Objective:To investigate the value of a deep learning radiomics (DLR) nomogram model based on intra-tumoral and peri-tumoral MRI features for differentiating IgG4-related ophthalmic disease (IgG4-ROD) from orbital mucosa-associated lymphoid tissue (MALT) lymphoma.Methods:This was a case-control study. The clinical and imaging data of 233 patients pathologically confirmed with either IgG4-ROD or orbital MALT lymphoma were retrospective collected between January 2020 and December 2024 from the Second Hospital of Jilin University (Center 1) and Beijing Tongren Hospital, Capital Medical University (Center 2). Patients from Center 1 ( n=158) were used as the training cohort, while those from Center 2 ( n=75) served as the validation cohort. Among the cases, 102 were IgG4-ROD (70 in training, 32 in validation) and 131 were orbital MALT lymphoma (88 in training, 43 in validation). Univariate and multivariate logistic regression analyses were used to identify independent clinical imaging predictors and build a clinical imaging model. Based on T 1WI, T 2WI, and diffusion weighted images, intra-tumoral regions were manually delineated, a 2 mm peri-tumoral margin was automatically generated, and both regions were combined as a single region of interest for radiomics feature extraction. Deep learning features were extracted using a ResNet-50 backbone, and after feature selection and dimensionality reduction, a DLR model was constructed. The clinical imaging features and DLR features were integrated to build a combined nomogram model. Model performance in differentiating IgG4-ROD from orbital MALT lymphoma was assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis. The area under the curve (AUC) were compared using the DeLong test. Results:Bilateral orbital involvement ( OR=1.983, 95% CI 1.166-2.843, P=0.046) and extraocular muscle involvement ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as independent predictors for distinguishing IgG4-ROD from orbital MALT lymphoma and were used to construct the clinical model. Fourteen features (9 radiomics and 5 deep learning features) were selected for the DLR model, and a nomogram was developed. In the training set, the AUCs for the clinical model, DLR model, and nomogram were 0.762 (95% CI 0.712-0.812), 0.865 (95% CI 0.822-0.908), and 0.943 (95% CI 0.909-0.953), respectively. In the validation set, the AUCs were 0.733 (95% CI 0.675-0.791), 0.823 (95% CI 0.762-0.884), and 0.924 (95% CI 0.902-0.958), respectively. The nomogram showed significantly higher AUCs than those of the clinical and DLR models alone (training set: Z=3.92, 2.87, P0.001, P=0.004; validation set: Z=3.25, 2.46, P=0.001, 0.014). Calibration curves indicated good agreement between predicted and actual IgG4-ROD incidence, and decision curve analysis demonstrated the highest net benefit for the nomogram. Conclusion:A nomogram that incorporates both intra-tumoral and peri-tumoral DLR features and clinical imaging characteristics demonstrates excellent performance in distinguishing IgG4-ROD from orbital MALT lymphoma.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

Objective:To investigate the value of a deep learning radiomics (DLR) nomogram model based on intra-tumoral and peri-tumoral MRI features for differentiating IgG4-related ophthalmic disease (IgG4-ROD) from orbital mucosa-associated lymphoid tissue (MALT) lymphoma.Methods:This was a case-control study. The clinical and imaging data of 233 patients pathologically confirmed with either IgG4-ROD or orbital MALT lymphoma were retrospective collected between January 2020 and December 2024 from the Second Hospital of Jilin University (Center 1) and Beijing Tongren Hospital, Capital Medical University (Center 2). Patients from Center 1 ( n=158) were used as the training cohort, while those from Center 2 ( n=75) served as the validation cohort. Among the cases, 102 were IgG4-ROD (70 in training, 32 in validation) and 131 were orbital MALT lymphoma (88 in training, 43 in validation). Univariate and multivariate logistic regression analyses were used to identify independent clinical imaging predictors and build a clinical imaging model. Based on T 1WI, T 2WI, and diffusion weighted images, intra-tumoral regions were manually delineated, a 2 mm peri-tumoral margin was automatically generated, and both regions were combined as a single region of interest for radiomics feature extraction. Deep learning features were extracted using a ResNet-50 backbone, and after feature selection and dimensionality reduction, a DLR model was constructed. The clinical imaging features and DLR features were integrated to build a combined nomogram model. Model performance in differentiating IgG4-ROD from orbital MALT lymphoma was assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis. The area under the curve (AUC) were compared using the DeLong test. Results:Bilateral orbital involvement ( OR=1.983, 95% CI 1.166-2.843, P=0.046) and extraocular muscle involvement ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as independent predictors for distinguishing IgG4-ROD from orbital MALT lymphoma and were used to construct the clinical model. Fourteen features (9 radiomics and 5 deep learning features) were selected for the DLR model, and a nomogram was developed. In the training set, the AUCs for the clinical model, DLR model, and nomogram were 0.762 (95% CI 0.712-0.812), 0.865 (95% CI 0.822-0.908), and 0.943 (95% CI 0.909-0.953), respectively. In the validation set, the AUCs were 0.733 (95% CI 0.675-0.791), 0.823 (95% CI 0.762-0.884), and 0.924 (95% CI 0.902-0.958), respectively. The nomogram showed significantly higher AUCs than those of the clinical and DLR models alone (training set: Z=3.92, 2.87, P0.001, P=0.004; validation set: Z=3.25, 2.46, P=0.001, 0.014). Calibration curves indicated good agreement between predicted and actual IgG4-ROD incidence, and decision curve analysis demonstrated the highest net benefit for the nomogram. Conclusion:A nomogram that incorporates both intra-tumoral and peri-tumoral DLR features and clinical imaging characteristics demonstrates excellent performance in distinguishing IgG4-ROD from orbital MALT lymphoma.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

