Objective:To identify the function of extracellular soluble vimentin that promotes proliferation, activation and chemotaxis of inflammatory cells. Methods: The proliferation of rat splenocytes stimulated with vimentin was evaluated in vitro. The lymphocyte counts and vimentin-antibody levels of peripheral blood in mice immunized with vimentin were detected in vivo. Peritoneal macrophages were collected and cultured with different concentrations of vimentin to detect the effect on phagocytosing chicken red blood cells. The chemotaxis of NIH3T3 fibroblast towards vimentin was observed in transwell chamber. Results:In vitro vimentin dose dependently promoted the proliferation of splenocytes. The proliferation indexes of primed and naive splenocytes cultured with 16μg/ml vimentin were reached up to ( 196. 0 ± 9. 7 )% and ( 208. 9 ± 4. 6 )% respectively without significant difference. In vivo vimentin significantly enhanced the lymphocytes number(109 L-1)of peripheral blood(5. 74±0. 51 vs. 1. 69±0. 13)and the levels of vimentin specific antibody( OD value 2. 31 ± 0. 06 vs. 0. 19 ± 0. 08 ) that shown no significant difference from immunization with vimentin plus CFA. In vitro vimentin dose dependently stimulated phagocytic ability of macrophages and performed the chemotactic effects on NIH3T3 fibroblasts. Conclusion:Extracellular soluble vimentin promotes the proliferation,activation and chemotaxis of concerned inflammatory cells and possesses the functions as an alarmin.

Objective: To analyze the effect of Argon-Helium cryosurgery (AHCS) on CD4+ CD25+ regulatory T cells (Treg) and its implication in patients with advanced renal carcinoma.Methods:,Peripheral venous blood samples were ob-tained from 32 patients with advanced renal cell carcinoma before and after AHCS.The proportions of Treg cells and T lym-phocyte subsets (CD3+ T, CD4+ T, CD8+ T, CD4+ T/CD8+ T, and NK cells) in the peripheral blood were measured by flow cytometry.Enhanced CT or enhanced MRI was used to observe the necrosis of tumor at 1 month after AHCS.The areas with no imaging enhancement in tumor were regarded as tumor necrosis.The necrosis rate was measured by Cavalieri method and the tumor burden was evaluated.Results: At 3 months after AHCS, the percentages of Treg cells were gradual-ly decreased from 4.18%±1.58% to 1.96%±0.54%, with a significant difference (P=0.001).At 3 months after AHCS, the pro-portions of CD3+ T, CD4+ T, NK and CD4+ T/CD8+ T were gradually increased from 19.26%±7.52%, 43.54%±12.99%, 1.15%±0.57%, and 17.49%±8.36% to 30.83%±5.69%, 49.58±10.76%, 1.84%±0.12%, and 27.63%±8.20%, with a statistical significance (P=0.000, P=0.003, P=0.02, and P=0.001).The proportion of CD8 + T was decreased from 40.86%±8.89% to the lowest ratio (26.74%±4.29%) at 3 months after AHCS, with a significant difference (P=0.000).At 3～6 months after cryo-therapy, there was only a slight change in the proportions of CD3 + T, CD4 + T, CD4 + T/CD8 + T, NK, CD8 + T, and Treg cells, with no significant difference (P>0.05).Correlation analysis showed that the decrease in tumor burden was positively correlated with the decrease of the proportion of Treg cells (r=0.793, P<0.01).Conclusion: After AHCS, the distribution of T-lymphocyte subsets can be improved and the anti-tumor immune response was strengthened.The percentage of Treg cells is correlated with tumor burden.

Objective To analyze the clinical and pathological factors which can influence the occurrence of the recurrent occlusion of metallic stents in patients with malignant biliary obstruction. Methods The clinical data of 50 patients with malignant biliary obstruction, who suffered repeated metallic stents obstruction and were admitted to authors" hospital during the period of March 2006-September 2008, were retrospectively analyzed. Of 50 patients, liver carcinoma was diagnosed in 12, pancreatic carcinoma in 17 and carcinoma of bile duct in 21. The relevant factors which might bear a relation to the occurrence of repeated metallic stents obstruction were evaluated. Results Single factor analysis of variance indicated that the denomination of carcinoma, clinical stage of carcinoma, location of obstruction, whether infection being accompanied or not, and the anti-tumor therapy after biliary stenting treatment were the significant factors closely linked to the occurrence of repeated metallic stents obstruction in patients with malignant biliary obstruction, Logistic regression analysis demonstrated that clinical stage of carcinoma, location of obstruction and whether infection being accompanied or not were the important factors that determined the occurrence of repeated metallic stents obstruction. Conclusion Clinical stage of carcinoma, location of obstruction and whether infection being accompanied or not are important reference factors for judging the occurrence of occlusion of metallic stents in malignant biliary obstruction.

