Based on the theory of "shaoyang（少阳） resembling the pivot" and collateral diseases， this article proposes that pulmonary fibrosis （PF） can be divided into three stages including wind bi （痹）， constraint bi， and atrophy bi. The core pathogenesis of PF is the obstruction of the pivot and pulmonary collateral obstruction. In terms of treatment， the basic principles are to harmonize and regulate the pivot， and to promote the circulation of the lung collaterals. Depending on the different characteristics of the "essence-attribute-function"， treatment methods such as harmonizing and regulating the pivot， resolving phlegm and removing stasis， supplementing deficiency and harmonizing collaterals are suggested. This approach ensures the regulation of the pivot， smooth circulation of qi and blood， unblocking of the lung collaterals and nourishing the lung body， achieving the goals of balancing the ascending and descending of qi， removing phlegm and stasis， and relieving cough and wheezing.

Objective In this study,we investigated the correlation between the scores for different Liebowitz Social Anxiety Scale(LSAS)subscale models and the metabolic activity in specific regions of the brain using 18F-fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT)(18F-FDG PET),thereby improving the understanding of the neurobiological characteristics of social anxiety.Methods A total of 39 cognitively normal participants(29 men and 10 women,aged 30-63 years)were enrolled.All participants underwent LSAS assessment and brain 18F-FDG PET scanning.Correlations between metabolic activities in various brain regions and scores from the different LSAS subscales were analyzed accordingly.Results LSAS subscale scores were significantly correlated with metabolic activity in specific brain regions.In the Safren model,the score for the observation by others subscale was positively correlated with the left fusiform gyrus(P<0.001,false discovery rate[FDR]-corrected)and the left caudate tail(P<0.001,FDR-corrected),suggesting a close association between mood states related to observation by others and the metabolic activity in these regions.In the Baker model,the score for the eating and drinking subscale was negatively correlated with the right precuneus(P<0.001,FDR-corrected),while the score for the assertiveness subscale was positively correlated with the left caudate nucleus(P<0.001,FDR-corrected).These findings revealed the complex associative patterns between various mood and behavioral dimensions and metabolic activities in specific brain regions.Conclusion Social anxiety symptoms are closely associated with metabolic changes in specific brain regions,including the left insula,left caudate tail,and right precuneus.Moreover,different social situations activate distinct brain regions.Compared with individuals with social anxiety disorder,normal individuals exhibit involvement of fewer brain regions when experiencing social anxiety.These findings provide new experimental evidence for understanding the neural mechanisms underlying social anxiety.

Objective:To assess the prevalence of exercise addiction among college students and explore its relationship with negative emotion and exercise frequency.Methods:A total of 837 college students were enrolled from January 1, 2022 to December 31, 2022. The cross-sectional survey was administered using the exercise dependence scale revised(EDS-R) and the depression, anxiety, and stress scale 21 items (DASS-21). Data analysis was conducted with SPSS 26.0 software, including partial correlation analysis and hierarchical regression.Results:Among college students, the students in the group with risk and symptoms of exercise addiction accounted for 4.9%(EDS-R score (110.32±11.51), DASS-21-depression score 21.00(10.50, 25.00), DASS-21-anxiety score 21.00(11.50, 24.00), DASS-21-stress score 42.00(22.00, 47.50)). The students in the group without risk but with symptoms accounted for 42.53%(EDS-R score (60.02±12.91), DASS-21-depression score 8.00(1.00, 14.00), DASS-21-anxiety score 8.00(3.00, 14.00), DASS-21-stress score 15.00(4.00, 28.00)), and the students in the group without risk and symptoms accounted for 52.57%(EDS-R score (31.57±7.51), DASS-21-depression score 8.00(5.00, 12.00), DASS-21-anxiety score 7.00(3.00, 10.00), DASS-21-stress score 15.00(6.00, 21.00)). Exercise addiction scores were positively correlated with stress ( r=0.303, P<0.001), anxiety ( r=0.327, P<0.001), and depression ( r=0.259, P<0.001). The results of the hierarchical regression analysis also showed that the main risk variables were anxiety (△ R2=0.175, F=60.954) and exercise frequency (△ R2=0.044, F=21.401). Additionally, male college students had a higher risk of exercise addiction than female( P<0.01), but there was no gender difference in negative emotions( P>0.05). Conclusion:The college students were susceptible to developing an exercise addiction, especially among individuals with high exercise frequency and anxiety symptoms.It provides robust behavioral evidence in support of early detection and treatment of high-risk exercise addiction groups.

