OBJECTIVE: To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA). METHODS: The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples t test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-t test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at P < 0.05. RESULTS: The levels of LUM were elevated in the RA patients than in the HCs (P < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all P < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (P>0.05). The levels of serum LUM were elevated in the RF positive patients (P < 0.000 1), and in the RF and anti-CCP positive patients (P < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (P>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (P < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (P < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (P < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (P>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (P>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (P < 0.05). CONCLUSION LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activity and immune activity in RA.
Humans ; Arthritis, Rheumatoid/immunology* ; Lumican/blood* ; C-Reactive Protein/metabolism* ; Female ; Male ; Rheumatoid Factor/blood* ; Middle Aged ; Adult ; Chondroitin Sulfate Proteoglycans/blood* ; Blood Sedimentation ; Keratan Sulfate/blood* ; Enzyme-Linked Immunosorbent Assay ; Aged

ObjectiveTo study the effects of Huangjing Jiannao granules on learning and memory abilities and cerebral blood flow in the rat model of vascular cognitive impairment （VCI） and to explore the mechanism of Huangjing Jiannao granules in the treatment of VCI. MethodSeventy-two SPF-grade male SD rats were randomly selected， with 12 rats as the sham operation group. The remaining rats were subjected to bilateral carotid artery ligation （2-VO） for the modeling of VCI. According to the randomized block design， the successfully modeled rats were grouped as follows： model， donepezil hydrochloride （0.50 mg·kg^-1）， and low-， medium-， and high-dose （2.36， 4.72， 9.44 g·kg^-1， respectively） Huangjing Jiannao granules. After 6 weeks of treatment， Morris water maze test and new object recognition test were conducted to evaluate the learning and memory abilities of the rats. After continuous gavage for 8 weeks， the cerebral blood flow was recorded by a laser microcirculation blood flow imager， and the survival and injury of hippocampal neurons were observed by Nissl staining. The expression of neuronal nuclear antigen （NeuN） in the hippocampus was detected by immunohistochemistry （IHC）. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay. The protein levels of phosphatidylinositol 3-kinase （PI3K）， phosphorylated protein kinase B （p-Akt）， nuclear factor-κB p65 （NF-κB p65）， and nuclear factor-κB inhibitor α （IκBα） in the hippocampus were determined by Western blot. ResultCompared with the sham operation group， the model group showed weakened learning and memory abilities （P<0.01）， reduced blood flow in the whole brain， forebrain， and hindbrain （P<0.01）， damaged neurons and reduced survived neurons in the hippocampal CA1 region （P<0.01）， down-regulated expression of NeuN （P<0.01）， elevated levels of IL-1β and TNF-α in the serum （P<0.01）， up-regulated protein levels of PI3K， p-Akt， and NF-κB p65 in the hippocampal tissue， and down-regulated protein level of IκBα （P<0.01）. Compared with the model group， medium- and high-dose Huangjing Jiannao granules improved the learning and memory abilities （P<0.05，P<0.01）. High-dose Huangjing Jiannao granules increased the blood flow in the whole brain， forebrain， and hindbrain （P<0.05，P<0.01）， and medium-dose Huangjing Jiannao granules increased the blood flow in the whole brain （P<0.05）. All the doses of Huangjing Jiannao granules increased the number of survived neurons （P<0.05，P<0.01） and up-regulated the protein level of NeuN （P<0.05，P<0.01）. Medium and high-dose Huangjing Jiannao granules lowered the level of TNF-α （P<0.05，P<0.01）， down-regulated the protein levels of PI3K， p-Akt， and NF-κB p65 （P<0.05，P<0.01）， and up-regulated the protein level of IκBα （P<0.01）. ConclusionHuangjing Jiannao granules can improve the learning and memory abilities and promote the recovery of cerebral blood flow in the rat model of VCI induced by 2-VO by regulating the expression of proteins involved in the PI3K/Akt signaling pathway， inhibiting inflammation， and reducing hippocampal neuron injury.

