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.

BACKGROUND:Pauwels Ⅲ femoral neck fracture is a typical unstable fracture characterized by high vertical shear force and high incidence of postoperative complications.At present,there are many fixation methods for Pauwels Ⅲ fracture,and there is no clear conclusion as to which internal fixation is the best fixation method for Pauwels Ⅲ femoral neck fracture in young adults. OBJECTIVE:To compare the clinical effect of three inverted triangle cannulated screws assisted transverse lag screws and femoral neck system in fixing Pauwels Ⅲ femoral neck fractures of young adults. METHODS:From May 2021 to December 2022,21 young and middle-aged patients with Pauwels Ⅲ femoral neck fracture were treated with three inverted triangle cannulated screws assisted by transverse lag screws and femoral neck system in Affiliated Hospital of Southwest Medical University.Of them,9 patients were treated with three inverted triangle cannulated screws and one transverse lag screws perpendicular to the fracture line as the 3+1 cannulated screw group and 12 patients were treated with femoral neck system as the femoral neck system group.The two fixation methods were compared in terms of operation time,intraoperative blood loss,total incision length,intraoperative fluoroscopy times,fracture healing time,and limb function. RESULTS AND CONCLUSION:(1)All patients were followed up.Patients in the 3+1 cannulated screw group were followed up for 10-25 months,with a mean of(17.44±4.30)months.The patients in the femoral neck system group were followed up for 8-24 months,with a mean of(15.58±4.68)months.(2)The intraoperative fluoroscopy times and Harris score at 3 months postoperatively in the femoral neck system group were better than those in the 3+1 cannulated screw group,and the difference was statistically significant(P<0.05).The intraoperative blood loss,total incision length,and femoral neck shortening distance in the 3+1 cannulated screw group were better than those in the femoral neck system group,and the differences were statistically significant(P<0.05).There was no significant difference in operation time,fracture healing time,and Harris score at the last follow-up between the two groups(P>0.05).(3)It is indicated that three inverted triangle cannulated screws assisted transverse lag screw and femoral neck system can achieve good clinical effects in the treatment of young and middle-aged Pauwels Ⅲ femoral neck fracture.The femoral neck system has fewer intraoperative fluoroscopy times and better early overall stability,while the 3+1 cannulated screw is more minimally invasive,easier to operate.Both fixation methods are worthy of clinical application and promotion,and can be selected according to the actual clinical situation.

Objective:To investigate the prognostic value of serum suppressor of cytokine signaling 3 (SOCS3) and thioredoxin-interacting protein (TXNIP) levels in transcatheter arterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC) .Methods:A total of 107 HCC patients who underwent TACE treatment in Wuhan Hanyang Hospital from December 2019 to July 2021 were selected as the observation objects. According to the situation after TACE treatment, the patients were divided into poor prognosis group ( n=47) and good prognosis group ( n=60). Serum SOCS3 and TXNIP levels were detected by enzyme-linked immunosorbent assay, the prognostic factors were analyzed by logistic regression. The predictive value of serum SOCS3 and TXNIP levels before treatment for TACE treatment prognosis in patients with HCC was analyzed by receiver operator characteristic (ROC) curve. Results:There were no statistically significant differences between good prognosis group and poor prognosis group in age ( χ2=0.56, P=0.453), gender ( χ2=0.06, P=0.800), tumor size ( χ2=1.46, P=0.227), Child-Pugh grade ( χ2=0.26, P=0.608), tumor number ( χ2=0.77, P=0.382), cirrhosis ( χ2=0.03, P=0.860), TACE times ( χ2=0.16, P=0.691), alpha-fetoprotein level before treatment ( χ2=0.79, P=0.374), and hepatitis B surface antigen ( χ2=0.58, P=0.446). The proportion of TNM stage Ⅲ patients in the poor prognosis group (57.45%, 27/47) was higher than that in the good prognosis group (25.00%, 15/60), with a statistically significant difference ( χ2=11.64, P=0.001). The serum levels of SOCS3 and TXNIP in the good prognosis group before treatment were (114.34±20.39) and (45.64±6.41) pg/ml, respectively, while those in the poor prognosis group were (82.83±15.97) and (34.82±6.36) pg/ml, respectively, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=8.71, P<0.001; t=8.70, P<0.001). After treatment, the serum SOCS3 and TXNIP levels in the good prognosis group were (139.65±24.32) and (64.75±7.58) pg/ml, respectively, while those in the poor prognosis group were (92.41±16.15) and (41.74±7.23) pg/ml, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=11.48, P<0.001; t=15.90, P<0.001). Serum SOCS3 and TXNIP levels in both groups were significantly higher after treatment than before (all P<0.05). Multivariate analysis showed that TNM stage ( OR=2.53, 95% CI: 1.27-5.02, P=0.008) was an independent risk factor for prognosis in HCC patients after TACE treatment, SOCS3 ( OR=0.65, 95% CI: 0.44-0.96, P=0.031) and TXNIP ( OR=0.57, 95% CI: 0.36-0.89, P=0.014) were independent protective factors for prognosis in HCC patients after TACE treatment. ROC curve analysis showed that the sensitivity and specificity of the combined detection of serum SOCS3 and TXNIP before treatment in predicting prognosis of TACE treatment in HCC patients were 81% and 92%, respectively, the area under the curve was 0.92 (95% CI: 0.85-0.96) . Conclusion:The low levels of serum SOCS3 and TXNIP before TACE treatment in HCC patients may indicate poor prognosis after TACE treatment. The combined detection of the two has certain predictive value for judging the prognosis of HCC patients after TACE treatment.

