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 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 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 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 clinical value of thyroid globulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)in the diagnosis and treatment of papillary thyroid microcarcinoma(PTMC).Methods A total of 346 patients with thyroid nodules who underwent surgical treatment in the hospital from August 2012 to October 2021 were selected as the research objects.According to the postoperative pathologi-cal results,the patients were divided into the benign nodule group,PTMC group and non-micro papillary thy-roid carcinoma(PTC)group.The general data of the patients and thyroid function indexes[free triiodothyro-nine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH),TgAb and TPOAb]before and after operation were collected,the tumor recurrence or lymph node metastasis after operation were ob-served,and the relationship between serum TgAb and TPOAb and the risk and prognosis of PTMC was ana-lyzed.Results The positivity rate of TgAb in the PTMC and non-micro PTC groups was significantly higher than that in the benign nodule group(P<0.05).The TPOAb positivity rate was not significantly different among the three groups(P>0.05).Only the TSH level in the PTMC group was higher than that in the non-micro PTC group(P<0.05).Multivariate logistic analysis showed that younger age,higher TSH and positive TgAb were independent risk factors for PTMC and non-micro PTC(P<0.05).However,the risk of PTC didn't increase with increasing TgAb titres.The positivity rate of TgAb in the PTMC and non-micro PTC groups didn't change significantly within one month after operation,but decreased in one year after operation(P<0.05).The TPOAb positivity rate decreased after operation,but the difference was not statistically sig-nificant(P>0.05).In the PTMC group,four cases had tumor recurrence or lymph node metastasis,and the TgAb level increased by 88.4%,49.5%,5.7%and 84.0%respectively when the tumor recurred or metasta-sized.Among them,the TPOAb level increased by 51.6%,30.0%and 2.9%respectively in three cases and decreased by 53.9%in one case.In the PTMC group,there were 11 patients with cervical lymph node enlarge-ment,and there was no statistical difference in TgAb and TPOAb levels when the condition changed(P>0.05).Conclusion TgAb is a risk factor for PTMC,and can be followed up regularly during the diagnosis and treatment of PTMC.The specificity of TPOAb is not as good as that of TgAb,and appropriate follow-up can be chosen during the course of the disease.

ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L^-1 glucose+10% blank serum）， model （30 mmol·L^-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L^-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L^-1 glucose+10% blank serum+1 μmol·L^-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe²⁺ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L^-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe²⁺， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe²⁺， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

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.