Objective To investigate the effect of Osteoporosis Self-Assessment Tool for Asia(OSTA)index on brachial ankle pulse wave velocity(baPWV)and its predictive value for peripheral atherosclerosis in menopausal women.Methods A total of 1 138 menopausal women who underwent physical examination at our hospital from January 2022 to December 2022 were enrolled in the study.General clinical data were collected,the OSTA index was calculated,and baPWV was measured.Patients were divided into the control group(n=539)and the peripheral atherosclerosis group(n=599)according to the baPWV values(peripheral atherosclerosis occurs with baPWV≥1 400 cm/s).Linear regression and Logistic regression were used to analyze the effect of OSTA index on baPWV in menopausal women.The predictive value of peripheral atherosclerosis was evaluated using the receiver operating characteristic(ROC)curve.Results The OSTA index was lower in the peripheral atherosclerosis group than that in the control group[-0.40(-2.20,1.00)vs.0.40(-0.60,1.40),P＜0.05].Univariate linear regression analysis was used to conclude that the OSTA index was an influencing factor of baPWV,and after correcting for risk factors,multivariate linear regression analysis indicated that OSTA index still affected the value of baPWV(P＜0.05).The linear regression equation was baPWV=-27.911-39.752×OSTA+6.444×SBP+7.008×DBP+11.506×HCY+27.942×Hs-CRP.Logistic regression analysis suggested that increased OSTA index was a protective factor for peripheral atherosclerosis(OR=0.664,95%CI:0.535-0.823,P＜0.001).ROC curve analysis suggested that OSTA index was-1.25 as the optimal cutoff point,which predicted peripheral atherosclerosis with an area under the curve of 0.619,a sensitivity of 36.2%and a specificity of 86.3%.Conclusion In menopausal women,OSTA index is an influential factor for baPWV,and increased OSTA index is a protective factor against peripheral atherosclerosis,which can be used to predict baPWV value.

Objective:To analyze the drug-resistant gene loci of Mycoplasma pneumoniae (MP) using metagenomic next-generation sequencing (mNGS). Methods:From November 2022 to October 2023, 697 clinical samples (including sputum, alveolar lavage fluid and blood) of 686 children with Mycoplasma pneumoniae positive detected by mNGS were retrospectively analyzed. Samples were divided into intensive care unit (ICU) group and non-ICU group, Chi-square test was used to compare groups, and Mann-Kendall trend test was used to analyze the change trend of the detection rate of drug resistance gene loci over time. Results:Of the 697 samples, 164 were from the ICU group and 533 were from the non-ICU group. The detection rate of Mycoplasma pneumoniae resistance gene was 44.3% (309/697), and all detected drug-resistant gene loci of MP were A2063G. The detection rate of Mycoplasma pneumoniae in ICU group was 50.0% (82/164), and the detection rates of Mycoplasma pneumoniae resistance gene loci in sputum, alveolus lavage fluid and blood samples were 75.0% (18/24) and 48.4% (62/128), respectively. The detection rate in sputum was higher than alveolus lavage fluid samples ( χ2=5.72, P=0.017). The detection rate of Mycoplasma pneumoniae in non-ICU group was 42.6% (227/533), the detection rate of Mycoplasma pneumoniae resistance gene loci in sputum and alveolar lavage fluid was 40.0% (16/40), 44.3% (201/454), and no detection rate in blood samples (0/12). There was no significant difference in the detection rate of alveolar lavage fluid and sputum ( χ2=0.27, P=0.602). From November 2022 to October 2023, the detection rate of submitted samples showed an increasing trend month by month (overall: Z=3.99, ICU inspection group: Z=2.93, non-ICU group: Z=3.01, all P<0.01). Among the bacteria commonly detected with Mycoplasma pneumoniae, Streptococcus pneumoniae accounted for the highest proportion, the detection rate was 15.5% (108/697), and Epstein-Barr virus accounted for the highest proportion of 17.6% (123/697). Conclusions:From November 2022 to October 2023, the detection rate of Mycoplasma pneumoniae drug resistance gene loci showed an increasing trend. The detection rate of drug resistance gene loci in sputum samples of ICU group was higher than alveolus lavage fluid. No new drug resistance site were detected.

