Objective: To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment. Methods: This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA. Results: Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01). Conclusion During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

Solid tumor meningeal metastasis is a catastrophic complication in the late stage of tumors,with a poor prognosis and currently lacking effective treatment methods.As a treatment method for meningeal metastasis,intrathecal chemotherapy has been recommended by many guidelines or expert consensus,and is often used in clinical practice.However,the efficacy of intrathecal chemotherapy has always lacked high-quality research evidence to support it.The efficacy of commonly used intrathecal chemotherapy drugs such as methotrexate,cytarabine,and thiotepa is not ideal.This article summarizes the usage,efficacy,and safety of new intrathecal injection drugs.

Objective To explore the influencing factors of renal injury in elderly patients with cor pulmonale, and to provide information for the prevention of renal injury in patients with cor pulmonale. Methods A total of 309 elderly patients with cor pulmonale over 60 years old treated in our hospital from June 2019 to December 2020 were included in the study. According to the patients with renal injury , they were divided into cor pulmonale renal injury group (case group) and cor pulmonale non renal injury group (control group). The basic information of the two groups and the influencing factors of potential renal injury in the past were collected, The influencing factors of renal injury in elderly patients with cor pulmonale were analyzed by univariate analysis and regression model. Results The single factor analysis of the case group was higher than that of the control group, with a male age of 80 years, smoking history, family history of diabetes, concurrent infection, diabetes mellitus and left ventricular ejection fraction (LVEF) <56.00% ratio. The difference between the case group and the control group was higher than that of the control group (P<0.05). The above univariate analysis results were brought into the multiple regression model. The final multiple regression analysis showed that age > 80 years old (or = 3.142), smoking history (or=2.115) , concurrent infection (or=4.263) , and excessive systolic blood pressure (or=2.279) were the risk factors potentially increasing the risk of renal injury, which were statistically significant (P < 0.05). Conclusion Elderly patients with cor pulmonale over 80 years old , with smoking history and abnormal blood pressure , as well as those complicated with infection , have an increased risk of renal injury. It is worthy of clinical attention and relevant preventive measures to improve the prognosis of patients.

Objective:To investigate the clinical features of adenoviral encephalitis (AE), and to provide reference for clinical diagnosis and treatment of adenoviral encephalitis.Methods:From January 2012 to December 2020, 1 185 cerebrospinal fluid (CSF) samples of hospitalized children with suspected central nervous system infection in the Second Affiliated Hospital of Shantou University Medical College were collected for the detection of 22 common respiratory pathogens and common pathogens for encephalitis by polymerase chain reaction. Records of patients with adenovirus positive in CSF were reviewed and relevant clinical manifestations, laboratory tests and imaging examination results were collected for analysis.Results:Among 1 185 CSF samples, 242 samples were positive for viral nucleic acid, with detection rate of 20.4%, including 1.9%(23/1 185) of adenovirus. As for 23 children diagnosed with AE, 18 were male, five were female, with the age of (44.8±35.9) months, ranging from two months and 19 days to 10 years. Of 23 children, 21(91.3%) presented with fever, followed by convulsions (16 cases, 69.6%), headache (four cases, 17.4%), vomiting (11 cases, 47.8%), consciousness change (11 cases, 47.8%) and emotion disturbance (three cases, 13.0%). Among 23 children, eight cases had white blood cell counts (WBC) of (6 to <10)×10 9/L, 10 cases had WBC of (10 to 20)×10 9/L and the white blood cell classification was mainly neutrophils (21 cases, 91.3%), and C reactive protein of 20 cases (87.0%) was in the normal range. Cerebrospinal fluid examination showed that WBC were less than 15×10 6/L in 20 cases (87.0%), and WBC ≥15×10 6/L in three cases, which were up to 500×10 6/L; the protein of 19 cases was in the normal range, the glucose of 15 cases was in the normal range, and the chloride of 19 cases was in the normal range. Among 16 cases with brain magnetic resonance imaging examination, eight cases did not show abnormality, six cases with local meningeal linear enhancement, one case with small intracranial malacia, and one case with extensive intracranial lesions. For 13 cases who received electroencephalogram (EEG) test, seven cases showed normal EEG or marginal state, four cases showed extensive medium and high amplitude slow wave, one case showed spike wave or spike slow wave and one case had both of the above two changes. Among 23 children, 22 cases recovered including one case had secondary epilepsy, and the remaining one case had severe brain dysfunction and was unable to suck when discharged, with an indwelling gastric tube and accompanied by secondary epilepsy. Conclusions:The clinical manifestations and auxiliary examinations of children with AE have no obvious specificity. Most children with AE have a good prognosis, but a small number of them may have serious sequelae.

