Hyaluronic acid (HA) possesses excellent biocompatibility, biodegradability, and non-immunogenicity, and exhibits active targeting capability to receptors such as cluster of differentiation 44 (CD44). Therefore, HA has become an important material for the design and preparation of drug delivery carriers in recent years. HA is rich in functional groups that can be chemically modified, but different modification methods and sites can affect its biological properties. This paper summarizes and discusses the effects of chemical modification on the biological properties of HA based on the formation mechanisms of such properties, as well as the derivatization and characterization methods of HA, so as to provide some reference for rational research on chemical modification of HA.

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 impact on ¹⁸F fluorodeoxyglucose （¹⁸F-FDG） positron emission tomography （PET） image quality when block sequential regularized expectation maximization （BSREM） algorithm and ordered subset expectation maximization （OSEM） algorithm were used at various acquisition times （ATs）, and to discuss the feasibility of AT optimization with BSREM algorithm. Methods In the phantom experiment, the NEMA/IEC PET phantom was adopted. In the clinical study, 66 pulmonary nodules with high uptake values from 61 patients who underwent a ¹⁸F-FDG PET-CT examination for pulmonary nodules from March to September 2020 were included. PET images were reconstructed according to BSREM algorithm and OSEM algorithm at various ATs in both the phantom experiment and the clinical study. Coefficient of variation, signal-to-noise ratio, contrast-to-noise ratio, and activity values （uptake value in the phantom experiment; standardized uptake value in the clinical study） were compared between the above sequence images for quality evaluation. Results The phantom experiment showed that the image quality of 120 s BSREM sequence was superior to that of 120 s OSEM sequence, and the image quality of 75 s BSREM sequence was similar to that of 120 s OSEM sequence. The clinical study showed that the image quality of 120 s BSREM sequence was superior to that of 120 s OSEM sequence, and the image quality of 75 s BSREM sequence was slightly better than that of 120 s OSEM sequence. Conclusion In the PET phantom experiment and the clinical study of pulmonary nodules with high uptake values, BSREM algorithm can significantly improve the image quality as compared to OSEM algorithm, and the image quality of 75 s BSREM sequence is slightly better than that of 120 s OSEM sequence.

Objective: To study the correlation between left atrial sphericity (LASP) and thromboembolic events (TE) in patients with atrial fibrillation (AF). Methods: This study was conducted in patients with AF underwent radiofrequency ablation in the Department of Cardiology of First Affiliated Hospital of Zhengzhou University from January 2011 to October 2018. The AF patients with TE (study group, n=157) and the AF patients without TE (control group, n=157) were matched for age and gender. The differences of LASP and other related indexes between the two groups were compared, and the correlation between LASP and TE was analyzed by conditional logistic regression. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of LASP for TE. Results: (1) The LASP in the study group was significantly higher than that in the control group [ (87.5±7.1) % vs. (82.8±6.1) %, P=0.001]. (2) Conditional logistic regression analyses showed that LASP (OR=1.10, 95%CI 1.05-1.16, P=0.001), left atrial volume index (OR=1.01, 95%CI 1.00-1.02, P=0.016) and CHA₂D-VASc score (OR=1.77, 95%CI 1.30-2.41, P=0.001) were independently and positively correlated with TE. (3) The ROC curve analysis showed that the area under the curve (AUC) of left atrial sphericity (AUC=0.712, 95%CI 0.656-0.768, P=0.001) was larger than the AUC of either left atrial volume index (AUC=0.650, 95%CI 0.589-0.710, P=0.001) or CHA₂D-VASc score (AUC=0.612, 95%CI 0.550-0.674, P=0.001). (4) CHA₂D-VASc-LASP₂ score was positively correlated with TE (OR=1.95, 95%CI 1.55-2.42, P=0.001). Conclusion LASP is independently and positively correlated with TE in patients with AF.

