Objective:To observe the clinical effect of arthrocentesis combined with liquid phase con-centrated growth factor(CGF)injection in the treatment of unilateral temporomandibular joint osteoarthri-tis(TMJOA),in order to provide a new treatment option for TMJOA patients.Methods:In this non-randomized controlled study,patients diagnosed with unilateral TMJOA who visited the center for tem-poromandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects.The patients were divided into experi-mental group and control group,which were selected by patients themselves.The experimental group re-ceived arthrocentesis combined with liquid phase CGF injection and the control group received arthrocen-tesis combined with HA injection.Both groups were treated 3 times,once every two weeks.The clinical effect was evaluated by the maximum mouth opening,pain value and the degree of mandibular function limitation 6 months after treatment.The change of condylar bone was evaluated by cone beam CT(CBCT)image fusion technology before and after treatment.Results:A total of 20 patients were included in the experimental group,including 3 males and 17 females,with an average age of(34.40± 8.41)years.A total of 15 patients were included in the control group,including 1 male and 14 females,with an average age of(32.20±12.00)years.There was no statistical difference in general information between the two groups(P＞0.05).There were no statistical differences in the mouth opening,pain value and the degree of jaw function limitation between the two groups before treatment(P＞0.05),and all of them improved 6 months after treatment compared with before treatment(P＜0.05).However,the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment(P＜0.05),and the degree of jaw function limitation was significantly lower than that of con-trol group(P＜0.05).CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment,and image fusion results showed that 10 patients(50.0％)in the experimental group and 5 patients(33.3％)in the control group had reparative remodeling area of con-dylar bone,and there was no statistical difference between them(P＞0.05).Except for one CGF pa-tient,the other patients in both groups had some absorption areas of condylar bone.Conclusion:The ar-throcentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term,and is better than HA in increasing mouth opening and impro-ving jaw function.CBCT fusion images of both patient groups show some cases of condylar bone repara-tive remodeling and its relevance to treatment plans still requires further study.

Acute ischemic stroke (AIS) is a kind of central nervous system disease that seriously threatens human health and life. Current treatment for AIS is mainly reperfusion. However, the time-sensitive of reperfusion limits its clinical application, and a considerable part of patients within the time window cannot achieve the expected effect after reperfusion; related complications of reperfusion have not been completely solved. So far, some clinical trials have confirmed that neuroprotectants are useful supplements and adjuncts to reperfusion. This paper reviews the recent advance in neuroprotectants combined with reperfusion in AIS to provide references for AIS treatment.

Objective:To evaluate the role of Ras homolog gene family member A (RhoA) in hydrogen-induced alleviation of lipopolysaccharide (LPS)-caused damage to pulmonary microvascular endothelial cell(PMVEC) barrier function in mice.Methods:PMVECs were cultured in DMEM/F12 medium containing 10% fetal bovine serum and 1% penicillin/streptomycin until 4-6 passage. These cells were divided into 6 groups ( n=36 each) using a random number table method: control group (group A), hydrogen-rich medium group (group B), LPS group (group C), LPS + hydrogen-rich medium group (group D), LPS + RhoA inhibitor C3 enzyme group (group E) and LPS + hydrogen-rich medium + RhoA agonist U-46619 group (group F). Cells were cultured within normal medium in group A, group C and group E and within hydrogen-rich medium in group B, group D and group F. LPS at a final concentration of 1 μg/ml was simultaneously added in group C, group D, group E and group F. C3 enzyme at a final concentration of 3 μg/ml was added at 2 h before addition of LPS in group E. U-46619 at a final concentration of 10 mg/ml was added at 3 h before addition of LPS in group F. The expression of vascular endothelial (VE)-cadherin and occludin was determined by Western blot at 6, 12 and 24 h after incubation with LPS. At 24 h after incubation with LPS, the release rate of LDH was measured by LDH method, cell viability was measured by MTT method, and the activity of RhoA was determined by GST pull-down method. Results:Compared with group A, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group C ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group D ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group E ( P<0.05). Compared with group D, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group F ( P<0.05). Conclusions:RhoA is involved in hydrogen-induced alleviation of LPS-caused damage to PMVEC barrier function in mice.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective To investigate the dynamic changes and molecular mechanisms of myocardial injury and autophagy as the body's self-protective mechanism at different time points after cerebral ischemia/reperfusion(CI/R).Methods A CI/R model was established in male Sprague-Dawley rats using the Longa thread method.Rats that underwent CI/R following middle cerebral artery occlusion were classified into 6-,12-,24,and 48-hour groups according to the reperfusion time.The concentrations of reactive oxygen species and reac-tive nitrogen species were measured to evaluate myocardial oxidative stress.Cardiomyocyte apoptosis and autophagosomes were observed in the myocardium.Additionally,dynamic changes in myocardial autophagy,autophagic flux,and protein and gene expression of auto-phagy regulators were detected.Results Oxidative-stress-induced injury and apoptosis were observed in the myocardium after CI/R.The number of autophagosomes in cardiomyocytes increased,peaking in the 12 h group,and autophagic flux was impaired during the first 12 h after CI/R.Beclin 1,mammalian target of rapamycin(mTOR),and adenosine monophosphate-activated protein kinase(AMPK)expression levels in the myocardium increased during the first 48 h after CI/R,peaking in the 12 h group.This was consistent with changes in autophagy,which showed significant differences compared with the control group.Conclusion These results indicated that autophagy plays a protective role against CI/R-induced myocardial injury.Furthermore,Beclin 1-mediated autophagy/apoptosis and mTOR-mediated autophagy mutual feedback pathways play important roles in the regulation of autophagy.

