Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

Objective : To evaluate the vertical distance between the maxillary first molars (MFMs) and the maxillary sinus floor (MSF) and its interrelationship with sex, age, and vertical facial pattern in skeletal ClassⅡ patients to provide a reference for clinical orthodontic treatment. Methods: Sixty teenagers and sixty adults with skeletal Class Ⅱ malocclusion who met the inclusion criteria were selected to evaluate the vertical relationship between the MFMs and the MSF on cone-beam CT (CBCT) images. The vertical distance between the roots of the MFMs and the MSF was measured. Statistical analysis was used to assess differences between patients by sex, age, and vertical facial pattern. Results: The contact percent of the roots of MFMs and MSF was 85% and 56% in skeletal Class Ⅱ teenagers and adults, respectively. The contact percent and penetration percent of the roots with MSF were higher in teenagers than in adults（P<0.05）. The penetration percent of the high-angle (HA) and the normal-angle(NA) groups was 34.1% and 36.6% respectively, which was significantly higher than that in the low-angle (LA) group(20.8%)（P<0.05）. The difference between the distance of the bilateral MFMs and the MSF was not significant in skeletal Class Ⅱ patients (P>0.05); No significant difference was found between different sexes of skeletal Class Ⅱ patients when comparing the distance of the MFMs and the MSF (P>0.05). The MFMs of skeletal Class Ⅱ teenagers were closer to the MSF than those of adults (P<0.05). In the adult group, the distance was not significantly different in different vertical facial patterns (P>0.05). In the teenager group, the MFMs were more closely related to the MSF in the NA and HA groups than in the LA group. Among them, the difference between the mesiobuccal roots and distalbuccal roots was significantly different (P<0.05). There was no significant difference between the groups of the palatal roots (P>0.05). Conclusion The MFMs were closer to the MSF in skeletal Class Ⅱ teenagers than in adults. The distance between the MFMs and MSF was associated with the vertical facial pattern in skeletal Class Ⅱ teenagers, while it was not associated with the vertical facial pattern in adult patients.

Gaining a better understanding of autoprotection against drug-induced liver injury(DILI)may provide new strategies for its prevention and therapy.However,little is known about the underlying mechanisms of this phenomenon.We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells(NPCs)in autoprotection against DILI,using acetaminophen(APAP)as a model drug.Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice,followed by a higher dose in a secondary challenge.NPC subsets and dynamic changes were identified in the APAP(hepatotoxicity-sensitive)and APAP-resistant(hepatotoxicity-resistant)groups.A chemokine(C-C motif)ligand 2+endothelial cell subset almost disappeared in the APAP-resistant group,and an R-spondin 3+endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection.Moreover,the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation.DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group.In addition,the natural killer cell subsets NK-3 and NK-4 and the Sca-1-CD62L+natural killer T cell subset may promote autoprotection through interferon-y-dependent pathways.Furthermore,macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity.Overall,this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