Animals ; Brain ; growth & development ; Child ; Eyelids ; abnormalities ; Female ; Humans ; Intellectual Disability ; genetics ; Limb Deformities, Congenital ; genetics ; Mice ; Microcephaly ; genetics ; Mutation, Missense ; N-Myc Proto-Oncogene Protein ; genetics ; Tracheoesophageal Fistula ; genetics

Objective To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on autophagy and the secretion of chemokine receptor CXCR4 induced by low-dose immunosuppressive durgs.Methods Flow cytometry was used to detect the changes of hUC-MSCs surface markers after treatment with low-dose tacrolimus and rapamycin.The effect of treatment with tacrolimus and rapamycin on proliferation of hUC-MSCs was analyzed with WST-1 assay.Regular RT-PCR was applied to analyze the mRNAs expression of ligands such as LC3B,Atg5 and Beclin1 in hUC-MSCs.Western blotting was carried out to detect the expression of LC3B,Atg5,Beclin1 and p-ULK1 in hUC-MSCs after treatment with tacrolimus and rapamycin.The secretion of chemokine receptor CXCR4 in hUC-MSCs was analyzed under the state of autophay by flow cytometry.Results Flow cytometry analysis confirmed low-dose immunosuppressive drugs tacrolimus and rapamycin did not cause changes in hUC-MSCs phenotypes significantly.Low-dose tacrolimus had no cytotoxic effect on hUC-MSCs,while,rapamycin could inhibit the proliferation of hUC-MSCs after 24 h or 48 h,with survival rate being 73.66％ and 68.81％ (P＜0.05) of controls,respectively.Moreover,both tacrolimus and rapamycin could inhibit PI3K/AKt/mTOR signaling pathway to activate hUC-MSCs autophagy,and the related proteins of LC3B,Atg5 and Beclin1 increased significantly and induced the up-regulation of CXCR4 secretion.Conclusion Our results here demonstrated that low-dose tacrolimus and rapamycin induce autophagy in hUC-MSCs and promote the secretion of CXCR4.

Objective To study the correlation between the diffusion-weighted imaging (DWI) measurements and glomerular filtration rate (GFR), Katafuchi scores in IgA nephropathy. Methods Thirty-five patients with IgA nephropathy (IgAN group) and twenty healthy volunteers (control group) were enrolled in this study. All of the subjects underwent bilateral renal DWI measurements with 3.0T MRI scanner. The values of apparent diffusion coefficient (ADC) of renal cortex and medulla were measured. GFR of IgAN group was detected with 99Tcm-DTPA scintigraphy. Based on the Lee classification and the Katafuchi score system, the pathological grading was carried out in patients of IgAN group. The ADC values were compared between control group and different grades of IgAN group. The correlations between ADC and GFR values were analysed in defferent groups. The correlations between ADC values and Katafuchi scores were analysed in IgAN group. Results The renal cortical ADC values were significantly higher than medulla ADC values in both control group and IgAN group (P < 0.05). There were statistically significant differences in renal cortical ADC values and medulla ADC values between control group and IgAN subgroups (P<0.05). But there was no significant difference in renal cortical ADC value between IgANⅠgroup and control group (P>0.05). There was a positive correlation between the renal cortical and medulla ADC values and the GFR values in IgAN group (P<0.01). Negative correlation was found between the renal cortical and
medulla ADC values and the Katafuchi scores in IgAN group (P<0.05). Conclusion The diffusion-weighted imaging can reflect the physiological functions of kidney. It was feasible for application DWI in IgA nephropathy, which can be used for assessing the renal filtration function and the pathological damage. However, DWI measurement is not sensitive to early renal disease.

[ ABSTRACT] AIM: To explore the relationship between FRAS 1 protein and brain metastases of non-small cell lung cancer (NSCLC).METHODS:The mRNA expression of FRAS1 in the brain metastatic tumor tissues and primary tumor tissues of NSCLC was detected by qPCR .The protein expression of FRAS 1 in the tumor tissues and normal tissues adjacent to tumor tissues of NSCLC was measured by SP method of immunohistochemistry .The protein expression of FRAS 1 in NSCLC primary tumor tissues with or without brain metastases was also determined .RESULTS:The mRNA expression of FRAS1 in the brain metastatic zone was nearly 10 times higher than that in the primary tumor tissues , and there was sig-nificant difference between the 2 groups (P<0.05).FRAS1 protein was expressed in the NSCLC primary tumor tissues , but was not found in the normal tissues adjacent to primary tumor tissues .The protein expression of FRAS 1 in the NSCLC with brain metastases was significantly higher than that without brain metastases ( P<0.01 ) .CONCLUSION: FRAS1 protein may be associated with the occurrence of NSCLC .The over-expression of FRAS1 protein may be related to brain metastases with NSCLC .

OBJECTIVETo carry out genetic analysis for two patients affected with congenital heart disease, developmental delay with or without cleft palate.

METHODSCytogenetic and molecular genetic methods including karyotyping, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphisms array (SNP-array) were employed to detect potential mutations. For parents of both patients, MLPA was used to analyze whether they were carrier of the deletion.

RESULTSFor neither patient, no abnormality was detected upon karyotype analysis. However, FISH analysis has indicated the presence of 22q11.2 deletion. SNP-array analysis has confirmed that both patients have carried a 2.5 Mb deletion in the 22q11.2 region. MLPA analysis suggested none of the parents has carried the same deletion.

CONCLUSIONAlthough the phenotypes of our patients were not identical, they were both diagnosed as 22q11.2 deletion syndrome by multiple methods. The deletions in both cases were de novo in nature. Precise delineation of the genotype can facilitate better understanding of the patients' phenotype.

Abnormalities, Multiple ; genetics ; pathology ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; genetics ; pathology ; Ear, External ; abnormalities ; Genotype ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; Microarray Analysis ; methods ; Phenotype ; Polymorphism, Single Nucleotide ; Syndrome