Objective Helicobacter pylori（ ）， To investigate the infection status of HP and analyze the correlation between HP Methods infection and serum bilirubin in railway drivers. A total of 2 731 railway drivers in Zhengzhou locomotive depot were - selected as study subjects using judgment sampling method. Carbon 13 urea breath test was used to evaluate the HP infection ， status. The metabolic indexes of HP positive group and HP negative group were compared and the relationship between HP Results （ ） ， infection and serum bilirubin was analyzed. The HP infection rate was 42.3% 1 156/2 731 . The older the age the ， （ ）， （ P ） longer the work years and the higher the body mass index BMI the higher the HP infection rate all <0.01 . The infection （P ） rate of HP in married people was higher than that in unmarried people <0.01 . The HP infection rate of smokers was higher - （P ） - ， than that of non smokers <0.01 . Compared with the HP negative group fasting blood glucose and serum levels of total ， （ - ）， （ ） - cholesterol low density lipoprotein cholesterol LDL C triglyceride and homocysteine Hcy were increased in the HP （ P ） （ - ）， ， positive group all <0.05 . The serum levels of high density lipoprotein cholesterol HDL C total bilirubin direct bilirubin （ ） - （ P ） DBIL and indirect bilirubin were lower than those in HP negative group all <0.05 . Logistic regression analysis showed that （ P ） HP infection was associated with low serum total bilirubin and low DBIL all <0.01 after adjusting for the confounding effects ， ， ， ， ， ， ， - ， - ， of age work years marital status smoking history fasting blood glucose total cholesterol triacylglycerol LDL C HDL C Conclusion ， ， ， and Hcy. The age work length BMI smoking and marital status are the influencing factors of HP infection in railway drivers. HP infection is associated with low levels of total bilirubin and DBIL.

Objective To investigate the changes of C- reactive protein( CRP ) and homocysteine ( Hcy)in the type 2 diabetes with depression,and its clinical significance and potential mechanism. Methods One hundred and twenty-four cases with type 2 diabetes were divided into the depression group(63 cases)and non-depression group( 61 cases ) according to the Self-Rating Depression Scale and verified by Self-Rating Anxiety Scale. The information including age,sex,education degree,body mass index,course of disease and the number of complications were recorded. The levels of CRP,Hcy,fasting plasma glucose( FPG ),glycosylated hemoglobin(HbA1c)and blood lipid were measured. The depression group was divided into mild,medium and heavy group to compared the changes of Hcy and CRP. Results The levels of Hcy,HbA1c and the number of complications in depression group were 11. 5( 8. 6,15. 6 )μmol/L,( 10. 13 ± 2. 17 )%,and 2( 1,3 ) respectively,higher than that of non-depression group(8. 6(7. 4,11. 2)μmol/L,(9. 33 ± 2. 20)%,1(0,2)), while the education degree of depression group((9. 75 ± 3. 36)years)was lower than that of non-depression group((11. 56 ± 3. 73)years),and the differences were significant( t/Z = -3. 537,0. 952,-2. 339,0. 228 respectively;P ﹤0. 05). The levels of Hcy in mild,medium and heavy depression group were(8. 75(7. 45, 10. 45)μmol/L,12. 2(8. 90,14. 40)μmol/L,19. 50(14. 33,28. 03)μmol/L respectively and the difference was significant(F =25. 963,P =0. 000). No significance difference was found in terms of CRP level(2. 35 (1. 10,4. 92)mg/L,3. 25(1. 11,5. 68)mg/L,2. 32(1. 27,5. 41)mg/L;F=0. 194,P=0. 907). There was significant correlation between depression scores and Hcy( r=0. 615,P=0. 000). Conclusion Type 2 diabetes with depression is associated with the level of blood glucose,education degree and the course of disease. Hcy,not CRP is an independent risk factor of type 2 diabetes with depression.