This paper summarized the characteristics of constitution， disease， and syndrome of five different phenotypes of bronchial asthma including allergic asthma， cough variant asthma， chest tightness variant asthma， psychological stress asthma， and hormone-dependent asthma， and systematically expounds the application of three-dimensional diagnosis and treatment pattern， that is differentiation of constitution， disease and syndromes in the five phenotypes of bronchial asthma. It is considered that the allergic constitution is the main one of bronchial asthma， which is usually combined with the constitutions of qi-deficiency， yin-deficiency， yang-deficiency， qi-stagnation and others. In the treatment of bronchial asthma， constitution， disease and syndromes should all be taken into account but applied flexibly according to the order of the urgency and priority. The three-dimensional diagnosis and treatment pattern can reflect the essential characteristics and clinical panorama of bronchial asthma more comprehensively and objectively and provide effective intervention measures and management programs for the prevention and treatment by traditional Chinese medicine.

OBJECTIVE:There are many kinds of biological agents for the treatment of rheumatoid arthritis in clinic,but the differences in therapeutic efficacy and safety are still unclear.The purpose of this study is to compare the differences in effectiveness and safety of different biological agents for the treatment of rheumatoid arthritis. METHODS:CNKI,VIP,WanFang,China Biomedical Literature System,PubMed,Cochrane Library,Web of Science,and Embase databases were searched to collect the randomized controlled trials on biological agents for rheumatoid arthritis that meet the requirements from inception to October 1,2022.The literature was selected by EndNote software,and the quality of the included literature was evaluated by RevMan 5.3 software.The software Stata 14.2 was used for direct meta-analysis and network meta-analysis of ACR20(American College of Rheumatology 20%response),ACR50(American College of Rheumatology 50%response),ACR70(American College of Rheumatology 70%response),erythrocyte sedimentation rate,and adverse reactions. RESULTS:Totally 39 articles were included,including 5 low-risk articles,4 high-risk articles,and the remaining 30 articles contained unknown risk bias,with a total of 13 treatment measures.The results of network meta-analysis:(1)In ACR20,infliximab combined with methotrexate(OR=5.54,95%CI:1.33-23.01,P<0.05),abatacept+methotrexate tablets(OR=3.21,95%CI:1.13-9.10,P<0.05),and tocilizumab(OR=2.95,95%CI:1.61-5.44,P<0.05)were better than methotrexate tablets.The probabilistic ranking of ACR20 was:infliximab+methotrexate tablets>abatacept+methotrexate tablets>tocilizumab>certlizumab>etanercept+methotrexate tablets.(2)In the aspect of ACR50,etanercept combined with methotrexate tablets(OR=4.04,95%CI:2.13-7.66,P<0.05),infliximab combined with methotrexate tablets(OR=4.79,95%CI:1.19-19.26,P<0.05),and tocilizumab combined with methotrexate tablets(OR=3.54,95%CI:1.36-9.22,P<0.05)had better therapeutic effects than methotrexate tablets.The probabilistic ranking of ACR50 was:etanercept+methotrexate tablets>infliximab+methotrexate tablets>tocilizumab+methotrexate tablets>tocilizumab>certlizumab+methotrexate tablets.(3)In terms of ACR70,the therapeutic effects of infliximab combined with methotrexate tablets(OR=8.00,95%CI:2.31-27.69,P<0.05),etanercept combined with methotrexate tablets(OR=4.26,95%CI:2.51-7.21,P<0.05),and tocilizumab combined with methotrexate tablets(OR=3.51,95%CI:1.82-6.80,P<0.05)were better than methotrexate tablets.The probabilistic ranking of ACR70 was infliximab+methotrexate tablets>etanercept+methotrexate tablets>tocilizumab+methotrexate tablets>certlizumab>adalimumab+methotrexate tablets.(4)In erythrocyte sedimentation rate,etanercept combined with methotrexate tablets(SMD=-9.23,95%CI:-16.55 to-1.92,P<0.05)was better than etanercept and methotrexate tablets(SMD=14.59,95%CI:7.28-21.91,P<0.05).The probabilistic ranking of erythrocyte sedimentation rate was etanercept+methotrexate tablets>infliximab+methotrexate tablets>etanercept>adalimumab+methotrexate tablets>methotrexate tablets.(5)In terms of adverse reactions,placebo(OR=0.62,95%CI:0.39-0.99,P<0.05)was better than infliximab and certlizumab(OR=0.44,95%CI:0.25-0.78,P<0.05).The probabilistic ranking of adverse reactions was placebo>infliximab>etanercept+methotrexate tablets>certlizumab>etanercept. CONCLUSION:Based on evidence from 39 randomized controlled trials,infliximab combined with methotrexate tablets(highly recommended)can be the first choice in clinic,and etanercept combined with methotrexate tablets(highly recommended)can be the second choice in terms of good effectiveness and safety.

