OBJECTIVE To investigate the effect of Huangqin decoction （HQD）-based self-assembled nanoparticles （SAN） co-loaded with terbinafine （TBF） （TBF-HQD-SAN NPs） on the transdermal absorption of TBF. METHODS High-speed centrifugation combined with dialysis was used to separate HQD-SAN， and TBF-HQD-SAN NPs were obtained by loading TBF using the ultrasound magnetic stirring method； the particle size distribution， Zeta potential and polydispersity index （PDI） of the nanoparticle were characterized， and the encapsulation efficiency （EE） and drug loading （DL） of TBF were determined； using in vitro and in vivo transdermal experiments， the differences in transdermal performance between TBF-HQD-SAN NPs and TBF raw materials， as well as TBF and HQD-SAN physical mixture （TBF-HQD-SAN PM）， were compared and analyzed. RESULTS TBF- HQD-SAN NPs were spherical with a particle size of （177.60±2.57） nm， a PDI of 0.197 4±0.007 9， and a Zeta potential of （－14.63±0.85） mV. The EE and DL of TBF were （99.49±0.71）% and （3.22±0.10）% ， respectively. In vitro transdermal experiments， compared with TBF raw materials， the steady-state permeation rate （Jss） and skin retention of TBF-HQD-SAN NPs increased by 3.34 times and 27.56 times， respectively （P＜0.05）； compared with TBF-HQD-SAN PM， its Jss and skinretention were increased by 2.04 times and 7.44 times， respectively （P＜0.05）. In vivo transdermal experiments 69号） showed that， the area under the drug-time curve and the maximum concentration of TBF-HQD-SAN NPs increased by 2.13 times and 2.06 times respectively compared to TBF raw materials， and increased by 1.59 times and 1.65 times respectively compared to TBF-HQD-SAN PM （P＜0.05）. CONCLUSIONS TBF-HQD-SAN NPs can significantly enhance the in vitro and in vivo transdermal absorption efficiency and skin retention of TBF.

Objective:To analyze the bone turnover markers in systemic lupus erythematosus (SLE) patients with different disease activity and the risk factors of osteoporosis.Methods:In this retrospective study, a total of 417 SLE inpatients were enrolled from the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi′an Jiaotong University, from March 2019 to June 2020. According to SLEDAI score, the patients were divided into 3 groups: 281 patients disease with inactive disease group; 99 patients with mild active disease group; and 37 patients with moderate/severe active disease. ANOVA test was used to compare the differences in serum bone turnover markers (PTH, NOST, VITDT, β-crossl, TP1NP, Ca and P) and bone density (Spine L 1~4 and left femur) among the three groups, and Tukey's method was used for the two groups comparison. Logistic regression analysis was used to investigate the risk factors of osteoporosis. Results:Serum VITDT, β-crossl and Ca levels were significantly different among the 3 groups ( F=11.66, P<0.001; F=7.22, P<0.001; F=29.38, P<0.001). Compared with patients in the inactive group, patients with both the mild disease group (VITDT: t=3.94, P<0.001; Ca: t=5.10, P<0.001) and the moderate/severe disease group (VITDT: t=3.33, P<0.001; Ca: t=7.19, P<0.001) had lower VITDT levels [(20.3±9.7) ng/ml vs. (15.9±9.3) ng/ml vs. (14.8±7.4) ng/ml] and serum Ca levels [(2.19±0.15)mmol/L vs. (2.09±0.21)mmol/L vs. (2.00±0.16)mmol/L]. Moreover, the moderate/severe disease group patients had much lower serum Ca levels ( t=2.36, P<0.05), compared with patients with the mild disease group. Compared with the patients with inactive group, both the mild activey group ( t=3.06, P<0.01) and the moderate/severe activie group ( t=2.99, P<0.01) patients had higher serum β-crossl levels [(419±316) pg/ml vs. (543±424) pg/ml vs. (586±343) pg/ml]. Compared with patients with the inactive disease group both patienes with the mild active group and the moderate/severe disease group patients had significantly decreased spine BMD ( t=2.75, P<0.01; t=2.71, P<0.01), Z-score ( t=5.65, P<0.001; t=4.70, P<0.001), T-score ( t=3.02, P<0.01; t=3.37, P<0.001), whereas, no difference was found between the mild disease group and moderate/severe disease group. Compared with the inactive group patients, both the mild active group and moderate/severe disease group patients had lower left femur BMD levels ( t=2.83, P<0.001; t=2.65, P<0.001) and T-score ( t=2.24, P<0.05; t=1.977, P<0.05) and no difference was found between the mild disease group and the moderate/severe disease group. Logistic regression analysis showed that age [ HR (95% CI)=1.080 (1.052, 1.109), P<0.001], BMI [ HR (95% CI)=0.801 (0.704, 0.911), P<0.001], SLEDAI score [ HR (95% CI)=1.047 (1.025, 1.076), P<0.05] and cumulative glucocorticoids dose [1.046 (1.006, 1.087), P<0.05] were associated with osteoporosis of SLE patients. Conclusion:Abnormal bone metabolism and decreased bone density are associated with SLE disease activity in SLE patients, especially in those with advanced age, low BMI and receiving high cumulative dose of glucocorticoids. Osteoporosis should be proactively prevented in the SLE patients.