Lung cancer tops the disease list in the world due to the high incidence and mortality， and about 85% of lung cancer cases is non-small cell lung cancer （NSCLC）. Most NSCLC patients are in the advanced stage at the time of diagnosis， with a low 5-year survival. Traditional Chinese medicine （TCM） plays a role in the comprehensive treatment of malignant tumors. Oral Chinese patent medicines， as an important part of TCM， have the advantages of stable preparations， mild taste， simple package， and accurate effective ingredients， which are different from decoctions. They have been widely used in the adjuvant treatment of NSCLC. In clinical practice， the combination of oral Chinese patent medicines with chemotherapy， targeted therapy， or radiotherapy， as well as the application of the oral Chinese patent medicines alone， can increase efficiency， reduce toxicity， prolong the survival time of patients， and improve the quality of life. The mechanisms of oral Chinese patent medicines in the treatment of NSCLC mainly include inhibiting the proliferation， invasion， and metastasis of lung cancer cells， promoting the apoptosis of lung cancer cells， inhibiting tumor neovascularization， reversing multidrug resistance， and regulating the immune functions， which reflects the multi-pathway and multi-target manner of TCM. The oral Chinese patent medicines commonly used in the clinical treatment of NSCLC include Jinfukang oral liquid， Shenyi capsules， Pingxiao capsules， Xiao'aiping tablets， Kanglaite capsules， compound Cantharis capsules， Huisheng oral liquid， Yangzheng Xiaoji capsules， Xihuang pills， Zilongjin tablets， and Cinobufagin capsules. There are many clinical and basic studies about the treatment of NSCLC with these medicines， while a systematic review remains to be carried out. Therefore， we systematically reviewed the mechanisms and clinical application of commonly used oral Chinese patent medicines in the adjuvant treatment of NSCLC， aiming to provide reference for follow-up research and clinical treatment.

Objective To explore the effects of Kaixin Jieyu Pill(KJP)on peroxisome proliferator-activated receptor alpha(PPARα),serum and hippocampal tissue fibroblast growth factor 21(FGF21)and hippocampal tissue fibroblast growth factor receptor 1(FGFR1)in rats with depression model.Methods A rat chronic stress model was prepared using the chronic unpredictable mild stimulus method(CUMS)to observe behavioral changes in depression.Hippocampal FGF21,FGFR1 and liver PPARα protein and mRNA expression levels were measured in hippocampal tissues by western blot and real-time fluorescence quantification(RT-qPCT).Results The expression levels of PPARα,FGF21 and FGFR1's protein and their mRNA were dramatically decreased in the CUMS model rats compared with the normal group(P<0.001).KJP could modify the depressive-like behaviors of rats(P<0.001),upregulate the protein expression level of PPARα,FGF21,and FGFR1(P<0.05,P<0.01,P<0.01);markedly modify the mRNA expression levels of PPARα,FGF21,and FGFR1(P<0.001,P<0.01,P<0.01).Conclusion PPARα/FGF21/FGFR1 pathway may participate in the pathogenesis of depression;upregulation of PPARα/FGF21/FGFR1 pathway may be related to the antidepressant mechanism of KJP.

Objective To evaluate the dynamic efficacy of Invigorating Qi and Dissipating Depression Herbs in the treatment of depressive disorders and its effect on recurrence rate and suicidal thoughts.Methods The prospective cohort study was used to divide the patients into three cohorts according to the different exposure factors(treatment regimens):Western medicine group,integrated traditional Chinese and Western medicine group,and Invigorating Qi and Dissipating Depression Herbs group,and followed up for 2 years,and the treatment effects of each cohort at half a year,one year,one and a half years,and two years were observed respectively,and the evaluation indicators were Montgomery Depression Scale(MADRS),Hamilton Anxiety Scale(HAMA)and Social Deficit Screening Scale(SDSS)reduction rates,and endpoint events(relapse,suicidal ideation)incidence;By comparing the efficacy and endpoint event rate of the three cohorts,the effect of Invigorating Qi and Dissipating Depression Herbs on improving depressive disorders was evaluated.Results A total of 409 patients(67 in the Western medicine group,131 in the integrated traditional Chinese and Western medicine group,and 211 cases in the Invigorating Qi and Dissipating Depression Herbs group)were enrolled,and the rate of score reduction after treatment with MADRS,HAMA and SDSS increased compared with the pre-treatment treatment with the extension of the drug taking time.The difference between the MADRS and SDSS reduction rates in the Invigorating Qi and Dissipating Depression Herbs group on taking the drug for half a year and the SDSS reduction rate on one year of taking the drug were statistically significant compared with the Western medicine group,and there was no significant difference compared with the integrated Chinese and Western medicine group.On one and a half years and two years of medication,the integrated Chinese and Western medicine group had more advantages in MADRS reduction rate than the Invigorating Qi and Dissipating Depression Herbs group.The recurrence rates of depression in the three groups within 2 years were 20.9％,30.5％and 36.0％,and the difference was not statistically significant,and the length of taking medication was used as a protective factor by logistic regression analysis.The incidence rates of suicidal thoughts were 44.8％,19.1％and 17.5％,and the differences were statistically significant,and the exposure factors and income level were the protective factors by logistic regression analysis.Conclusion Invigorating Qi and Dissipating Depression Herbs can significantly improve the depressive state of patients,promote the recovery of social function,reduce the occurrence of long-term suicidal ideation,and appropriately extend the time of taking medicine can increase the long-term efficacy and reduce recurrence.

