Objective:Treat-to-target strategies for psoriatic arthritis (PsA) have been proposed for several years, however, the status of target and goal achievement in China is unknown. Therefore, we aimed to investigate the target achievement of PsA patients, and differences of treatment goals were further analyzed.Methods:A total of 360 PsA patients from Peking University First Hospital PsA patient cohort (PKUPsA) between January 2016 and March 2024 were included. We retrospectively analyzed the disease activity of patients at their enrollment. Minimal disease activity (MDA), disease activity index for PsA (DAPSA), clinical DAPSA (cDAPSA) and disease activity score based on 28 joint counts (DAS28) were evaluated. Interclass correlation coefficient (ICC) was used to test the consistency of all these assessments.Results:Three hundred and sixty patients were included in this study, with 149 females (41.4%), median age 47 (36, 57) years and duration of PsA for 2.0(1.0, 6.8) years. 129 (35.8%) patients reported family history of PsO. The most common comorbidities were hyperlipidemia (101, 28.1%) and hypertension (78, 21.7%). There were 217 (60.3%), 75 (20.8%) and 18 (5.0%) patients treated with conventional synthetic DMARDs, biologics and JAK inhibitors respectively. Forty-nine (13.6%) patients ever received intra-articular injection of glucocorticoid. Based on the different definitions, the rates of target achievement were 33.9% (MDA), 56.1% (DAPSA), 60.8% (DAS28-ESR), 63.9% (DAS28-CRP) and 64.2% (cDAPSA). The main limiting factors for MDA attainment among those who had achieved DAPSA or DAS-defined targets were pain VAS, Psoriasis Area and Severity Index (PASI), tender/swollen joint count, patient global assessment, HAQ, and number of enthesitis, based on leeds Enthesitis Index(LEI). The ICCs of these evaluation methods were 0.489~0.819 ( P<0.001). The consistency was the best between DAPSA and cDAPSA, medium between DAS28-CRP and DAS28-ESR, and worst between MDA and DAS28-CRP. Moreover, DAPSA was more consistent with DAS28 than cDASPA. MDA showed moderate consistency with all other assessments. Conclusion:33.9%~64.2% of PsA patients achieved targets based on different definitions. MDA was the most stringent target, while cDAPSA was the most loose one. In general, MDA was not well consistent with other assessments.

Objective:To explore the distribution variation of ultrasound-detected inflammatory lesions with clinical signs in patients with psoriatic arthritis (PsA).Methods:This was based on the Peking University First Hospital Psoriatic Arthritis (PKUPsA) cohort. Patients enrolled from January 2019 to June 2024 were inchuded, patients with complete data of physical examination and ultrasonographic evaluations of 62 joints in the hand and foot. The ultrasound-detected inflammatory lesions including synovitis, tenosynovitis, enthesitis, and soft tissue inflammation were compared with joint tenderness/swelling. The χ2 test was employed to analyze differences between groups. Results:A total of 7 440 joints in 120 PsA patients were included. Overall, the proportion of joints with clinical signs (tenderness or swelling) was higher than those with ultrasound-detected inflammatory lesions [9.14%(680/7 440) vs. 7.93%(590/7 440), χ2=1 245.928, P<0.001], with more tenderness joints than swelling joints [7.72%(574/7 440) vs. 6.14%(457/7 440), χ2=3 264.45, P<0.001]. Clinical signs were primarily observed in hand proximal interphalangeal (PIP), distal interphalangeal (DIP), wrist and ankle joints, mostly in DIP2 joints [19.58%(47/240)]. Ultrasound-detected inflammatory lesions were predominantly found in metatarsophalangeal (MTP), wrist, and ankle joints, mostly in MTP2 joints (18.75%, 45/240). Clinical signs were more prevalent than ultrasound-detected inflammatory lesions in hand PIP1-3, PIP5, DIP2, and DIP5 joints ( P<0.05), whereas more frequent ultrasound-detected inflammatory lesions than clinical tenderness/swelling were in MTP1-4 joints ( P<0.05). Among ultrasound-detected inflammatory lesions, synovitis in MTP2 joints (18.75%, 45/240), tenosynovitis in ankle joints (10.00%, 24/240), enthesitis in hand DIP2 joints (8.75%, 21/240), and soft tissue inflammation in MTP4 joints (2.50%, 6/240) most commonly observed. Dactylitis was more frequently observed in toes than in fingers, with the fourth toe most commonly affected(16.67%, 40/240). Ultrasound-detected inflammatory lesions were observed in 72.37%(55/240) of fingers/toes with clinical dactylitis, mainly presenting as synovitis, tenosynovitis, or combinations of these. Conclusion:PsA exhibits significant heterogeneity in the inflammatory lesions across different joints and lesion types. The discrepancies between clinical findings and ultrasonic inflammatory changes highlight the limitations of physical examination in fully capturing the pathological features of PsA. As a critical tool for PsA evaluation, ultrasonography offers distinct advantages in detecting subclinical inflammation and differentiating inflammatory from non-inflammatory lesions.

