Intrahepatic cholangiocarcinoma has low resectability rate, high recurrence and short survival. It is very important to formulate and optimize the strategy of surgical treatment. The only potentially effective treatment for intrahepatic cholangiocarcinoma is surgical resection. Liver transplantation also has some application prospects. Intrahepatic cholangiocarcinoma can be divided into four types: mass forming type, intraductal growth type, periductal infiltration type, mass forming + periductal infiltration(mixed)type. Clinically, the treatment strategy is mainly determined according to the general classification. The application of methods such as preoperative portal vein embolism, neoadjuvant therapy and lymph node dissection make it possible for more patients to undergo surgical resection and improve the surgical effect. Adjuvant treatment including chemotherapy and radiotherapy can significantly improve the prognosis of the patients. The rapid development of molecular targeted therapy and immunotherapy is gradually changing the clinical treatment of intrahepatic cholangiocarcinoma.

Objective To analyze the changes in lung function and inflammatory indicators such as eosino-phils(EOS),Creola bodies and exhaled nitric oxide(FeNO),and to explore their value in early diagnosing asthma. Methods One hundred and thirty-five infants with high-risk asthma were selected as an observation group who were admitted to Department of Respiratory,Childrenˊs Hospital of Soochow University from April 2016 to August 2017 due to asthmatic bronchitis and asthmatic bronchopneumonia,and a total of 200 non -asthmatic and non -allergic healthy children who were screened and followed up at the Department of Cardiology in the same period were selected as a healthy control group for the measurement of moist respiratory lung function and FeNO. In the observation group,the bronchial dilation test(BDT),EOS and Creola bodies were performed simultaneously. Classification of lung function:23%≤time to peak ratio(TPTEF/Te)<28% had mild obstruction,15%≤TPTEF/Te<23% had moderate obstruc-tion,and TPTEF/Te<15% showed severe obstruction. Results The TPTEF/Te[17. 20%(8. 10%)],volume to peak ratio(VPEF/Ve)[21. 20%(6. 20%)],tidal volume per kilogram of body weight(VT/kg)[7. 80(3. 70)]and ratio of tidal expiratory flow 25% to peak tidal expiratory flow(25/PF)[0. 54(0. 20)]in the observation group were signifi-cantly lower than those in the healthy control group[22. 30%(9. 22%),27. 15%(7. 10%),8. 90(3. 17),0. 60 (0. 18)],and the differences were statistically significant(Z＝ -6. 81,-9. 35,-3. 16,-3. 52,all P<0. 05). BDT positive rate in the mild obstruction group was 20. 00%(3/15 cases),BDT positive rate in the moderate obstruction group was 26. 56%(17/64 cases),and BDT positive rate in the severe obstruction group was 48. 72%(19/39 cases). The higher the degree of obstruction,the higher the value of BDT positive diagnosis(F＝6. 353,P<0. 05). BDT of VPEF/Ve,25/PF and TPTEF/Te were consistent and statistically significant(Kappa＝0. 78,0. 49,all P<0. 001). Ti-dal expiratory flow 50% -remaining(TEF50% -r)[(117. 86 ± 42. 16)mL/s],tidal expiratory flow 25% -remai- ning(TEF25% -r)[(82. 82 ± 35. 44)mL/s]in the second wheezing group were higher than those in the first whee-zing group[(92. 81 ± 28. 40)mL/s,(65. 22 ± 24. 93)mL/s],and the differences were statistically significant( t＝3. 34,2. 77,all P <0. 05). There was no statistically significant difference in sputum EOS,FeNO and Creola body scores among wheezing children between the first and second groups(all P>0. 05). FeNO in the observation group [3. 80(5. 43)μg/L]was significantly lower than that in the healthy control group[9. 60(11. 3)μg/L],and the diffe-rence was statistically significant(Z＝14. 56,P<0. 05). Sputum EOS had a positive correlation with blood EOS and Creola bodies(r＝0. 20,0. 21,all P<0. 05);there was no correlation between lung function parameters and inflamma-tory indices(all P>0. 05). Conclusions In the acute phase of infant asthma attack,the pulmonary function presents different degrees of obstructive ventilation dysfunction,the higher the degree of obstruction,the higher the diagnostic value of BDT. The value of single FeNO measurement is limited,and continuous dynamic monitoring may be more mea-ningful in predicting the occurrence of asthma. Detection of Creola bodies may be helpful in predicting asthma.