AIM:To investigate the mechanism by which wogonin(WOG)induces ferroptosis in collagen-in-duced arthritis rat fibroblast-like synoviocytes(rat CIA-FLS cells)through the nuclear factor E2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.METHODS:Rat CIA-FLS cells were divided into:control group,low,medium,and high dose of(25,50 and 100 μmol/L)WOG group,ferroptosis inhibitor(LIP-1)group,LIP-1+high dose WOG group,HO-1 agonist cobalt protoporphyrin(COPP)group,and COPP+high dose WOG group.CCK-8 assay was used for cell viability.Crystal violet staining was used for for cell morphology.The levels of oxidative stress markers gluta-thione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.DCFH-DA fluorescent probe was used to detect the intracellular reactive oxygen species(ROS)content as well as Western blot to detect the protein ex-pression levels of Kelch-like ECH-associated protein 1(KEAP-1),NRF2 and HO-1.RESULTS:Compared with the nor-mal control group,administration of WOG treatment resulted in a significant decrease in CIA-FLS cell viability(P<0.01),a significant increase in the level of oxidative stress(P<0.01),a significant increase in the content of ROS(P<0.01),a significant decrease in the level of expression of NRF2 and HO-1 proteins(P<0.01),and a significant increase in the level of KEAP-1(P<0.01)in the rat.Compared with the WOG group,the LIP-1-treated group showed a significant increase in cell viability(P<0.01),a significant decrease in the level of oxidative stress(P<0.01),and a significant de-crease in the content of ROS(P<0.01).Compared with the WOG group,the addition of COPP resulted in a significant in-crease in the protein expression levels of NRF2 and HO-1(P<0.01)and a significant decrease in KEAP-1 levels(P<0.01).CONCLUSION:WOG can induce ferroptosis in rat CIA-FLS cells by promoting oxidative stress through the NRF2/HO-1 signaling pathway.

Objective:To investigate the effect of systemic lupus erythematosus (SLE) on the status of hepatitis B virus (HBV) infection, and provide data for clarifying the relationship between autoimmunity and infection.Methods:SLE patients in the department of rheumatology and immunology of the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to December 2019 were screened. A retrospective case-control study was carried out. SLE patients with positive hepatitis B surface antigen (HBsAg) were gender and age matched with chronic hepatitis B (CHB) in a 1∶4 ratio. Chi-square test was used to compared the positive rates of hepatitis B e antigen (HBeAg) and Paired-Samples t test or Signed rank Wilcoxon test was used to compare the HBV DNA load and HBsAg titer. Results:The positive rate of HBsAg in SLE patients was lower than the prevalence rate of HBsAg in general population in the second Chinese National Hepatitis Seroepidemiological Survey in 2006 [2.2%(27/1 227) vs 7.2%], but the positive rate of HBcAb was not obviously different from that in general population in China [33.9%(416/1 227) vs 34.1%]. Compared with matched CHB patients, the positive rate of HBeAg [37.0%(10/27) vs 58.3%(63/108), χ2=3.94, P=0.047], the HBV DNA load [0(0, 3.7) lg U/ml vs 4.8(2.2, 3.7) lg U/ml, Z=-5.37, P<0.001] and HBsAg titer [(2.0±1.5) lg U/ml vs (3.3±1.1) lg U/ml, t=-4.26, P<0.001] in SLE patients were lower. Conclusion:The HBV infection status of SLE patients is different from that of patients with chronic hepatitis B and the HBV infection is more likely to be controlled.