Objective:Treat-to-target strategies for psoriatic arthritis (PsA) have been proposed for several years, however, the status of target and goal achievement in China is unknown. Therefore, we aimed to investigate the target achievement of PsA patients, and differences of treatment goals were further analyzed.Methods:A total of 360 PsA patients from Peking University First Hospital PsA patient cohort (PKUPsA) between January 2016 and March 2024 were included. We retrospectively analyzed the disease activity of patients at their enrollment. Minimal disease activity (MDA), disease activity index for PsA (DAPSA), clinical DAPSA (cDAPSA) and disease activity score based on 28 joint counts (DAS28) were evaluated. Interclass correlation coefficient (ICC) was used to test the consistency of all these assessments.Results:Three hundred and sixty patients were included in this study, with 149 females (41.4%), median age 47 (36, 57) years and duration of PsA for 2.0(1.0, 6.8) years. 129 (35.8%) patients reported family history of PsO. The most common comorbidities were hyperlipidemia (101, 28.1%) and hypertension (78, 21.7%). There were 217 (60.3%), 75 (20.8%) and 18 (5.0%) patients treated with conventional synthetic DMARDs, biologics and JAK inhibitors respectively. Forty-nine (13.6%) patients ever received intra-articular injection of glucocorticoid. Based on the different definitions, the rates of target achievement were 33.9% (MDA), 56.1% (DAPSA), 60.8% (DAS28-ESR), 63.9% (DAS28-CRP) and 64.2% (cDAPSA). The main limiting factors for MDA attainment among those who had achieved DAPSA or DAS-defined targets were pain VAS, Psoriasis Area and Severity Index (PASI), tender/swollen joint count, patient global assessment, HAQ, and number of enthesitis, based on leeds Enthesitis Index(LEI). The ICCs of these evaluation methods were 0.489~0.819 ( P<0.001). The consistency was the best between DAPSA and cDAPSA, medium between DAS28-CRP and DAS28-ESR, and worst between MDA and DAS28-CRP. Moreover, DAPSA was more consistent with DAS28 than cDASPA. MDA showed moderate consistency with all other assessments. Conclusion:33.9%~64.2% of PsA patients achieved targets based on different definitions. MDA was the most stringent target, while cDAPSA was the most loose one. In general, MDA was not well consistent with other assessments.

Objective:To explore the distribution variation of ultrasound-detected inflammatory lesions with clinical signs in patients with psoriatic arthritis (PsA).Methods:This was based on the Peking University First Hospital Psoriatic Arthritis (PKUPsA) cohort. Patients enrolled from January 2019 to June 2024 were inchuded, patients with complete data of physical examination and ultrasonographic evaluations of 62 joints in the hand and foot. The ultrasound-detected inflammatory lesions including synovitis, tenosynovitis, enthesitis, and soft tissue inflammation were compared with joint tenderness/swelling. The χ2 test was employed to analyze differences between groups. Results:A total of 7 440 joints in 120 PsA patients were included. Overall, the proportion of joints with clinical signs (tenderness or swelling) was higher than those with ultrasound-detected inflammatory lesions [9.14%(680/7 440) vs. 7.93%(590/7 440), χ2=1 245.928, P<0.001], with more tenderness joints than swelling joints [7.72%(574/7 440) vs. 6.14%(457/7 440), χ2=3 264.45, P<0.001]. Clinical signs were primarily observed in hand proximal interphalangeal (PIP), distal interphalangeal (DIP), wrist and ankle joints, mostly in DIP2 joints [19.58%(47/240)]. Ultrasound-detected inflammatory lesions were predominantly found in metatarsophalangeal (MTP), wrist, and ankle joints, mostly in MTP2 joints (18.75%, 45/240). Clinical signs were more prevalent than ultrasound-detected inflammatory lesions in hand PIP1-3, PIP5, DIP2, and DIP5 joints ( P<0.05), whereas more frequent ultrasound-detected inflammatory lesions than clinical tenderness/swelling were in MTP1-4 joints ( P<0.05). Among ultrasound-detected inflammatory lesions, synovitis in MTP2 joints (18.75%, 45/240), tenosynovitis in ankle joints (10.00%, 24/240), enthesitis in hand DIP2 joints (8.75%, 21/240), and soft tissue inflammation in MTP4 joints (2.50%, 6/240) most commonly observed. Dactylitis was more frequently observed in toes than in fingers, with the fourth toe most commonly affected(16.67%, 40/240). Ultrasound-detected inflammatory lesions were observed in 72.37%(55/240) of fingers/toes with clinical dactylitis, mainly presenting as synovitis, tenosynovitis, or combinations of these. Conclusion:PsA exhibits significant heterogeneity in the inflammatory lesions across different joints and lesion types. The discrepancies between clinical findings and ultrasonic inflammatory changes highlight the limitations of physical examination in fully capturing the pathological features of PsA. As a critical tool for PsA evaluation, ultrasonography offers distinct advantages in detecting subclinical inflammation and differentiating inflammatory from non-inflammatory lesions.

