Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective To develop a quantitative method ology for assessing the aortic media damage induced by the stent-graft,and study the influence of various stent oversizing ratios(ORs)on damage of the aortic media.Methods Based on experimetal data from uniaxial tensile test on human aortic dissection,the material parameters of aortic wall's constitutive equation were determined,including damage parameters.A finite element model was constructed to simulate the deployment process of the stent-graft in blood vessel.Damage factor was determined to analyze the stress distribution and the result ant damage within aortic media at different ORs of the stent-graft.Results The distribution of damage factor and von Mises stress was basically consistent,with both peaking at the large curvature side near the aortic arch.Additionally,stress concentration was observed in distal anchoring region of the aortic wall.An increment in OR was correlated with a proportional increase in both peak values.At ORs of 10％,15％and 20％,the maimum von Mises stresses were 469,480 and 580 kPa,respectively,with increments of 2.3％and 20.8％.Correspondingly,the maximum damage factors were 0.01,0.011 and 0.014,with an elevation of 10％and 27.3％.Conclusions An increment in OR is associated with a pronounced increase in peak value of the damage factor and the rate of increase,indicating a more severe impact on the aortic media.The distribution of the damage factor aligns closely with that of the von Mises stress,with both exhibiting peak values at the large curvature side of aortic arch.This correlation underscores the damage factor's efficacy as a reliable indicator of the aortic media's integrity and can accurately reflect the degree of medial layer injury in the aortic wall,thereby providing a theoretical basis for the subsequent assessment of endovascular interventional treatment risks through damage factor analysis.

Objective:To screen the optimal machine learning model for predicting the recurrence condition of hepatocellular carcinoma (HCC) at different time points post-surgery, based on the cutoff value of the Ki67 positive proliferation index condition calculated from recurrence-free survival and combined with various clinical features.Methods:retrospective study included initially treated patients with solitary HCC who underwent radical surgery at the Fifth Medical Center of the PLA General Hospital from January 2013 to March 2023. Data included general clinical data, preoperative laboratory parameters, and surgical pathology information about the subjects. The postoperative recurrence status was assessed by querying the medical record system or by telephone follow-up. The Ki67 positive index cutoff value was determined by the X-tile software based on the patient's recurrence-free survival status and time analysis. Survival rates were calculated using the Kaplan-Meier method, and survival curves were plotted. The study population was randomly divided into training and testing groups in a 7:3 ratio using a computer-generated random number method. The minimum redundancy maximum relevance (mRMR) method was used for feature variable selection. Predictive models for postoperative HCC recurrence conditions in patients with HCC were constructed using random forest, support vector machine, logistic regression, and gradient boosting decision tree machine learning algorithms. Inter-group comparisons for continuous data were performed using the t-test or Mann-Whitney U test. Inter-group comparisons of enumeration data were performed using the Pearson χ2 test, continuity-corrected χ2 test, or Fisher's exact test. Results:The cutoff values for the Ki67 positivity index were 0.3 and 0.5 in 510 cases, with a follow-up time ranging from 1.2 to 11.4 years (median: 6.2 years). The recurrence-free survival time was between 1 and 135 months (median: 32 months), with recurrence-free survival rates post-surgery at 1, 2, 3, and 5 years were 87.5%, 77.1%, 61.2%, and 54.5%, respectively. The top five variables predicted HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years, in accordance with information obtained by the mRMR screen out. The Ki67 positivity index screened a successfully constructed machine learning model to predict HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years. The machine learning model based on the gradient boosting decision tree algorithm had the best prediction performance among them (areas under the receiver operating characteristic curves for predicting HCC recurrence within six months in the training and validation sets were 0.996 and 0.946, and accuracies were 0.972 and 0.935, respectively).Conclusion:A machine learning model was successfully constructed using the Ki67 positivity index combined with four readily available clinical features to predict HCC recurrence. The machine learning model based on the gradient boosting decision tree algorithm demonstrated the best performance in terms of predicting HCC recurrence within six months after surgery.