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 examine the efficacy and safety of pregabalin in patients with neuropathic cancer pain (NCP).Methods A prospective randomized control multicenter trial was conducted in five hospitals;from January 2015 to January 2016,one hundred and twenty two eligible inpatients and outpatients were divided into pregablin treatment group (n=60) and control group (n=62).Patients in the pregablin group added pregablin to opiod background analgesia,while those in the control group raised opioid dose instead.The Numerical Pain Rating Scale (NRS) scores,paraesthesia scale scores,Hamilton's Depression (HAMD) scale scores,analgesia dose,patiends satisfaction,and adverse events were recorded 14 d after each treatment.Results After each treatment,the NRS scores were decreased by (2.3 ±1.1) and (1.3±1.5),the paraesthesia scale scores were decreased by (1.6±0.6) and (0.4±0.3),and the HAMD scale scores were decreased by (4.4±1.2) and (2.4±1.0) in the pregablin treatment group and control group,respectively,with significant differences (P＜0.05).Morphine dose for breakthrough pain in pregabalin group was statistically less than that in control group ([30.6±3.5] mg/d vs.[70.9±12.3] mg/d,P＜0.05).Patients satisfaction in the pregablin treatment group was significantly higher than that in the control group (P＜0.05).Pregabalin treatment group had less severe adverse effects (3/56,5％) as compared with control group (10/59,16.1％,P＜0.05).Conclusion Pregabalin has positive roles in patients with NCP already receiving opioid;pregabalin has better pain-control and mood improvement.

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) are very two important pathogens that have coursed huge economic losses in swine production in worldwide. In this study,a vector pCMV-TJM containing the full-length cDNA clone of PRRSV attenuated strain TJM-F92 was firstly constructed by PCR method. Then a gene sequence containing Afl II/Mlu I e restriction enzyme sites and a transcription regulatory sequence for ORF6 (TRS6) was inserted be- tween ORF7 and 3'UTR, yielding a expression vector pCMV-TJM-TRS. Subsequently, a plasmid pCMV-TJM-Cap was constructed by cloning of PCV2 ORF2 gene into the unique sites Afl II /Mlu I of pCMV- TJM-TRS plasmid DNA. Then three recombinant PRRSV, rTJM, rTJM/TRS and rTJM/Cap, were rescued by transfection of pCMV-TJM, pCMV-TJM-TRS and pCMV-TJM-Cap into Marc-145 cells, respectively,and confirmed by the genome sequence, restriction enzyme digestion, Western Blot and IFA. They all had the molecular markers which was different from the parent virus. The growth characteristics of the rescued viruses were similar to that of parent virus. rTJM/Cap could also express efficiently PCV2 Cap protein in Marc-145 cells. At passage 8, it still had PCV2 ORF2 gene which examined by RT-PCR. It indicated that the full-length cDNA clone of PRRSV attenuated strain TJM-F92 and recombinant PRRSV rTJM/Cap expressing PCV2 Cap protein were successfully constructed. It made an important foundation for studying on the pathogenic mechanisms of PRRSV and PRRSV-PCV2 vaccine in the future.
Animals ; Capsid Proteins ; genetics ; immunology ; Cell Line ; Circoviridae Infections ; veterinary ; virology ; Circovirus ; classification ; genetics ; metabolism ; Gene Expression ; Open Reading Frames ; Porcine Reproductive and Respiratory Syndrome ; virology ; Porcine respiratory and reproductive syndrome virus ; genetics ; metabolism ; Recombination, Genetic ; Swine ; Swine Diseases ; virology ; Viral Vaccines ; genetics ; immunology

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 .

Objective To evaluate the role of NF-κB in astrocytes in the spinal dorsal horn in a rat model of neuropathic pain induced by paclitaxel.Methods Twenty 6 year old male SD rats weighing 180-200 g were randomly divided into 2 groups ( n =10):control group (group C) and neuropathic pain group (group NP).Neuropathic pain was induced by intraperitoneal injection paclitaxel of 2 mg/kg every other day for 4 times in group NP.While the equal volume of normal saline was given instead of paclitaxel in group C.Body weight,mechanical pain threshold and heat pain threshold were determined before and at 1,7,14 d after administration.The animals were sacrificed and the spinal dorsal horn were removed for determination of NF-κB p65 expression in astrecytes by immunofluorescence analysis at 14 d after administration.Results There was no significant difference in body weight between the two groups( P ＞ 0.05).Compared with group C,mechanical pain threshold and heat pain threshold were significantly decreased 7 and 14 d after administration,the expression of NF-κB p65 in astrocytes in the spinal dorsal horn was up-regulated in group NP( P ＜ 0.05 or 0.01 ).Conclusion Activation of NF-κB in astrocytes in the spinal dorsal horn may play an important role in neuropathic pain induced by paclitaxel in rats.