Tumor necrosis factor alpha (TNF-α) is a homotrimeric protein encoded within the major histocompatibility complex (MHC). TNF-α can bind its receptors in the body to play a role in immune regulation and to participate in the various pathophysiology processes including fever, inflammation, infection, wound healing and tumors necrosis. TNF-α, an important component of inflammatory pathways, is up-regulated in the synovial tissue, synovial fluid and serum of rheumatoid arthritis (RA) patients. In RA patients, TNF-α along with many kinds of tissue factors and matrix proteins together promotes the inflammatory response, abnormal apoptosis of synovial cells, pannus formation and cartilage and bone destruction, which maintain the sustainability of the progress of RA. Thus, TNF-α may be a clinical indicator of RA activity as well as an effective target for RA.

Objective To investigate the effects of simvastatin on the production of interleukin (IL)-17and B-cell activating transcription factor (BATF) in the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals.Methods PBMCs were isolated from heparinized blood of healthy donors or RA patients using Ficoll-Hypaque density gradient centrifugation.The cells were stimulated by PMA and ionomycin in the absence or presence of simvastatin or MVA at 37 ℃ 5％CO2.The mRAN level of IL-17,BATF and GAPDH was detected by RT-PCR; the protein level of IL-17 in supernatants was assayed by ELISA kit; and the protein level of BATF was detected by Western Blotting.The comparison between the two groups was carried out by paired-t test and Chi-square test was used for muhi-group comparison.Results PBMCs of healthy donors [(69.2±12.2) vs (8.1±2.2) pg/ml,P＜0.05; (76.6±14.7) vs (10.2±7.2) pg/ml,P＜0.05] and RA patients [(79.6±12.7) vs (15.8±5.8) pg/ml,P＜0.05; (90.3±9.7) vs (12.9±7.9) pg/ml,P＜0.05] were stimulated with PMA and ionomycin to produce high levels of IL-17.After treatment with simvastatin,the expression and secretion level of IL-17 in healthy controls and RA PBMCs were markedly decreased.The inhibition of simvastatin on the production of IL-17 was reversed by mevalonic acid (MVA),but no significant changes of BATF after treating with simvastatin.Conclusion Simvastatin inhibits the production of IL-17 in the PBMCs at gene and protein levels,which is not targeted at suppressing the expression of IL-17 transcription factor BATF.

Objective To investigate the clinical features and pathogenesis of severe congenital neutropenia (SCN) by detecting the gene mutation of a SCN patient suspected by clinical diagnosis. Methods The intravenous anticoagulant and clin-ical data and laboratory results of this child were collected;the phagocyte and oxidation function of neutrophils were evaluated by flow cytometry;ELANE, HAX1, WAS, GFI1, CSF3R and CXCR4 genes were screened by PCR amplification and sequencing. Results The neutrophil function of this patient was normal; sequencing results revealed no mutation occurred in ELANE, HAX1, WAS, GFI1, CSF3R and CXCR4;and granulocyte colony-stimulating factor (G-CSF) can obviously enhance the level of neutrophils. Conclusion SCN is a kind of genetic heterogeneity syndrome associated with multiple gene mutations, gene diag-nosis will contribute to understanding of the pathogenesis of the disease and provide theoretical basis for treatment. Though more and more pathogenic genes were found to be connected with SCN, the cases of unknown mutation still account for a large proportion of this disease.

Objective To screen the sequence of fibroblast growth factor receptor 3 (FGFR3) genes in children with dys-chondroplasia and their family members for searching the mutations. Methods The sequence of exon 10 and exon 13 in muta-tion hot spot region of FGFR3 gene in seven families was analyzed using polymerase chain reaction (PCR) and DNA sequenc-ing technology. Results The c.1138G>A missense mutation in exon 10 was found in 4 probands who were diagnosed as achon-droplasia (ACH), while this mutation was absent in their parents. The c.1620C>A missense mutation in exon 13 was found in one girl and her mother who both were diagnosed as hypochondroplasia (HCH) with mild symptoms. Neither mutation men-tioned above was found in the other two probands. Conclusions Through detecting the mutation in exon 10, exon 13 of FGFR3 gene, most patients of ACH or HCH can be finally diagnosed. However, it is necessary to perform the mutation screening on the other zones of FGFR3 gene and on other related genes for a few cases.