Objective:To investigate brain damage and treatment efficacy in patients with first-episode schizophrenia with comorbid auditory and visual hallucinations and cognitive decline based on brain magnetic resonance imaging (MRI).Methods:This study adopted a retrospective cohort design. Eighty patients with first-episode schizophrenia who received treatment at Wenzhou Seventh People's Hospital from January to June 2024 were included in this study. The patients were divided into an observation group (40 cases of first-episode schizophrenia with comorbid auditory and visual hallucinations) and a control group (40 cases of first-episode schizophrenia without comorbid auditory and visual hallucinations) based on whether they had symptoms of comorbid auditory and visual hallucinations. Forty healthy individuals who concurrently underwent physical examinations were included in the normal group. All patients received standardized treatment. Cranial MRI data were collected from all subjects. Cranial MRI data, Positive and Negative Syndrome Scale (PANSS) score, Global Assessment of Functioning (GAF) score, and changes in cognitive function were compared among the three groups. Additionally, the changes in cranial MRI data, PANSS score, GAF score, and the score of MATRICS Consensus Cognitive Battery (MCCB) in the observation group were compared between before and after treatment.Results:The horizontal distance between the corpus callosum and the underside of the cingulate gyrus, the vertical distance between the corpus callosum and the underside of the cingulate gyrus, and PANSS and GAF scores in the observation group were all significantly higher than those in the normal and control groups (all P < 0.05). The scores on all MCCB scales in the observation group were significantly lower than those in the normal and control groups (all P < 0.05). After treatment, the left horizontal distance between the corpus callosum and the underside of the cingulate gyrus [(5.72 ± 0.71) mm] and the right horizontal distance [(5.13 ± 0.55) mm], as well as the left vertical distance [(6.37 ± 0.69) mm] and the right vertical distance [(5.61 ± 0.67) mm], were all significantly lower than the pre-treatment values [(6.98 ± 0.83) mm, (6.07 ± 0.49) mm, (7.54 ± 0.58) mm, and (6.52 ± 0.51) mm, t = 7.30, 8.07, 8.21, 6.84, all P < 0.05]. Post-treatment PANSS scores [(39.95 ± 6.65)] were significantly lower than pre-treatment scores [(97.47 ± 18.47)], while post-treatment GAF scores [(71.26 ± 8.87)] were significantly higher than pre-treatment scores [(34.68 ± 7.71), t = 18.53, 19.69, both P < 0.05]. Post-treatment scores for the MCCB [(8.57 ± 2.45), (2.25 ± 0.47), (25.16 ± 2.43), (24.10 ± 2.64), (17.08 ± 2.25), (20.43 ± 3.76), (2.07 ± 0.36), (22.16 ± 3.24), (57.81 ± 7.69), (0.28 ± 0.05)] were significantly higher than pre-treatment scores [(5.65 ± 1.37), (1.62 ± 0.34), (21.21 ± 2.27), (20.27 ± 1.78), (12.16 ± 2.08), (14.56 ± 2.34), (1.71 ± 0.25), (17.92 ± 1.64), (40.29 ± 6.56), (0.21 ± 0.03), t = 6.58, 6.87, 7.51, 7.61, 10.15, 8.38, 5.19, 7.38, 10.96, 7.59, all P < 0.05]. Conclusions:The comorbid auditory and visual hallucinations in patients with first-episode schizophrenia, based on brain MRI findings, are closely related to cognitive decline and brain damage. After treatment, both cognitive function and cranial damage in these patients have considerably improved, which is worthy of clinical consideration.

Objective To develop a quantitative method ology for assessing the aortic media damage induced by the stent-graft,and study the influence of various stent oversizing ratios(ORs)on damage of the aortic media.Methods Based on experimetal data from uniaxial tensile test on human aortic dissection,the material parameters of aortic wall's constitutive equation were determined,including damage parameters.A finite element model was constructed to simulate the deployment process of the stent-graft in blood vessel.Damage factor was determined to analyze the stress distribution and the result ant damage within aortic media at different ORs of the stent-graft.Results The distribution of damage factor and von Mises stress was basically consistent,with both peaking at the large curvature side near the aortic arch.Additionally,stress concentration was observed in distal anchoring region of the aortic wall.An increment in OR was correlated with a proportional increase in both peak values.At ORs of 10％,15％and 20％,the maimum von Mises stresses were 469,480 and 580 kPa,respectively,with increments of 2.3％and 20.8％.Correspondingly,the maximum damage factors were 0.01,0.011 and 0.014,with an elevation of 10％and 27.3％.Conclusions An increment in OR is associated with a pronounced increase in peak value of the damage factor and the rate of increase,indicating a more severe impact on the aortic media.The distribution of the damage factor aligns closely with that of the von Mises stress,with both exhibiting peak values at the large curvature side of aortic arch.This correlation underscores the damage factor's efficacy as a reliable indicator of the aortic media's integrity and can accurately reflect the degree of medial layer injury in the aortic wall,thereby providing a theoretical basis for the subsequent assessment of endovascular interventional treatment risks through damage factor analysis.

