Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

Objective:To investigate the effects of hydroxysafflor yellow A (HSYA) on depressive-like behavior and expression of type A γ-aminobutyric acid receptor(GABAAR)in hippocampus of chronic restraint stress model mice.Methods:The SPF grade male C57BL/6C mice were divided into Control group, HSYA group, Model group, Model + HSYA group and Model + fluoxetine group according to random number table method, with 12 mice in each group.Mice model of depression was established by chronic restraint stress.Mice in HSYA group and Model+ HSYA group were intraperitoneally injected with HSYA(20 mg/kg), mice in Model+ fluoxetine group were injected intraperitoneally with fluoxetine (10 mg/kg), and mice in Control group and Model group administered with 0.9% sodium chloride solution intraperitoneally once a day for 14 days.Then, the forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and the protein expression levels of different subtypes of GABAAR in the hippocampus of mice were determined by Western blot.SPSS 19.0 and GraphPad Prism 8.0 software were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-HSD test was used for further pairwise comparison.Results:(1) In the behavioral tests, there were significant differences in swimming immobility time of FST and tail suspension immobility time of TST among the five groups ( F=21.59, 20.81, both P<0.05). The swimming immobility time ((143.91±9.97) s) and tail suspension immobility time (( 107.00±6.54) s) in Model group were higher than those in Control group ((52.92±6.70) s, ( 43.50±5.96) s, both P<0.05). There were no significant difference in swimming immobility time and tail suspension immobility time between Model+ HSYA group ((26.17±7.69)s, ( 20.17±7.89)s) and Model+ fluoxetine group ((61.60±16.22)s, (34.14±10.74)s)(both P>0.05), but the swimming immobility time and tail suspension immobility time in these two groups were lower than those in Model group (both P<0.05). (2) The Western blot results showed that there were significant differences in the expression of GABAARβ1 and GABAARβ2 protein in hippocampus among the four groups ( F=12.21, 11.40, both P<0.05). The expression levels of GABAARβ1(45.60±10.76) and GABAARβ2 (46.27±4.82) protein in hippocampus of Model group were lower than those in Control group ((100.00±3.44), (100.00±3.26), both P<0.05). Compared to Model group, the expression of GABAARβ1 (79.91±5.00) and GABAARβ2 (79.08±5.53) protein in hippocampus of Model+ HSYA group were higher (both P<0.05). In addition, the expression of GABAARα1 and GABAARγ1 proteins in hippocampus were not significantly different among the four groups( F=0.23, 0.10, both P>0.05). Conclusion:HSYA can effectively alleviate depressive-like behavior in depression model mice, which may be related with the upregulation of GABAARβ1 and GABAARβ2 of hippocampus tissue.

Objective:To explore the application effect of anesthesia management based on cerebral oxygen saturation monitoring in elderly non-small cell lung cancer (NSCLC) radical surgery and its impact on patient cognitive function.Methods:Ninety elderly NSCLC patients who were treated at the Sixth Affiliated Hospital of South China University of Technology from June 2022 to January 2023 were selected. The patients were divided into an observation group ( n=45) and a control group ( n=45) using the envelope method. Both groups underwent radical lung cancer surgery under general anesthesia, while the control group received routine anesthesia management and the observation group received anesthesia management based on cerebral oxygen saturation monitoring. The surgical time, intraoperative blood loss, anesthesia time, remifentanil dosage, and propofol dosage were observed in two groups. At the same time, differences in serum interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and other levels were compared between the two groups. Results:There was no statistically significant difference in surgical time, intraoperative blood loss, anesthesia time, and remifentanil dosage between the two groups (all P>0.05); The dosage of propofol in the observation group was (880.41±41.06)mg, significantly lower than that in the control group ( P<0.05). The mean arterial pressure (MAP) and heart rate (HR) in the observation group were significantly higher than those in the control group at 5 minutes (T 1) and 30 minutes (T 2) after anesthesia (all P<0.05); The local cerebral oxygen saturation (rSO 2) and bispectral index (BIS) of the observation group at T 1, T 2, and postoperative (T 3) were significantly higher than those of the control group (all P<0.05). The serum levels of IL-6, CRP, PCT, tumor necrosis factor α (TNF-α), and S-100b in the observation group at 24 hours postoperatively were (13.36±1.22)mg/L, (10.08±1.12)ng/L, (0.94±0.15)ng/ml, (11.15±1.26)ng/L, and (1 445.15±180.05)ng/L, respectively, significantly lower than those in the control group (all P<0.05). The MMSE score of the observation group at 24 hours post surgery was (25.78±1.02), significantly higher than that of the control group ( P<0.05). The incidence of postoperative cognitive impairment in the observation group and the control group was 4.44%(2/45) and 8.89%(4/45), respectively, with no statistically significant difference ( P=0.673). Conclusions:Anesthesia management based on cerebral oxygen saturation monitoring has a good application effect in elderly NSCLC radical surgery, with small fluctuations in patient hemodynamic indicators, which can inhibit inflammatory factor levels and have a mild impact on postoperative cognitive function.

