Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

The key to the onset and progression of the functional impairments of orthopedic diseases is imba-lance of deficiency and excess， disharmony of movement and stillness， dislocation of sinews and bones， imbalance of rigidity and flexibility， and disharmony of body and spirit. Based on this， the "five views" treatment principle has been proposed for traditional Chinese medicine （TCM） orthopedic rehabilitation， which include the view of balancing deficiency and excess， combining movement and stillness， focusing on both sinews and bones， integrating rigidity and flexibility， and harmonizing body and spirit. Correspondingly， the "five views" collaborative rehabilitation clinical model is established， providing a reference for enhancing the systematization and targeting of TCM orthopedic rehabilitation.

Objective To evaluate the diagnostic value of black blood computed tomography(BBCT)in vulnerable plaques at the carotid bifurcation.Methods The imaging data of 73 patients with suspected carotid atherosclerosis were retrospectively analyzed.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of conventional computed tomography angiography(CTA)ima-ges and BBCT images were compared by paired sample t-test.The 5-level scoring method was applied to evaluate the image quality subjectively,and the Friedman test was used to compare the differences in the subjective evaluation of image quality among the groups.Taking high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)as the gold standard,the diagnostic value between BBCT and conventional CTA was compared,and the consistency of BBCT and HRMR-VWI in the evaluation of vulnerable plaques was calculated.Results The standard deviation(SD)value of BBCT images was lower than that of conventional three-phase CTA images,indicating better quality of BBCT images(P＜0.001).The mean CT value and CNRplaque-lumen of non-calcified plaques were higher in BBCT images than those in conventional three-phase CTA images,suggesting that BBCT had a higher contrast with sur-rounding tissues and could better display the fine structure of non-calcified plaques(P＜0.001).BBCT images achieved the highest scores in the subjective evaluation of image quality(P＜0.001).Compared with conventional CTA images,BBCT had higher sensi-tivity(88.2％vs 29.4％)and accuracy(90.9％vs 54.5％)in identifying vulnerable plaques(P＜0.001).The Kappa value between BBCT and HRMR-VWI was 0.813,showed good consistency.Conclusion The image quality of neck BBCT is superior to that of conventional CTA.BBCT has a better effect than conventional CTA in identifying vulnerable plaques at the carotid bifurcation,which is comparable to HRMR-VWI.

Objective To evaluate the application of high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)in identifying high-risk features of intracranial atherosclerotic plaques,and to analyze the correlation between plaque characteristics and stroke recurrence under varying degrees of stenosis.Methods The data from 368 patients with intracranial atherosclerotic stenosis(ICAS)across two centers were retrospectively analyzed.Based on the degree of stenosis,all patients were categorized into mild-to-moderate stenosis group(luminal stenosis<70%,n=155)and severe stenosis group(luminal stenosis≥70%,n=213).HRMR-VWI images and clinical information of the patients were collected and analyzed,and the culprit plaques were quantitatively analyzed.Univariate and multivariate logistic regression analyses were employed to identify the risk factors for stroke recurrence,and the predictive performance was evaluated using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results Higher normalized wall index(NWI)[odds ratio(OR)=1.082,95%confidence interval(CI)1.050-1.118,P<0.05]and the presence of intraplaque hemorrhage(IPH)(OR=1.843,95%CI 1.120-3.036,P<0.05)were risk factors for stroke recurrence in all patients.And these two factors were also significant in the mild-to-moderate stenosis group(NWI:OR=1.088,95%CI 1.009-1.186,P<0.05;IPH:OR=4.049,95%CI 1.227-16.065,P<0.05).A predictive model for stroke recurrence was constructed using the combination of IPH and NWI,with the best performance in the mild-to-moderate stenosis group(AUC=0.813,95%CI 0.723-0.906).Conclusion In patients with luminal stenosis<70%,the increase of NWI and the presence of IPH have been validated as significant and effective indicators for predicting stroke recurrence,demonstrating notable predictive performance.In contrast,among patients with luminal stenosis≥70%,the utility of plaque characteristics in predicting stroke recurrence is relatively lower,indicating that the correlation between plaque characteristics and stroke recurrence varies across different degrees of stenosis.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective To observe the value of T1WI deep learning models for evaluating brain injury of neonatal hyperbilirubinemia(NHB).Methods Totally 106 NHB(defined as newborns with neonatal behavioral neurological assessment≤37,NHB group)and 119 non-NHB newborns(control group)in center A,as well as 34 NHB and 18 non-NHB newborns in center B were collected.ROI was delineated based on bilateral globus pallidus on T1WI.A total of 690 slices were obtained by preprocessing data of center A and then were divided into training set(n=552)and test set(n=138)at a ratio of 8∶2.ResNet18,DenseNet121 and EfficientNetB0 models was established,respectively.External validation was performed based on data of center B.Receiver operating characteristic curves were drawn,area under the curves(AUC)were calculated to evaluate the performance of models for assessing NHB brain injuries compared with traditional visual analysis.Results The AUC of ResNet18 model for evaluating NHB brain injury was 0.910-0.990,significantly higher than that of DenseNet121 model(0.710-0.820)and EfficientNetB0 model(0.640-0.740)(all P＜0.001).The accuracy,sensitivity and precision of ResNet18 model for evaluating NHB brain injury were all higher than those of visual analysis(all P＜0.05),while no significant difference of specificity was found between the above two(P＞0.05).Conclusion T1WI ResNet18 model showed excellent performance and generalization ability for evaluating NHB brain injury.

