37.21 ± 0.21) nm, polydispersion index (PDI) of (0.24 ± 0.04), Zeta potential of ? (15.68 ± 0.19) mV, drug loading (DL) capacity of (10.22 ± 0.34) %, and encapsulation efficiency (EE) of (42.73 ± 1.15) %. Compared with the currently reported nano-formulations of DAS, the drug loading of PEG-DSA/DAS micellar formulations was significantly increased with potential for further development.

As a typical BCS Ⅱ drug, felodipine exhibits low solubility and high permeability. We herein investigated the effects of different solubilization strategies on the oral absorption of felodipine. Firstly felodipine tablets based on 200 μm, 150 μm and 25 μm particle size of bulk drug were prepared. Meanwhile, felodipine solid dispersion and felodipine nanosuspension with average particle size of (168.90 ± 6.22) nm, PDI of 0.11 ± 0.06 were prepared. The absorption rate, apparent permeability coefficient (Papp), absorption quality in duodenum, jejunum, ileum and colon of rats and in vivo pharmacokinetics of the above different felodipine preparations were investigated. The results of rat single-pass intestinal perfusion showed that the absorption of felodipine preparations in duodenum, jejunum and ileum was better than in colon. Felodipine had a wide absorption window in the small intestine, with the best absorption site in the small intestine. Papp of different felodipine preparations was greater than 2.0 × 10-5 cm/s. Thus, the low solubility was the main factor limiting the absorption. In vivo pharmacokinetic experiments demonstrated the solubilization strategies significantly improved the bioavailability. The bioavailabilities of felodipine tablets with particle sizes of 150 and 25 μm, as well as nanosuspension, and solid dispersion were 138.75%, 173.01%, 208.65% and 314.53% that of the tablets with particle size of 200 μm, respectively. Solubilization strategies can significantly improve the gastrointestinal absorption rate and absorption quality of felodipine, and thus improve its bioavailability, which provides some reference for the research on the improvement of oral absorption of BCS II drugs.

Objective:To investigate the correlation among clinical manifestations, pathological changes and immunofluorescence in children with primary IgA nephropathy (IgAN).Methods:The data of a total of 222 cases diagnosed with IgAN by the Department of Nephrology, Jiangxi Children′s Hospital in recent 10 years were collected for the analysis of clinical and pathological features and their correlation.Results:(1)Immunofluorescence showed that 115 cases (51.8%) IgA patients had only mesangial deposition, and 107 cases (48.2%) IgA patients had both mesangial deposition and capillary loop deposition.Most IgA patients (122 cases, 55.0%) had immunofluorescence intensity+ + .In IgA patients, IgM deposition was the most common [168 cases (75.7%)], followed by C 3 deposition [160 cases (72.1%)]. Patients with C 4 deposition were the least[7 cases (3.2%)]. (2) Hypertension were positively correlated with IgM, C 3 deposition, IgA deposition intensity and IgA with vascular loop deposition(all P<0.05). Hyperuricemia was positively correlated with IgM deposition, IgG deposition, C 3 deposition and IgA with vascular loop deposition(all P<0.05); hypoalbuminemia was negatively correlated with IgM deposition, C 3 deposition, IgA deposition intensity and IgA with vascular loop deposition(all P<0.05). Hypercholesterolemia were positively correlated with C 3 deposition and IgA with vascular loop deposition(all P<0.05). Urine protein quantification were positively related to IgM, IgG and IgA with vascular loop deposition (all P<0.05). The estimated glomerular filtration rate(eGFR)was negatively related to IgA with vascular loop deposition( P<0.05). (3) Lee′s grade were positively correlated with IgM and C 3 deposition, IgA deposition intensity and IgA with capillary loop deposition(all P<0.05). (4) Oxford type mesangial hypercellularity(M1)were positively correlated with C 3 deposition and IgA deposition intensity(all P<0.001). Endocapillary hypercellularity(E1)lesions were positively correlated with IgA deposition intensity and IgA with capilla-ry loop deposition(all P<0.05). Segmental glomerulosclerosis(S1)lesions had no correlation with immunofluorescence pathology.Tubular atrophy and interstitial fibrosis(T1)was positively correlated with IgG and C 3 deposition(all P<0.05). (5) There was no correlation between glomerulosclerosis and immunofluorescence pathology.Crescent was positively correlated with IgM deposition, IgG deposition, C 3 deposition, IgA deposition intensity and IgA capillary loop deposition(all P<0.05). Renal artery thickening was positively correlated with IgG deposition and IgA capillary loop deposition(all P<0.05). Conclusions:IgA intensity of + + and IgM deposition are most commonly found in immunofluorescence of children with primary IgAN.IgA patients with capillary loops or C 3 deposition have more severe clinical manifestations and light microscopy results.

