Lymphoma is a malignancy of mature lymphocytes. Signalling through the B cell receptor ( BCR ) is central to the development and maintenance of B cells. In light of the numer-ous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co-opt this receptor to promote their own growth and survival. Compounds that inhibit various components of this pathway, in-cluding spleen tyrosine kinase(Syk), Bruton’s tyrosine kinase (Btk), and phosphoinositol-3 kinase(PI3K), have been devel-oped. In this paper,the B-cell receptor signaling and its targeted inhibitors of lymphoid malignancies are reviewed.

Objective To evaluate the effect of salicylic acid on skin barrier function and the efficacy of salicylic acid combined with flumetasone ointment for the treatment of atopic dermatitis (AD).Methods Sixtyfour patients with AD (including 31 males and 33 females) aged 18 to 58 years were recruited into the present study.Four lesional areas of similar size and severity were selected at the similar body sites of both sides of each patient,and randomly classified into four groups to be topically treated with compound flumetasone ointment (containing 0.02％ flumetasone and 3％ salicylic acid,compound flumetasone group),flumetasone 0.02％ ointment (flumetasone group),salicylic acid 3％ ointment (salicylic acid group) and vehicle (control group),respectively;two normal skin areas were chosen from apparently normal skin on the similar body sites of both sides of each patient and topically treated with salicylic acid 3％ ointment (salicylic acid group) and vehicle (control group) respectively.All of these preparations were applied twice a day for 3 weeks.Transepidermal water loss (TEWL) was measured by a Tewameter MPA580 (Courage & Khazaka,Germany) at the baseline as well as on week 1,2 and 3 after initiation of treatment.Symptom and sign scores were evaluated before and after the treatment.Meanwhile,two normal skin areas were selected on bilateral forearm of 30 healthy controls and treated with 3％ salicylic acid ointment (salicylic acid group) and vehicle (control group) respectively twice a day for 3 weeks,and TEWL was measured before treatment as well as on week 1 and 3 after initiation of treatment.Results In the healthy controls,TEWL value showed no significant difference between the salicylic acid group and control group at any of these time points.As far as the lesional skin was concerned,no statistical difference was observed in TEWL value at the baseline between the four groups ((34.26 ± 20.82) vs.(33.02 ±16.71) vs.(34.16 ± 18.03) vs.(33.81 ± 17.11) g· m-2· h-1,P ＞ 0.05),but significant difference was noted after treatment (repeated measurement data analysis of variance,F =39.57,P ＜0.01),with the TEWL value being (22.38 ± 16.16),(17.04 ± 12.74),and (15.34 ± 13.13) g·m-2·h-1 respectively in the compound flumetasone group on week 1,2 and 3,(24.63 ± 17.08),(20.37 ± 9.53),(19.06 ± 9.17) g·m-2·h-1 respectively in the flumetasone group,(26.49 ± 8.59),(21.91 ± 8.46),(21.20 ± 9.38) g·m-2·h-1 respectively in the salicylic acid group,and (29.80 ± 12.48),(26.16 ± 8.31),(25.52 ± 6.05) g·m-2·h-1 respectively in the control group.In detail,the decrease in TEWL value was stronger in the compound flumetasone group than in the flumetasone group on week 1,2,and 3 (all P ＜0.05),in the salicylic acid group than in the control group (P ＜0.05 or 0.01),but similar between the flumetasone group and salicylic acid group.In non-lesional skin,the salicylic acid group showed a more intense decrease in TEWL value compared with the control group on week 2 and 3 (both P ＜0.05).Both the cure rate and response rate were significantly higher in the compound flumetasone group than in the flumetasone group (53.1％ vs.34.4％,x2 =4.57,P＜0.05;83.1％ vs.64.1％,x2 =6.90,P＜0.01).Conclusions The salicylic acid 3％ ointment shows a reparative effect on skin barrier in patients with AD,and the compound flumetasone ointment is superior to the flumetasone ointment in the treatment of AD.

