1.Optineurin restrains CCR7 degradation to guide type II collagen-stimulated dendritic cell migration in rheumatoid arthritis.
Wenxiang HONG ; Hongbo MA ; Zhaoxu YANG ; Jiaying WANG ; Bowen PENG ; Longling WANG ; Yiwen DU ; Lijun YANG ; Lijiang ZHANG ; Zhibin LI ; Han HUANG ; Difeng ZHU ; Bo YANG ; Qiaojun HE ; Jiajia WANG ; Qinjie WENG
Acta Pharmaceutica Sinica B 2025;15(3):1626-1642
Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.
2.Influencing factors for meropenem-related liver injury and their predictive value
Yan HE ; Hongqin KE ; Hongliang LI ; Jianyong ZHU ; Lijun ZHAO ; Huibin YU
Journal of Clinical Hepatology 2025;41(3):506-512
ObjectiveTo analyze the factors influencing meropenem-related liver injury (MRLI) and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted, and the Chinese Hospital Pharmacovigilance System (CHPS) was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group (n=62) and control group (n=1 563) based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups, while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established, and the predictive value of these factors was assessed using the receiver operating characteristic (ROC) curve. ResultsThe results of univariate analysis indicated that the rates of male patients, hypoproteinemia, shock, intensive care unit (ICU) admissions, sepsis, and liver, gallbladder, and cardiovascular diseases, the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), creatinine (CREA), and procalcitonin (PCT), and the number of hospitalization days were significantly higher in the case group than in the control group (P<0.05), and that the platelet levels in the case group were significantly lower than those in the control group (P<0.05). The multivariate Logistic regression analysis showed that male sex (odds ratio [OR]=2.080, 95% confidence interval [CI]: 1.050 — 4.123, P=0.036), admission to the ICU (OR=8.207, 95%CI: 4.094 — 16.453, P<0.001), comorbidity with gallbladder disease (OR=8.240, 95%CI: 3.605 — 18.832, P<0.001), ALP (OR=1.012, 95%CI: 1.004 — 1.019, P=0.004), GGT (OR=1.010, 95%CI: 1.005 — 1.015, P<0.001), and PLT (OR=0.997, 95%CI: 0.994 — 0.999, P=0.020) were the influential factors for MRLI. The areas under the ROC curve of ALP, GGT, and PLT were 0.589, 0.637, and 0.595, respectively, and the AUC of them combined was 0.837. ConclusionMale sex, ICU admission, comorbidity with gallbladder disease, increased ALP, increased GGT, and decreased PLT were influencing factors for MRLI, and a combination of factors has a better predictive value for the occurrence of MRLI.
3.Effects of ascites grading and the application of non-selective beta-blockers on the 1-year prognosis of acute-on-chronic liver failure
Wanshu LIU ; Lijun SHEN ; Xi HE ; Hua TIAN ; Qinghui ZHAI ; Dongze LI ; Shaojie XIN ; Shaoli YOU
Chinese Journal of Hepatology 2025;33(1):57-62
Objective:To investigate the effects of ascites grading and the application of non-selective beta-blockers (NSBBs) on the 1-year prognosis of acute-on-chronic liver failure (ACLF).Methods:1 386 ascitic cases with ACLF were graded and followed up for one year. The 1-year prognostic effect of ascites grade and NSBBs was analyzed on ACLF by the Kaplan Meier Log-rank test, Cox stepwise regression, and multivariate regression.The t-test, Mann-Whitney U, or Kruskal-Wallis test were used for intergroup comparison of measurement data. The χ2 test was used for intergroup comparison of numerical data. Results:The incidence rate of ascites at admission was 77.56% in 1 386 ACLF cases. The Log-rank (Mantel-Cox) of the 1-year survival curve test for 1 386 ACLF patients with ascites grade was 21.384, P<0.01. Multivariate regression and Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin activity (PTA), urea, MELD-Na score, and the use of NSBBs were closely related to the 1-year prognosis of ACLF. The log rank (Mantel-Cox) of NSBBs treatment in the grade 2/3 ascites group was 6.113, P=0.013, and the difference was statistically significant, suggesting that NSBBs treatment can help improve the 1-year survival rate in ACLF patients with grade 2 and 3 ascites. Conclusions:Ascites grading and the use of NSBBs affect the prognostic factor of ACLF at one year. NSBBs may be beneficial for the long-term prognosis of ACLF, and treatment can be continued in patients who have already received NSBBs prior to the onset of ACLF.