Objective:To investigate brain damage and treatment efficacy in patients with first-episode schizophrenia with comorbid auditory and visual hallucinations and cognitive decline based on brain magnetic resonance imaging (MRI).Methods:This study adopted a retrospective cohort design. Eighty patients with first-episode schizophrenia who received treatment at Wenzhou Seventh People's Hospital from January to June 2024 were included in this study. The patients were divided into an observation group (40 cases of first-episode schizophrenia with comorbid auditory and visual hallucinations) and a control group (40 cases of first-episode schizophrenia without comorbid auditory and visual hallucinations) based on whether they had symptoms of comorbid auditory and visual hallucinations. Forty healthy individuals who concurrently underwent physical examinations were included in the normal group. All patients received standardized treatment. Cranial MRI data were collected from all subjects. Cranial MRI data, Positive and Negative Syndrome Scale (PANSS) score, Global Assessment of Functioning (GAF) score, and changes in cognitive function were compared among the three groups. Additionally, the changes in cranial MRI data, PANSS score, GAF score, and the score of MATRICS Consensus Cognitive Battery (MCCB) in the observation group were compared between before and after treatment.Results:The horizontal distance between the corpus callosum and the underside of the cingulate gyrus, the vertical distance between the corpus callosum and the underside of the cingulate gyrus, and PANSS and GAF scores in the observation group were all significantly higher than those in the normal and control groups (all P < 0.05). The scores on all MCCB scales in the observation group were significantly lower than those in the normal and control groups (all P < 0.05). After treatment, the left horizontal distance between the corpus callosum and the underside of the cingulate gyrus [(5.72 ± 0.71) mm] and the right horizontal distance [(5.13 ± 0.55) mm], as well as the left vertical distance [(6.37 ± 0.69) mm] and the right vertical distance [(5.61 ± 0.67) mm], were all significantly lower than the pre-treatment values [(6.98 ± 0.83) mm, (6.07 ± 0.49) mm, (7.54 ± 0.58) mm, and (6.52 ± 0.51) mm, t = 7.30, 8.07, 8.21, 6.84, all P < 0.05]. Post-treatment PANSS scores [(39.95 ± 6.65)] were significantly lower than pre-treatment scores [(97.47 ± 18.47)], while post-treatment GAF scores [(71.26 ± 8.87)] were significantly higher than pre-treatment scores [(34.68 ± 7.71), t = 18.53, 19.69, both P < 0.05]. Post-treatment scores for the MCCB [(8.57 ± 2.45), (2.25 ± 0.47), (25.16 ± 2.43), (24.10 ± 2.64), (17.08 ± 2.25), (20.43 ± 3.76), (2.07 ± 0.36), (22.16 ± 3.24), (57.81 ± 7.69), (0.28 ± 0.05)] were significantly higher than pre-treatment scores [(5.65 ± 1.37), (1.62 ± 0.34), (21.21 ± 2.27), (20.27 ± 1.78), (12.16 ± 2.08), (14.56 ± 2.34), (1.71 ± 0.25), (17.92 ± 1.64), (40.29 ± 6.56), (0.21 ± 0.03), t = 6.58, 6.87, 7.51, 7.61, 10.15, 8.38, 5.19, 7.38, 10.96, 7.59, all P < 0.05]. Conclusions:The comorbid auditory and visual hallucinations in patients with first-episode schizophrenia, based on brain MRI findings, are closely related to cognitive decline and brain damage. After treatment, both cognitive function and cranial damage in these patients have considerably improved, which is worthy of clinical consideration.