Objective: To explore the application value of biochemical and immunological assembly line in emergency test by comparatively analyzing the changes in sample test process and turnaround time (TAT) in emergency test before and after installation of the assembly line. Methods: A retrospective study was performed with the run data of the emergency biochemical and immunodetection project in Department of Clinical Laboratory in Tongji Hospital Affiliated to Tongji University from July to September in 2017 and from July to September in 2018. (1)The changes in sample circulation mode and test process were compared in emergency test before and after installation of the assembly line.(2)The changes in TAT of sample test and distribution of time interval in emergency laboratory report were statistically analyzed before and after installation.(3)The number of samples tested between instruments and occurrence of instrument failure were statistically compared before and after installation. (4)Biosafety risk assessment was performed on the sample test process before and after installation to analyze the effects of the assembly line installation on biosafety control in emergency test. Results: (1) By applying the assembly line, the sample test process was well controlled and the workload for laboratorians was eased greatly through reduction of manual work.(2) Report TAT was remarkably shortened after installation compared to that before installation; the TAT of dry biochemistry and myocardial zymogram report in emergency test was shorted from 39 min and 48 min to 34 min and 42 min respectively, with a reduction of 12.82% an 12.50% compared to those before installation; the TAT of dry biochemistry and myocardial zymogram report in inpatient emergency was shorted from 37 min and 43 min to 29 min and 35 min respectively, with a reduction of 21.61% an 18.60% compared to those before installation; distribution of report TAT was comparatively analyzed, the percentage of reports in 0-30 min and 31-45 min increased remarkably compared to that before installation, the percentage of TAT of dry biochemistry report falling into 0-45 min increased to 74.58% and 85.66% after installation from 57.91% and 78.28% before installation, respectively in emergency and inpatient emergency. (3)For the model VITROS5600, the percentage of samples tested changed from 30.29% and 69.71% before installation to 47.63% and 52.37% after installation, respectively; for the model DXI800, the percentage of samples tested changed from 28.77% and 71.23% before installation to 53.49% and 46.51% after installation, respectively. After installation, there was a tendency of balance in the number of samples tested between instruments. Instrument failure was significantly reduced: for the model VITROS5600, the frequency of instrument failure decreased from 3.5 times a month/instrument before installation to 2 times a month/instrument after installation on average; for the model DXI800, the frequency of instrument failure decreased from 2.8 times a month/instrument before installation to 1.8 times a month/instrument after installation on average.(4) Installation of the assembly line lowered the risks biosafety events in sample test process in emergency test and the two risks of accidental contact with aerosol in sample tubes before detection and accidental contact with biological specimen due to overturning and spilling during detection were reduced from a high level before installation to a low level after installation. Conclusion In emergency test, biochemical and immunological assembly line is of certain value in process improvement, reduction of workload for laboratorians, improvement of work efficiency, TAT reduction and optimization, as well as control of biosafety conditions.

Objective To purify native F1 antigen from E pestis EV76 strain and determine its ef-ficacy against Y. pestis. Methods A new purification method was developed by the substitution of physical disruption ( glass beads) for organic solvent ( acetone and toluene) one, followed by a combination of ammo-nium sulfate fractionation and SephacrylS-200HR column filtration chromatography. Groups of mice were im-munized with F1 antigen adsorbed to 25% aluminum hydroxide in PBS by intramuscular route. The immu-nized animals were challenged subeutaneously(s, c. ) with 104 CFU of Y. pestis strain 141 at 18 weeks after the primary immunization. Results There was no IgG titre difference between two groups of mice with one-dose immunization, whereas in the two-dose immunization groups, the group F1-40 μg induced a statistically higher antibody titre than the group F1-20 μg. Complete protection was observed for animals immunized with purified F1 antigen by s.c. route. In contrast, the control mice immunized with aluminum hydroxide suc-cumbed to a same dose of Y. pestis 141 challenge. Conclusion This purification strategy is a simple and ef-fective, and can be operated in a large scale. Native F1 antigen extracted from Y. pestis EV76 is highly im-munagenic, and can be used as a key antigen component to develop sub-unit vaccine of plague.

