OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

Objective To explore the effects of long non-coding RNA(lncRNA)HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease(NAFLD).Methods Wild-type C57BL/6(WT)mice and myeloid cell-specific HEM2M knock-in(MYKI)mice were fed normal(ND)or high-fat diet(HFD)for 12 weeks.After intraperitoneal glucose tolerance and insulin tolerance tests,the mice were euthanized for detection of liver function indicators in the serum and liver tissue.HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies,and the levels of IL-6,IL-1β,and TNF-α in the liver tissues were determined with ELISA.The mRNA expressions of HEM2M and the markers of M1 macrophages(TNF-α,iNOS,and IL-6)and M2 macrophages(Arg-1,YM-1,and IL-10)were detected using qRT-PCR,and the protein expressions of P-AKT,T-AKT,NLRC4,caspase-1 and GSDMD were assayed using immunoblotting.Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay.Results Compared with HFD-fed WT mice,MYKI mice with HFD feeding showed milder liver function damage(P<0.01),alleviated hepatic steatosis,and reduced liver macrophage infiltration,glucose tolerance impairment and insulin resistance(P<0.01).The levels of IL-6,IL-1β,and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased(P<0.01)and those of M2 type markers increased(P<0.01)in the liver tissues of HFD-fed MYKI mice,which also showed reduced NLRC4 inflammasome activity,caspase-1 activation,and GSDMD-N protein expression compared with their WT counterparts(P<0.05).Conclusion Overexpression of HEM2M reduces the production of hepatic inflammatory factors,improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation,which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.

Objective To explore the effects of long non-coding RNA(lncRNA)HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease(NAFLD).Methods Wild-type C57BL/6(WT)mice and myeloid cell-specific HEM2M knock-in(MYKI)mice were fed normal(ND)or high-fat diet(HFD)for 12 weeks.After intraperitoneal glucose tolerance and insulin tolerance tests,the mice were euthanized for detection of liver function indicators in the serum and liver tissue.HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies,and the levels of IL-6,IL-1β,and TNF-α in the liver tissues were determined with ELISA.The mRNA expressions of HEM2M and the markers of M1 macrophages(TNF-α,iNOS,and IL-6)and M2 macrophages(Arg-1,YM-1,and IL-10)were detected using qRT-PCR,and the protein expressions of P-AKT,T-AKT,NLRC4,caspase-1 and GSDMD were assayed using immunoblotting.Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay.Results Compared with HFD-fed WT mice,MYKI mice with HFD feeding showed milder liver function damage(P<0.01),alleviated hepatic steatosis,and reduced liver macrophage infiltration,glucose tolerance impairment and insulin resistance(P<0.01).The levels of IL-6,IL-1β,and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased(P<0.01)and those of M2 type markers increased(P<0.01)in the liver tissues of HFD-fed MYKI mice,which also showed reduced NLRC4 inflammasome activity,caspase-1 activation,and GSDMD-N protein expression compared with their WT counterparts(P<0.05).Conclusion Overexpression of HEM2M reduces the production of hepatic inflammatory factors,improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation,which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.

OBJECTIVE To explore the clinical characteristic manifestation of Rosai-Dorfman disease(RDD)involving the nasal cavity and paranasal sinuses.METHODS The clinical data of 16 patients with RDD involving the nasal cavity and paranasal sinuses who received treatment in Department of Rhinology of Beijing Tongren Hospital Affiliated to Capital Medical University from December 2016 to December 2023,were retrospective analyzed.RESULTS The male to female ratio was 1:3,with an average age of 47.4 years and an average disease duration of 22.34 months.There were 14,3,5,6 and 1 patients who complained of nasal congestion,dry nose,decreased sense of smell,head and face pain,and bulging/diplopia,respectively.There were 9 patients who had external nasal swelling.There were 14 RDD patients who were involved at least the nasal septum,12 patients who were simply affected in the nasal cavity,and 3 cases who involved the paranasal sinuses.There was 1 case belonged to a mixed type of RDD.There were 8 of 10 cases who were misdiagnosed or missed due to intraoperative rapid freezing.Endoscopic examination showed bilateral bulging in 9 patients'nasal septum,and nodular or granular new growth on 7 patients'nasal floor and inferior turbinate surface.Sinus CT found 9 patients'the nasal septum area showed a circular uniform soft tissue shadow or symmetrical soft tissue thickening shadow,5 patients'nasal floor and inferior turbinate showed obvious soft tissue thickening shadow.CONCLUSION RDD involving the nasal cavity and paranasal sinuses has certain typical features in external nasal manifestations,endoscopic and imaging examinations.Comprehensive judgment can help improve the feasibility of clinical diagnosis of RDD.