Objective: To analyze the epidemiological characteristics of influenza virus type A (FluA) in children with respiratory tract infection, and to provide scientific basis for clinical diagnosis and treatment. Methods: Sputum specimens of 35 529 cases of hospitalized children with respiratory tract diseases from January 2006 to December 2015 in Suzhou were collected. FluA was detected by direct immunofluorescence and the FluA detection result was analyzed. Groups were compared with chi-square test. Results: The FluA infection rate was 1.60% in 35 529 children. The FluA infection rate of boys was 1.58%, and the rate of girls was 1.63%. There was no obvious statistically significant difference in sex (χ²=0.139, P=0.709). The FluA infection rates of children at the age of less than 1 year, less than 3 years, less than 7 years and older than 7 years respectively were 1.12%, 2.49%, 1.78%, and 1.24%; there was significant differences among these result (χ²=75.401, P=0.000). The FluA infection rates in spring, summer, autumn and winter respectively were 0.88%, 1.44%, 1.32%, 2.70%. The rates in four seasons had significant difference (χ²=105.432, P=0.000). The FluA infection rate was the highest in winter and the lowest in spring. The FluA infection rate was 6.55% in the autumn of 2008, which was the highest in the recent ten years. Conclusions FluA is one of the important pathogens of respiratory tract infection in children in Suzhou area. The infection rate of infant is higher and the epidemic peak is in winter. The FluA infection has obvious epidemic season and year. The FluA infection rates in Suzhou area are 0.64%-3.49%, and there was no outbreak in the recent ten years.

