Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

Objective:To develop an exercise rehabilitation program based on the Temporal Self-regulation Theory and evaluate its effectiveness in elderly patients with hip fractures.Methods:A total of 84 elderly patients with hip fractures admitted to the Department of Trauma Orthopedics at the First Affiliated Hospital of University of South China from May to August 2024 were enrolled using convenience sampling. Participants were randomly assigned to an experimental group ( n=42) and a control group ( n=42) using a random number table. The control group received routine exercise rehabilitation, while the experimental group received an exercise rehabilitation program constructed based on the Temporal Self-regulation Theory. The program included components such as establishing a unified concept of "exercise-rehabilitation", enhancing time-limited efficacy, achieving behavioral advantages, and improving self-regulation of active movement. Both groups received interventions for 12 weeks. Functional exercise adherence, activities of daily living, and hip joint function were assessed using the Orthopedic Exercise Adherence Scale, Modified Barthel Index, and Harris Hip Score at four time points: before intervention, on the day of discharge, and at 4 and 12 weeks postoperatively. Results:During the study, two patients from each group dropped out. Results of the generalized estimating equations showed group effects, time effects, and interaction effects in adherence scores with statistically significant differences ( P<0.01). On the day of discharge, and at 4 and 12 weeks postoperatively, the adherence scores in the experimental group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05). Repeated measures ANOVA indicated that group effects, time effects, and interaction effects were also statistically significant in scores for daily living ability and hip joint function ( P<0.05). The experimental group scored higher than the control group at each time point with statistically significant differences ( P<0.05) . Conclusions:The exercise rehabilitation program based on the Temporal Self-regulation Theory is scientifically sound and practical. It can effectively improve functional exercise adherence, enhance daily living ability, and promote postoperative recovery of hip joint function in elderly patients with hip fractures.

Objective:To develop an exercise rehabilitation program based on the Temporal Self-regulation Theory and evaluate its effectiveness in elderly patients with hip fractures.Methods:A total of 84 elderly patients with hip fractures admitted to the Department of Trauma Orthopedics at the First Affiliated Hospital of University of South China from May to August 2024 were enrolled using convenience sampling. Participants were randomly assigned to an experimental group ( n=42) and a control group ( n=42) using a random number table. The control group received routine exercise rehabilitation, while the experimental group received an exercise rehabilitation program constructed based on the Temporal Self-regulation Theory. The program included components such as establishing a unified concept of "exercise-rehabilitation", enhancing time-limited efficacy, achieving behavioral advantages, and improving self-regulation of active movement. Both groups received interventions for 12 weeks. Functional exercise adherence, activities of daily living, and hip joint function were assessed using the Orthopedic Exercise Adherence Scale, Modified Barthel Index, and Harris Hip Score at four time points: before intervention, on the day of discharge, and at 4 and 12 weeks postoperatively. Results:During the study, two patients from each group dropped out. Results of the generalized estimating equations showed group effects, time effects, and interaction effects in adherence scores with statistically significant differences ( P<0.01). On the day of discharge, and at 4 and 12 weeks postoperatively, the adherence scores in the experimental group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05). Repeated measures ANOVA indicated that group effects, time effects, and interaction effects were also statistically significant in scores for daily living ability and hip joint function ( P<0.05). The experimental group scored higher than the control group at each time point with statistically significant differences ( P<0.05) . Conclusions:The exercise rehabilitation program based on the Temporal Self-regulation Theory is scientifically sound and practical. It can effectively improve functional exercise adherence, enhance daily living ability, and promote postoperative recovery of hip joint function in elderly patients with hip fractures.