ObjectiveTo evaluate the animal model of rheumatoid arthritis （RA） induced by inactivated Mycobacterium tuberculosis （Mtb） from inflammation， apoptosis and autophagy， compare the rat RA model of wind-damp-heat arthralgia （FSR） induced by Mtb with the rat RA model of adjuvant arthritis （AA）， and provide experimental evidence for improving the disease-syndrome combined model and developing drugs for the prevention and treatment of RA. MethodThirty 6-week-old SD rats were randomly assigned into 3 groups： a normal group， an AA group and a FSR group， with 10 rats in each group. The RA rat model was established by injection of Mtb suspension （1 mg/rat）， and the rats in the normal group were injected with the same volume of normal saline. The invention in the FSR group lasted for 16 days. The general conditions， body weight， spleen index， swelling of ankle joints， arthritis index （AI）， and the symptoms of arthritis in the hind feet of the rats in each group were observed and measured. The expression levels of serum interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of IL-1β， TNF-α， apoptosis-related protein B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）， autophagy-related protein 1 light chain 3 （LC3）， autophagy key molecule yeast Atg6 （Beclin1），and p62 mRNA expression levels were detected by Real-time polymerase chain reaction （Real-time PCR）. The protein expression levels of Bcl-2， Bax， LC3， Beclin1 and p62 were detected by Western blot. ResultCompared with those of the normal group， the rats of AA and FSR groups grew slowly and presented dull hair， soft or loose stool， slow movement， swelling of spleen， redness and swelling of ankle joints， increased AI， and histopathologic changes in the synovium and ankle joints. Moreover， the modeling elevated the levels of IL-1β and TNF-α in the serum， up-regulated the mRNA levels of IL-1β and TNF-α in the synovium， up-regulated the mRNA and protein levels of Bcl2， LC3， Beclin1， and down-regulated the mRNA and protein levels of Bax and p62. Compared with the AA group， the FSR group showed severe symptoms， slowly increased body weight （P<0.01）， early appearance of obvious redness and swelling of ankle joints， increased AI （P<0.05）， increased spleen index （P<0.05）， and obvious pathologic changes of synovial tissue and ankle joints， the inflammatory infiltration in the synovial tissue， and the damage of joint structure. Moreover， the FSR group had higher expression levels of IL-1β， TNF-α， Bcl-2， LC3， and Beclin1 （P<0.05） and lower expression levels of Bax and p62 than the AA group （P<0.05）. ConclusionThe animal model of RA （syndrome of wind-damp-heat arthralgia） can be induced successfully with the symptoms consistent with clinical manifestations of RA. The FSR group has lower apoptosis level and higher autophagy level than the AA group， which indicates that the FSR group is more appropriate for the research on the RA with the syndrome of wind-damp-heat arthralgia.