Objective:To explore the efforts of applying mindfulness stress reduction therapy in alleviating stress reactions and burnout among head nurses in the context of the Coronavirus disease 2019 (COVID-19).Methods:This was a quasi experimental study. In June 2021, 109 head nurses with mild or above burnout measured by Maslach Burnout Inventory (MBI) from 12 hospitals in Zhangjiagang City were selected as the research objects to implement mindfulness-based stress reduction therapy for 8 weeks, and the scores of the Five Facet Mindfulness Question-naire (FFMQ), Stress Response Questionnaire (SRQ) and MBI of the head nurses were compared before and after the intervention.Results:The five dimensions of observation, description, perceived action, non-judgment, and non-response and the total scores of the FFMQ were (26.28 ± 1.32), (26.94 ± 1.29), (25.49 ± 0.99), (25.45 ± 1.05), (23.48 ± 1.01), and (127.63 ± 3.78) of the post-intervention, which were higher than the pre-intervention scores of (25.04 ± 1.37), (25.04 ± 1.37), (25.37 ± 1.18), (24.15 ± 1.00), (24.09 ± 0.98), (22.26 ± 1.04), and (120.90 ± 4.06), with statistically significant differences ( t values were -39.21- -15.36, all P<0.01). The three dimensions of emotional, somatic, and behavioral responses and total scores of the post-intervention SRQ were (27.70 ± 6.12), (20.75 ± 4.20), (15.19 ± 3.11), and (65.99 ± 12.43), respectively, lower than the pre-intervention scores of (29.19 ± 6.91), (21.86 ± 5.20), (16.48 ± 4.16), and (70.12 ± 15.97), with statistically significant differences ( t values were 5.70-9.33, all P<0.01); the scores of dimensions of emotional exhaustion and depersonalization in post-intervention MBI were (26.24 ± 4.60) and (5.96 ± 1.25), lower than the pre-intervention scores of (29.66 ± 6.02) and (6.90 ± 1.59). The post-intervention scores of personal fulfillment (32.37 ± 5.02), higher than the pre-intervention scores of (28.60 ± 6.04), all with statistically significant differences ( t=15.36, 13.50, -9.65, all P<0.01). Conclusions:The implementation of mindfulness stress reduction therapy for the head nurses can relieve their work pressure due to the prevention and control of the COVID-19 epidemic, reshape their healthy psychology, and reduce job burnout.

Objective:To analyze the clinical characteristics of elderly-onset gouty arthritis and risk factors of tophi.Methods:A total of 1 239 gout patients were retrospective selected in the outpatient department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from 2016 to 2022. According to age of onset, they were divided into the young and middle-aged group(aged<60) consisted of 826 cases, and the elderly group(aged≥60) consisted of 413 cases. Compare the clinical characteristics of elderly with Young and Middle-aged patients.Results:The systolic blood pressure, fasting blood glucose, creatinine, regular exercise, comorbidities, and tophi in the elderly group was higher than that in the middle-aged and young group. The proportion of diastolic blood pressure, serum triglycerides, eGFR, serum uric acid, alcohol consumption rate, and family history of gout was lower than that of young and middle-aged group( P<0.05); In the elderly-onset group, the initial site of arthritis was commonly observed in the first metatarsophalangeal joint. The proportion of the first attack with the upper limb joint was higher in old age group than in young and middle age group( P<0.05). Renal underexcretion type was the main subtype in the elderly group, and the proportion of overproduction type was higher than that of the young and middle-aged group( P<0.05). The logistic regression analysis showed that age, urea nitrogen, disease duration≥10 years and family history of gout were risk factors for tophi in elderly patients( P<0.05). Conclusion:The elderly-onset gout has unique clinical characteristics, characterized by a higher prevalence of tophi, a higher rate of complications. An initial site of arthritis commonly observed in the first metatarsophalangeal joint and the predominant type of uric acid excretion is renal excretion impairment. Early diagnosis and treatment, control of blood uric acid levels, smoking cessation and alcohol, regular exercise should be applied to prevent or delay the formation of tophi.

In this study, a polyethylene glycol and dodecaldehyde modified bovine serum albumin (PEG-DSA) was developed, and its feasibility as a new high-efficiency micellar carrier for dasatinib (DAS) was explored.Circular dichroism, 1H NMR, elemental analysis, FT-IR and other methods were used to characterize the material structure and the single factor method was used to optimize the process of PEG-DSA/DAS micelles and non-PEGylated control micelles DSA/DAS.The results indicated that the optimal formulation was obtained with a mass ratio of 4∶1 between PEG-DSA and DAS, with average particle size of (37.21 ± 0.21) nm, polydispersion index (PDI) of (0.24 ± 0.04), Zeta potential of ? (15.68 ± 0.19) mV, drug loading (DL) capacity of (10.22 ± 0.34) %, and encapsulation efficiency (EE) of (42.73 ± 1.15) %. Compared with the currently reported nano-formulations of DAS, the drug loading of PEG-DSA/DAS micellar formulations was significantly increased with potential for further development.