Objective To elucidate clinical significance of the varied concentration of cytokines in patients , the concentration of endothelin-1(ET-1) in cerebrospinal fluid(CSF) and serum were investigated in 36 patients with acute craniocerebral injury .Methods In this study ,36 patients with acute craniocerebral injury were divided into two groups by their GCS scores ( GCS≤12 as moderate-severe injury group ,GCS>12 as mild injury group ) .Concentration of ET-1 in CSF and serum in 36 patients with acute craniocerebral injury were detected by ELISA .Results The con-centration of ET-1 was(38.89 ±9.50)μg/L in cerebrospinal fluid ( CSF) in moderate to severe patients ,which were significantly higher than that in mild injury groups [(22.25 ±8.55)μg/L](t=5.453,P=0.000) and control groups [(15.67 ±7.72)μg/L](t=8.347,P=0.000).And the levels of ET-1 in CSF in the mild injury groups were also obviously higher than that of the control groups (t=2.390,P=0.023).On the other hand,the concentration of ET-1 was(107.02 ±17.25)μg/L in sera in moderate to severe patients ,which were also significantly higher than that in mild injury groups[(46.21 ±11.19)μg/L](t=12.176,P=0.000)and control groups[(32.34 ±10.64)μg/L] (t=16.163,P=0.000).And the levels of ET-1 in sera in the mild injury groups were obviously higher than that of the control groups(t=3.751,P=0.001).The concentration of ET-1 in sera was significantly higher than that of CSF (t=9.974,P=0.000).Conclusion The concentration of ET-1 in CSF and sera in patients with acute craniocere-bral injury were associated with severe of brain injury .

Objective To investigate the effect of different concentrations of methotrexate (MTX) on IL-17 from peripheral blood mononuclear cells(PBMCs) and To clarify the active mechanisms of MTX on RA. Methods PBMCs were isolated from heparinized blood of healthy donors or patients with RA using Ficoll-Hypaque density gradient centrifugation. The cells were pretreated with various concentrations of MTX and then stimulated by anti-human CD3/anti-human CD28 at 37℃5%CO2. The IL-17 mRAN level was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The supernatants were harvested and the protein level of IL-17 was tested by ELISA kit. The percentage of CD4+IL-17+cells in PBMCs was detected by flow cytometry. Results For the four different concentrations of MTX groups (0.1,1.0, 5, 25μg/ml), the IL-17 mRNA/GAPDH ratio(0.58±0.09,0.48±0.11, 0.50±0.09, 0.51±0.14) were lower than those of the non-drug group(0.76±0.08). Paired-t test or independent-samplet test showed significant difference between the MTX treatment group and the non-drug group(P＜0.01). The level of IL-17 of the four MTX groups was(121±54)pg/ml and(104±45)pg/ml and(90±36)pg/ml and(115±41)pg/ml, which was lower than the non-drug group(370±187)pg/ml(P＜0.01). The average C D4+IL-17+cell ratio was reduced, but had no statistically signficant differences(P＞0.05). Conclusion MTX can decrease Th17 cells differentiation and suppress IL-17 production of PBMCs, but no association can be found between its effect on the expression of IL-17 and the concentration of MTX.

ObjectiveTo evaluate the clinical and radiological efficacy of TNFR Ⅱ -Fc combined with methotrexate( MTX ) in treatment of patients with moderate and severe rheumatoid arthritis.MethodsThree hundred and ninty-six RA patients were randomized into the combined treatment group,the TNFR Ⅱ -Fc only group and MTX only group.All patients were treated for 24 weeks.ACR-N,ACR20,ACR50,ACR70,DAS28-ESR and Sharp score of both hands were measured for efficacy,and the side-effects were analyzed by one-way ANOVA.Results After 24-week therapy,the ACR-N of the combined treatment group [( 12.79±9.24)％-year] was significantly improved than that of the TNFR Ⅱ-Fc only group [(9.56±11.16)％-year,P＜0.05] and that of the MTX only group[(5.08±11.10)％-year,P＜0.05],and the TNFR Ⅱ-Fc group was significantly improved than that of the MTX group(P＜0.05).The ACR20 response rate of the combined group(80.4％) was significantly higher than that of the TNFR Ⅱ -Fc group(71.1％,P＜0.05) and the MTX group(56.7％,P＜0.01 ).The ACRS0 response rate of the combined group(53.6％) was significantly higher than that of the MTX group(30.8％,P＜0.01 ).The ACR70 response rate of the combined group was 27.7％,which was significantly different from that of the TNFR Ⅱ -Fc group (15.8％) and MTX group (7.7％,P＜0.05or P＜0.01 ).DAS28-ESR in the combination group was significantly reduced than those of the TNFR Ⅱ -Fc group and MTX group,and the DAS28-ESR of the TNFR Ⅱ -Fc group was significantly reduced than MTX group.The average total Sharp score of both hands,which demonstrated the radiographic changes,was significantly reduced in the combination group than the MTX group(P=0.03).The total adverse events in the combined group(40.9％) was significantly high than that of the MTX group(28.8％,P＜0.05).Conclusion TNFR Ⅱ -Fc combined with MTX can effectively control the activity of RA and radiological progress.

Objective To observe the morphological changes of carotid artery wall by ultrasonography in patients with Takayasu arteritis,and to evaluate the diagnostic value of contrast-enhanced ultrasonography for active Takayasu arteritis.Methods High-frequency ultrasound technique was used to analyze the morphological changes of the carotid artery in 40 patients.NIH score was used as the gold standard and the complete clinical data and acute phase reactors were recorded.T test,Chi-square test,sensitivity and specificity were calculated for statistical analysis.Results The thickness of carotid artery wall in active group was much more thickened than the non-active group [(2.2±0.6) mm vs (1.8±0.5) mm,t=-2.142,P＜0.05].The CDD [(0.89±0.06) in active group vs (0.95±0.03) in non-active group,t=3.683,P＜0.01] and RDD [(0.17±0.06 in active group vs (0.09±0.05) in non-active group,t=-4.020,P＜0.01] were significantly different between the two groups.The distribution of neovascularization in the carotid artery wall of the active group was more diffuse in the central part of the wall.The sensitivity and specificity of contrast-enhanced ultrasonography to diagnose the active of Takayasu arteritis were 72.7％ and 87.5％ respectively,and the positive predictive value and the negative predictive value were 80.0％ and 82.4％ respectively.Conclusion Contrast-enhanced ultrasonography can be used as an effective way to assess the disease activity of TA patients.