Objective:To explore the clinical application of ultrasound-guided anterior serratus plane block (SAPB) in anesthesia and postoperative analgesia of thoracoscopic surgery and to provide theoretical basis for clinical practice.Methods:From June 2018 to June 2019, a total of 90 patients with thoracoscopic surgery in Nanhai District People's Hospital of Foshan were randomly divided into three groups, 30 cases in each group. Group A received routine general anesthesia; Group B received preoperative SAPB+ routine general anesthesia; Group C was treated preoperatively SAPB+ single dose of 1 μg/kg dexmedetomidine+ routine general anesthesia. The mean arterial pressure (MAP) and heart rate (HR) of the three groups were compared after entering the room, immediately after intubation, during skin incision and immediately after extubation. The intraoperative dosage of propofol and remifentanil, the effective pressing times of analgesic pump within 48 hours, the dosage of sufentanil, the level of analgesia, adverse reactions and satisfaction were compared.Results:There was no significant difference in MAP and HR of the three groups of patients when they entering the room ( P>0.05); the MAP and HR of the three groups at the time of intubation, skin incision and extubation were higher than those at the time of entry ( P<0.05); the MAP and HR of B group and C group were lower than group A at the time of intubation, skin incision and extubation (all P<0.05). There was no significant difference in the intraoperative doses of remifentanil and propofol among the three groups (all P>0.05). The effective pressing times of analgesic pump and the dosage of sufentanil in group B and group C within 48 hours were lower than those in group A (all P<0.05). The pain scores in resting state and cough state at 2, 4, 12 and 24 hours after operation in group C were lower than those in group B and group A (all P<0.05). The incidence of postoperative adverse reactions in group B and group C was lower than that in group A (all P<0.05). The postoperative satisfaction of group B and group C was higher than that of group A (all P<0.05). Conclusions:SAPB guided by ultrasound combined with general anesthesia and single dose of dexmedetomidine can effectively improve hemodynamic indexes, relieve pain, and have high safety and satisfation in patients undergoing thoracoscopic surgery. The treatment effect is significant and can be widely used in clinical practice.

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNT） against adjuvant arthritis （AA） rats with wind-dampness-heat arthralgia by quantitative proteomics. MethodSixty SD rats were randomly divided into normal group， model group， angelica came pain soup low， medium and high dose group and methotrexate （MTX） group， each group of 10， only the rat tail root subcutaneously inactivated mycobacterium tuberculosis （Mtb） of adjuvant to build model of AA， artificial climate box intervention 16 d rheumatic fever bi syndrome model is set up， building the day began to drug intervention， The intervention lasted for 28 days. The proteins of synovial tissues in experimental rats were extracted. The differential proteins in the medium-dose DGNT group and the model group were detected and analyzed by 4D label-free quantification （4D-LFQ） proteomics. The differentially expressed proteins associated with mitochondrial pathway apoptosis were verified by immunohistochemistry and Western blot. ResultA total of 4 756 proteins were identified from rat synovial tissues， of which 4 234 proteins contained quantitative information. There were 814 differential proteins between the model group and the DGNT group. As revealed by Gene Ontology （GO） and Kyoto Encyclopedia of Gene and Genome （KEGG） enrichment analyses， DGNT had an effect on the synovial proteome of AA rats with wind-dampness-heat arthralgia， and the differential proteins were enriched in the regulation of the immune system， response to acute inflammation， and apoptosis regulation. As demonstrated by the results of immunohistochemistry and Western blot， compared with the model group， the DGNT groups and the MTX group showed increased protein expression of B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax） and cytochrome C （Cyt C）（P<0.05， P<0.01）， reduced Bcl-2 level （P<0.05， P<0.01）， elevated level of cleaved cysteinyl aspartate-specific protease 9 （Caspase-9）/Caspase-9 （P<0.01）， and decreased level of phosphorylated protein kinase B （p-Akt）/Akt（P<0.05， P<0.01）. ConclusionDGNT involved multiple targets in the treatment of AA with wind-dampness-heat arthralgia and it may exert its effect in the prevention and treatment by regulating the Akt/Bax/Bcl-2 pathway and promoting the cell apoptosis in the mitochondrial pathway.