Objective To evaluate the effect of modified vertical tooth preparation with full zirconium crown resto-ration in molar area.Methods A randomized study was conducted in 84 patients with all-ceramic crown restoration of posterior teeth.90 full crown restorations were collected and randomly divided into two groups:45 teeth in exper-imental group were treated with modified vertical tooth preparation,while 45 teeth in control group were treated with conventional horizontal tooth preparation with full zirconium crown restoration.When patients wore teeth,the resto-ration effects of the two groups were evaluated respectively,and then the marginal and internal fitness of the two groups were measured by silicone rubber replication method;gingival index(GI)and sulcus bleeding index(SBI)scores were recorded 6 months after wearing teeth.Results The results of chair-side evaluation of the two groups showed that the marginal fitness of the experimental group was better than that of the control group,and the differ-ence was statistically significant(P=0.036);the measured value of marginal fitness of prostheses in experimental group was better than that in control group,and the difference was statistically significant(P＜0.001);after 6 months,there was no mechanical complication between the two groups,and there was no significant difference in GI and SBI scores of periodontal soft tissue indexes.Conclusion Modified vertical tooth preparation abutment can significantly improve the marginal fitness of all-ceramic crown,which will not change the health status of peri-crown gingiva.

Objective To construct a machine learning model for predicting benign and malignant pulmonary nodules based on CT features.Methods A total of 129 patients with single solid nodules on CT from January 2021 to January 2023 in Hai'an People's Hospital were selected.All of them underwent chest CT scan,and the quantitative parameters,morphological features and radiomics features were recorded.The differentiation of benign and malignant pulmonary nodules was carried out according to relevant diagnostic criteria.The cases were divided into the training set and the internal test set.The constructed models included radiomics labels,morphological model,CT model and combined model.Results There were 98 cases in the training set(27 malignance and 71 benign)and 31 cases in the internal test set(7 malignance and 24 benign).Univariate analysis showed that there were significant differences in age,lesion diameter,mean density,burr sign,pleural depression sign,vacuole sign and air bronchial sign between malignant group and benign group(P<0.05).Compared with benign group,malignant group had higher proportions of burr sign,pleural depression sign,vacuole sign,air bronchial sign,and larger lesion diameter and mean density(P<0.05).LinkDocAI intelligent diagnosis system for pulmonary nodules was used to outline regions of interest and from which 1 000 radiomics features were extracted.The feature selection was performed in 98 cases,and 20 features were screened out after standardized treatment and correlation testing,excluding missing features,low importance feature values and highly correlated features.Through LASSO regression and 10-fold cross validation,λ1se was selected as the optimal λ to construct radiomics labels,and the two most meaningful features(LBP_Glszm_ZoneEntropy and Gradient_Shape_MinorAxis)were enrolled.CT model was considered as the optimal model in this study,and it had an area under receiver operating characteristic curve of 0.912 and 0.889 in the training set and the internal testing set,respectively.Conclusion The machine learning model to predict benign and malignant lung nodules based on CT features has good predictive efficiency,and it can realize the differential diagnosis of benign and malignant pulmonary nodules.