Objective To explore the presence and potential interactions of microbes and bacteriophages in the blood of healthy individuals by employing in-depth bioinformatics mining to analyze the structure and function of the blood microbi-ome ecosystem.Methods Blood plasma samples from 1 600 voluntary blood donors collected at Mianyang Central Blood Station from 2012 to 2018 were subjected to DNA extraction and library construction.High-throughput sequencing was con-ducted using the Illumina HiSeq 4500 platform,followed by extensive bioinformatics analysis.Microbial abundance in blood samples was analyzed using metagenomic analysis software such as Bowtie2,Trimmomatic and Kraken.Subsequent phage-ome analysis included sequence quality control,assembly,identification,clustering and functional annotation using software such as Megahit,geNomad,CheckV and eggNOG-mapper.Phylogenetic trees,species annotation and host analysis and pre-diction for the identified blood bacteriophages were constructed using iTOL,BLAST and PhaBOX software.Results Met-agenomic sequencing identified microbes across 36 phyla,151 orders,338 families,338 genera and 3 757 species in the plasma samples.At the species level,the most abundant species included Bacillus cereus,Lactobacillus murinus,L.johnso-nii,Faecalibacterium prausnitzii,B.thuringiensis,L.reuteri,Cutibacterium acnes,Dietzia sp.JS16-p6b,Mycoplasma hyo-rhinis,M.hyopneumoniae and Staphylococcus aureus.Through phageome analysis,202 viral Operational Taxonomic Units(vOTUs)were identified,revealing 24 types of bacteriophages.Host analysis using the viral host database completed mat-ches for 15 potential bacteriophage hosts,including Stenotrophomonas maltophilia,Rhodoferax lacus,Pseudoalteromonas marina,Thalassotalea loyana,Vibrio alginolyticus,V.tasmaniensis,V.vulnificus,Pseudomonas sp.,Agrobacterium sp.ST15.13/040,Enterococcus gallinarum,Flavobacterium sp.,Thermotoga naphthophila,Chryseobacterium sp.RU33C,L.acidipiscis and Neisseria mucosa.Conclusion The study of the healthy human blood microbiome and phageome reveals the presence of microbes and phages in the blood,which may have profound impacts on human health.

【Objective】 To explore the correlation between CSAG1 expression and the prognosis and tumor-infiltrating lymphocytes in renal clear cell carcinoma (RCCC), and to predict the survival and tumor progression. 【Methods】 The gene expression profiles and clinical information of CSAG1 were downloaded from the Cancer Genome Atlas (TCGA). Based on the differential mRNA expression, GO annotation and KEGG pathway analysis were performed. The relationship between CSAG1 and tumor immune infiltration was assessed with Tumor Immunoassay Resource (Timer 2.0) database. The mRNA expression of CSAG1 in human RCCC specimens was validated with qRT-PCR. 【Results】 CSAG1 expression was significantly higher in RCCC tissues than in normal tissues (P<0.05). The qRT-PCR results revealed that the mRNA level of CSAG1 was consistent with that predicted by bioinformatic analysis. The KEGG analysis and GO annotation indicated high GSAG1 expression in RCCC was related to transmembrane transport, tricarboxylic acid cycle and lysosome. CSAG1 expression was positively related to the infiltration of pDC, aDC, CD8⁺ T cells, cytotoxic cells, TFH, TH1 cells, Tem, NK CD56^dm cells, Treg and T cells, but negatively correlated with macrophage infiltration. 【Conclusion】 CSAG1 may be associated with poor prognosis of RCCC and become a potential immunotherapy target.

Objective:To learn about the characteristics of natural foci and the spatial distribution of mosquitoes and ticks in Yadong County, Tibet Autonomous Region (Tibet for short).Methods:The eco-geographical characteristics, demographic information, agricultural and animal husbandry data of the natural foci in Yadong County, Tibet were collected from the Yadong County 2020 statistical yearbook, vector data were collected from the Yadong County Center for Disease Control and Prevention, and the data of the meteorological station in Yadong County from 2010 to 2021 were collected from the World Weather Network. In July 2021, a total of 20 mosquito and tick sampling points were selected for field investigation according to the distribution characteristics of vegetation and animal husbandry of Yadong County. The light trap method was used to trap mosquitoes, and the manual inspection and flag dragging method were used to catch ticks. The spatial distribution characteristics of mosquitoes and ticks were analyzed.Results:The natural epidemic foci in Yadong County, Tibet, were high in the north and low in the south, with an elevation difference of about 5 000 m. It was rich in water resources, and the average runoff of Yadong River was 20.1 m 3/s. The climate in the north was cold and dry, and the south was mild and humid. From 2010 to 2021, the annual average station air pressure in Yadong County was 452.8 mmHg (1 mmHg = 0.133 kPa), the maximum monthly average temperature, precipitation and relative humidity of air were 8.7 ℃, 134.5 mm and 81.3%, respectively, all in July. A total of 6 897 diptera insects were attracted by the light trap method, all of which were non-blood-sucking mosquitoes. The total density was 163.77 pieces/(lamp·h), the dominant population was Muscaridae, accounting for 89.69% (6 186/6 897). In different sampling areas, Xiayadong Township collected the most mosquitoes, accounting for 67.17% (4 633/6 897); the others were Yadong County and Shangyadong Township, accounting for 27.36% (1 887/6 897) and 5.47% (377/6 897), respectively. A total 2 014 host animals were examined, and 23 parasitic ticks were caught, of which 20 were of the genus Ixodes and 3 were of the genus Haemophilus. No free ticks were caught in all ticks sampling points. Conclusions:The climate and ecological environment of the natural foci in Yadong County, Tibet have obvious vertical gradient. Mosquitoes and ticks are active, but the density is not high, the density of mosquitoes is generally high in the south and low in the north.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Objective: To evaluate the value of Kirschner wire internal fixation in the treatment of sagittal mandibular condylar fractures. .Methods : From January 2019 to January 2020, 13 patients (19 sides) with mandibular condylar sagittal fracture treated by Kirschner wire internal fixation at the Stomatological Medical Center, Foshan Hospital of Traditional Chinese Medicine were retrospectively analyzed. After conventional surgical incision and exposure and reduction of the mandibular condyle, 2-4 Kirschner wires were used for fixation, and other maxillofacial fractures were treated simultaneously. The reduction accuracy and stability of the free mandibular condyle were evaluated by CBCT one week after the operation, and the occlusion relationship, opening degree and opening type were evaluated by clinical examination. Results: All patients had good fracture alignment and no twisting, breaking or loosening of the Kirschner wire. The occlusion relationship, opening degree and opening shape recovered well after the operation. Conclusion Kirschner wire is effective in treating sagittal fractures of mandibular condyles.