Objective:To analyze the influencing factors of gout patients and explore whether there is an interaction between serum uric acid and diastolic blood pressure affecting the onset of tophi.Methods:A total of 4 798 gout patients were retrospective selected in the outpatient Department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from September 2016 to May 2020. It was divided into tophi group and non-tophi group to compare the differences in indicators. A logistic regression model was used to analyze the influencing factors of tophi, and an interaction model was constructed to analyze the interactions.Results:Multivariate logistic regression analysis showed significant associations between age, diastolic blood pressure, alcohol consumption history, gout family history, blood uric acid, urea nitrogen, and creatinine clearance and tophi formation. The results of blood uric acid-related interaction analysis showed a significant interaction between blood uric acid and diastolic blood pressure( Pinteraction=0.014), and the risk of developing tophi in low diastolic blood pressure and high diastolic blood pressure group increased by 34.4%( OR=1.344, 95% CI 1.105-1.635, P=0.003) and 95.4%( OR=1.954, 95% CI 1.558-2.450, P<0.001) in the high blood uric acid group compared with the low blood uric acid group. The results of diastolic blood pressure and blood uric acid subgroup analysis showed that there was no statistical difference in the risk of developing tophi in people with low uric acid levels( P=0.238), but in people with high uric acid levels, the risk of developing tophi was 67%( OR=1.670, 95% CI 1.379-2.022, P<0.001) higher than that in the low uric acid group. Conclusion:Age, diastolic blood pressure, combined alcohol consumption history and gout family history, blood uric acid, renal function are related to the occurrence of tophi. High uric acid and high diastolic blood pressure have interaction on the occurrence of tophi. Attention and proactive intervention shall be applied to this group of patients.

Objective: To investigate the clinical effect of percutaneous transhepatic bile duct drainage guided by ultrasound. Methods: From June 2016 to June 2018, 100 patients with obstructive jaundice in Lishui Central Hospital were treated with ultrasound-guided percutaneous transhepatic bile duct drainage.The success rate and postoperative complications of the patients were analyzed. Results: Among 100 cases, 98 cases were successful, 2 cases failed, and the failure rate was 2%.The success rate of one-time catheterization in 0.5-2.0 cm patients with intrahepatic bile duct diameter(98.91%) was significantly higher than that in intrahepatic bile duct diameter 0.3-0.4 cm patients(87.50%), compared with two different diameter puncture catheterization, the difference was statistically significant(χ²=12.369, P<0.05). All 98 cases with successful puncture were followed up after operation (P<0.05), and there was no statistically significant difference between the two groups(P<0.05). The drainage tube was removed in 2 cases, bile duct infection was found in 2 cases, the remaining patients were unobstructed, and there were no obvious complications. Conclusion Ultrasound-guided percutaneous transhepatic catheterization and drainage for the treatment of obstructive jaundice caused by malignant tumor is simple, reliable, safe and effective, and has a certain clinical value.It is worthy of popularizing and application.