OBJECTIVES: In light of the rise in the global aging population, this study investigated the potential of the oxidative balance score (OBS) as an indicator of phenotypic age acceleration (PhenoAgeAccel) to better understand and potentially slow down aging. METHODS: Utilizing data from the National Health and Nutrition Examination Survey collected between 2001 and 2010, including 13,142 United States adults (48.7% female and 51.2% male) aged 20 and above, OBS and PhenoAgeAccel were calculated. Weighted generalized linear regression models were employed to explore the associations between OBS and PhenoAgeAccel, including a sex-specific analysis. RESULTS: The OBS demonstrated significant variability across various demographic and health-related factors. There was a clear negative correlation observed between the higher OBS quartiles and PhenoAgeAccel, which presented sex-specific results: the negative association between OBS and PhenoAgeAccel was more pronounced in male than in female. An analysis using restricted cubic splines revealed no significant non-linear relationships. Interaction effects were noted solely in the context of sex and hyperlipidemia. CONCLUSIONS A higher OBS was significantly associated with a slower aging process, as measured by lower PhenoAgeAccel. These findings underscore the importance of OBS as a biomarker in the study of aging and point to sex and hyperlipidemia as variables that may affect this association. Additional research is required to confirm these results and to investigate the biological underpinnings of this relationship.

Objective:To investigate the clinical characteristics and short-term follow-up outcomes of primary nephrotic syndrome (PNS) children infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron variant outbreak in Shanghai, and to provide a reliable reference for clinicians in the diagnosis and treatment.Methods:It was a case-control study. The clinical data of children with PNS (PNS group) who were diagnosed and followed-up up to 1 year in the nephrology department of four children's medical centers in Shanghai, and the children (control group) who had no underlying diseases and were infected with SARS-CoV-2 in Shanghai Jinshan Public Health Center, including the data when they were infected with SARS-CoV-2, were retrospectively analyzed.Results:(1) From March 30th to April 13th, 2022, 6 PNS children in Shanghai were infected with SARS-CoV-2, including 5 boys and 1 girl. The median age was 4.5 (2.0, 11.0) years old. And 30 children were matched by sex, age and disease type as control group, including 20 males and 10 females. The median age was 4.5 (2.0, 9.0) years. There were no significant differences between the PNS group and the control group in clinical symptoms (including fever duration), treatment regimens, vaccine doses and virus clearance time (all P>0.05). (2) The 6 children with PNS included 3 cases of steroid-sensitive type, 3 cases of steroid-resistant type, 2 cases of minimal change disease, 2 cases of focal segmental glomerulosclerosis and 2 cases with no renal biopsy. Before SARS-CoV-2 infection, their primary disease-PNS were stable, and urine protein was negative, four of them were under maintenance treatment with oral steroids or immunosuppressive drugs. At the time of SARS-CoV-2 infection, the symptoms of all of the 6 cases were mild, no severe, critical or fatal cases, and they were all cured and discharged from hospital through medical isolation observation or symptomatic treatment of infections. (3) Five cases of them still had discomfort symptoms such as cough, anorexia, and fatigue after being discharged from the hospital, which lasted for about 1 week. Within 1 year of follow-up, none of the children have suffered from "recurrent positive PCR results" or "secondary infection" of the SARS-CoV-2. (4) Among them, 4 cases of PNS relapsed after SARS-CoV-2 infection, timely addition of steroids was effective, their urine protein quickly turned negative, and there was no recurrence after 1 year of follow-up. (5) Before infection with SARS-CoV-2, the levels of immunoglobulin IgG were lower than the normal reference value in the 4 cases with PNS recurrence. Conclusions:During the Omicron variant outbreak in Shanghai, the infection of SARS-CoV-2 in children with PNS are resulted in high transmission among household contacts. Most of them have mild symptoms and good prognosis. PNS is prone to relapse after SARS-CoV-2 infection, and steroid therapy is effective and safe for these relapse. IgG may be a potential marker for the prognosis of PNS children infected with SARS-CoV-2.