【Objective】 To evaluate musculoskeletal ultrasound (MSUS) detected subclinical synovitis of rheumatoid arthritis (RA) with different clinical remission criteria so as to explore the clinical characteristics of subclinical synovitis. 【Methods】 Forty-six consecutive patients with RA in clinical remission [disease activity score-28 (DAS28)≤2.6] underwent clinical and MSUS examinations at baseline and 1 year follow-up. Clinical remission was defined according to the DAS28 using the erythrocyte sedimentation rate (DAS28-ESR) and C-reactive protein level (DAS28-CRP), clinical disease activity index (CDAI), simplified clinical disease activity index (SDAI), and American College of Rheumatology/European League Against Rheumatism criteria Boolean (ACR/EULAR criteria). Subclinical synovitis was assessed by MSUS. Differences between the subclinical synovitis and non-subclinical synovitis groups were analyzed. 【Results】 The percentages of patients who achieved DAS28-ESR, DAS28-CRP, CDAI, SDAI, and ACR/EULAR remission at baseline and 1 year were 97.8%, 95.6%, 67.4%, 54.3%, 52.2% and 91.3%, 93.5%, 54.3%, 50.0%, and 45.6%, respectively. Subclinical synovitis was detected in 55.5%, 54.5%, 45.2%, 40.0%, 41.6% and 45.2%, 46.5%, 40.0%, 39.1%, and 38.1% of these patients, respectively. There were 45.6% and 41.3% patients who fulfilled all the criteria, yet 38.1% and 36.8% still had evidence of subclinical synovitis at baseline and 1 year. Compared with the patients without subclinical synovitis, those with subclinical synovitis had a significantly positive rate of anti-CCP antibody and a higher disease activity score at baseline (P<0.05). 【Conclusion】 MSUS detected subclinical synovitis is common. The positive anti-CCP antibody and higher disease activity score at baseline may be related to subclinical synovitis in patients with RA in clinical remission.

【Objective】 To investigate the clinical characteristics and risk factors of systemic lupus erythematosus （SLE） combined with symptomatic knee osteonecrosis （KON）. 【Methods】 We retrospectively analyzed the clinical data of 26 cases of SLE with KON treated in the Department of Rheumatology and Immunology， The First Affiliated Hospital of Xi’an Jiaotong University， from April 2013 to December 2019. 【Results】 The age of the 26 patients （2 males and 24 females） was （35.3±9.0） years old at the diagnosis of KON， and the course of SLE was （48.7±35.1） months. The time from glucocorticoids initiation to the development of KON was （37.8±42.7） months， the maximum dosage of methylprednisolone was （197.7±290.7）mg and the cumulative dosage was （6.02±6.66）g. Six of the patients had a history of large-dose glucocorticoids impulse therapy. All of them had a history of immunosuppressant treatment. SLEDAI score was （11.23±5.46） at the onset of SLE and （4.46±4.81） at the onset of KON. The most common initial symptoms were edema and arthritis. The most common systemic damages were blood system damage and lupus nephritis. The most common immunological abnormalities were positive antinuclear antibody （25/26）， positive anti-SSA/Ro52kD antibody （16/26）， and positive anti-SmD1 antibody （15/26）. There were 4 patients with positive anticardiolipin antibody （ACA）. Bone metabolism was characterized by vitamin D3 （Vit-D3） deficiency， insufficient N-terminal osteocalcin （N-OST）， and increased β-C-terminal telopeptide of type I collagen （β-CTx）. In 9 out of the 26 patients， SLE was combined with aseptic necrosis of the femoral head. Multifocal bone necrosis （at least 3 lesions） was common （12/26）. Longer disease course and glucocorticoids using time， larger cumulative dose and ACA positive were seen in patients with multifocal bone necrosis compared with those who had one lesion site. 【Conclusion】 KON most possibly occurs 3 to 4 years after the diagnosis of SLE， which is associated with high disease activity， large hormone dose， and long duration in the treatment process. Multifocal bone necrosis is easily seen in patients with severe disease， large initial hormone dose and high cumulative dose， as well as in ACA positive patients.