Objective:To investigate whether the prophylactic use of a dose of sensitive antibiotics before revision for periprosthetic joint infection (PJI) may affect the positive rate of intraoperative specimen culture.Methods:This prospective study recruited the patients who underwent revision due to PJI from July 1, 2017 to February 1, 2019 at Department of Orthopaedics, The First Affiliated Hospital to Fujian Medical University. After use of antibiotics was stopped in all patients for 2 weeks before operation, synovial fluid was extracted for culture to confirm pathogenic bacteria and drug sensitivity and some/all of the prostheses were removed during operation. According to their sequence number of admission, the patients were randomly divided into group A and group B. Samples were taken in group A after a dose of sensitive antibiotics was administered 30 to 60 minutes before revision while a dose of sensitive antibiotics was given in group B after all samples were taken. Intra-operatively, synovial fluid, tissue grinding fluid (TGF) and ultrasonic prosthesis lysate (UPL) were taken for aerobic and anaerobic culture. According to whether there was a positive culture of at least one microbiological specimen, the preoperative and intraoperative culture results were analyzed and compared between the 2 groups.Results:A total of 32 PJI patients were included in this study due to positive culture of synovial fluid before operation, with 16 cases in group A and 16 in group B. The most common infection bacteria were staphylococci (59.3%, 19/32). There was no significant difference in age, gender, mode of operation, Tsukayama classification, prosthesis removal, preoperative ESR, CRP, synovial fluid white blood cell count (SF-WBC) or polymorphonuclear cell percentage (PMN) between the 2 groups. The positive rates of synovial fluid, tissue, TGF and UPL were 81.3% (13/16), 62.5% (10/16), 93.8% (15/16) and 93.8% (15/16) for group A, and 87.5% (14/16), 68.8% (11/16), 93.8% (15/16) and 100.0% (16/16) for group B, showing insignificant differences between the 2 groups ( P>0.05). The positive rates of TGF and UPL culture showed no significant difference between them in group A or in group B ( P>0.05), but they were significantly higher than those of traditional tissue culture ( P<0.05). Conclusions:As prophylactic use of antibiotics before PJI revision may not affect the positive rate of intraoperative specimen culture, it is not necessary to postpone use of prophylactic antibiotics before PJI revision. Furthermore, as positive rates of TGF and UPL culture are similar but significantly higher than those of traditional tissue culture, tissue grinding can be used to improve the positive rate of tissue culture.

OBJECTIVE: To explore the effect of decoction (DGNTD) on cell apoptosis and TNF receptor super family 6 (Fas)/caspase-8 pathway in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). METHODS: FLS isolated from the synovial tissue of RA patients were cultured and identified using immunofluorescence staining. The cells were treated with 10% blank serum (blank control group), 10% sera containing low, moderate or high doses of DGNTD, or 20 μmol/mL KR-33493 (a Fas inhibitor) combined with 10% serum containing high-dose DGNTD. MTT assay was used to detect the proliferation of the cells after the treatments. Apoptosis of the cells was detected at 48 h in each group using Hoechst 33342 staining and flow cytometry with annexin V-FITC/PI staining. The mRNA and protein expressions of Fas, FADD, caspase-8 and caspase-3 in the cells at 48 h were detected using qPCR and Western blotting. RESULTS: Immunofluorescence staining identified the cultured cells as FLS. Treatment with DGNTD-containing sera significantly inhibited the proliferation of FLS, and the inhibitory effects were enhanced as the dose and intervention time increased ( < 0.05). Hoechst 33342 staining and flow cytometry showed that the sera containing different doses of DGNTD significantly promoted apoptosis of FLS ( < 0.05). The expression levels of Fas, FADD, caspase-8, and caspase-3 at both mRNA and protein levels were significantly increased in the cells after treatment with different doses of DGNTD-containing sera ( < 0.05). The application of KR-33493 obviously reversed the effects of DGNTD on the FLS ( < 0.05). CONCLUSIONS DGNTD can induce apoptosis of the FLS by activating Fas/caspase-8 signaling pathway.
Apoptosis ; Arthritis, Rheumatoid ; Caspase 8 ; Cell Proliferation ; Cells, Cultured ; Fibroblasts ; Synovial Membrane ; Synoviocytes