Objective:To screen the optimal machine learning model for predicting the recurrence condition of hepatocellular carcinoma (HCC) at different time points post-surgery, based on the cutoff value of the Ki67 positive proliferation index condition calculated from recurrence-free survival and combined with various clinical features.Methods:retrospective study included initially treated patients with solitary HCC who underwent radical surgery at the Fifth Medical Center of the PLA General Hospital from January 2013 to March 2023. Data included general clinical data, preoperative laboratory parameters, and surgical pathology information about the subjects. The postoperative recurrence status was assessed by querying the medical record system or by telephone follow-up. The Ki67 positive index cutoff value was determined by the X-tile software based on the patient's recurrence-free survival status and time analysis. Survival rates were calculated using the Kaplan-Meier method, and survival curves were plotted. The study population was randomly divided into training and testing groups in a 7:3 ratio using a computer-generated random number method. The minimum redundancy maximum relevance (mRMR) method was used for feature variable selection. Predictive models for postoperative HCC recurrence conditions in patients with HCC were constructed using random forest, support vector machine, logistic regression, and gradient boosting decision tree machine learning algorithms. Inter-group comparisons for continuous data were performed using the t-test or Mann-Whitney U test. Inter-group comparisons of enumeration data were performed using the Pearson χ2 test, continuity-corrected χ2 test, or Fisher's exact test. Results:The cutoff values for the Ki67 positivity index were 0.3 and 0.5 in 510 cases, with a follow-up time ranging from 1.2 to 11.4 years (median: 6.2 years). The recurrence-free survival time was between 1 and 135 months (median: 32 months), with recurrence-free survival rates post-surgery at 1, 2, 3, and 5 years were 87.5%, 77.1%, 61.2%, and 54.5%, respectively. The top five variables predicted HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years, in accordance with information obtained by the mRMR screen out. The Ki67 positivity index screened a successfully constructed machine learning model to predict HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years. The machine learning model based on the gradient boosting decision tree algorithm had the best prediction performance among them (areas under the receiver operating characteristic curves for predicting HCC recurrence within six months in the training and validation sets were 0.996 and 0.946, and accuracies were 0.972 and 0.935, respectively).Conclusion:A machine learning model was successfully constructed using the Ki67 positivity index combined with four readily available clinical features to predict HCC recurrence. The machine learning model based on the gradient boosting decision tree algorithm demonstrated the best performance in terms of predicting HCC recurrence within six months after surgery.

Objective:To investigate the effects and mechanism of exosome (EXO)-loaded kringle V11 (KV11) delivery on corneal neovascularization (CNV).Methods:KV11 was bound to the surface of endothelial cell-derived exosomes by using CP05, an EXO-targeting anchoring peptide, to produce EXO-KV11.The binding efficiency and optimal concentration ratio were determined using the Apogee flow system.A total of 100 8-week-old healthy male SPF grade SD rats were selected, 10 of which were randomly selected as a normal control group without any treatment.The CNV model was established by alkali burn in the other 90 rats, which were randomly divided into three groups, EXO-KV11 group, KV11 group, and normal saline group by the random number table method, with 30 rats in each group.Each group was injected subconjunctivally with 100 μl of EXO-KV11 (25 μg), KV11 (25 μg), or normal saline every other day from the first day after the alkali burn, respectively.The CNV of rats was observed on days 1, 4, 7, and 14 after alkali burn.The CNV area was calculated by ventricular perfusion with fluorescein isothiocyanate-dextran (FITC-dextran) and corneal angiography.The amount of CNV lumen was observed by hematoxylin and eosin staining.The distribution of CD31 in rat corneas was determined by immunohistochemical method.The expression levels of voltage-dependent anion channel 1(VDAC1), endoplasmic reticulum stress, autophagy and apoptosis-associated proteins were detected by Western blot.This study was approved by the Animal Ethics Committee of Peking University People's Hospital (No.20210019). All animal procedures complied with the regulations of the Vision and Ophthalmology Association and the Animal Protection and Use Committee of Peking University.Results:The optimal concentration ratio of KV11 to EXO was 4∶1 and the binding affinity reached up to 87.5% by Apogee flow cytometers.On days 7 and 14 after alkali burn, there were significant differences in CNV area among the four groups ( F=4.613, 15.590; both at P<0.05). On day 7 after alkali burn, the CNV area was smaller in EXO-KV11 group than in KV11 and normal saline groups, with statistically significant differences (both at P<0.05). On day 14 after alkali burn, the CNV area was smaller in EXO-KV11 and KV11 groups than in normal saline group, and smaller in EXO-KV11 group than in KV11 group, showing statistically significant differences (all at P<0.05). The results of quantitative analysis of corneal fluorescence mounts showed that the relative CNV fluorescence area of the normal saline group, KV11 group and EXO-KV11 group were (8.3±1.7)%, (5.2±1.6)%and (3.4±0.7)%, respectively, showing a statistically significant overall comparison difference ( F=11.735, P<0.01). The relative CNV fluorescence area was larger in KV11 and normal saline groups than in EXO-KV11 group, and larger in normal saline group than in KV11 group, showing statistically significant differences (all at P<0.05). On day 14 after alkali burn, massive neovascular lumens were observed in the matrix of the normal saline group.The number of neovascular lumens in KV11 group was smaller than that in normal saline group.The corneal structure appeared normal in EXO-KV11 group, and neovascular lumens were rare.Numerous CD31-positive cells were observed in the corneal stroma of the normal saline group, which formed into lumen structures.The number of lumens surrounded by CD31-positive cells in the corneal stroma was smaller in KV11 group than in normal saline group, and smaller in EXO-KV11 group than in KV11 group.There were significant differences in the relative expression levels of VDAC1, protein kinase R-like endoplasmic reticulum kinase (PERK), p62, cleaved caspase 3 among the four groups ( F=35.960, 8.947, 17.791, 101.168; all at P<0.01). The relative expression levels of VDAC1, PERK, p62, cleaved caspase 3 were higher in EXO-KV11 group than in KV11 and normal saline groups, showing statistically significant differences (all at P<0.001). There was no significant difference in the relative expression of microtubule-associated proteins 1A/1B light chain 3B (LC3B)Ⅱ/LC3BⅠ protein among all four groups ( F=0.445, P=0.727). Conclusions:EXO-KV11 can inhibit CNV more remarkably than KV11.EXO-KV11 inhibits CNV by promoting the expression of VDAC1 and PERK and suppressing the autophagic flux.