Objective To investigate the role of p16,Ki-67 and human papilloma virus(HPV)type in the shunt treatment of cervical intraepithelial neoplasia (CIN) Ⅱ. Methods The paraffin block on file and the pathological results from loop electrosurgical excision procedure (LEEP) of 377 CIN Ⅱpatients diagnosed with colposcope examination accompanied by cervical high-risk HPV infection in the Affiliated Hospital of Inner Mongolia Medical University of Obstetrics and Gynecology Department from January 2014 to October 2016 were collected. The paraffin sections were stained with p16 and Ki-67 immunohistochemistry. The correlation between the expression of p16 and Ki-67 in biopsy tissues and the pathological results after LEEP was analyzed.HPV type and pathological results after LEEP were also analyzed.Results LEEP postoperative pathological grade in 337 cases of CINⅡpatients was divided into two groups(＜CINⅡ and ≥CINⅡ). There was no statistical difference in age between the two groups (t = 3.078, P = 0.063). There were statistical differences in the expressions of p16+and Ki-67+between the two groups[3.6 %(8/233) vs. 88.5 % (92/104), χ 2=235.54,P<0.001; 3.0 %(7/233) vs. 76.9 % (80/104), χ 2= 197.63, P< 0.001]. There was a statistical difference in HPV infection type between the two groups (χ2= 12.713, P = 0.005). The sensitivity and specificity of p16+and Ki-67+for LEEP postoperative≥CINⅡ was 88.89 % vs.77.78 % and 95.96 % vs.95.80 % respectively. There was a statistical difference in group type of p16 and Ki-67 in both groups (χ2=304.28, P< 0.001). The sensitivity of p16+Ki-67+was 90.73 % and the specificity was 98.74 % in CINⅡpatients for LEEP postoperative. Conclusions The expressions of p16 and Ki-67 can guide the colposcopic biopsy for the treatment of CINⅡ. For CINⅡpatients with p16+Ki-67+, the active treatment should be taken. Close observation needs to follow for p16 and Ki-67 single negative or double negative patients. Active treatment should be performed for CINⅡpatients with HPV16 type infection in CINII. Age can not be used as the basis for the patients with shunt CINⅡ.

Objective: To further understand the interaction protein spectrum of heterogeneous ribonucleoprotein AB (hnRNP AB), and to investigate their clinical significance in hepatocellular carcinoma (HCC). Methods: We carried out mass spectrometry to reveal the specific peptides of KRAB-associated protein 1 (Kap1) and hnRNPAB, and verified their interaction by immunocoprecipitation and western blotting. Expression of hnRNPAB/Kap1 proteins were detected by immunohistochemical staining in the tissue microarrays. Categorical data were analyzed by the chi square test or Fisher exact test; enumeration data between groups were compared using Student t-test or Wilcocon signed rank test; the cumulative recurrence and survival rates were evaluated using the Kaplan-Meier method and the differences were assessed using the log-rank test. Results: We identified Kap1 as a molecular partner for hnRNPAB in HCCLM3 cells and HepG2 cells as well. We found that the 5-year survival rate of the Kap1high patients was significantly lower than the survival rate of those of the Kap1low group (36% vs 59% , HR = 1.67, P < 0.001). Similarly, Kap1high HCC patients had the poorest prognosis at 5-years, with higher cumulative recurrence rate than Kap1low patients (72% vs 54%, HR = 1.66, P = 0.001). Univariate and Multivariate analyses revealed that hnRNPAB /Kap1 alone (HR = 1.35 /1.28, P = 0.001) or in combination with Kap1 (HR =1.24 /1.27, P < 0.05) were independent prognostic indicators for overall survival and time to recurrence. Conclusion In HCC cells, hnRNPAB and Kap1 form protein complexes. The expression levels of hnRNPAB alone or in combination with Kap1 in HCC patients are important because they provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.