Objective : To explore the effect of negative pressure sealing drainage on the treatment of maxillofacial-neck-mediastinal infection in multiple spaces. Methods: Vacuum sealing drainage (VSD) was applied in five patients with maxillofacial-neck-mediastinal infection caused by odontogenic infection accompanied by diabetes or renal failure and other systemic diseases. After extensive debridement, a negative pressure drainage sponge was placed in the pus cavity and then the wound was closed. Continuous negative pressure drainage was continued after the operation. At the same time, multidisciplinary consultation was applied to control basic diseases and, strengthen anti-inflammatory responses, and nutrition and other systemic treatments were applied. Results: Four patients underwent continuous negative pressure drainage and successful removal of the negative pressure sponge after inflammatory symptoms subsided. One patient′s inflammatory symptoms became more serious after the operation, and we performed another operation to change the placement of the negative pressure sponge. All 5 patients underwent VSD with negative pressure sponge replacement ranging from 1 to 3 times during treatment. After multidisciplinary consultation, they were all cured and discharged from the hospital. Conclusion For infection of the mediastinum, maxillofacial region and neck, local treatment and systemic treatment are emphasized, as well as the treatment of infected lesions and basic diseases. Negative pressure closure and drainage technology promotes the alleviation of inflammation, and multidisciplinary combined treatment is beneficial for the control of basic diseases.

Objective:To analyze the molecular epidemiological characteristics of GⅡNorovirus (NoV) infection in children in Tianjin Children′s Hospital in 2018.Methods:Single center study. From January to December 2018, a total of 2 185 stool specimens were collected from the children with acute gastroenteritis suspected caused by virus infection in Tianjin Children′s Hospital. Norovirus was detected by real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR).The capsid protein VP1(VP1) region of positive samples was amplified and sequenced. The phylogenetic tree was constructed by MEGA5.05 for analyzing the results. The detection of NoV in different age groups and different months were compared by SPSS 20.0.Results:Among the 2 185 stool specimens,610 were NoV positive, the positive rate was 27.9% (610/2 185).All of the positive samples were GⅡgenogroup. Seven genotypes were found, with GⅡ.3 subtype accounting for 46.2%(151/327),GⅡ.4 subtype accounting for 40.1%(131/327),GⅡ.2 subtype accounting for 4.6%(15/327), other subtypes accounting for 9.1%(30/327).There was a significant difference in NoV detection rate among different age groups (χ 2=17.050, P=0.002). Among the positive specimens, the detection rate of less than or equal to 3 years old was the highest which is accounting for 89.2%.Also there was a significant difference in NoV detection rate among different months(χ 2=225.153, P<0.001).November and December are the most frequent months. There was significant difference between GⅡ.3 and GⅡ.4 NoV infection in children with granulocytopenia (χ 2=11.270, P=0.001) , and also in children with respiratory symptoms (χ 2=7.257, P=0.007) . Conclusions:GⅡ.3 and GⅡ.4 were the main genotypes of NoV infection in children in Tianjin in 2018. The Multiple genotypes suggests that the monitoring and prevention of NoV infection in children should continue to be strengthened in the future.