ObjectiveTo explore the relationship between the occupational noise exposure and arteriosclerosis in mechanical manufacturing workers. Methods A total of 453 employees of a machinery manufacturing enterprise were selected as the study subjects using the judgment sampling method. The noise exposure levels in their workplaces were measured, and their cumulative noise exposure (CNE) was assessed based on the type of job-noise exposure matrix and occupational hazard exposure history. Pure-tone audiometry was performed on the research subjects, and their brachial-ankle pulse wave velocity (baPWV) was measured. Results The CNE was (91±11) dB(A) per year and the median baPWV was 1 278.0 cm/s in the research subjects. The results of the generalized linear regression model analysis showed that for every one dB(A) per year increase in CNE, the baPWV of the general population increased by 0.20% ［95% confidence interval (CI) 0.10%-0.30%, P<0.01］, with an increase of 0.17% in males (95%CI 0.06%-0.28%, P<0.01) and 0.28% in females (95%CI 0.07%-0.49%, P<0.01). Using the hearing loss as an outcome indicator for high intensity noise exposure, the results showed that baPWV increased by 7.04% (95%CI 2.42%-11.87%, P<0.01) in individuals with bilateral hearing loss, and by 9.84% and 6.53% (95%CI 3.07%-17.07% and 2.13%-11.11%, all P<0.01) in individuals with elevated high-frequency hearing thresholds in both ears and in either ear, respectively. There was no significant association in elevated speech-frequency hearing thresholds and arteriosclerosis (P>0.05). Conclusion Occupational noise exposure may increase the risk of arteriosclerosis.

Objective To analyze the effect of night-shift work, anxiety and their interaction on work-related musculoskeletal disorders (WMSDs) among electronics manufacturing employees. Methods A total of 2 676 employees from 58 electronic manufacturing enterprises in the Pearl River Delta region of Guangdong Province were selected as the research subjects using the judgment sampling method. The Basic Situation Survey Scale, Generalized Anxiety Disorder 7-item Scale and Questionnaire of Musculoskeletal Disorders were used to assess night-shift work, anxiety and the prevalence of WMSDs in employees. The multivariate logistic regression model was used to analyze the effects of night-shift work, anxiety and their combined effects on the risk of WMSDs. Results The proportion of night-shift work was 30.3%, and the detection rates of anxiety and WMSDs were 26.8% and 41.3%, respectively. The results of multivariate logistic regression analysis showed that night-shift work and anxiety were independent risk factors of WMSDs in the research subjects, after excluding the influence of confounding factors such as age, marital status, enterprise size and length of service [odds ratio (OR) and 95% confidence interval (CI) were 1.307 (1.092-1.564) and 3.282 (2.739-3.934), respectively, both P<0.01]. Compared with those without night-shift work or anxiety, the risk of WMSDs was higher in individuals with only night-shift work, only anxiety, or both night-shift work and anxiety [OR and 95%CI were 1.347 (1.091-1.663), 3.395 (2.727-4.227) and 4.117 (3.072-5.519), respectively, all P<0.01]. Conclusion Both night-shift work and anxiety can increase the risk of WMSDs among electronic manufacturing employees, and these two factors exhibit a synergistic effect in increasing the risk of WMSDs.