Objective To analyze the clinical features and validation of Brighton criteria in Guillain-Barré syndrome (GBS) patients from southern China.Methods The clinical data of hospitalized GBS patients from 69 hospitals of 14 provinces/cities in southern China,the area south of the Huaihe River,between 1 January 2013 and 30 September 2016,were collected and analyzed retrospectively,and patients were classified according to the Brighton criteria of case definition,ranging from a highest (defined as level one) to a lowest (level four) level of diagnostic certainty.Results A total of 1 358 GBS patients were collected,including 51 cases with cranial nerve variants,157 with Miler-Fisher syndrome and 1 150 with classic GBS characterized by flaccid weakness of limbs.Among 1 150 cases of classic GBS,49.57％ (570/1 150) patients had antecedent events,with respiratory infection predominated (71.23％,406/570);83.74％ (963/1 150) presented limb weakness at onset,99.21％ (1 124/1 133) reached the peak within four weeks,with a score of 3.15 ± 1.16 for Hughes Disability Scale;99.56％ (1 128/1 133)developed bilateral weakness and 95.39％ (1 097/1 150) manifested flexia or hyporeflexia;the cerebrospinal fluid showed albuminocytologic dissociation in 80.58％ (772/958) patients whose lumbar puncture was performed;demyelinating GBS accounted for 48.14％ (401/833) and axonal subtype 18.01％ (150/833) respectively in patients with findings of nerve conduction studies available.According to Brighton criteria,the patients were stratified as level one in 44.09％ (507/1 150),level two in 45.74％ (526/1 150),level three in 7.57％ (87/1 150) and level four in 2.61％ (30/1 150) of all the patients,and 69.55％ (507/729),28.67％ (209/729),0％ (0/729) and 1.78％ (13/729),respectively in the patients with complete data (n =729).Conclusions In southern China,demyelinating subtype of GBS is predominant,whereas the proportion of axonal subtype is remarkably lower than that in northern China.The Brighton criteria have a high sensitivity for the diagnosis of GBS in southern China,and examination of cerebrospinal fluid and electrodiagnostic studies are necessary for stratified diagnosis.

Objective:To explore the short-term prognostic factors for Guillain-Barré syndrome (GBS) in children.Methods:The clinical data of children with GBS from 24 hospitals in 10 provinces/municipalities/autonomous regions in southern China (south of Huaihe River) from January 1, 2013 to September 30, 2016 were retrospectively analyzed. The factors affecting the short-term prognoses of children were explored.Results:In these 78 children (50 males and 28 females), the average age was 9.53±5.44 years, and 19 were under 5 years old. Fifty children had history of prodromal events; 28 children had cranial nerve involvement, and 22 had autonomic nerve involvement. Five children needed assisted respiration, and one died during hospitalization. There was no statistically significant difference in percentage of children having poor short-term prognosis (scores of Hughes GBS disability scale≥3 at discharge) between children with different ages, children having different days from onset to admission, children with different clinical classifications or electrophysiological classifications, children with different treatment plans, children having presence or absence of prodromal events, children having presence or absence of cranial nerve involvement ( P>0.05). The proportion of children having poor short-term prognosis in children with autonomic nerve involvement was significantly higher than that of children without autonomic nerve involvement (31.8% vs. 10.7%, P<0.05). Conclusion:The short-term prognosis of children with autonomic nerve involvement is poor.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Objective    To evaluate the midterm effect of valve-sparing aortic root replacement (VSRR) on aortic root aneurysm and moderate to severe aortic regurgitation (AR). Methods    The clinical data of patients with aortic root aneurysm and moderate to severe AR undergoing VSRR and surviving from the operation from October 2013 to May 2020 were retrospectively analyzed. There were 31 males and 9 females, with an average age of 47.1±13.4 years. There were 30 patients with true aneurysm of aortic root and 10 patients with dissecting aneurysm of aortic root. There were 3 patients with bicuspid aortic valve, and 12 patients with Marfan syndrome. The AR measured by the echocardiogram was moderate in 18 patients and severe in 22 patients. The average diameter of aortic annulus was 27.0±3.9 mm, and the mean largest diameter of aortic sinus was 52.3±6.1 mm. Results    A total of 32 patients underwent David technique and 8 patients underwent Yacoub technique, and 10 patients underwent aortic cusp repair simultaneously. All 40 patients  completed the follow-up, and the follow-up period was 12-86 (45.7±18.9) months. During the period, 1 patient died of heart failure, 2 had reoperation due to new-onset Stanford B aortic dissection, and no patients had reoperation related to aortic valve. The postoperative New York Heart Association cardiac function classification (1.6±0.5 vs. 2.8±0.8), left ventricular end-diastolic dimension (52.2±7.8 mm vs. 61.4±10.6 mm) and left ventricular end-diastolic volume (136.0±58.8 mL vs. 193.3±83.9 mL) of the patients were significantly improved compared with preoperative ones (P<0.05). By echocardiography, 19 patients had no AR, 18 patients had mild AR, 3 patients had mild-moderate AR, and no patients had moderate or higher AR. Conclusion    In patients with aortic root aneurysm and moderate to severe AR, VSRR technique avoids prosthetic valves and anticoagulation-related complications, has lower rate of AR recurrence and reoperation, and improves the quality of life in the midterm period.