BACKGROUND:With unique structure and physicochemical property, carbon nanotubes have promising application prospects in the fields of drug delivery, biosensor and biomaterials. However, carbon nanotubes are highly hydrophobic and trend to aggregate, and thus carbon nanotubes are hard to be dispersed in solution. Furthermore, carbon nanotubes induce blood coagulation and have cytotoxicity, which greatly limit the application of carbon nanotubes. OBJECTIVE:To prepare heparinized single-wal ed carbon nanotubes and to study the effects of heparin-immobilization on the water solubility, stability as wel as biocompatibility of carbon nanotubes. METHODS:By the method of covalent grafting, heparinized single-wal ed carbon nanotubes was fabricated and characterized by Fourier transform infrared spectroscopy and carbazole assay. Transmission electron microscopy was used to investigate the dispersing performance and suspension stability of heparinized single-wal ed carbon nanotubes in aqueous solution. Anti-Xa activity and activated partial thromboplastin time assays were used to measure the anticoagulation activity of heparinized single-wal ed carbon nanotubes. MTT assay was used to evaluate the cytocompatibility of heparinized single-wal ed carbon nanotubes.
RESULTS AND CONCLUSION:Heparin was covalently linked to the surface of single-wal ed carbon nanotubes successful y. The amount of heparin on single-wal ed carbon nanotubes was measured to be 257.53 mg/g. Heparinized single-wal ed carbon nanotubes were wel dispersed and stable in an aqueous solution without aggregation. The anti-Xa activity of heparinized single-wal ed carbon nanotubes was measured to be 36.53 U/mg, suggesting a significant anticoagulant activity. Further study of activated partial thromboplastin time assay found that the anticoagulant effect of heparinized single-wal ed carbon nanotubes could be prolonged. MTT assay revealed that heparinized single-wal ed carbon nanotubes had no cytotoxicity and showed good cytocompatibility. Taken together, the immobilization of heparin on single-wal ed carbon nanotubes wil not only improve its solubility and stability in water, but also endow it with excellent biocompatibility.

Objective To analyze the related factors of lymph node metastasis in N2 group of patients with non-small cell lung cancer,and found its meaning for lymph node dissection.Methods A retrospective analysis was made on 110 patients with non-small cell lung cancer from July 2014 to May 2016 in our thoracic surgery department.Potential related factors were collected,single factor analysis and variate analysis were carried out to find the relationship between N2 lymph node metastasis and potential related factors.Results Univariate analysis showed that the longest diameter of the tumor ＞ 2 cm (P =0.016),lymph node imaging (P =0.021),pleural involvement (P =0.002) were related factors of lymph node metastasis in N2 group,and these three factors were independent related factors of lymph node metastasis in N2 group.Conclusions The longest diameter of the tumor,lymph node imaging and pleural involvement are related factors of N2 lymph node metastasis.Systematic lymph node dissection is strongly recommended for patients with three related factors at the same time.

Objective To investigate the predictive value of serum albumin level in patients with severe sepsis .Methods One hundred and twenty cases of patients with severe sepsis admitted to Qilu Hospital ,Shandong University from April 2014 to October 2014 were prospectively enrolled .The serum albumin levels were measured and the laboratory and clinical data were collected at the onset of severe sepsis .Acute Physiology and Chronic Health Evaluation (APACHE ) Ⅱ score and Sequential Organ Failure Assessment (SOFA) score were calculated .Patients were grouped according to the prognosis by day 28 or stratified by albumin level . Prognostic factors were analyzed by multivariable Logistic regression .Results A total of 120 patients were enrolled with mean age of (57 .6 ± 18 .3) years ,among which 75 were male .The mean duration of hospitalization was (20 .1 ± 17 .8) days .The 28‐day mortality was 25 .8% (31/120) .The most common infection sources were respiratory tract (56 .7% ) ,abdominal/pelvis (19 .2% ) and bloodstream (9 .2% ) .Serum albumin level in survival group was significantly higher than that in death group ([32 .1 ± 6 .4] g/L vs [27 .5 ± 5 .5] g/L ,t=3 .562 ,P=0 .001) .Compared with survival group ,the patients in death group had higher APACHE Ⅱ and SOFA scores (22 .0 ± 9 .1 vs 13 .4 ± 7 .2;7 .1 ± 3 .7 vs 4 .3 ± 3 .5 ;t= —5 .372 and —3 .690 ,both P<0 .05) .Along with the decrease of serum albumin level ,the incidence of bloodstream infection ,solid tumor ,septic shock ,acute kidney injury and liver injury significantly increased .Patients with lower albumin level had significantly higher SOFA scores and 28‐day mortality (all P<0 .05) .Multivariable regression analysis showed that albumin level lower than 28 g/L and higher APACHE Ⅱ score were independent risk factors for mortality (OR=4 .156 ,95% CI:1 .198—14 .415 ;OR=1 .121 ,95% CI:1 .039—1 .210;both P<0 .05) .Conclusions A significantly lowered serum albumin level would increase the risk of mortality in patients with severe sepsis .The combination of albumin level and APAHCE Ⅱ score might be beneficial to evaluate the prognosis .