Objective:To investigate the effect of helicobacter pylori (HP) infection and eradication treatment on small intestinal bacterial overgrowth (SIBO) in children.Methods:A prospective case-control study was conducted to select 68 children with symptoms of abdominal distension, abdominal pain, diarrhea and suspected digestive system diseases admitted to the Affiliated Hospital of Xuzhou Medical University from June 2021 to June 2022. They were divided into HP negative group and HP positive group according to HP infection. HP positive group received triple standardized HP eradication treatment, 14 days as a course of treatment. The baseline SIBO positive rate and gastrointestinal symptom rating scale (GSRS) score of the two groups were compared. The HP positive group was followed up for 4 and 12 weeks after drug withdrawal for quantitative assessment of gastrointestinal symptoms and LHBT. The SIBO positive rate, GSRS score of the two groups and the change of SIBO positive rate and GSRS score of the HP positive group before and after treatment were compared. The measurement data with normal distribution were expressed, and independent sample t-test was used for comparison between the two groups. M( Q1, Q3) was used to represent the measurement data of non normal distribution, and Mann Whitney U test was used to compare the two groups; Friedman test was used for comparison between multiple time points, and Nemenyi test was used for pairwise comparison. Four grid table or paired χ 2 test was used to compare the counting data between groups. Results:The positive rate of SIBO in HP negative group was lower than that in HP positive group (36.1% (13/36) vs 62.5% (20/32)), the difference was statistically significant (χ 2=4.72, P=0.030). Four weeks after drug withdrawal, the SIBO positive rate in HP positive group was higher than that before treatment (87.5% (28/32) vs 62.5% (20/32)), and 12 weeks after drug withdrawal was lower than that before treatment (21.9% (7/32) vs 62.5% (20/32)), with statistically significant differences (χ 2=8.00, P=0.008; χ 2=13.00, P<0.001). There was no statistically significant difference in GSRS score between HP negative group and HP positive group ( P=0.098). The clinical symptoms of 32 children in HP positive group were improved 4 and 12 weeks after HP eradication was stopped. GSRS scores were lower than those before treatment (8.0 (6.0, 12.8), 7.0 (5.0, 9.0) points vs 15.0 (12.0, 19.0) points) , and the differences were statistically significant ( Z values were -3.91, -4.68, respectively; all P<0.001). Conclusions:HP infection can increase the positive rate of SIBO in children with suspected digestive system diseases. The standardized triple HP eradication therapy may further aggravate the overgrowth of intestinal bacteria while treating HP infection, but this effect can be eliminated after 12 weeks of treatment.

ObjectiveTo investigate the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell and the mechanism. MethodMethyl thiazolyl tetrazolium （MTT） assay， hematoxylin-eosin （HE） staining， 4'，6-diamidino-2-phenylindote （DAPI） staining， colony formation assay， scratch assay， and flow cytometry were employed for the analysis of apoptosis and cell cycle. Thereby， the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell was investigated. Then the Pharm Mapper， UniProt， Swissdock， STRING， and Metascape were used for target screening， gene annotation， molecular docking， protein-protein interaction （PPI） network construction， Gene Ontology （GO） term and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis to explore the mechanism. ResultHederasaponin B （15， 30， 60， 120 μmol·L^-1） can significantly reduce the survival rate of HGC-27 cell （P<0.01） in a time-dependent and dose-dependent manner compared with the blank group. It had no significant toxicity to normal GES-1 cell at concentration below 120 μmol·L^-1. Compared with the blank group， hederasaponin B （30， 60， 120 μmol·L^-1） induced cytoplasmic vacuolization， and nuclear deformation and karyopyknosis， inhibited the migration of HGC-27 cell （P<0.01）， and brought about the apoptosis （P<0.05， P<0.01） and cell cycle arrest of HGC-27 cell （P<0.05， P<0.01）. Hederasaponin B （10， 20， 30 μmol·L^-1） also suppressed the independent survival ability and proliferation ability of HGC-27 cell （P<0.01）. The possible action targets were kinesin-like protein KIF11， cGMP-specific 3，5 cyclic phosphodiesterase， caspase-3， serine/threonine protein kinase Chk1， proto-oncogene tyrosine protein kinase， epidermal growth factor receptor， and mitogen-activated protein kinase （MAPK） 8. The mechanism may be related to MAPK signaling pathway （pathways in cancer）， adhesion connection， focal adhesion and proteoglycans in cancer （epithelial cell signaling pathways in Helicobacter pylori infection）. ConclusionHederasaponin B exerts significant inhibitory effect on gastric cancer HGC-27 cell through multiple targets and multiple pathways.