Purpose To explore the value of amide proton transfer(APT)imaging combined with diffusion kurtosis imaging(DKI)in the differential diagnosis of prostate carcinoma and benign prostatic hyperplasia.Materials and Methods A retrospective analysis was conducted on 120 patients who underwent multi-parameter prostate MRI and pathological biopsy at the First Affiliated Hospital of Xinxiang Medical University from January 2020 to August 2021,including 66 cases of benign prostatic hyperplasia and 54 cases of prostate carcinoma.The parameters of APT imaging and DKI,including magnetization transfer ratio asymmetry(MTRasym),mean kurtosis(MK),mean diffusion coefficient(MD)and fraction anisotropy were measured,and the parameters between the two groups were compared and analyzed.The receiver operating characteristic curve and Delong test were used to analyze the efficacy of each parameter,APT or DKI sequence alone and their combined diagnosis,and the correlation among the parameters was analyzed.Results Compared with the benign prostatic hyperplasia group,the MTRasym,MK and fraction anisotropy of the prostate carcinoma group were significantly higher,while the MD was significantly lower,with statistical significance(t=8.23,12.53,2.20,-11.12,all P<0.05).The areas under the curve for the above parameters were 0.852,0.933,0.615 and 0.910,respectively.The diagnostic efficacy of APT combined with DKI for differentiating prostate carcinoma from benign prostatic hyperplasia is numerically higher than that of APT alone or DKI alone,with the areas under the curve being 0.994,0.988 and 0.852,respectively,as well as a sensitivity of 96.30%and a specificity of 98.48%.There was a statistically significant difference in efficacy between the APT+DKI combined approach and APT alone(Z=4.387,P<0.05),while no statistically significant difference exists between the combined approach and DKI alone(Z=1.375,P>0.05).MTRasym was positively correlated with MK(r=0.45,P<0.001).MD was negatively correlated with MTRasym and MK(r=-0.439,-0.500,both P<0.001).Conclusion The parameters MTRasym,MK and MD of APT and DKI have relatively high value in distinguishing prostate carcinoma from benign prostatic hyperplasia,and the combined diagnostic efficiency of the two sequences tends to increase,with some parameters showing correlation.

Objective To explore the effect of endoscopic retrograde appendicitis therapy on inflammatory reaction,oxidative stress and immune level in patients with acute appendicitis.Methods 82 patients with acute appendicitis who were treated from January 2020 to September 2023,and divided into control group(41 cases)and treatment group(41 cases).The grouping method was random number table method.The control group was given laparoscopic appendectomy,and the treatment group was given endoscopic retrograde appendicitis therapy.Both groups observed that the patients were discharged from hospital and were followed up for 1 week.The operation-related indexes,levels of inflammatory factors[serum procalcitonin(PCT),soluble intercellular adhesion molecule-1(sICAM-1),lipoxin A4(LXA4),soluble P-selectin(sP-s)and C-reactive protein(CRP)],oxidative stress[serum superoxide dismutase(SOD)and malondialdehyde(MDA)]and immune function[immunoglobulin M(IgM)and immunoglobulin G(IgG)]before and 24 h after operation,score of pain before operation,12 h and 24 h after operation and complications(during the study period)were compared between the two groups.Results Compared with the control group,the amount of bleeding in the treatment group was relatively less,and the time of lying on bed,hospitalization,anal exhaust and body temperature returning to normal after operation were relatively shorter,the differences were statistically significant(P＜0.05).Compared with pre-operation,the levels of serum sICAM-1,LXA4 and sP-s in both groups decreased at 24 h after operation,while the level of serum PCT and CRP increased,the treatment group was significantly lower than the control group(P＜0.05).Compared with pre-operation,the levels of serum SOD,IgM and IgG in the two groups decreased at 24 h after operation,but the levels in the treatment group were relatively higher,while the levels of serum MDA all increased,which was lower in the treatment group(P＜0.05).Compared before operation,the scores of pain in the two groups showed a downward trend from 12 and 24 h after operation,and compared with the control group,the scores of pain in the treatment group were relatively lower(P＜0.05).During the study period,compared with 26.83%in the control group,the total incidence of complications in the treatment group was 7.32%,which was relatively lower(P＜0.05).Conclusion Endoscopic retrograde appendicitis therapy for acute appendicitis can effectively reduce patients'oxidative stress and inflammatory reaction,protect their immune function,shorten patients'postoperative recovery time,relieve their pain and reduce the incidence of postoperative complications.