Objective To investigate the application value of dynamic single-photon emission computed tomography (SPECT) 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection (99 Tcm-GSA) scintigraphy assessing regional liver function changes before and after portal vein embolization (PVE).Methods The retrospective cross-sectional study was conducted.The clinical data of 11 patients with Bismuth Ⅲ a hilar cholangiocarcinoma who were admitted to the General Hospital of People's Liberation Army (10 patients) and Beijing Tsinghua Changgung Hospital (1 patient) from October 2010 to October 2016 were collected.B ultrasound-guided percutaneous transhepatic ipsilateral exbolization was performed before radical resection of hilar cholangiocarcinoma.Dynamic SPECT 99 Tcm-GSA scintigraphy was performed to calculate and compare the changes of functional liver volume (FLV),morphological liver volume (MLV) and functional liver density (FLD) in embolized lobe and non-embolized lobe before PVE and 2 weeks after PVE.Observation indicators:(1) the changes of serum indexes in 2 weeks before and after PVE;(2) the changes of FLV,MLV and FLD in the whole liver,embolized and non-embolized lobes in 2 weeks before and after PVE;(3) surgical and postoperative situations of hilar cholangiocarcinoma;(4) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative serum toal bilirubin (TBil) level,with or without peritoneal effusion and survival up to June 2017.Measurement data with normal distribution were represented as x-±s.The comparisons of pre-and post-operative data were analyzed by the paired t test.Results (1) The changes of serum indexes in 2 weeks before and after PVE:11 patients underwent successful right PVE.The alanine aminotransferase (ALT),TBil,albumin (Alb),Platelets (PLT) and prothrombin time (PT) were respectively (113±20) U/L,(73± 8) μmol/L,(35.0±2.5) g/L,(209±58) × 109/L,(11.4±0.7) seconds in 2 weeks before PVE and (120± 18) U/L,(36± 7) μmol/L,(34.4± 3.2) g/L,(224± 82) × 109/L,(11.2±0.8)seconds in 2 weeks after PVE,with a statistically significant difference in TBil level (t=-10.592,P＜0.05) and no statistically significant difference in ALT,Alb,PLT and PT (t=0.981,-0.350,-0.591,0.533,P＞0.05).(2) The changes of FLV,M LV and FLD in the whole liver,embolized and nonembolized lobes in 2 weeks before and after PVE:the FLV,MLV and FLD of the whole liver were respectively (894±255) mL,(1 552±504) mL,0.59±0.14 in 2 weeks before PVE and (812±206) mL,(1 521±422) mL,0.55±0.16 in 2 weeks after PVE,with no statistically significant difference (t =1.569,0.666,1.980,P＞ 0.05).The FLV,MLV and FLD of the embolized lobe were respectively (623±275) mL,(1 047± 394) mL,0.62±0.14 in 2 weeks before PVE and (375±240) mL,(865±337) mL,0.44±0.24 in 2 weeks after PVE,with statistically significant differences (t =5.909,3.736,3.359,P ＜ 0.05);the descending percentages were respectively 38.1％,9.8％ and 24.6％.The FLV,MLV and FLD of the non-embolized lobe were respectively (274±152)mL,(530±176)mL,0.52±0.21 in 2 weeks before PVE and (436±149) mL,(656±133)mL,0.68± 0.24 in 2 weeks after PVE,with statistically significant differences (t =-6.019,-6.345,-3.933,P＜0.05);the elevated percentages were respectively 80.1％,19.9％ and 23.8％.(3) Surgical and postoperative situations of hilar cholangiocarcinoma:of 11 patients,10 received successful peri-hilar right hemihepatectomy,the right hepatic atrophy and an obvious demarcation line between left and right liver were found intraoperatively;1 stopped operation due to detect intraoperatively peritoneal metastasis of tumor.The operation time,volume of intraoperative blood loss and time of postoperative abdominal drainage-tube removal were respectively (585± 194)minutes,(472± 274)mL and (8±5)days.Of 10 patients undergoing operations,2 were complicated with massive peritoneal effusion at 2 days postoperatively,volume of peritoneal effusion remained more than 500 mL up to 7 days after drainage,and were improved by 1-month conservative treatment;other 8 patients were not complicated with hepatic dysfunction.Duration of hospital stay of 11 patients was (16± 4) days.(4) Follow-up and survival situations:10 patients were followed up for 4-72 months,with a median time of 39 months.During the follow-up,there was no evaluated TBil level and peritoneal effusion in 10 patients.The median survival time,1-,3-and 5-year overall survival rates were 88.8％,74.6％ and 36.8％,respectively.Conclusions The dynamic SPECT 99Tcm-GSA scintigraphy can effectively evaluate liver function changes of embolized and non-embolized lobes before and after PVE.The increased rate of FLV of non-embolized lobe is higher than that of MLV.

Objective To investigate the risk factors of single and multiple bronchoscopic lavage therapy in children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods Retrospective analysis was conducted of the clinical data of 332 RMPP children at Department of Respiratory Disease,Children's Hospital of Soochow University from January 2011 to December 2016.The patients were divided into the single group and the multiple group (≥2 times),and the correlative index were compared between the 2 groups.Logistic regression analysis was performed to analyze the risk factors of multiple bronchoscopic lavage therapy in RMPP patients.Results Among 332 children,223 cases were in the single group and 109 cases in the multiple group.Children undergoing multiple bronchoscopy had the fever duration ≥ 10 days before the bronchoscopy and course of disease ≥ 10 days before the bronchoscopy,more than those in the single group [118 cases (52.9％) vs.71 cases (65.1％),69 cases (29.6％) vs.45 cases(41.3％)],and the differences were statistically significant(all P ＜ 0.05).At the same time,the use of glucocorticoid,macrolide,glucocorticoid combined with macrolide antibiotics in the first week of illness were significantly lower in the multiple groups than those in the single group,and the differences were statistically significant (all P ＜ 0.05).In the multiple group,the percentage of neutrophils (N),C-reactive protein (CRP),CRP ＞ 44 mg/L,lactate dehydrogenase (LDH) and LDH ＞ 480 U/L were higher than those in the single group,and the differences were significant (all P ＜ 0.05).In addition,the mixed infection and pleural effusion of multiple group were higher than those of the single group.The proportion of bronchoscopy in the multiple group was higher than that of the single group.In bronchoscopy,the mucus plug blocking and mucosal erosion were more than those of the single group,and the differences were statistically significant (x2 =5.397,13.31,all P ＜ 0.05).After adjusted by multiple regression analysis,6 factors were independent risk factors for multiple bronchoscopic procedures.They were the fever duration before the bronchoscopy ≥ 10 days[odds ratio (OR) =19.504,95 ％ confidence interval (CI):7.350-51.754,P =0.000],the unuse of macrolide antibiotics in the first week of illness (OR =5.072,95％ CI:2.230-11.537,P =0.000),the unuse of glucocorticoid in the first week of illness (OR =14.051,95 ％ CI:4.755-41.522,P =0.000),CRP ＞ 44 mg/L (OR =2.638,95 ％ CI:1.356-5.133,P =0.004),LDH ＞ 480 U/L(OR =2.326,95％ CI:1.302-4.157,P =0.004) and mucosal erosion (OR =11.15,95％ CI:2.503-49.715,P =0.002).Conclusion Severe inflammatory reaction and whether or not to actively resist infection and inflammation in the early stage,were important risk factors for multiple bronchoscopic procedures.