4.Progress of research on artificial intelligence technology in radiographic diagnosis of periodontitis
Mengke HE ; Jiawei LU ; Hui DUAN ; Lijun LUO
STOMATOLOGY 2025;45(6):460-464
Early diagnosis and therapy of the periodontitis are crucial for the prognosis.Although the latest international classification of periodontal diseases and peri-implant diseases in 2018 can improve the accuracy of diagnosis and reduce the misdiagnosis and missed diagnoses,it is extremely complex in practice.At present,the application of artificial intelligence in the field of dentistry is becoming more and more extensive,which has good performance in detecting tooth types and periodontal bone loss.The use of artificial intelli-gence to detect periodontal lesions and calculate periodontitis staging and grading,and guide clinical personalized and precise treatment has become a hot topic of current research.This paper summarizes and analyzes the current research status of artificial intelligence in periodontal radiographic diagnosis,and provides ideas for further research.
5.Clinical significance of cytokeratin 19 fragment in anti-melanoma differentiation-associated protein-5 antibody positive patients
Wenjuan GUAN ; Lijun LIU ; Panpan ZHANG ; Cong WANG ; Xin ZHANG ; Lijuan ZHANG ; Lishuai HAN ; Yinli ZHANG ; Yujie HE ; Shengyun LIU
Chinese Journal of Rheumatology 2025;29(3):189-196
Objective:To investigate the clinical significance of elevated cytokeratin 19 fragment (CYFRA21-1) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:142 consecutive cases with newly onset anti-MDA5(+) (MADEDM)-DM admitted to the first affiliated hospital of Zhengzhou University from June 2018 to October 2021 were enrolled. They were divided into two groups, the low serum CYFRA21-1 group (CYFRA21-1≤4 ng/ml) and the high serum CYFRA21-1 group (CYFRA21-1>4 ng/ml). The clinical manifestations, laboratory tests results, imaging examinations treatment and outcome were collected for statistical analysis. Enumeration data were expressed as the number of cases and percentage (%). Normally distributed parameters were tested by t-test. Parameters with skewed distribution were tested by Mann-Whitney Wilcoxon analysis. Categorical variables were compared by the Chi-square test or Fisher′s exact test. Risk factor analysis was performed using Logistic regression. Cumulative survivals were described by Kaplan-Meier curves. Results:The age of onset in the high CYFRA21-1 group [(56±9)years vs. (50±10) years, t=-3.50, P=0.001] was higher than that in the low CYFRA21-1 group. Fever [63.3% (38/60) vs. 40.2% (33/82), χ2=7.39, P=0.007] was more common in the high CYFRA21-1 group, and arthritis [41.7% (25/60) vs. 69.5%(57/82), χ2=11.01, P=0.001] was less common. Myalgia, myasthenia, rashes, Raynaud′s phenomenon and skin ulcers had no significant difference between the two groups. The WBC count [5.2(4.1, 6.9)×10 9/L vs. 4.3(3.2, 6.2)×10 9/L, Z=-2.57, P=0.010], neutrophil count [4.0(2.9, 5.5)×10 9/L vs. 2.9(2.1, 4.5)×10 9/L, Z=-3.25, P=0.001] and neutrophil/lymphocyte ratio [5.75(3.50, 9.20) vs. 3.55(2.64, 5.41), Z=-3.77, P<0.001] in high CYFRA21-1 group were significantly higher than those in low CYFRA21-1 group. At the same time, LDH [384(302, 519)U/L vs. 318(260, 405)U/L, Z=-2.98, P=0.003], ferritin [1 204(677, 2 039)ng/ml vs. 570(229, 846)ng/ml, Z=-4.78, P<0.001], KL-6 [995(658, 1 491)U/ml vs. 750(563, 1 197)U/ml, Z=-2.49, P=0.013], ESR [36(22, 61)mm/1 h vs. 28(15, 46)mm/1 h, Z=-2.18, P=0.029] and CRP [9.2(4.7, 31.5)mg/L vs. 3.1(1.1, 11.6)mg/L, Z=-3.53, P<0.001] were significantly increased in the high level of CYFRA21-1 group, while serum albumin[(32±5)g/L vs. (35±5)g/L, t=3.92, P<0.001] was significantly decreased. There was no significant difference in the titers of serum anti-MDA5 antibodies between the two groups. The