ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

AIM:To assess the evolving burden of cataracts in China from 1990 to 2019.METHODS: Data on disease burden related to cataracts in China were retrieved from the Global Burden of Disease(GBD)2019 study based on large public databases. Utilizing data from the GBD 2019 study, we extracted information on cataract-related disease burden in China from extensive public databases. Analysis of prevalence and disability-adjusted life years(DALYs)associated with cataracts in China was conducted based on GBD 2019 findings. The variable characteristics of age-standardized prevalence rates(ASPR)and age-standardized DALYs rates(ASDR)in China and its neighboring countries were also explored.RESULTS: Between 1990 and 2019, the number of prevalent cases of blindness and vision loss caused by cataracts in China increased by 223.54%, and the corresponding DALYs raised by 142.14%. Over the past 30 years, females exhibited higher age-standardized prevalence and DALYs rates compared to males. Meanwhile, individuals aged 65 to 84 years were found to be more susceptible to cataracts than other age groups. Compared with neighboring countries, China ranked from the 9th position in 1990(867.09, 95%UI: 761.36 to 975.42, per 100 000 population)to the 11th in 2019(991.56, 95%UI: 861.52 to 1131.04, per 100 000 population)in ASPR, while from the 9th in 1990(65.85, 95%UI: 46.39 to 89.41, per 100 000 population)to the 10th position in 2019(59.16, 95%UI: 41.70 to 80.15, per 100 000 population)in ASDR. However, on a global scale, China maintained relatively low ASDR and ASPR for cataracts in 2019.CONCLUSION: The study highlights a substantial rise in the prevalence and DALYs associated with blindness and vision loss due to cataracts from 1990 to 2019 in China, and underscores the urgent need for increased early screening of cataracts, particularly among the elderly and females.

The nasal swab samples of swine influenza(SI)suspected pigs were collected and tested for H3 subtype swine influenza virus(SIV)positive by RT-qPCR.The positive samples were inoc-ulated into SPF chicken embryos for virus isolation.The full genome sequencing and sequence anal-ysis of the isolated H3N2 subtype SIV were conducted,and its pathogenicity was studied.The re-sults showed that a strain of SIV was successfully isolated and identified as H3N2 subtype by RT-PCR,named A/Swine/Yunnan/KM/06/2023(H3N2).The BLSAT results showed that the eight segments of SIV H3N2 KM had the highest homology with eight different strains of swine influ-enza or human influenza viruses,reaching 95.41％-97.49％.The HA and NA segments were de-rived from H3N2 subtype SIV,the NP segment was derived from H1N1 subtype human influenza virus,the M segment was derived from H1N2 subtype SIV,and all other segments were derived from H1N1 subtype SIV.The key receptor sites(190D,223V,226I,228S)of HA protein remained unchanged.The pathogenicity experiment results showed that infected piglets exhibited symptoms such as fever,sneezing,runny nose,the virus could be detoxified to the outside through the nasal cavity,and the lungs had different degrees of lesion.Immunohistochemistry(IHC)showed that the virus could replicate in the lungs.In conclusion,a strain of H3N2 subtype SIV was successfully iso-lated,and the genetic evolution,molecular characteristics and pathogenicity of the virus were stud-ied.It revealed that H3N2 subtype SIV is constantly evolving and had pathogenicity to piglets,pro-viding a reference for monitoring and preventing SIV epidemics in China,and provided a candidate strain for SI vaccine development.

Objective:To investigate the expression of anaplastic lymphoma kinase (ALK), tropomyosin receptor kinase (TRK), and recombinant C-Ros oncogene 1, receptor tyrosine kinase (ROS1) in Spitz tumors, and to analyze their associations with clinical and histopathological features of Spitz tumors.Methods:Clinical and histopathological characteristics, as well as follow-up data, were collected from patients with Spitz tumors at Department of Pathology, Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to August 2023, and retrospectively analyzed. Immunohistochemical staining for ALK, pan-TRK, and ROS1 was performed on skin tissues, and associations between the expression of these kinase proteins and clinicopathological features were analyzed.Results:A total of 57 patients with Spitz tumors were collected, including 36 females and 21 males. Immunohistochemical staining showed that 30 (52.6%) patients were positive for ALK, 4 (7.0%) were positive for ROS1, only 2 (3.5%) were positive for TRK, and 21 (36.8%) were negative for the three kinase proteins. Among the 30 ALK-positive patients, the median age was 9.5 years, 21 (70.0%) were females, and 15 (50.0%) presented with lesions on the face, which mainly manifested as papules or nodules; histologically, 29 (96.7%) patients had hypopigmented tumors with an exophytic growth pattern, and the tumor cells were mainly large and long spindle cells arranged in long cord-like, plexiform or fascicular patterns. Among the 4 ROS1-positive patients, there were 3 females and 1 male, presenting with exophytic papules or polyps; histologically, tumor cells were mostly arranged in small nests, without obvious clefts around cell nests. Two TRK-positive patients were both males aged 20 and 50 years respectively, and presented with brown and skin-colored flat papules, respectively; histologically, the tumors were located superficially with a flat base, and tumor cells spread in a pagetoid pattern in the epidermis, with some epithelioid cells and small cell nests. Among the 21 patients negative for the 3 kinase proteins, 9 were males and 12 were females, and they clinically presented with macules, papules and polypoid lesions; histologically, most tumors were located superficially, consisting of a mixture of epithelioid cells and spindle cells, with rare cytological atypia and mitotic figures, and 2 cases showed mild tissue structural and cellular atypia. Fifty-seven patients were followed up for 2 - 83.3 months, with a median follow-up of 19.2 months. Only 1 ALK-positive child experienced a recurrence, and no recurrence or lymph node metastasis was observed in the other cases.Conclusions:Among the three kinase proteins, ALK showed the highest positive rate in Spitz tumors in this study, while TRK- and ROS1-positive cases were sporadic. Histopathologically, ALK-positive Spitz tumor cells were mainly long spindle cells arranged in long cord-like or plexiform patterns, while TRK- and ROS1-positive Spitz tumors tended to have small cell nests. Both the kinase protein-positive and -negative Spitz tumors mostly had a good prognosis.