Objective To analyze the epidemiological characteristics of Streptococcus pneumonia (SP) in children with respiratory tract infection in Suzhou area,and the correlation between the air pollutants and the epidemiological characteristics of SP.Methods The real-time air quality test data of Suzhou in Jiangsu province was recorded from January 2012 to December 2014,and sputum specimens of 6 653 cases of hospitalized children with respiratory tract diseases in the same period were collected.The SP detection content and the correlation between SP and the concentration level of PM2.5,PM 10,nitrogen dioxide (NO2),sulfur dioxide (SO2),carbon monoxide (CO),ozone (O3) in Suzhou were analyzed.Results The SP detection rate was 9.94％ in 6 653 children.The SP detection rates were respoctively 7.69％ (183/2 381 cases),10.87％ (235/2 161 cases),11.51％ (243/2 111 cases) between 2012 and 2014.The SP detection rates of children at the age of ≤ 1 year old,＞ 1-3 years old,＞ 3-＜ 7 years old and ≥ 7 years old more respectively were 7.11％ (227/3 192 cases),13.48％ (244/1 810 cases),13.76％ (168/1 221 cases),5.12％ (22/430 cases).The SP detection rate of children at the age of ＞ 1-3 years old and ＞3-＜7 years old was higher than that of ≤ 1 years old and ≥7 years old,and the difference was significant (x2 =84.980,P ＜ 0.001).The SP detection rates in spring,summer,antumn and winter respectively were 9.79％ (173/1 768 cases),7.66％ (130/ 1 697 cases),11.76％ (187/1 590 cases),10.70％ (171/1 598 cases).The SP detection rate of children in summer was the lowest (x2 =4.897,15.839,9.165,all P ＜ 0.05).The concentrations of PM2.5,PM 10,SO2,NO2,CO and O3 were in a state of fluctuation during the survey period.The SP detection rate had positive correlation with the concentration of PM2.5,PM10,SO2,NO2,CO and O3 (r =0.650,0.586,0.680,0.467,all P ＜ 0.005),and there was no obvious correlation between the SP detection rate and the concentration of CO,O3 (all P ＞ 0.05).Conclusions SP is one of the important pathogens of respiratory tract infection in children in Suzhou area,and the detection rate in infants and preschoolers is higher but the detection rate in summer is lower.The SP detection rate is closely correlated with the concentration of PM2.5,PM10,SO2,NO2.

OBJECTIVETo investigate the correlation of apolipoprotein AI (ApoAI), ApoB, ApoB/ApoAI and the severity of brain white matter lesions (WML).

METHODSA total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (=386) and moderate to severe WML group (=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML.

RESULTSUnivariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups ( < 0.05), but ApoB levels were similar between them ( > 0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95% : 3.622-36.229, < 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95% : 0.018-0.262, < 0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML ( < 0.001).