Objective To investigate the role of immunoglobulin superfamily containing leucine-rich repeat protein(ISLR)in the malignant progression of osteosarcoma cells and its potential regulatory mechanism.Methods ISLR mRNA levels in osteosarcoma tissues and cells were detected by quantitative real time polymerase chain reaction(qRT-PCR).U2OS cells were transfected with ISLR short hairpin RNA(shRNA)sequence or negative-control shRNA(NC shRNA)sequence,thus the cells were treated with phosphatidylinositol 3 kinase(PI3K)activator 740 Y-P.The cell viability,invasion ability and apoptosis rate were detected by CCK-8 assay,Transwell assay and flow cytometry,respectively.Western blot was used to detect the expressions of ISLR protein,epithelial-mesenchymal transition(EMT)-related proteins[Epitheia-cadherin(E-cadherin),Nerve cadherin(N-cadherin),Vimentin,Snail],PI3K/protein kinase B(AKT)pathline-related proteins,apoptotic proteins[Cysteinyl aspartate-specific proteinase-3(Caspase-3),B cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax)]and proliferation marker Ki67 protein.Lentivirus was used to transfect U2OS cells,and the cells were injected into nude mice to construct a xenograft tumor model,and tumor growth was monitored.Results ISLR mRNA level in osteosarcoma tissue(5.14±1.63)was up-regulated compared with para-cancerous tissue(1.01±0.02),and the difference was significant(t=-14.332,P＜0.001).Compared with normal osteoblasts hFOB1.19(1.01±0.01),osteosarcoma cells MG63(3.05±0.57),U2OS(4.55±0.79),HOS(2.46±0.41),the relative expression of ISLR mRNA in Saos-2(2.62±0.44)and 143B(3.62±0.51)were increased,and differences were significant(t=4.883,8.473,3.471,3.854,6.247,all P＜0.05).Silencing ISLR inhibited the proliferation of U2OS cells(t=6.593,6.835)and invasion(t=8.621,8.448),but promoted cell apoptosis(t=25.505,25.574),and the differences were significant(all P＜0.05).Silencing ISLR promoted Caspase-3 activity in U2OS cells(t=13.489,13.366)and Bax protein(t=8.628,8.524),but inhibited Bcl-2 protein expression(t=10.948,10.775),with significant differences(all P＜0.05).Silencing ISLR promoted EMT-related protein E-cadherin(t=15.168,15.087),inhibited N-cadherin(t=10.220,10.058),Vimentin(t=8.303,8.164)and Snail(t=9.211,9.384),but reduced the phosphorylation levels of PI3K and AKT(t=17.441,14.452),with significant differences(all P＜0.05).Additionally,740 Y-P treatment reversed the effect of silencing ISLR on U2OS cells.Experimental results in vivo showed that knockdown of ISLR significantly inhibited tumor growth.Conclusion ISLR could promote EMT,proliferation and invasion,but inhibit apoptosis of osteosarcoma cells by activating the PI3K/AKT pathway,there by promoting osteosarcoma progression.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors.Methods:In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children′s Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors.Results:Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis ( HR=2.55, 95% CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant ( HR=2.96, 95% CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions:Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

AIM:To study the expression level of S100 calcium-binding protein A4 (S100A4) in synovial tissue of the knee joint in rheumatoid arthritis (RA) patients and normal persons, and the effect of S100A4 on the angiogenesis induced by rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs).METHODS:The synovial tissue was taken from the knee joint of the RA patients (RA group) and the normal persons (control group).The protein expression of S100A4 and vascular endothelial growth factor (VEGF) in the synovial tissue of the 2 groups was observed by immunohistochemistry.RAFLSs were isolated from synovial tissue of patients with active RA.ELISA was used to detect the effect of S100A4 on the secretion of VEGF by RAFLSs.The effect of S100A4 on the angiogenesis of HUVECs cultured with conditioned medium from RAFLSs was also detected.RESULTS:The protein of S100A4 and VEGF was highly expressed in the synovial tissues of RA group (P<0.05).rhS100A4 significantly stimulated the secretion of VEGF in RAFLSs in a time-and dose-dependent manner (P<0.05).Cultured with conditioned medium from RAFLSs, rhS100A4 significantly promoted HUVECs to form tube-like structures in vitro.CONCLUSION:S100A4 protein is highly expressed in synovial tissue of the knee joint in RA patients, and S100A4 stimulates synovial angiogenesis by promoting RAFLSs to generate VEGF, indicating that S100A4 may be used as a potential target for the treatment of RA.