ObjectiveTo explore the imbalance of paravertebral muscle group for patients with unilateral lumbar disc herniation. MethodsFrom January, 2022 to January, 2023, 30 patients with unilateral lumbar disc herniation (observation group) and 30 healthy people matching in general data (control group) were measured the tension and stiffness of multifidus and erector spinae with MyotonPRO, while the observation group was assessed with Visual Analogue Scale (VAS) for pain and Japanese Orthopaedic Association (JOA) score, and the time of disease was also recorded. ResultsThe mean of bilateral tension and hardness of multifidus and erector spinae was more in the observation group than in the control group (|t| > 5.407, P < 0.001), and the tension and hardness of multifidus and erector spinae of the affected side were more than those of the unaffected side in the observation group (|t| > 11.219, P < 0.001). The tension and hardness of multifidus and erector spinae of the affected side were positively correlated with VAS score (r > 0.942, P < 0.001), and negatively correlated with JOA score (|r| > 0.886, P < 0.001). ConclusionThe tension and hardness of multifidus and erector spinae of the affected side increase after unilateral lumbar disc herniation, resulting in asymmetry.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Objective:To develop a nomogram to predict the probability of prostate cancer after transeperineal prostate biopsy, and verify the diagnostic efficacy and clinical applicable value of the model.Methods:The clinicopathologic data of 475 patients who underwent prostate biopsy at Yijishan Hospital of Wannan Medical College between January 2019 to August 2021 were retrospectively reviewed. Of all the patients, 367 patients from January 2019 to December 2020 were in the development cohort and 108 patients from January 2021 to August 2021 were in the validation cohort. Patients in the development cohort were (68.86±9.00) years old. The tPSA level was 13.6(8.6, 23.3)ng/ml, and Prostate Imaging Reporting and Data System (PI-RADS) score was 4(3, 4) points. Patients in the validation cohort were (68.89±8.67) years old. The tPSA was 13.1(8.7, 25.6)ng/ml, and PI-RADS score was 4 (3, 5) points. Univariate and multivariate logistic regression were used to analyze prostate cancer risk factors in the development cohort. Then the nomogram prediction model was established by the risk factors. The prediction model's performance was evaluated using receiver operating characteristic (ROC) curves, calibration maps, and decision curve (DCA) analysis in the development cohort. The performance of the model was verified in the validation cohort.Results:The pathological results showed 180 patients with prostate cancer and 187 patients without prostate cancer in the development cohort. The validation cohort included 53 patients with and 55 without prostate cancer. Based on the results of the univariate and multivariate logistic regression analysis, this model incorporates factors including age ( OR=1.059, P=0.003), platelet-to-monocyte ratio (PMR) ( OR=0.002, P=0.011), f/tPSA ( OR=0.009, P=0.020), and PI-RADS score ( OR= 3.076, P<0.001). The calibration curve revealed a great agreement. Internal validation of the nomogram showed that the area under the ROC curve was 0.845 (95% CI 0.794-0.895). The Hosmer-Lemeshow test was also performed( χ2=1.476, P=0.224). The validation group with an area under the ROC curve was 0.869 (95% CI 0.797-0.941). The results of the decision curve analysis indicated that the decision curve was located above the positive and negative lines in the threshold range of 10% to 90%, within which the model has clinical application. Conclusions:The nomogram, which combines patient age, PMR, f/t PSA, and PI-RADS scores, has high predictive efficacy for prostate cancer and has clinical application value.

ObjectiveTo explore the typical behavior characteristics of children with autism in symbolic play and the value of Symbolic Play Test (SPT) in the early identification of autism. MethodsFrom November, 2021 to September, 2022, a total of 260 children with language problems were collected from Department of Children's Health Care of Binzhou Medical University Hospital. A total of 193 children with autism were as observation group and 67 normal children were as control group. All children played symbolic games. The typical behavioral characteristics of children with autism in SPT were explored, and a reliability and validity analysis based on the results of SPT was conducted. They were assessed with the adaptive and personal social scores of Gesell Development Scale, and the correlation of the scores of Gesell Development Scale and the score of SPT was analyzed. ResultsThe Cronbach's α coefficient of SPT of children with autism was 0.835 to 0.935, and the total score of SPT, the scores of surrogate object, fictional attribute and fictional object were positively correlated with each other (r > 0.607, P < 0.001). The SPT scores decreased in the observation group (t > 9.615, P < 0.001), and SPT score positively correlated with adaptability and personal-social development quotient (r > 0.609, P < 0.001). ConclusionTypical behavior of children with autism can be reflected in symbolic play, and SPT can provide clues for early identification of autism.