positive rate of anti-RO52 antibody [44(74.6%) vs. 44(53.7%), χ2=6.40, P=0.011] in high CYFRA21-1 group was higher than that in low CYFRA21-1 group. The ground glass opacity (GGO) score [1.75(1.33, 2.42) vs. 1.09(0.67, 1.67), Z=-4.60, P<0.001] based on high resolution CT (HRCT) was also significantly increased in the CYFRA21-1 high level group. Compared with the low CYFRA21-1 group, the high CYFRA21-1 group had a higher probability of RP-ILD [48.3%(29/60) vs. 23.2%(19/82), χ2=9.80, P=0.002] and a higher 6-month mortality rate[48.3%(29/60) vs.13.4%(11/82), χ2=19.70, P<0.001]. Logistic regression analysis showed that age ≥53 years old [ OR(95% CI)=5.197(1.781, 15.165), P=0.003], duration < 2 months [ OR(95% CI)=3.314 (1.058, 10.378), P=0.040], NE/LYMP >5 [ OR(95% CI)=3.443(1.120, 10.586), P=0.031], CRP>5 mg/L[ OR(95% CI)=6.271(1.749, 22.480), P=0.005], CA125>14 U/ml[ OR(95% CI)=7.500 (2.409, 23.345), P=0.001] and CYFRA21-1>4 ng/ml[ OR(95% CI)=3.665(1.258, 10.676), P=0.017] were independent risk factors for death within 6 months in MDA5-DM patients. Kaplan-Meier survival curve showed that the survival rate of the high CYFRA21-1 group was significantly lower than that of the low CYFRA21-1 group( P<0.001). Conclusion:Elevated CYFRA21-1 is an independent risk factor for early mortality in MDA5-DM patients and can serve as a novel serological marker for risk stratification in these patients.
6.Application of IFN-induced protein 44-like gene methylation detection by methylation sensitive-high resolution melting in the diagnosis of systemic lupus erythematosus
Qian CHEN ; Dong′e TANG ; Yue MENG ; Lijun ZHANG ; Song HE ; Zihua YANG ; Xiaoping HONG ; Yang CUI ; Tieying HOU ; Yong DAI ; Yongzhe LI
Chinese Journal of Rheumatology 2025;29(8):639-644
Objective:To evaluate the clinical efficacy of methylation sensitive-high resolution melting curve (MS-HRM) detection of IFN-induced protein 44-like (IFI44L) gene methylation in the diagnosis of systemic lupus erythematosus (SLE), as well as the relationship between IFI44L gene markers and the early onset of SLE.Methods:From February 2020 to September 2022, the MS-HRM was used to detect the methylation level of the IFI44L gene in peripheral blood mononuclear cells of 602 SLE patients and 524 other autoimmune disease patients (excluding SLE) from Beijing Peking Union Medical College Hospital, Guangdong Provincial People′s Hospital, and Shenzhen People′s Hospital, totaling 1 126 patients. Compared with the 2012 SLICC criteria, the suspected cases were followed up for 6 months until the onset and clinical diagnosis of SLE were confirmed. The measurement data of normal distribution were expressed as mean±SD, and the consistency analysis was performed using the Kappa consistency test. The clinical diagnostic efficacy indicators were calculated using the receiver operating characteristic (ROC) curve. Results:RR (95% CI) of early suspected cases was 17.06 (9.43, 30.82). The results of IFI44L gene methylation level were in good agreement with the 2012 SLICC criteria, and the sensitivity, specificity and total coincidence rate were 90.53%, 92.56% and 91.47%, respectively. The Kappa value (95% CI) was 0.829(0.796, 0.862) ( P<0.001). The diagnostic efficiency of IFI44L gene methylation level ( Kappa value 0.817) was superior to anti-nuclear antibody, anti-SM antibody and anti-dsDNA antibody ( Kappa value 0.418, 0.216 and 0.440, respectively). The Kappa values (95% CI) of methylation between MS-HRM and pyrosequencing was 0.861(0.806, 0.916), P<0.001. Conclusion:The hypomethylation of IFI44L gene methylation level detected by MS-HRM is closely related to the occurrence and development of SLE, and its diagnostic performance is better than that of three autoantibodies in SLE diagnosis, which can be used for the early diagnosis of SLE.