CONCLUSIONSAn increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.

Objective To analyze the correlation between response to hepatitis B virus (HBV) vaccine and cellular immunity and clinical characteristics in children with respiratory infection.Methods Nine hundred and sixty children in Department of Respiratory in Children's Hospital of of Soochow University,who were over 7 months old and had full course of HBV vaccination between January and December 2015 were enrolled in this study.Peripheral blood (1-2 mL) was collected,and antigen-antibody of HBV was detected by using enzyme-linked immunosorbent assay and PCR included HBV surface antigen,hepatitis B antibody,HBV e antigen,HBV e antibody,HBV core antibody,and HBV nucleic acid.According to the results,these children were divided into 4 groups:non response group,low response group,normal response group and high response group according to their responses to HBV vaccine.Cellular immunity was detected by using flow cytometry and patients' clinical data was collected.Results There was no statistical differences of CD3 + CD4 +,which were (3.43 ± 0.28) ％,(3.42 ± 0.30) ％,(3.43 ± 0.36) ％ and (3.52 ± 0.29) ％,among the four groups (F =0.520,P =0.669).CD3 + CD8 + in non response group was (3.18 ±0.28)％,which was significantly higher than that in low response group,normal response group and high response group [(3.08 ± 0.36)％,(3.05 ±0.34)％,(2.93 ±0.30)％],the differences were significant (all P＜0.05);CD4/CD8 in non response group (0.26 ± 0.43) were significantly lower than that in normal response group (0.40 ± 0.50),the differences were significant (P =0.001).There was no significant difference of CD3 +,CD3 + CD8 + and CD4/CD8 among low response group,normal response group and high response group (all P ＞ 0.05).CD3-CD19 + and CD19 + CD23 + level were lowest in non response group [(3.00 ± 0.57) ％,(2.25 ± 0.67) ％] and highest in high response group [(3.33 ± 0.45) ％,(2.57 ± 0.38) ％],the differences were significant (all P ＜ 0.05).Among the 4 groups,children in normal response group had the shortest average hospitalization days [(1.88 ±-0.31) d],which was significantly shorter than that in non response group,low response group and high response group [(1.96 ± 0.39) d,(1.95 ± 0.38) d,(1.96 ±0.15) d],the differences were significant (all P ＜0.05),there was no significantly difference of average hospitalization days among other 3 groups (all P ＞ 0.05).Proportion of severe pneumonia was significantly higher in non response group [6.1％ (22/363cases)] and high response group [13.3％ (2/15 cases)] compared to those in normal response group [2.6％ (7/274cases)],the differences were statistically significant (x2 =4.417,P =0.036;x2 =5.476,P =0.019).The total white blood cell number was lowest in non response group (F =4.695,P =0.003).Platelet number was increased with higher degree of response to HBV (F =6.598,P ＜ 0.001).Conclusions Cellular immunity is lower in respiratory infection children with non response or low response to HBV vaccine.After they have respiratory infection,children with non response to HBV vaccine may have a longer course of disease and worse condition.