Objective To observe the effects of needle-knife tendon-sparing and knot-dissolving technique on NF-κB/Bcl-2 pathway activity and the expression of TNF-α,IL-1β,IL-6,Bax and caspase-3 in synovial tissue of knee joints of rabbits with rheumatoid arthritis(RA)model;To explore the mechanism of its inhibitory effect on RA synovial inflammation.Methods Totally 24 New Zealand white rabbits were randomly divided into normal group,model group,drug group and needle-knife group,with 6 rabbits in each group.Except for the normal group,the other groups were injected with ovalbumin and Freund's complete adjuvant into the knee joint cavity to replicate the RA model,and corresponding interventions were given for 18 consecutive days.The knee pain threshold and knee circumference were measured,ultrasound was used to observe the joint cavity effusion,synovial thickness and internal blood flow signals,the synovial tissue morphology were observed by HE staining,the apoptosis of fibroblast-like synoviocytes(FLS)in synovial tissue was observed by TUNEL staining,the expression of TNF-α,IL-1β and IL-6 in synovial tissue were detected by immunohistochemistry,RT-PCR was used to detect NF-κBp65 and Bcl-2 mRNA expression in synovial tissue,Western blot was used to detect the protein expression of NF-κBp65,p-NF-κBp65,Bcl-2,Bax and caspase-3 in synovial tissue.Results Compared with the normal group,the knee pain threshold decreased,knee circumference increased,ultrasonic score and pathological score of synovial tissue increased in the model group;FLS apoptosis rate decreased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue increased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein increased,while the expression of Bax,caspase-3 protein decreased,with statistical significance(P<0.05).Compared with the model group,the knee pain threshold increased in the drug group and the needle knife group,the circumference of the knee joint decreased,the ultrasonic score and pathological score of synovial tissue were significantly decreased;the apoptosis rate of FLS increased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue decreased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein decreased,and the expression of Bax and caspase-3 protein increased,with statistical significance(P<0.05).Conclusion Needle-knife tendon-sparing and knot-dissolving technique may promote FLS apoptosis and reduce TNF-α,IL-1β and IL-6 production,inhibit synovial inflammation in RA,reduce knee joint swelling,and raise pain threshold by reducing the activity of synovial tissue NF-κB/Bcl-2 pathway.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

OBJECTIVETo compare the differences in the clinical therapeutic effects on juvenile myopia between's stunt needling technique and traditional even needling technique.

METHODSA total of 166 cases of mild juvenile myopia (diopter <-3.00D) were randomized into an observation group ('s stunt needling technique) and a control group (traditional even needling technique), 83 cases in each one (166 affected eyes). Taiyang (EX-HN 5), Fengchi (GB 20), Cuanzhu (BL 2), Hegu (LI 4) and Guangming (GB 37) were used in the two groups. In the observation group, theneedling technique was adopted at Taiyang (EX-HN 5), theneedling technique at Fengchi (GB 20) andneedling technique at Cuanzhu (BL 2). The traditional needling technique was used at Hegu (LI 4) and Guangming (GB 37). In the control group, traditional even needling technique was applied at all the acupoints. The treatment was given once every day, continuously for 6 times as one course. There was 1 day at interval. After treatment for 4 courses, the changes in visual acuity, diopter and axial length were observed before and after treatment. The therapeutic effects were evaluated.

RESULTSAfter treatment, the visual acuity of the naked eyes, and diopter were remarkably improved in the patients of the two groups (all<0.05). The improvements in the observation group were better than those in the control group (both<0.05). The axial length did not change in the two groups (both>0.05). The total effective rate was 78.3% (130/166) in the observation group, which was better than 57.8% (96/166) in the control group (<0.05). .

CONCLUSION 's stunt needling technique effectively improves the vision, rectifies the refractive error and delays the progression of myopia. The therapeutic effects of it are better than traditional even needling technique.

OBJECTIVETo explore heat-reinforcing needling for the metabolite profiling changes in serum of rheumatoid arthritis (RA) rabbits with liquid chromatograph-mass spectrometer (LC-MS) technique, and to investigate its mechanisms.

