Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, thereby offering innovative insights and strategies for the management of the associated conditions.Methods:Using the protein quantitative trait locus(pQTL) data derived from extensive proteomics studies, a two-sample Mendelian randomization was conducted to preliminarily identify potential drug therapeutic targets. Following this, sensitivity analyses were performed to evaluate potential confounding factors, including heterogeneity and horizontal pleiotropy. A leave-one-out sensitivity analysis was also conducted, systematically excluding each single nucleotide polymorphism (SNP) to evaluate their individual impact. Additionally, co-localization analysis was carried out to determine the presence of shared genetic variants between the identified plasma proteins and the relevant traits.Results:The proteomic data analyzed in this investigation encompassed 4 907 pQTLs, while the genetic data pertaining to hair pigmentation and shaft abnormalities included 124 cases and 432 686 controls. Through the Mendelian randomization screening, six candidate protein genes were identified: HLA-DQA2, CTSB, KIR2DS2, SVEP1, HOMER2, and HOMER1. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among these proteins. The leave-one-out sensitivity analysis demonstrated that no single SNP significantly affected the overall findings. Notably, HOMER2 was substantiated by co-localization analysis, which provided robust evidence of its potential role in regulating the genetic mechanisms associated with hair pigmentation and shaft integrity.Conclusion:This study successfully identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 exhibiting the most compelling evidence. These findings pave the way for novel therapeutic approaches in the treatment of hair color and hair shaft disorders.

Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, providing novel insights and approaches for managing related conditions.Methods:Using the pQTL data from large-scale proteomics studies, a two-sample Mendelian randomization (TwoSampleMR) was conducted to preliminarily identify potential drug therapeutic targets. Subsequently, sensitivity analysis was performed to evaluate potential confounding factors such as heterogeneity and horizontal pleiotropy, and a leave-one-out sensitivity analysis was conducted by eliminating each single nucleotide polymorphism (SNP) one by one. Finally, co-localization analysis was carried out to explore whether there are shared genetic variants between the identified plasma proteins and traits.Results:The proteomic data used in this study included 4, 907 pQTLs, while the genetic data related to hair pigmentation and shaft abnormalities comprised 124 cases and 432, 686 controls. After Mendelian randomization screening, six candidate protein genes were identified: HLA-DQA2, CTSB, KIR2DS2, SVEP1, HOMER2, and HOMER1. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among these proteins. Leave-one-out sensitivity analysis indicated that no single SNP significantly influenced the overall result. Notably, HOMER2 was supported by colocalization analysis with strong evidence, suggesting its potential role in regulating genetic mechanisms underlying hair pigmentation and shaft health.Conclusions:This study identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 showing stronger evidence. These findings provide novel directions for the treatment of hair color and hair shaft abnormalities.

Objective To analyze the epidemiological characteristics and immunization history of pertussis cases in Yichang City, Hubei Province from 2018 to 2023. Methods Data on the incidence and immunization history of pertussis cases were collected in Yichang City from 2018 to 2023, and the epidemiological characteristics was analyzed and described. Results A total of 109 cases of pertussis were reported in Yichang from 2018 to 2023, and the annual average reported incidence rate was 0.45/100,000. The incidence rate reported in each year was between 0～1.58/100,000. The area with the highest annual reported incidence rate was Xiling District (1.19/100,000). There was a statistically significant difference in the incidence rate between different years (χ²=208.26, P < 0.001). The annual reported incidence rate showed a significant increasing trend (χ² trend =125.71, P < 0.001). The ratio of male to female cases was 1.22. There was no significant difference in the annual reported incidence rates between males and females (χ²=0.85, P=0.36). Children aged 3-9 years accounted for 60.55%. Students and scattered children accounted for 45.87% and 36.70%, respectively. Before the onset of the disease, 72.48% had a history of immunization with pertussis-containing vaccine, and 27.52% had no history of immunization. The shortest interval between the last dose of pertussis-containing vaccine and the onset of the disease was 8 days, the longest was 4057 days, and the median was 1882 days. Conclusion From 2018 to 2023, the reported incidence of pertussis in Yichang City has been on the rise, with the majority of cases occurring in children and students under the age of 9. It is recommended to strengthen pertussis disease monitoring.

Objective:To investigate changes in psychological status before and after sequential therapy in patients with skin circulatory disorders following hyaluronic acid injection.Methods:A retrospective study was conducted on 17 female patients, with a mean age of 28-54 (39.5±1.2) years, admitted to the Fourth Medical Center of PLA General Hospital from December 2021 to July 2022. Patients received ultrasound-guided percutaneous arterial puncture or digital subtraction angiography (DSA) guided catheter intervention for hyaluronidase injection, alongside corticosteroid pulse therapy, diuretic administration, neurotrophic support, wound protection, and laser therapy. Psychological assessments, including the Minnesota multiphasic personality inventory (MMPI) and symptom check list-90 (SCL-90), were performed at admission and 30-45 days post-discharge. Changes in assessment scores and patient satisfaction were analyzed.Results:Two patients failed to complete all assessments, leaving 15 cases for final analysis. Affected anatomical regions included the nose/perinasal area (13 cases), temporal region (3 cases), lips (3 cases), and forehead (7 cases). MMPI scores for hypochondriasis, depression, hysteria, psychopathic deviation, paranoia, psychasthenia, and hypomania showed statistically significant reductions compared to baseline (all P<0.05). SCL-90 scores for somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism, and sleep/appetite disturbances also demonstrated significant decreases (all P<0.05). Among the 15 patients, 7 patients reported being very satisfied, 6 patients were satisfied, and 2 patients were moderately satisfied, with no dissatisfaction reported. Conclusion:Sequential therapy is associated with improved psychological outcomes in patients with skin circulatory disorders secondary to hyaluronic acid injection.

Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, thereby offering innovative insights and strategies for the management of the associated conditions.Methods:Using the protein quantitative trait locus(pQTL) data derived from extensive proteomics studies, a two-sample Mendelian randomization was conducted to preliminarily identify potential drug therapeutic targets. Following this, sensitivity analyses were performed to evaluate potential confounding factors, including heterogeneity and horizontal pleiotropy. A leave-one-out sensitivity analysis was also conducted, systematically excluding each single nucleotide polymorphism (SNP) to evaluate their individual impact. Additionally, co-localization analysis was carried out to determine the presence of shared genetic variants between the identified plasma proteins and the relevant traits.Results:The proteomic data analyzed in this investigation encompassed 4 907 pQTLs, while the genetic data pertaining to hair pigmentation and shaft abnormalities included 124 cases and 432 686 controls. Through the Mendelian randomization screening, six candidate protein genes were identified: HLA-DQA2, CTSB, KIR2DS2, SVEP1, HOMER2, and HOMER1. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among these proteins. The leave-one-out sensitivity analysis demonstrated that no single SNP significantly affected the overall findings. Notably, HOMER2 was substantiated by co-localization analysis, which provided robust evidence of its potential role in regulating the genetic mechanisms associated with hair pigmentation and shaft integrity.Conclusion:This study successfully identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 exhibiting the most compelling evidence. These findings pave the way for novel therapeutic approaches in the treatment of hair color and hair shaft disorders.

Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, providing novel insights and approaches for managing related conditions.Methods:Using the pQTL data from large-scale proteomics studies, a two-sample Mendelian randomization (TwoSampleMR) was conducted to preliminarily identify potential drug therapeutic targets. Subsequently, sensitivity analysis was performed to evaluate potential confounding factors such as heterogeneity and horizontal pleiotropy, and a leave-one-out sensitivity analysis was conducted by eliminating each single nucleotide polymorphism (SNP) one by one. Finally, co-localization analysis was carried out to explore whether there are shared genetic variants between the identified plasma proteins and traits.Results:The proteomic data used in this study included 4, 907 pQTLs, while the genetic data related to hair pigmentation and shaft abnormalities comprised 124 cases and 432, 686 controls. After Mendelian randomization screening, six candidate protein genes were identified: HLA-DQA2, CTSB, KIR2DS2, SVEP1, HOMER2, and HOMER1. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among these proteins. Leave-one-out sensitivity analysis indicated that no single SNP significantly influenced the overall result. Notably, HOMER2 was supported by colocalization analysis with strong evidence, suggesting its potential role in regulating genetic mechanisms underlying hair pigmentation and shaft health.Conclusions:This study identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 showing stronger evidence. These findings provide novel directions for the treatment of hair color and hair shaft abnormalities.

Objective:To investigate changes in psychological status before and after sequential therapy in patients with skin circulatory disorders following hyaluronic acid injection.Methods:A retrospective study was conducted on 17 female patients, with a mean age of 28-54 (39.5±1.2) years, admitted to the Fourth Medical Center of PLA General Hospital from December 2021 to July 2022. Patients received ultrasound-guided percutaneous arterial puncture or digital subtraction angiography (DSA) guided catheter intervention for hyaluronidase injection, alongside corticosteroid pulse therapy, diuretic administration, neurotrophic support, wound protection, and laser therapy. Psychological assessments, including the Minnesota multiphasic personality inventory (MMPI) and symptom check list-90 (SCL-90), were performed at admission and 30-45 days post-discharge. Changes in assessment scores and patient satisfaction were analyzed.Results:Two patients failed to complete all assessments, leaving 15 cases for final analysis. Affected anatomical regions included the nose/perinasal area (13 cases), temporal region (3 cases), lips (3 cases), and forehead (7 cases). MMPI scores for hypochondriasis, depression, hysteria, psychopathic deviation, paranoia, psychasthenia, and hypomania showed statistically significant reductions compared to baseline (all P<0.05). SCL-90 scores for somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism, and sleep/appetite disturbances also demonstrated significant decreases (all P<0.05). Among the 15 patients, 7 patients reported being very satisfied, 6 patients were satisfied, and 2 patients were moderately satisfied, with no dissatisfaction reported. Conclusion:Sequential therapy is associated with improved psychological outcomes in patients with skin circulatory disorders secondary to hyaluronic acid injection.

Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.