Humanized medical service should take Benevolence as the goal and run throughout the whole process of diagnosis and treatment of rheumatic immune diseases.Through the discussion on improving doctors' medical skills and paying attention to patients' mental health and physiological needs in the department of rheumatology and immunology,this paper put forward that it should improve the patient's disease control rate,prolong the survival,improve the quality of life and build a harmonious relationship between doctors and patients through the humanized treatment program,health education and follow-up.

Following rapid social and economic development over the past several decades,pollution by heavy metals has been both serious and widespread in many areas of the world,including China.The situations of heavy metal pollution in China were reviewed,and the health risk and control policy of such pollution were also analyzed and discussed in present paper.

Objective To investigate the clinical characteristics of patients with polymyositis(PM) and dermatomyositis (DM), and compare the differences of PM/DM to help the understanding of clinical diagnosis and treatment. Methods One hundred and forty-five hospitalized PM/DM patients from Department of Rheumatology of the First Affiliated Hospital of Xiˊan Jiaotong University were collected from May 2008 to December 2014, and the clinical manifestations, muscle enzymes, electromyogram, muscle biopsy, treatment outcome were retrospectively analyzed. Mann-Whitney U test and χ2 test were used for statistical analysis. Results The most common initial symptom of PM was muscle weakness, accounted for 51.2%, while rash was the initial presentation in most DM patients(43.1%). The incidence of interstitial lung disease (ILD) (62.7% vs 39.5%, χ2=11.009, P=0.001), and the elevation of CRP (48.9% vs 26.8%, χ2=10.272, P=0.001) were all higher in DM than PM, while the elevation of level of CK (85.4% vs 61.8%, U=-2.668, P=0.008) and CKMB (82.9%vs 41.2%, U=-3.303, P=0.001) were more common in PM compared with DM. The pathological study showed degeneration of muscle fiber, connective tissue hyperplasia in most PM patients, and perimysium atrophy, vacuoles degeneration, muscle bundles, perivascular inflammatory cell infiltration were observed in most DM patients. During the follow-up, the clinical remission rate was 57.5%, the relapse rate and the mortality rate was 7.5%and 31.1%respectively. The mortality rate was higher in DM than PM (34.6% vs 21.4%, χ2=4.861, P=0.027). Infection and tumors were the major causes of death, and the lung was the most common site of infection. Conclusion Differences in the clinical features, muscle enzymes, CRP level, pathology and the mortality rate between PM and DM are evident, while ILD, infection and the higher mortality rate are more common in DM than in PM.

Objective To observe the effect of four-handed technique in light cured resin veneer in the treatment of dental fluorosis. Methods Eighty outpatients with dental fluorosis in our hospital from January 2011 to January 2014 were randomly divided into two groups: 40 in the study group were treated with four-handed technique and another 40 in the control group with one-doctor manual operation. The two groups were compared in terms of treatment duration and curative effect. Result The treatment duration in the study was significantly shorter than that of the control group and the curative effect was significantly better than that of the control group (all P<0.05). Conclusion As for the light cured resin veneer in the treatment of patients with dentalfluorosis in the process , the four-handed technique is better than one-doctor manual operation.