OBJECTIVE To establish an HPLC method for determination of the related substances in papaverine hydrochloride. METHODS NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃. RESULTS The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%. CONCLUSION The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.

Objective:To observe the effect of metformin on intestinal metabolites and its protective effect on lung injury in an elderly sepsis rat.Methods:SD rats were fed at the Animal Laboratory Center of Zhengzhou University, fourteen elderly SD rats were randomly divided into three groups: sham surgery (age-Sham, AgS group, n=4), cecal ligation and perforation induced sepsis (age-Cecal ligation and puncture, AgCLP group, n=5), and oral administration of metformin (100 mg/kg) after 1 h of CLP treatment (age-Metformin, AgMET group, n=5). Collected rat feces 24 h after modeling, and analyzed the composition and inter group differences of metabolites in the feces using liquid chromatography tandem mass spectrometry non targeted metabolomics. Collected rat lung tissues and detected the expression levels of inflammation related genes and pathological changes in the tissue. The visualization of metabolic changes between groups were presented using orthogonal partial least squares discriminant analysis, heatmaps, and unsupervised principal component analysis, respectively. MetaboAnalyst 3.0 was used to evaluate the Pathway analysis of metabolites, and this software was based on the KEGG database and the human metabolome database. Results:The expressions of CCL4 ( F=203.00, P<0.001), CXCL1( F=65.69, P<0.001), IL-6 ( F=38.94, P<0.002), TNF-α ( F=14.85, P=0.005) between two groups of rats were significantly different (all P<0.05). However, there was no significant difference in CCL2 expression between AgCLP group and AgMET group. Furthermore, compared with the AgS group, the relative intensities of 17 metabolites such as 7-methylxanthine, N-Arachidonylglycine and Manolide in AgCLP group were significantly increased, whereas the 9 metabolites such as Phenazone, Gly-Phe and Valyproline were significantly decreased, and metformin treatment could reverse these changes of the above metabolites. Correlation analysis showed that the IL-6 and TNF-α levels were positively correlated with the relative strength of 7-Methylxanthine, N-Arachidonylglycine and other metabolites, but negatively correlated with the Phenazone and Gly-Phe. CCL4 and CXCL1 were positively correlated with Manolide, but negatively correlated with Valyproline. Conclusion:The results of this study showed that metformin improved sepsis induced acute lung injury and regulates the host intestinal metabolites, which might provide a potential and effective treatment for elderly sepsis induced acute lung injury.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To analyze the molecular characteristics of hemagglutinin-neuraminidase (HN) gene of human parainfluenza virus type 3 (HPIV3) among the cases with acute respiratory tract infection (ARI) in Henan Province.Methods:Nasal/throat swab samples collected from patients with severe acute respiratory tract infection (SARI) in Luohe and patients with influenza-like illness (ILI) in Zhengzhou were used in this study. HPIV nucleic acids in the samples were detected using real-time fluorescent PCR. HPIV3-positive samples were subjected to RT-PCR for the amplification of HN genes and the sequences were analyzed with Sanger method. CExpress and MEGA7.0 software were used for sequences editing, evolution tree construction and gene sequence analysis.Results:A total of 374 throat swab samples collected form ARI cases in Luohe and Zhengzhou were tested and 20 (5.3%) of them were positive for HPIV3. Eighteen HPIV3 HN gene sequences were successfully amplified and all belonged to C3 subgroups, including 16 sequences of C3f genotype and two sequences of C3a genotype. The 18 HN gene sequences shared the homology of 97.6%-100.0% in nucleotide and 99.3%-100.0% in amino acid, but the differences between them and the prototype strain Wash/47885/57 were significant. There were 12 amino acid mutations shared by them, including four function-related mutations (H295Y, I391V, D556N and I53T). There were no significant differences in the nucleotide or amino acid sequences as compared with the epidemic strain of China/BCH4210A/2014.Conclusions:The C3f and C3a branches of HPIV3 were the epidemic genotypes in Henan Province in recent years and a local circulating prevalence might be established. Continuous and in-depth monitoring of HPIV3 C3 subtype would be of great significance for the prevention and control of HPIV3-associated diseases.