Immune Checkpoint Inhibitors ; Transcriptome ; Immunotherapy ; Biomarkers, Tumor

Objective:To investigate whether stress hyperglycemia (SH) is an independent risk factor for the occurrence and mortality of sepsis-associated encephalopathy (SAE).Methods:From August 2016 to October 2021, sepsis patients admitted to the ICU of Guangdong Provincial People's Hospital were selected as the study subjects. According to whether they developed to SH (RBG>11.1 mmol/L) within 7 days of enrollment, the pat ients were divided into the SH group and the non-SH group for analysis. Logistic regression was used to analyze whether SH was an independent risk factor for SAE occurrence, and ROC curve was used to analyze the predictive value of SH to SAE. Kaplan-Meier curve was used to compare the 90-day survival of SAE patients with or without SH. Cox regression analysis was used to analyze the risk factors of 28-day and 90-day death in SAE patients.Results:A total of 183 sepsis patients were included, including 62 patients in the SH group and 121 in the non-SH group. Logistic regression analysis demonstrated that SH was an independent risk factor for SAE ( OR=4.452, 95% CI: 2.021-9.808, P <0.001). ROC curve demonstrated that SH could accurately predict SAE (AUC=0.831; Sensitivity=78.4%; Specificity=76.8%; and Yoden index=0.553). Kaplan-Meier curve demonstrated that the 90-day survival of SAE patients with SH significantly declined (log-rank test: P<0.01). Cox regression analysis suggested that SH was a risk factor for death at day 28 and day 90 in SAE patients (28 d, HR=2.272, 95% CI: 1.212-4.260, P=0.010; 90 d, HR=2.456, 95% CI: 1.400-4.306, P<0.01). Conclusions:SH is an independent risk factor for SAE and can predict SAE occurrence. SH significantly reduces 90-day survival and increase mortality at 28 and 90 days in SAE patients.

Objective:To explore the effect of triglyceride glucose(TyG) index, single nucleotide polymorphism of Toll-like receptor 4(TLR4) and NOD-like receptor thermal protein domain associated protein 3(NLRP3) genes, and its interaction on the risk of gout.Methods:A total of 315 male patients with gout and 499 men for health checkup at the same period were selected. General data were collected through questionnaires, and peripheral venous blood was collected for biochemical test. Three single nucleotide polymorphisms(SNPs) of NLRP3 and TLR4 were detected with multiplex ligase assay reaction, and logistic regression analysis was applied to compare the correlation between NLRP3 and TLR4 alleles and gout risk. The interaction of SNP and TyG index with gout was analyzed by generalized multi-factor dimensionality reduction(GMDR) model and logistic regression.Results:After adjusting for smoking, drinking, and other factors, the risk of gout increased by 61.1% for each standard deviation increase in TyG index. CC genotypes of rs10754558, rs10759932, and rs7525979 were high risk genotypes of gout in Han ethnicity. GMDR results showed significant differences in the interaction models of rs10754558-TyG index, rs7525979-TyG index, and rs10759932-TyG index between control group and gout group( P<0.05), suggesting an interaction between the three genotypes of SNPs selected and TyG index. Stratified analysis of the three selected SNPs and TyG index showed that after adjusting for age, smoking, and other factors, the high TyG index patients carrying C/C or C/G genotype at rs10754558 displayed an increased risk of gout compared with those carrying GG genotype and low TyG index( OR=2.127, P<0.05). Conclusion:The CC genotypes of rs10754558, rs10759932, and rs7525979 are high risk genotypes for gout in Han ethnicity. The interaction between rs10754558 and TyG index may increase the risk of gout development.

OBJECTIVE: To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism. METHODS: A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. RESULTS: Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group. CONCLUSIONS PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Sepsis-Associated Encephalopathy ; Phosphates ; Actins ; Beclin-1 ; Interleukin-6 ; Autophagy ; Ubiquitin-Protein Ligases ; Cognitive Dysfunction ; Sepsis ; Mitochondria ; Protein Kinases

Objective To investigate the surgical outcomes and strategies selection of endoscopic endonasal approach and craniotomy in the treatment of cranial base chordomas.Methods Thirty-one patients diagnosed pathologically with cranial base chordoma in Tianjin huanhu hospital from Jan.2010 to Sep.2020 were analyzed retrospectively.The patients were divided into the endoscopic endonasal group and the craniotomy microscope group according to the different surgical approaches.The surgical results and follow-up between the two groups were compared.Results In the endoscopic endonasal group,there were 7 cases of gross total resection,9 cases of subtotal resection and 2 cases of partial resection.The main complications included death in 2 cases,cerebrospinal fluid leakage in 8 cases,cranial nerve injury in 2 cases and hypopituitarism in 1 case.In the craniotomy microscope group,there were 2 cases of gross total resection,10 cases of subtotal resection,and 1 case of partial resection.The main complications included cerebrospinal fluid leakage in 1 case,cranial nerve injury in 3 cases,epilepsy in 1 case and epidural hematoma in 1 case.There was no statistical significance in the resection rate between the two groups(P＞0.05).The rate of cerebrospinal fluid leakage in the endoscopic group was significantly higher than that in the craniotomy microscope group,and the comparison was statistically significant(P＜0.05).There was no statistically significant between the two groups for tumor recurrence or progression.Conclusions The endoscopic endonasal approaches for resection of cranial base chordomas have improved the gross total resection rate,but craniotomy is still an important surgical method for tumor resection.It is necessary to select an appropriate surgical approach according to the lesion location and pattern of tumor growth.