OBJECTIVE：To test and verify the piping cleaning effect in infusion solution productive process.METHODS:Targets of final washing water of pipe were determined.RESULTS:Targets of final washing water of pipe were that electrical conductivity of entrance of pipe was equal to that of exit of pipe essentially,limitation of bacteria and endotoxin were as follows:＜50CFU/ml,＜0.25EU/ml.CONCLUSIONS:According to the clean rules laid down by pharmaceutical Factory of Shanquan,Jinan,The desired cleaning effect of the pipe of infusion solution can be achieved.

Objective:To observe the efficacy and safety of dexzopiclone plus auricular acupressure in intervening primary insomnia.Methods:A total of 72 participants who met the inclusion criteria were enrolled in a randomized controlled trial,with 36 cases allocated to a treatment group and 36 cases allocated to a control group.Both groups were given dexzopiclone as the routine treatment.Patients in the treatment group were given auricular acupressure with Wang Bu Liu Xing (Semen Vaccariae) seeds at the auricular acupoints related to sleep and emotion based on meridian theory,whereas for patients in the control group,the medical plasters with Wang Bu Liu Xing (Semen Vaccariae) seeds were only gently stuck to acupoints unrelated to sleep without stimulation.Patients in both groups were required to visit the hospital once a week for replacing the seeds and plasters.The course of intervention lasted for 8 weeks and the patients were followed up for another 4 weeks.Pittsburgh sleep quality index (PSQI) and Karolinska sleep diary (KSD) were used to evaluate the outcomes.Meanwhile,adverse effects were monitored and recorded.Results:In the enrolled 72 cases,4 patients (one in the treatment group and three in the control group) reported thirst and a bitter taste,and one case in the control group reported nausea and vomiting.At last,3 cases in the control group dropped out for adverse reactions,and 69 cases completed the clinical trial.After 8 weeks of treatment,the global scores of PSQI in both treatment and control groups decreased significantly compared with the baseline (both P＜0.001).Furthermore,the global score of PSQI in the treatment group was lower than that in the control group (P＜0.01).The global scores of PSQI in both groups at the follow-up were significantly different from the baseline (both P＜0.001),but insignificantly different compared with the post-treatment results (both P＞0.05).According to KSD,both treatment protocols could prolong the total sleep time,shorten sleep-onset latency,improve sleep efficacy and sleep quality significantly,and the changes in the treatment group were more significant.The total effective rate was 88.9％ in the treatment group,higher than 81.8％ in the control group,though the difference was statistically insignificant (P＞0.05).Conclusion:Dexzopiclone plus auricular acupressure is effective and safe for patients with primary insomnia both in short and long terms,and it is more effective than monotherapy of dexzopiclone.

Objective:To explore the expression of type 2 complement receptor (CR2) in mesangial cells of the renal tissue in IgA nephropathy (IgAN) and its possible mechanism involved in complement C3 deposition.Methods:The demographic data, samples of plasma and renal tissues of primary IgAN patients diagnosed by renal biopsy in the Guangdong Provincial People's Hospital from August 2021 to May 2022 were collected. According to the fluorescent intensity of mesangial complement C3 deposition, the patients were divided into complement C3 deposition ≥2+ group and complement C3 deposition <2+ group. The circulating IgA and complement C3 levels were detected by enzyme linked immunosorbent assay (ELISA). The influencing factors of kidney prognosis, plasma IgA and complement C3 levels were compared between the two groups. Immunofluorescence was used to detect the expression of IgA, complement C3 and CR2 in the renal mesangial cells of IgAN patients and normal renal tissues around renal carcinoma. Human mesangial cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was incubated with IgA protein (2 g/L) for 8 hours. The expressions of CR2 protein and mRNA were measured by Western blotting and real-time fluorescence quantitative PCR. The biological function of differential genes was analyzed by gene ontology (GO) and Kyto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results:A total of 75 patients with IgAN were included in this study, including 50 patients in the complement C3 deposition ≥2+ group and 25 patients in the complement C3 deposition <2+ group. The proportions of patients with urine red blood cell count negative, 1+, 2+ and 3+-4+ in the complement C3 deposition ≥2+ group were 2.0%, 8.0%, 18.0% 72.0%, respectively, which were more serious than those in the complement C3 deposition <2+ group (4.0%, 4.0%, 52.0%, 40.0%) ( Z=-2.320, P=0.020). Meanwhile, the proportion of S1 in Oxford pathological classification in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group (68.0% vs. 40.0%, χ2=5.389, P=0.020), and there were no statistically significant differences in gender, age, 24-hour urinary protein, serum creatinine, other indicators of Oxford pathological classification between the two groups. ELISA results showed that plasma IgA concentration in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group [3.62 (2.95, 5.53) g/L vs. 2.72 (2.15, 4.24) g/L, Z=2.405, P=0.016], and the plasma complement C3 concentration was lower than that in the complement C3 deposition <2+ group [199.6 (116.0, 328.0) mg/L vs. 319.2 (158.3, 454.5) mg/L, Z=-2.383, P=0.017]. Spearman correlation analysis showed that the complement C3 deposition intensity was positively correlated with IgA deposition intensity in mesangial area ( rs=0.441, P<0.001). Immunofluorescence results showed that there was colocalization of IgA and complement C3 in the glomeruli of IgAN patients. The expression of CR2 in the kidney was consistent with complement C3 deposition, and CR2 was colocalization with complement C3. In vitro experiments, the expression of CR2 in IgA protein group was higher than that in the control group ( P<0.05). GO and KEGG enrichment analysis found that IgA protein induced active changes in various pathways of mesangial cells. Conclusion:IgA protein induces mesangial cells to express CR2 and participates in complement C3 deposition, which may be an important mechanism of complement C3 activation in IgAN.