Objective To study the characteristics of etiology of lobar pneumonia in hospitalized children.Methods Medical history and sputum specimens were collected from 1 179 hospitalized children with lobar pneumonia from January 2006 to December 2015.Multiple pathogenic joint detection combined with the history data were used for analysis.Seven kinds of common respiratory virus were detected by direct immunofluorescence.Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP) and human Bocavirus (hBoV) were detected by fluorescence quantitative polymerase chain reaction (PCR).Human Rhinovirus (HRV) and human Metapneumovirus (hMPV) were detected by reverse transcription PCR.Aspirates were cultured for bacteria.MP specific antibody IgG and IgM were tested by enzyme-linked immunosorbent assay (ELISA).Positive rates of each group were compared by χ2 test or Fisher exact test.Results Total etiology detection rate of lobar pneumonia in hospitalized children was 83.9% (989/1 179).The etiology detection rate of MP, virus, bacteria and streptococcus pneumoniae (SP) were 74.0%, 14.2%, 18.3% and 12.2%, respectively.The virus detection rate in 1-3 years old group was the highest, and that in ≥6 years old group was lower than other group (χ2=70.095, P<0.01).The MP detection rate increased with age (χ2=119.777, P<0.01).The bacteria detection rate in ≥6 years old group was significantly lower than those of <1 years old group, 1-3 years old group and 3-6 years old group (χ2=8.939, 14.319, 45.738, all P<0.01).The detection rates of total virus, MP, bacteria and mixed infection had no statistical difference in the four seasons (all P>0.05).The MP detection rate was above 70% in every season.The detection rates of SP and hBoV were basically the same in every season.The detection rate of HI was higher in spring, Pinf 3 and SA were higher in summer, HRV was higher in autumn, and respiratory syncytial virus (RSV) and moraxella catarrhalis (MC) were higher in winter.Conclusions Lobar pneumonia occurs more common in elder children.MP is the major pathogen of lobar pneumonia, and SP is the second.The MP detection rate increases with age.The pathogen detection rate varies with age, but the effect of seasonal factor is not obvious on pathogen detection in lobar pneumonia.

Objective To explore the preparation and identification of amyloid-β protein 1-42 (Aβ1-42) oligomers and their effect on in vitro cultured astrocytes in mice.Methods (1) Aβ1-42peptides were dissolved and 100 μ mol/L Aβ1-42 polypeptide was chosen as mother liquor;and then,they were incubated under different conditions (4 ℃ for 24 h,4 ℃ for 72 h,37 ℃ for 24 h and 37 ℃ for 72 h);the form of Aβ-42 was observed under electron microscope and the degrees of Aβ1-42 polymerization were detected by Western blotting.(2) Aβ1-42 oligomers of different concentrations (Aβ1-42 polypeptide as mother liquor being incubated under condition of 4 ℃ for 24 h) were added into the in vitro cultured astrocytes;CCK-8 assay was used to detect the effects ofAβ1-42 oligomers (0,0.1,0.5,1,5,10,50,and 100 μmol/L) on astrocytic viability;after 0,1,10,and 50 μmol/L Aβ1-42 oligomers treatment,immunofluorescence was employed to detect the morphological changes of astrocytes and Western blotting was used to detect the glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) expressions.Results (1) Different forms and degrees of polymerization of Aβ1-42 could be observed by electron microscope and Western blotting:100 μmol/L Aβ1-42 polypeptides could induce 10 nm granulated mixture of Aβ1-42 oligomers at 4 ℃ incubation for 24 h;proteins with relative molecular mass of 10 000 had decreased expression,and those of 15 000-25 000 had increased expression.(2) Twenty-four h after Aβ1-42oligomers treatment,the viability of astrocytes was increased gradually:as compared with the 0 μmol/L Aβ1-42 oligomer treatment group,the 10,50 and 100 μmol/L Aβ1-42 oligomer treatment groups had significantly increased viability of astrocytes (P＜0.05);immunofluorescent staining indicated that as compared with the 0 μmol/L Aβ1-42 oligomer treatment group,the one,10,and 50 μmol/L Aβ1-42 oligomer treatment groups had activated astrocytes:enlarged soma,increased cell processes and increased GFAP fluorescence intensity were noted;Western blotting indicated that following the increased oligomer concentrations,the protein expressions of GFAP and AQP4 increased:as compared with the 0 μmol/L Aβ1-42 oligomer treatment group,the 10 and 50 μmol/L Aβ1-42 oligomer treatment groups had significantly increased GFAP protein expression (P＜0.05);and as compared with the 0 μmol/L Aβ1-42 oligomer treatment group,the one,10,and 50 μmol/L Aβ1-42 oligomer treatment groups had significantly increased AQP4 protein expression (P＜0.05) Conclusions The Aβ1-42 oligomers could be prepared with 100 μmol/L peptide under 4 ℃ for 24 h.Aβ1-42 oligomers could activate astrocytes and up-regulate the AQP4 expression,which might be a self protective mechanism.