METHODSForty clean purple blue rabbits were randomized into a normal group, a model group, a reinforcing-reducing needling (RRN) group, a twirling-reinforcing needling (TRN) group, and a heat-reinforcing needling (HRN) group, 8 cases in each group. RA rabbits with cold syndrome were made with ovalbumin and freezing except those in the normal group. No treatment was given in the normal and model groups. The corresponding manipulations for 7 days were applied at "Zusanli" (ST 36) in the three acupuncture groups, 30 min a time, once a day. After intervention the pain threshold and the local skin temperature of each group were observed. Fresh serum from heart was collected for metabonomics detection. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were adopted. Several metabolites were screened by the variable importance in the projection values (VIP>1) andvalue (<0.05).

RESULTSThe pain threshold and the local skin temperature in the model group were lower than those in the normal group (both<0.05). The pain threshold and the local skin temperature in the three acupuncture groups were higher than those in the model group after intervention (all<0.05), which were better in the HRN group than those in the RRN and TRN groups (all<0.05). The serum metabolites of carnitine, LysoPC (14∶0), LysoPC (18∶3), LysoPE (0∶0/20∶5), LysoPE (0∶0/22∶1), decylic acid, stearic acid and lactic acid in the model group increased compared with those in the normal group, and other metabolites decreased, including leucine, valine, glutamine, pyroglutamic acid, α-ketoglutaric acid, succinic acid, fumaric acid, malic acid, galactose, mannose. Those metabolites were correlated fatty acid, amino acid, citric acid cycle, and glucose metabolism. The metabolites above-mentioned in the three acupuncture groups were regulated in various degrees (all<0.05). Lactic acid decreased and succinic acid, fumaric acid, malic acid, galactose, mannose increased more obviously in the HRN group than those in the RRN and TRN groups.

CONCLUSIONThe specificity of heat-reinforcing needling for RA presents the regulation for citric acid cycle and glucose metabolism.

OBJECTIVETo compare the difference in the clinical efficacy on post-stroke upper limb spasmodic hemiplegia between the combined therapy ofneedling technique and Bobath technology and simple Bobath technology.

METHODSSixty patients were randomized into an observation group and a control group, 30 cases in each one. The usual medication of neurological internal medicine was used in the two groups. In the control group, Bobath facilitation technology was applied to the rehabilitation training. In the observation group, on the basis of the treatment as the control group,needling technique was used to stimulate Zhongfu (LU 1), Tianfu (LU 3), Chize (LU 5), Quchi (LI 11), Jianshi (PC 5) and Daling (PC 7). The treatment was given once a day; 5 treatments made one session and totally 4-week treatment was required in the two groups. The modified Ashworth scale, the modified Fugle-Meyer assessment (FMA) and the Barthel index (BI) were adopted to evaluate the muscular tension, the upper limb motor function and the activities of daily living (ADL) before and after treatment in the two groups. The clinical efficacy was compared between the two groups.

RESULTSCompared with those before treatment, the modified Ashworth scale, Fugl-Meyer score and BI score were all improved after treatment in the two groups (all<0.01). The results in the observation group were better than those in the control group (all<0.01). The total clinical effective rate was 93.3% (28/30) in the observation group and was 80.0% (24/30) in the control group. The efficacy in the observation group was better than that in the control group (<0.05).

CONCLUSIONSTheneedling technique combined with Bobath therapy achieve the superior efficacy on post-stroke upper limb spasmodic hemiplegia as compared with the simple application Bobath therapy. This combined treatment effectively relieve spasmodic state and improve the upper limb motor function and the activities of daily living.

OBJECTIVETo compare the effects of different acupuncture methods on urine metabolites in rheumatoid arthritis (RA) rabbits, and to explore the specificity mechanism of heat-reinforcing acupuncture for RA.

METHODSA total of 40 clean purple-blue rabbits were randomly allocated to a normal group, a model group, a mild reinforcing-reducing needling (MRRN) group, a twirling-reinforcing needling (TRN) group and a heat-reinforcing needling (HRN) group, 8 rabbits in each one. Except the normal group, the rabbits in the remaining groups were treated with ovalbumin and freezing to establish RA model. The rabbits in the MRRN group, TRN group and HRN group were treated with MRRN, TRN and HRN at "Zusanli" (ST 36), respectively, 30 min per treatment, once a day for seven days. After treatment, 24-h urine was collected. The rabbits were sacrificed to collect synovial tissues of knee to perform morphology observation; the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS) was applied to measure urine metabolites. All the data were analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA).

RESULTSCompared with the normal group, the leucine-related metabolites, as main urine metabolites, were decreased in the model group (<0.05), while the purine-related metabolites and tryptophane-related metabolites were increased (<0.05). Compared with the model group, the leucine-related metabolites, as main urine metabolites, were increased in the three needling groups after treatment (<0.05), while the tryptophan-related metabolites andpurine-related metabolites were decreased (<0.05), moreover, the leucine-related metabolites in the HRN group were obviously higher than those in the MRRN group and TRN gruop (<0.05).

CONCLUSIONSMRRN, TRN and HRN can regulate the pathway of leucine metabolism (energy metabolism), purine metabolism (oxidative damage) and tryptophane metabolism (immune regulation) for RA, The specificity of HRN for RA focuses on regulation of leucine metabolism (energy metabolism).