Signal transduction in cells plays an important role in the process of cellular metabolism, segmentation, differentiation, biological behaviors and cell death. Direct and indirect involvement of kinases in tumor growth, metastasis and apoptosis make them the most promising targets for anticancer discovery. Most of the kinase inhibitors in clinical use or in late development stages are multi-target kinase inhibitors (MTKIs). These MTKIs are demonstrated to exert potent anti-tumor effects through several different pathways. This review presents in the view of a medicinal chemistry point, a brief account and analysis of transduction pathways of representative MTKIs in clinical use or in late development stages.
Antineoplastic Agents ; therapeutic use ; Clinical Trials, Phase III as Topic ; Drug Delivery Systems ; methods ; Humans ; Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Signal Transduction

OBJECTIVETo compare the functional parameters of the small airways and clinical characteristics between patients with typical asthma (TA) and cough-variant asthma (CVA).

METHODSForty-three newly diagnosed asthmatic patients were enrolled, including 15 with TA and positive bronchial provocation test [TA BPT(+)], 12 with TA and positive bronchial dilation test [TA BDT(+)] and 16 with CVA, and 27 healthy subjects served as the control group. All the subjects were required to complete data acquisition, asthma control test, asthma control test scale, fractional exhaled nitric oxide, airway resistance and pulmonary function tests, BPT or BDT.

RESULTSThe interval from onset to a definite diagnosis of TA BDT(+) was longer than that of TA BPT(+), while that of CVA was the shortest (P=0.022). The pulmonary functional parameters of TA BDT (+) was significantly lower than those of the other 3 groups (P<0.05). MMEF, MEF, MEF, and MEFin patients with TA BDT(+), TA BPT(+) and CVA were significantly lower than those in the control group (P<0.01). The resonant frequency, respiratory impedance, resistance at 5 Hz, resistance at 20 Hz, and reactance at 5 Hz were significant higher in patients with TA BDT (+) than in the control subjects, while these parameters showed no significant differences among TA BPT (+), CVA and control groups. The airway resistance in TA BPT(+), CVA, and control groups increased after BPT, and the patients with TA BPT(+) showed greater changes in airway resistance than those in CVA and control groups. In CVA patients, FeNO showed a strong positive correlation with respiratory impedance (r=0.523, P=0.038), resistance at 5 Hz (r=0.542, P=0.030), and resistance at 20 Hz (r=0.524, P=0.037), and the airway responsiveness showed a strong positive correlation with resistance at 20 Hz (Rho=-0.512, P=0.043).

CONCLUSIONCVA is the early stage of TA, and CVA, TA BPT(+), and TA BDT(+) may represent different stages of asthma. Uncontrolled, prolonged CVA may evolve into TA BPT (+), whose further progression can cause damages of the pulmonary function and small airway function and leads eventually to TA BDT (+).