Objective To investigate the evolution of nonspecific manifestations of pulmonary function in elderly people.Methods Retrospective analysis of the data of nonspecific pulmonary function(NSPF) on the initial PF testing in elderly people from the same PFT apparatus in Beijing Hospital were collected from January 2004 to December 2012.All the patients with complete clinical data and reexamination at least one time were enrolled into this analysis.NSPF was defined as normal FEV1/FVC and TLC combined with a decreased FEV1 or FVC or both.All the patients with complete clinical data were divided into blocking group,restricted group,NFSP group and normal group according to their PF.The comparison was performed among these groups.Kaplan-Meier was used for analysis of the turnover and outcome of elderly NSPF patients,log-rank test was used for comparing the difference of turnover and outcome and COX regression was used for analyzing single and multiple factors of different turnover and outcome.Results Overall 59 patients were diagnosed as NSPF,with male:female ratio of 52:7,the average age of(71.8 ± 8.8)years and at a median follow-up of 4 years.The statistically significant differences in age,sex,body mass index(BMI),smoking status,both the clinical manifestations and chest CT performance at first visit and during the following-up were not found among the groups(all P ＞0.05).The pulmonary functions of NSPF patients were transformed into an obstructive pattern(19.6 ％),into a restrictive pattern(7.6 ％)and into a normal pattern(8.8 ％) in 4 years cumulative incidence rate,with statistically significant in differences(x2 =7.411,P =0.024).An invariant pulmonary function in NSPF patients accounted for 64.0％ in the most,and the second was obstructive ventilation function disability.Monomial and multinomial Cox regression analysis showed that emphysema and bulla in the initial CT scan was the predictor of the change to the obstructive pattern from NSPF during follow-up(HR=4.325,P=0.045),age was the predictor of the change to the restrictive pattern(HR=1.143,P=0.020).And pleural thickening and disappearing of pleural effusion were the predictor of change to the normal pattern (HR =8.889,P =0.018) respectively.Conclusions Most NSPF in elderly people could exist consistently.Obstructive pattern is the maximal likelihood of NSPF changing to the other pattern.Emphysema and bulla in the initial CT scan is the predictor of the obstructive pattern.The change is related with emphysema and bulla in the initial CT scan.

Objective To explore the clinical value of combined detection of serum beta human chorionic gonadotropin (β-hCG),estradiol (E2),progesterone (P) and antiphospholipid antibodies (ACA) in predicting the outcomes of early threatened abortion.Methods 80 pregnant women were chosen from six to eight weeks singleton pregnancies,50 cases of threatened abortion and 30 cases of normal pregnancy.The serum levels of β-HCG,estradiol,progesterone and ACA-IgG,ACA-IgM and ACA-IgA were detected.The threatened abortion patients were given intramuscular progesterone 20 mg/day/time for 1 week,then,the pregnancy outcomes were analyzed and the serum levels of β-HCG,estradiol and progesterone were explored.Results The serum β-HCG,estradiol and progesterone of the threatened abortion group [(5 140.77 ± 2 365.47) IU/L,(680.28 ± 306.06) pg/mL,(15.59 ± 3.65) pg/L]were lower than those of the normal pregnant women [(14 520.4 ± 11 016.24) IU/L,(1 142.81 ± 670.57) pg/mL,(27.6 ± 4.78) pg/L] (t =3.224,P =0.003 ; t =2.43,P =0.022 ; t =7.72,P =0.001).According to pregnancy outcome,patients with threatened miscarriages were divided into the two groups,including 45 patients with continuing pregnancies and 5 patients with inevitable miscarriages.The serum levels of β-HCG,estradiol and progesterone in ongoing pregnancies group [(10 829.42 ± 6 926.28) IU/L,(832.9 ± 397.91) pg/mL,(25.62 ± 4.51) pg/L] were higher than those in inevitable miscarriages [(6 310.14 ± 2 593.19) IU/L,(487.14 ± 275.47) pg/mL,(13.6 ±4.84) pg/L] (P ＜ 0.05) ;The serum levels of ACA-IgG,ACA-IgM and ACA-IgA in 80 cases tested,only 2 cases who appeared in the threatened abortion group were detected with the positive of serum ACA-IgG,accounted for 4％ (2/50) (x2 =68.05,P =0.000),occurred spontaneous abortion in the end.Conclusion Combined detection of serum ACA,β-HCG,estradiol and progesterone may be helpful for prognosis of threatened abortion.However,the clinical predictive value of ACA needs further study in the early threatened abortion.