Methods for achieving diagnosis of Parkinson's disease (PD) based on speech data mining have been proven effective in recent years. However, due to factors such as the degree of disease of the data collection subjects and the collection equipment and environment, there are different categories of sample aliasing in the sample space of the acquired data set. Samples in the aliased area are difficult to be identified effectively, which seriously affects the classification accuracy of the algorithm. In order to solve this problem, a partition bagging ensemble learning is proposed in this article, which measures the aliasing degree of the sample by designing the the ratio of sample centroid distance metrics and divides the training set into multiple subsets. And then the method of transfer training of misclassified samples is used to adjust the results of subset partitioning. Finally, the optimized weights of each sub-classifier are used to integrate the test results. The experimental results show that the classification accuracy of the proposed method is significantly improved on two public datasets and the increasement of mean accuracy is up to 25.44%. This method not only effectively improves the classification accuracy of PD speech dataset, but also increases the sample utilization rate, providing a new idea for the diagnosis of PD.
Algorithms ; Data Mining ; Humans ; Machine Learning ; Parkinson Disease ; diagnosis ; Speech

Objective: To summarize the clinical manifestations and treatment of retinal artery occlusion and cerebral infarction caused by facial injection of hyaluronic acid. Methods: Fifteen cases (15 eyes) with vision lose caused by facial cosmetic injection of hyaluronic acid visited Xi＇an No.4 Hospital from December 2010 to January 2017. The clinical data were collected such as general medical history and treatment methods, and follow-up for 1 year. Results: All patients were female, 22-41 years old, with average age of 33. All patients were injected with hyaluronic acid. For 8 patients the fillers were injected in the forehead, 3 patients were in the glabellar region, 3 patients were in the nasolabial fold, and 1 patient was in the temporal of left eye. All patients had vision lose after injection, the visiting time was 1 to 6 hours. 13 patients were central retinal artery occlusion (CRAO). 1 patient was retinal branch artery occlusion (BRAO), 1 patient was ischemic optic neuropathy (ION), 13 patients manifested as no light perception (NLP), 1 patient was 0.6, 1 patient was CF/30 cm, and 14 patients with cerebral infarction, manifested as headache, dizziness. All patients were given emergency treatment, and 9 patients had treated with interventional thrombolysis therapy. After treatment 11 patients, visual acuity had no significant improvement, but 4 patients improved. Headache, dizziness symptoms disappeared, but cerebral infarction lesions still existed on MRI. Conclusions Human face is a rich blood supply; vision loss and cerebral infarction could occur after injection of hyaluronic acid. After urgent treatment visual acuity is not improved obviously, eventually leading to irreversible visual impairment or even loss.

Objective To evaluate the effect of resveratrol on mitochondrial function in renal tubular epithelial cells of rats with sepsis-induced acute kidney injury.Methods Ninety-six healthy SpragueDawley rats of both sexes,aged 5-7 weeks,weighing 180-220 g,were divided into 4 groups (n =24 each) using a random number table method:sham operation group (Sham group),sepsis group (group Sep),sepsis plus vehicle group (Sep+Ⅴ group) and sepsis plus resveratrol group (Sep+R group).Sepsis was induced by cecal ligation and puncture (CLP).Normal saline 0.5 ml,vehicle 0.5 ml and resveratrol 10 mg/kg were intraperitoneally injected at 6,12 and 18 h after CLP in Sep,Sep+Ⅴ and Sep+R groups,respectively.At 24 h after CLP,serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were measured,and kidney tissues were obtained for examination of the pathological changes (using transmission electron microscopy),and the damage to the renal tubules was scored.The renal tubular epithelial cells (RTECs) were isolated from the kidney cortex at 24 h after CLP for determination of mitochondrial transmembrane potential (by flow cytometry with the fluorescent probe JC-1),intracellular ATP content,mitochondrial permeability transition pore (mPTP) opening,lipid peroxide (LPO) content,and lysosomal membrane permeability.Results Compared with group Sham,the serum concentrations of Cr and BUN,renal tubular damage score,mPTP opening,LPO content and lysosomal membrane permeability were significantly increased,and mitochondrial transmembrane potential and ATP content were decreased in Sep and Sep+Ⅴ groups (P＜0.01).Compared with Sep and Sep+Ⅴ groups,the serum concentrations of Cr and BUN,renal tubular damage score,mPTP opening,LPO content and lysosomal membrane permeability were significantly decreased,and mitochondrial transmembrane potential and ATP content were increased in group Sep+R (P＜0.05).Conclusion Resveratrol improves mitochondrial function in renal tubular epithelial cells of rats with sepsis and reduces acute kidney injury,and the mechanism may be related to inhibiting oxidative stress and decreasing the lysosomal membrane permeability.

Objective To learn the clinical features of severe pneumonia in northeast sichuan ,and to improve the diagnosis and treatment level .Methods Basic disease or concomitant diseases and it′s clinical features were retrospective analyzed in different age patients with severe pneumonia in 2011 .Results (1)basic diseases and fatality cases /deteriorated cases were increased in elderly patients with the increase of age .There were 4 patients infected with HIV (3 cases under 65 years old ,1 case over 70 year old) .(2) onset pattern was given first place to suffer from cold ,but 40% were showed for symptoms of nervous system ,heart disease and other respiratory system ;(3)The main respiratory failure types of severe pneumonia is Ⅰ (about 70% ) ,30% of patients needed support of machine ventilation ;(4)community pneumonia were main type(75% );detection rate of Fungal infections and G -bacteria were 25% -30% ,normal bacteria (Streptococcus and Neisser bacteria )were over 1/3 ,Staphylococcus aureus were about 10% ;(6) More than 70% of the patients with different degree of hypoalbuminemia ;(7)Cure accounts for 2/3 ,poor prognosis accounted for 1/3 ,in which death and voluntary discharge were each 16 .6% ,ventilator-dependent ,multi-organ failure ,infections and some com-plex social factors were the prognostic factors .Conclusion Understanding the features and treatment difficulty of the local commu-nity acquired pneumonia is helpful to improve the timely diagnosis ,treatment and rescue level of patients with severe pneumonia .