OBJECTIVE To predict biomarkers of type 2 inflammation in chronic rhinosinusitis with nasal polyps(CRSwNP)by employing peripheral blood indicators.METHODS CRSwNP patients admitted to the Rhinology Department of Beijing Tongren Hospital from June 2020 to May 2022 were enrolled and their basic clinical data were collected.The blood percentage of eosinophils(Eos%),Eos count,periostin and total IgE,as well as mucosal interleukin-5(IL-5)and Staphylococcus aureus enterotoxin-immunoglobulin E(SE-IgE)were tested.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each blood indicator for positive mucosal expression of IL-5/SE-IgE.The logistic regression was employed to screen multiple blood indicators with predictive value for positive mucosal expression of IL-5/SE-IgE in order to construct a nomogram model.RESULTS The proportion of asthma,blood Eos%,periostin and total IgE in CRSwNP patients showed statistical differences between IL-5/SE-IgE positive and negative subgroups.ROC univariate analysis demonstrated that blood Eos%,Eos count,periostin and total IgE could predict mucosal IL-5 positivity with AUC ranging from 0.655 to 0.784,and mucosal SE-IgE positivity with AUC ranging from 0.721-0.802.The logistic regression confirmed that blood Eos%and total IgE,as well as blood periostin and total IgE were independent predictors for mucosal IL-5 and SE-IgE positivity,respectively.The nomogram models were constructed for predicting IL-5/SE-IgE positivity in CRSwNP mucosa,with consistency incides(C-index)of 0.804 and 0.81,indicating good predictive accuracy.CONCLUSION The nomograms constructed based on blood Eos%and total IgE,as well as blood periostin and total IgE,could have good predictive value for the positive mucosal expression of IL-5 and SE-IgE in the CRSwNP,which help to predict the severity of endotype and phenotype of CRSwNP.

Objective To investigate the positive rate of urine JC polyomavirus(JCV)and urine BK polyomavirus(BKV)in HIV patients,and to evaluate the relationship between urine JCV positive and renal function and lymphocyte count during long-term follow-up.Methods A total of 180 HIV-1 positive patients were enrolled in the Second Department of Infection,Xixi Hospital of Hangzhou,urine samples were collected for JCV and BKV detection.Renal function and CD4+cell count were collected at baseline before taking an-tiretroviral therapy(ART)and at 1,2,3,4,and 5 years of follow-up.Results The detection rates of JCV and BKV in urine of 180 HIV-1 positive patients were 25.55％(46/180)and 1.67％(3/180),respectively.Before ART,the total number of lymphocytes in urine JCV positive group was 1699.62±790.44/μl,which was lower than that in urine JCV negative group(2113.59±832.73/μl),and the difference was statistically significant(P=0.022).During ART initiation follow-up,serum creatinine levels in urine JCV posi-tive group were lower than those in urine JCV negative group.At the second year of follow-up,the serum creatinine level in urine JCV positive group was 70.00(64.00,77.00)μmol/L,which was lower than that in urine JCV negative group[76.00(67.00,85.00)μmol/L],and the difference was statistically significant(P=0.023).At the second year of follow-up,the glomerular filtration rate(GFR)of the urine JCV positive group was 118.00(106.25,133.75)ml/min,which was higher than that of urine JCV negative group[113.00(97.00,128.00)ml/min],and the difference was statistically significant(P=0.045).At the fourth year of follow-up,ser-um creatinine level in urine JCV positive group was 70.34±14.98μmol/L,which was lower than that in urine JCV negative group(76.6±14.45 μmol/L),and the difference was statistically significant(P=0.023).Conclusion The detection rates of JCV and BKV in urine of HIV-1 positive patients are negatively correlated with total lymphocyte levels.Urine JCV positive has a protective effect on the kidney,and urine JCV negative can be used as an early indicator of renal damage in HIV patients.

Chondroitin sulfate sodium is a sulphated glycosaminoglycan composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-galactosamine,prepared from the cartilage tissue of land or marine animal by a specific extraction and purification process.Chondroitin sulfate sodium is considered to have anti-osteoarthritis effect and many other potential physiological activities.It has broad application prospects and development space in the fields of health food,cosmetics,and drugs.This paper reviews the preparation process of chondroitin sulfate sodium,development and problems of microbial synthesis technology and the research status of anti-osteoarthritis activity based on cells models,animal models and clinical randomized controlled trials(RCT).The limitations of current research are analyzed and corresponding strategies are proposed to provide reference for further standardization and development of chondroitin sulfate sodium.

Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

Purpose To explore the value of a prediction model based on diffusion weighted imaging(DWI)deep learning features in endometrial cancer microsatellite instability status assessment.Materials and Methods DWI data of 32 microsatellite instability and 55 microsatellite stability endometrial cancer patients were analysed from June 2020 to April 2023 in Xinxiang Central Hospital,retrospectively.Apparent diffusion coefficient(ADC)values of the primary lesions were measured,and deep learning features and imaging histological features of the primary lesions were extracted using multilayer convolutional neural networks and PyRadiomics,respectively.The least absolute shrinkage and selection operator and random forest were used for feature screening and model building,respectively.The area under the receiver operating characteristic curve(AUC)and net reclassification improvement were used to evaluate model performance.Bootstrap based on 1 000 resamples was used for internal validation of the model.Results For the deep learning model,a total of 6 features were included,the 7th,57th,77th,82nd,97th and 108th features,with an AUC of 0.905(95％CI 0.823-0.957);for the radiomics model,a total of 6 features were included,1 neighborhood grey level difference matrix,4 grey level region size matrices and 1 grey level tour length matrix feature,with an AUC was 0.844(95％CI 0.751-0.913);for ADC values,the microsatellite instability group had smaller ADC values than the microsatellite stability group(t=-4.123,P＜0.001),with an AUC of 0.810(95％CI 0.712-0.886).Compared with the radiomics model and ADC values,the deep learning model showed improved risk prediction,with net reclassification improvements of 0.856 and 0.486(P＜0.01,P=0.024),respectively.In Bootstrap-based internal validation,the deep learning model also demonstrated higher performance than the radiomics model,with AUCs of 0.897(95％CI0.889-0.905)and 0.829(95％CI0.812-0.839),respectively.Conclusion A prediction model based on deep learning features of DWI images can provide a better assessment of microsatellite instability status in endometrial cancer patients than radiomics model and ADC values.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.