This study was aimed to illustrate the interaction mechanism between Chinese herbal medicines and CASP3 target,and to analyze the structural characteristics of CASP3 inhibitors.Molecular docking,molecular dynamics and binding energy were employed to analyze the interactions and mechanism between CASP3 target and ligands which were screened from a series of nature products.The results showed that the binding forces of tanshinone ⅡA and scutellarin with CASP3 target were stronger than others.And the theoretical stable structures of tanshinone ⅡA and scutellarin combined with CASP3 target were obtained by molecular dynamics method.It also can be found that hydrophobic interaction was crucial for tanshinone ⅡA binding to amino acid residues of CASP3 such as Phe256,Ser205 and Trp206.Meanwhile,one hydrogen bond was formed between ligand and receptor.The main interactions between scutellarin and CASP3 target were found to arise from hydrophobic effect in ligand and nine amino acid residues of receptor (such as Ser249,Trp214,and Trp206),four hydrogen bonds with different stabilities and electrostatic interaction.It was concluded that tanshinone ⅡA and scutellarin can form stable structures with CASP3 target.And their similar structures may be useful to screen effective CASP3 inhibitors.

Objective:To compare the similarities and differences of macrophage activation syndrome（MAS）combined with systemic juvenile idiopathic arthritis（sJIA）versus with juvenile onset systemic lupus erythematosus（JSLE）.Methods:The clinical data of 48 children with MAS admitted to the Department of Nephrology and Immunology in Children's Hospital of Hebei Province from May 2015 to January 2023 were retrospectively analyzed. The patients were divided into sJIA-MAS and JSLE-MAS group，and the clinical manifestations，laboratory indicators and treatment of the two groups were compared.Results:Among the 48 children（14 males and 34 females）with MAS，the average age of onset was 9.5（3.0，11.8）years. There were 28 cases（11males and 17 females）of sJIA-MAS and 20 cases（3 males and 17 females）of JSLE- MAS. All the 48 children with MAS had fever and hyperferinemia，and the fever with sJIA-MAS was mostly continued fever or remittent fever. Respiratory tract infection was the most common trigger in sJIA-MAS［15 cases（53.6%）］，and disease activity was the most common trigger in JSLE-MAS［13 cases（65.0%）］.Additionally，viral infections（EB virus and cytomegalovirus）were also one of the triggers in MAS［sJIA：7 cases（25%），JSLE：4 cases（20%）］.Compared with JSLE-MAS，the number of days with fever［15.0（12.0，21.0）days vs. 6.0（4.0，9.5）days， Z=-3.812， P=0.001］and the length of hospital stay［29.0（26.3，39.8）days vs.26.0（19.3，30.8）days， Z=-1.958， P=0.049］were longer in sJIA. Compared with JSLE-MAS，ALT［（685.32±561.67）U/L vs.（139.61±124.44）U/L， t=4.973， P=0.001］，AST［784.00（235.25，1 251.25）U/L vs.189.50（53.25，374.08）U/L， Z=-3.283， P=0.001］，CRP［11.48（3.56，28.89）mg/L vs.1.91（0.53，8.98）mg/L， Z=-3.200， P=0.001］，ferritin［32 167.0（12 384.8，65 963.8）μg/L vs.2 003.5（922.5，11 430.0）μg/L， Z=-4.130， P=0.001］，ferritin max/ESR min［1 353.35（355.75，4 342.53）vs.91.92（34.94，291.53）， Z=-4.120， P=0.001］were higher in sJIA.The decrease of CRP was greater in sJIA［80.04（45.64，143.71）mg/L vs.10.20（6.27，25.64）mg/L， Z=-4.433， P=0.001］.Compared with sJIA-MAS，peripheral white blood cell counting［4.05（2.90，7.73）×10 9/L vs.1.56（1.15，3.47）×10 9/L， Z=-3.577， P=0.001］and platelet counting［（162.68±92.19）×10 9/L vs.（110.10±72.99）×10 9/L， t=2.118， P=0.040］were lower in JSLE-MAS. Kidney involvement was more common in JSLE-MAS［10 cases（50%）vs.0 cases（0%）， χ 2=17.684， P=0.001］.There was no significant difference in the incidence of sJIA-MAS and JSLE-MAS meeting the criteria of hemophagocytic lymphohistiocytosis［6 cases（21.4%）vs.5 cases（25.0%）， χ 2=0.084， P=0.772］. Conclusion:Compared with JSLE-MAS，sJIA-MAS is more dangerous and difficult to control，while JSLE-MAS involves more organs，among which the blood system and kidney are more common.

Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis（sJIA）.Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected，and the clinical manifestations，efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score（sJADAS）was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children（4 males and 6 females）with refractory sJIA，the average age of onset was（7.5±3.3）years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was（4.4±1.7）years，and the longest course of disease was 8.3 years. Before the application of thalidomide，all the 10 children experienced relapses（ranging from 2 to 10 times）. The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes［（10.19±3.67）×10 9/L，（8.53±2.83）×10 9/L vs.（16.11±7.81）×10 9/L， F=7.918，11.084， P=0.020，0.009］，C-reactive protein［19.13（0.38，35.21）mg/L，8.05（0.10，18.00）mg/L vs. 59.34（24.20，131.90）mg/L， F=7.030，12.731， P=0.026，0.006］，sJADAS scores［6.00（1.50，12.50）scores，3.00（0，12.50）scores vs. 20.00（11.50，28.00）scores， F=14.710，17.870， P=0.004，0.002］were decreased significantly. The doses of prednisone［0.13（0，0.45）mg/（kg·d），0.02（0，0.06）mg/（kg·d）vs. 0.42（0.16，1.47）mg/（kg·d）， F=5.890，7.623， P=0.041，0.022］were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases，and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA，and can reduce the required dose of prednisone and prolong the tocilizumab free remission.

Objective To explore prescription and syndrome law of TCM in the treatment of non-alcoholic fatty liver disease(NAFLD);To provide reference for clinical medication.Methods The relevant literature on the treatment of NAFLD with TCM was retrieved from CNKI,VIP,Wanfang Data and CBM from the establishment of the databases to October 31,2023.Excel 2019,Lantern 5.0 and SPSS Modeler 18.0 software were used to analyze the latent structure model,association rules and frequency statistics of high-frequency drugs(≥3%)to explore the prescription and syndrome law of TCM in the treatment of NAFLD.Results A total of 453 prescriptions were included,involving 260 kinds of Chinese materia medica,with a cumulative frequency of 4 910 times.The high-frequency drugs were Crataegi Fructus,Salviea Miltiorrhizae Radix et Rhizoma,Alismatis Rhizoma,Bupleuri Radix,Poria and Atractylodis Macrocephalae Rhizoma,etc.The efficacy categories were mainly tonic medicine,diuretic dampness medicine,blood circulation-activating and stasis-resolving medicine,heat-clearing medicine and qi-regulating medicine.The latent structure model obtained 12 latent variables,24 latent classes,and 7 comprehensive clustering models.The commonly used prescriptions were Erchen Decoction,Yinchenhao Decoction,Danggui Shaoyao Powder,Sini Powder,Sijunzi Decoction,Weiling Decoction,Zhuyu Decoction and Dihuang Decoction categorized formula.Conclusion NAFLD is the syndrome of deficiency in root and excess in superficiality.Spleen deficiency is the root cause,phlegm,dampness,heat and blood stasis are the symptoms.In clinical practice,it is mainly based on tonifying qi and spleen,cooperating with the methods of resolving phlegm,eliminating dampness,clearing heat and activating blood circulation.

Objective:To explore the difference of high-risk factors between early-onset and late-onset pre-eclampsia, and to further understand high-risk factors of pre-eclampsia.Methods:Clinical data of pre-eclampsia pregnant women in 160 medical institutions in China in 2018 were retrospectively analyzed, including 8 031 cases of early-onset pre-eclampsia and 12 969 cases of late-onset pre-eclampsia. The proportion of high-risk factors, different body mass index (BMI) and age stratification between early-onset group and late-onset group were compared.Results:(1) Univariate analysis of high-risk factors: the proportions of high-risk factors in early-onset group and late-onset group were compared, and the differences were statistically significant (all P<0.05). Among them, the proportions of primipara and multiple pregnancy in early-onset group were lower than those in late-onset group, while the proportions of pregnant women with advanced age, irregular antenatal examination, obesity, family history of hypertension, pre-eclampsia, diabetes, kidney diseases, immune system diseases and assisted reproductive technology were higher than those in late-onset group. (2) Hierarchical analysis of BMI: the proportion of pregnant women with BMI≥24 kg/m 2 in early-onset group [48.2% (2 828/5 872) vs 45.5% (4 177/9 181), respectively; P=0.001] and the proportion of pregnant women with BMI ≥28 kg/m 2 in early-onset group [19.5% (1 143/5 872) vs 18.0% (1 656/9 181), respectively; P=0.028] were significantly higher than those in late-onset group. (3) Age stratification analysis: the proportion of pregnant women aged 35-39 years in the early-onset group [21.8% (1 748/8 023) vs 17.5% (2 110/12 068), respectively; P<0.01], the proportion of pregnant women 40-44 years old [6.8% (544/8 023) vs 5.4% (648/12 068), respectively; P<0.01], and the proportion of pregnant women ≥45 years old [0.7% (58/8 023) vs 0.5% (57/12 068), respectively; P=0.021] were significantly higher than those in the late-onset group. (4) Multivariate analysis: advanced age (≥35 years old), multiple pregnancy, irregular antenatal examination or transfer from other hospitals, family history of hypertension (including paternal, maternal and parental lines), previous history of pre-eclampsia, kidney diseases, immune system diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome) and assisted reproductive technology pregnancy were the risk factors affecting the severity of pre-eclampsia (all P<0.05). Conclusion:Pregnant women with high risk factors such as age ≥35 years old, BMI ≥24 kg/m 2 before pregnancy, family history of hypertension, history of pre-eclampsia, chronic kidney diseases, immune diseases (mainly including systemic lupus erythematosus and antiphospholipid syndrome) and assisted reproductive technology are more likely to have early-onset pre-eclampsia.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.