Objective To investigate the role of next generation sequencing technology in the detection of pathogenic bacteria in synovial fluid of prosthetic joint infection.Methods Nine samples of synovial fluid specimens of prosthetic joint infection patients with positive microbial culture from October,1 2016 to April 1,2017 were collected.Each specimen (200 μl) was used for next generation sequencing.Total DNA was extracted from synovial fluid samples.The collected DNA samples were amplified by PCR in the V4 region of 16S rDNA gene.The amplified products were sequenced using the Illumina Miseq platform,2× 250 bp double-end sequencing strategy.The sequencing results were compared with the SILVA database to analyze the types of bacteria and relative abundance in the DNA samples.A total of 200 μl sterile double-distilled deionized water was used as control.Results Nine cases of microbial culture positive prosthetic joint infection synovial fluid DNA samples were sequenced by 16S rDNA amplicon sequencing and yielded 3 132 415 high-quality reads and 3 752 operational taxonomic units (OTU).At the level of bacteria,a total of 9 different bacterial gates were detected on 9 DNA samples.At the level of bacteria,34 different bacteria were detected by 16S rDNA amplicon sequencing.Each DNA sample was detected by 16S rDNA amplicon sequencing and the bacterial genus was identical to that of laboratory culture.16S rDNA amplicon sequencing detected more species of bacteria [6(3,9.5)] than bacterial cultures [(1.0(1.0,1.0)].There was statistically significant difference in the number of bacteria detected in the same specimen between the 16S rDNA amplicon sequencing and the laboratory culture (Z=2.533,P=0.011).Among them,the dominant bacterial population (highest abundance) detected by 16S rDNA amplicon sequencing in four DNA samples was consistent with the results of laboratory culture.Conclusion In the prosthetic joint infection,the 16S rDNA amplicon sequencing technology can accurately detect pathogens that are consistent with the laboratory culture,and can detect other bacteria outside the laboratory culture.This technology can provide the basis for clinical diagnosis and antibiotic selection.

Objective To analyze the application effect of systematic rehabilitation intervention in postradiotherapy dysphagia of patients with nasopharyngeal carcinoma.Methods Totally 60 patients with nasopharyngeal carcinoma and postradiotherapy dysphagia admitted in our hospital from June 1st,2013 to Feburary 28th,2016 were selected and divided into the treatment group and the control group according to random number table,with 30 cases in each group. Patients in the control group were treated with conventional rehabilitation exercises,combined with routine care and conventional drug therapy,while those in the treatment group were treated with systematic rehabilitation intervention model,including rehabilitation exercises and swallowing apparatus. Improvement of swallowing function and satisfaction toward the nursing were compared between two groups.Results There were 14 effective cases and 16 ineffective cases in the control group. Two cases in the treatment group were cured. There were 23 effective cases and five ineffective cases in the treatment group. The total efficiency of the treatment group (83.33%) was significantly higher than that of the control group (46.67%) (χ2=2.159,P<0.05). The experimental results of drinking water and improvement of limitation of mouth opening in the treatment group were obviously better than that in the control group (Z=5.012,7.018;P<0.05). Satisfaction in the treatment group (86.67%) was obviously higher than that in the control group (43.33%) (χ2=6.321,P<0.05).Conclusions Systematic rehabilitation intervention in postradiotherapy dysphagia of patients with nasopharyngeal carcinoma can significantly improve patients' swallowing difficulties.