The research on the essence of triple energizer has not reached a consensus. The correspondence between the existing understanding and the classical theory of triple energizer is still limited in terms of structure and function. According to the traditional theory， nutrient-defense takes channels as the main circulatory system， while the operation of nutrient-defense in the triple energizer remains unclear. Since little is known about the physical structure of the triple energizer， the role of triple energizer as a collection of other Zang-fu organs has been ignored in most cases. The new progress in anatomy paves the way for the research on the essence of triple energizer. The function and structure of triple energizer are similar to those of interstitium and interfacial fluid flow， which enriches our understanding of the macro and micro structures of triple energizer. The triple energizer is distributed throughout the body and composed of membrane and interstitial space. The material structure of triple energizer includes fiber scaffold， collagen fiber， mesenchymal stem cells， histiocytes， pericytes， and interstitial fluid. The functions of triple energizer include passing body fluids， operating nutrient-defense， distributing original Qi， and transmitting and changing pathogenic Qi. According to the available theories and research achievements， we put forward the concept of vertical and horizontal triple energizer， pointed out that triple energizer had independent structure and the features of Zang-fu organs， and preliminarily defined the spatial distribution of triple energizer. The relationship between channels and triple energizer is essential for discussing the operation of nutrient-defense. Telocyte （Tc） and telopod （Tp） has the characteristics of channels in function and structure. The connective tissue with the distribution of Tc and Tp belongs to the same material as the basic structure of interstitial/interfacial fluid flow system and the fibrous skeleton of interstitium. It is clear that channels and triple energizer have material commonality. From the operation paths of nutrient-defense， we proposed that channels may be soaked and attached in triple energizer and put forward the model of channels soaked and attached in triple energizer. By combining the circulation of nutrient-defense with the vertical and horizontal triple energize， we developed the theory of triple energizer-nutrient-defense loop to comprehensively describe the generation， transport， and metabolism of nutrient-defense in channels and triple energizer， aiming to provide a theoretical model for future studies of disease transmission and change from exterior to interior.