7.Analysis on the effect of trend analysis for safe risk in management and control for infection of medical device
Gezhi ZHEN ; Jiejie LI ; Lijun QIN ; Xingxing YANG ; Yingli HE
China Medical Equipment 2025;22(9):109-113
Objective:To analyze application effect of trend analysis for safe risk in management and control for infection of medical devices,so as to optimize the management path for medical devices.Methods:Focusing on the main factors affecting the safety risks of medical devices,the least squares method of linear regression was applied for trend analysis to optimize the device management path and strengthen management.A total of 70 clinically used medical devices in the First Affiliated Hospital of Xi'an Jiaotong University from January to December 2024 were selected.These devices were managed using two models:the conventional management model and the trend analysis management model,with 35 devices under each model.The infection risk rate of medical equipment and the equipment management quality score were compared between the two management models.Additionally,160 patients managed under the two models(80 patients per model)were included to compare the patient infection rate.Results:In the 450 diagnostic and treated records of sampling inspection and consultation for medical devices from treatment equipment,diagnosis equipment,auxiliary imaging equipment and surgical equipment,the rate of infectious risk of using management mode with trend analysis were respectively 1.78%(8/450),2.22%(10/450),2.22%(10/450)and 2.44%(11/450),all of which were significantly lower than these of using conventional management mode,and the differences were significant(x2=9.904,8.902,10.465,10.770,P<0.05).The scores of cleaning quality,the quality of disinfection and sterilization,the quality of distribution,and the retrieving quality of the management mode with trend analysis for medical devices were significantly higher than those of the conventional management mode,and the differences were statistically significant(t=15.889,13.172,15.872,17.399,P<0.05).The infection rate of patients in the trend analysis management mode was 6.25%(5/80),which was significantly lower than that in the conventional management mode[22.50(18/80)],and the difference was statistically significant(x2=11.006,P<0.05).Conclusion:The trend analysis for safe risk can analyze the risk factors in use and operation for medical devices from multiple perspectives,and mining main factors and conduct intervention for the devices,and reduce the incidence of safe risks of medical devices and the patients'infection rate,and improve the quality of clinical services.
8.Analysis on the Regional Differences and Equity of High Quality Health Resource Allocation in Primary Healthcare Institutions
Hongbo YU ; Xiaodan HE ; Shuyun ZHANG ; Lijun GAO
Chinese Health Economics 2025;44(2):59-63
Objective:To analyze the regional differences and equity of the high-quality health resource allocation in primary healthcare institutions,and provide decision-making references for improving the equity of high-quality health resource allocation in primary healthcare institutions among provinces in China.Methods:The entropy weight method is used to determine the weights of indicators.Breakpoint method,Gini coefficient and grey correlation method are applied to conduct the classification,equity analysis and influencing factor analysis on the allocation levels of 31 provinces.Results:The Gini coefficients of the supply-demand ratio index in 2011,2016 and 2021 were 0.34,0.33 and 0.34,respectively.Population density,education level,education investment level,public service level,per capita GDP,regional income level and average altitude were the key influencing factors.Conclusion:There are significant differences in the high-quality health resource allocation among community-level medical and health care institutions in different provinces of China,and there are certain issues with equity.It is necessary to comprehensively consider multiple influencing factors to promote the balanced development of high-quality health resource allocation in community-level medical and health care institutions in China.
9.Comparison of lipid metabolism and its relationship with iodine nutritional status in patients with papillary thyroid carcinoma and benign thyroid nodules
Yashu ZHANG ; Yuqian ZHAI ; Yan HE ; Yu LI ; Lijun FAN
Chinese Journal of Endemiology 2025;44(7):517-524
Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.
10.Expert recommendations on the development content and functional specifications for the public vaccination service platform
Qi ZHU ; Qianli MA ; Ruili XIE ; Lijun LIU ; Lei LI ; Lin CHEN ; Yong HUANG ; Ronghai TAN ; Xiaoru CAI ; Jianfeng HE ; Wenzhou YU
Chinese Journal of Preventive Medicine 2025;59(9):1448-1453
To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

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