Objective:To investigate the application value of biological muscle flap in laparo-scopic radical proximal gastrectomy with esophagogastric anastomosis.Methods:The retrospec-tive and descriptive study was conducted. The clinicopathological data of 10 patients with adeno-carcinoma of esophagogastric junction who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from May 2023 to August 2023 were collected. All patients were males, aged (65±5)years. All patients underwent laparoscopic radical proximal gastrectomy and esophagogastric anastomosis with digestive tract reconstruction using the esophagogastric biological muscle flap. Observation indicators: (1) surgical situations and early complications; (2) follow-up and late com-plications. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations and early complications. All 10 patients success-fully completed the surgery without conversion to open surgery, and the operation time was (166±18)minutes. Cases with digestive tract reconstruction as end-to-side anastomosis and Overlap anas-tomosis were 1 and 9, respectively. The time of digestive tract reconstruction, the number of lymph node dissected, volume of intraoperative blood loss, time to postoperative first anal exhaust, time to postoperative first intake of liquid food, duration of postoperative hospital stay were (40±12)minutes, 24±6, (41±9)mL, (3.4±0.5)days, (4.1±1.0)days, (8.3±0.7)days in the 10 patients. Of 4 cases with postoperative early complications, 1 case developed pulmonary infection (Clavien-Dindo grade Ⅱ) on the second day after surgery, with pulmonary infection absorbed after 5 days of antibiotic treat-ment. Two cases experienced chest distress and shortness of breath on the third day after surgery, with the diagnosis of a small to moderate amount of pleural effusion after chest B-ultrasound examination. After pleural puncture and active treatment, the symptoms of them were improved and the pleural effusion disappeared. There was 1 case with choking sensation when eating solid food, which was started from the third week after surgery. Upper gastrointestinal imaging revealed mild anastomotic stenosis of Clavien-Dindo grade Ⅰ in the patient, who was improved after conservative treatment. On the 7th day after surgery, all 10 patients underwent upper gastrointestinal angiography, and no anastomotic leakage or stenosis occurred. There was no sign of contrast agent reflux in the supine position and 30° head down position. (2) Follow-up and late complications. All 10 patients were followed up for 59.5(range, 31.0-127.0)days. The esophageal reflux scale score of 10 patients was 1.4±0.3. During the follow-up, 1 case underwent gastroscopy on 40 days after surgery, which showed reflux esophagitis with Los Angeles grade as B and the Clavien-Dindo grade as Ⅰ. There was no clinical symptom such as heartburn or acid reflux. Results of 24-hour pH monitoring showed that the patient experienced 24 instances of reflux in an upright position and 15 instances of reflux in a supine position, with no prolonged reflux. The total reflux time within 24 hours was 75 minutes. The DeMeester score was 38.3. Results of esophageal pressure measurement showed that the esophageal contraction morphology was normal, but the anastomotic opening was not well relaxed. The rest of 9 cases had no complication such as reflux esophagitis.Conclusion:Biological muscle flap applied in the laparoscopic radical proximal gastrectomy with esophagogastric anastomosis is safe and feasible, with satisfied short-term efficacy.

Objective To investigate the current situation in Chinese rheumatologic physicians' clinical diagnosis and evaluation of Takayasu's arteritis (TA).Methods Nineteen rheumatology experts and three vascular surgery specialists in China were invited to make the nationwide investigation for the first time about the diagnosis and disease activity evaluation of TA in China,through the questionnaire survey on the internet.Weighted average was used to calculate the average scores of corresponding problems.Results Chinese experts mainly adopted 1990 American College of Rheumatology (ACR) classification criteria for clinical diagnosis of TA.In details,symptoms of age,limb claudication and amaurosis,signs including pulselessness or pulse weakening,vascular bruits,increasing bilateral pulse pressure and hypertension and acute phase reactants (APR) were critical to the clinical diagnosis of TA.Besides,noninvasive imaging examinations,such as computed tomography angiography (CTA),magnetic resonance angiography (MRA),vascular ultrasonography,and positron emission tomography (PET) were also of great importance.In the aspect of disease activity assessment,Chinese experts mainly used Kerr scoring tool.APR and noninvasive radiological examinations were considered with vital value.Some TA patients with carotid artery involvement were recommended using vascular ultrasonography,while others with pulmonary artery and thoracic/abdominal aorta trunk involvement were preferred CTA other than MRA.Conclusions APR and noninvasive imaging examinations were thought with great help to make clinical diagnosis and evaluation of TA for Chinese physicians.