Objective:To analyze the antibody levels and dynamic changes in patients infected with 2019-novel coronavirus(2019-nCoV).Methods:The average age of 72 corona virus disease 2019 (COVID-19) patients was (45.53±16.74)years(median age:47 year), including (44.88±17.09) years(median age:46 year) for 38 males and (46.32±16.52)years (median age:46 year) for 34 females in Loudi City, Hunan Province. There is no significant difference in genders between the severe and mild groups (χ2=0.916, P>0.05). There is a significant difference in the age between the severe and mild groups ( F=3.315, P<0.05). The blood samples of 72 discharged patients were collected and the consistence of IgM and IgG antibodies were detected by chemiluminescence method. SPSS25.0 was used for gender, age, case type and antibody analysis of variance, χ 2 test and other analysis. Results:The average time of the serum samples collection of 72 patients was (34.89±9.02)days (median time: 34 days) from onset of COVID-19, and (14.53±8.35) days (median time: 14 days) from discharge. The positive rate of IgM or IgG was 97.22% (70/72), and the positive rate of IgM and IgG was 48.61% (35/72) and 97.22% (70/72) respectively. Serum COVID-19 antibodies were detected in 72 patients from 1st to 40th days after discharge. The average concentration of IgM in 1-7 days, 8-14 days, 15-21 days, 22-28 days, above 29 days were 21.91(7.07-52.84)AU/ml, 14.16(6.19-32.88)AU/ml, 11.36(6.65-42.15)AU/ml, 8.15(3.66-30.12)AU/ml, 2.98(0.46-6.37)AU/ml. There was no significant difference in the time of IgM antibody concentration ( H= 8.439, P>0.05). The average concentrations of IgG in 1-7 days, 8-14 days, 15-21 days, 22-28 days, 29 days and above were 169.90 (92.06-190.91) AU/ml, 163.89 (91.19-208.02) AU/ml, 173.31 (95.06-191.28) AU/ml, 122.84 (103.19-188.34) AU/ml, 101.98 (43.75-175.30) AU/ml, respectively, ( H=2.232, P>0.05). The IgM becomes negative after the 3rd week of discharge and decreases rapidly with time. The IgG concentration higher than IgM during the same period, and keep at high level without any change, and decrease in the fourth week. Among them, 5 cases developed "re-infection" within 1-3 weeks after discharge, and the rate of "re-infection" was 6.94% (5/72 cases). Conclusions:After the COVID-19 patients are discharged from the hospital, the level of antibodies produced varies greatly among individuals, but the overall changes in antibodies have a certain pattern. It is recommended to strengthen the antibody monitoring during hospitalization and after discharge from the hospital to reduce the "re-infection" rate and potential risk of infection.

Objective:To analyze the antibody levels and dynamic changes in patients infected with 2019-novel coronavirus(2019-nCoV).Methods:The average age of 72 corona virus disease 2019 (COVID-19) patients was (45.53±16.74)years(median age:47 year), including (44.88±17.09) years(median age:46 year) for 38 males and (46.32±16.52)years (median age:46 year) for 34 females in Loudi City, Hunan Province. There is no significant difference in genders between the severe and mild groups (χ2=0.916, P>0.05). There is a significant difference in the age between the severe and mild groups ( F=3.315, P<0.05). The blood samples of 72 discharged patients were collected and the consistence of IgM and IgG antibodies were detected by chemiluminescence method. SPSS25.0 was used for gender, age, case type and antibody analysis of variance, χ 2 test and other analysis. Results:The average time of the serum samples collection of 72 patients was (34.89±9.02)days (median time: 34 days) from onset of COVID-19, and (14.53±8.35) days (median time: 14 days) from discharge. The positive rate of IgM or IgG was 97.22% (70/72), and the positive rate of IgM and IgG was 48.61% (35/72) and 97.22% (70/72) respectively. Serum COVID-19 antibodies were detected in 72 patients from 1st to 40th days after discharge. The average concentration of IgM in 1-7 days, 8-14 days, 15-21 days, 22-28 days, above 29 days were 21.91(7.07-52.84)AU/ml, 14.16(6.19-32.88)AU/ml, 11.36(6.65-42.15)AU/ml, 8.15(3.66-30.12)AU/ml, 2.98(0.46-6.37)AU/ml. There was no significant difference in the time of IgM antibody concentration ( H= 8.439, P>0.05). The average concentrations of IgG in 1-7 days, 8-14 days, 15-21 days, 22-28 days, 29 days and above were 169.90 (92.06-190.91) AU/ml, 163.89 (91.19-208.02) AU/ml, 173.31 (95.06-191.28) AU/ml, 122.84 (103.19-188.34) AU/ml, 101.98 (43.75-175.30) AU/ml, respectively, ( H=2.232, P>0.05). The IgM becomes negative after the 3rd week of discharge and decreases rapidly with time. The IgG concentration higher than IgM during the same period, and keep at high level without any change, and decrease in the fourth week. Among them, 5 cases developed "re-infection" within 1-3 weeks after discharge, and the rate of "re-infection" was 6.94% (5/72 cases). Conclusions:After the COVID-19 patients are discharged from the hospital, the level of antibodies produced varies greatly among individuals, but the overall changes in antibodies have a certain pattern. It is recommended to strengthen the antibody monitoring during hospitalization and after discharge from the hospital to reduce the "re-infection" rate and potential risk of infection.