Objective: To evaluate the effect of spermine oxidase (SMO) inhibitor SI-4650 on the proliferation of a human malignant melanoma cell line A375, and to explore its molecular mechanism. Methods: Some cultured A375 cells were divided into 6 groups to be treated with SI-4650 at concentrations of 0, 10, 20, 40, 80 and 160 μmol/L respectively for 24, 48 and 72 hours, and methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate changes in cellular proliferative activity. According to the cellular proliferative activity, 3 concentrations (0, 40, 80 μmol/L) were screened out. Some A375 cells were divided into 3 groups to be treated with 0 (control group) , 40 and 80 μmol/L SI-4650 for 48 hours. Chemiluminescence assay was conducted to detect the SMO activity in A375 cells, high-performance liquid chromatography (HPLC) analysis to determine the polyamine content in A375 cells, flow cytometry to analyze the cell cycle and detect the apoptosis, and Western blot analysis to determine the protein expression of apoptotic marker proteins Bax and c-PARP, inhibitor of apoptosis protein Bcl-2, and autophagy marker proteins Beclin-1 and LC3-Ⅱ. Statistical analysis was carried out by using one-way analysis of variance for comparison of means among several groups, and by using Student-Newman-Keuls (SNK) -q test for multiple comparisons. Results: MTT assay showed that there was a significant difference in the proliferative activity of A375 cells after the treatment with different concentrations of SI-4650 for different durations (F = 977.23, 5.16 respectively, both P < 0.001) . Significant differences were observed in the SMO activity in A375 cells (F = 242.58, P < 0.001) , spermine and the total polyamine content (F = 338.02, 2 931.07 respectively, both P < 0.001) , proportion of S-phase cells (F = 31.66, P < 0.001) , proportion of apoptotic cells (F = 100.68, P < 0.001) , expression of apoptosis-related proteins Bax, c-PARP and Bcl-2 (F = 35.51, 730.11, 27.54 respectively, all P < 0.001) , and expression of autophagy marker proteins Beclin-1 and LC3-Ⅱ (F = 35.87, 425.04 respectively, P < 0.001) among the control group, 40- and 80-μmol/L SI-4650 groups. Compared with the control group, the 40- and 80-μmol/L SI-4650 groups showed significantly lower SMO activity (luminous intensity: 61 432.85 ± 2 620.92, 43 337.35 ± 1 221.25 respectively, both P < 0.05) , lower spermine (1.97 ± 0.007, 1.88 ± 0.006 respectively, both P < 0.05) and total polyamine content (3.18 ± 0.03, 2.81 ± 0.01 respectively, both P < 0.05) , higher proportions of S-phase cells (27.61% ± 2.05%, 31.58% ± 1.45% respectively, both P < 0.05) and apoptotic cells (27.61% ± 2.05%, 31.58% ± 1.45% respectively, both P < 0.05) , higher expression of apoptotic marker proteins Bax (0.83 ± 0.12, 1.18 ± 0.16 respectively, both P < 0.05) and c-PARP (0.32 ± 0.002, 0.79 ± 0.035 respectively, both P < 0.05) and autophagy marker proteins Beclin-1 (1.00 ± 0.007, 1.14 ± 0.003 respectively, both P < 0.05) and LC3-Ⅱ (0.31 ± 0.001, 0.98 ± 0.003 respectively, both P < 0.05) , and lower expression of inhibitor of apoptosis protein Bcl-2 (0.65 ± 0.09, 0.12 ± 0.002 respectively, both P < 0.05) . Conclusion SI-4650 can inhibit the proliferation of A375 cells, likely by interfering with polyamine metabolism and inducing cell cycle arrest, apoptosis and autophagy.

Objective To evaluate the value of ultrasound elastography combined with serum markers in the assessment of chronic hepatitis B fibrosis. Methods 100 patients with chronic hepatitis B liver fibrosis who were diagnosed and treated in our hospital from January 2015 to December 2017 were randomly selected. All patients were given hepatic histopathological tests, serological tests, and ultrasound elastography. The liver biopsy results were taken as the final diagnosis results. The accuracy of classification of hepatitis B fibrosis by the combined diagnosis of ultrasound elastography and serum markers was observed. Results The total accuracy of the combined examination was 91.00％ with histological examination as the final results. There was no statistically significant difference between the results of the two examinations (P>0.05). The ultrasound elastography score and FIB4 score in the patients with hepatitis B fibrosis grade F1-F4 were increased along with the increase of grade, and there was statistically significant difference (P<0.05). Conclusion Ultrasound elastography combined with serum markers has an important clinical value in the assessment of the degree of chronic hepatitis B fibrosis. It is non-invasive, easy to operate and highly accurate, and can provide a reliable basis for disease diagnosis and staging.