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.

Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

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 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 investigate the efficacy and safety of sintilimab combined with the SOX regimen for adjuvant treatment of stage Ⅲgastric cancer after D2 radical resection and to provide a reference for individualized clinical treatment.Methods:The clinical data of 245 pa-tients with stage III gastric cancer who underwent D2 radical resection at the 940th Hospital of the Joint Support Force of the People's Liber-ation Army from June 2019 to May 2022 were retrospectively analyzed.The 180 patients who received only the SOX regimen were desig-nated the control group,and the 65 patients who received sintilimab combined with the SOX regimen were designated the experimental group.The 3-year disease-free survival(DFS)rate,overall survival(OS)rate,and adverse reactions among the two groups and different sub-groups(HER-2 positive,dMMR,CPS≥5)were compared.Results:The 3-year DFS(81.5%vs.59.4%)and OS(84.6%vs.70.6%)rates in the experimental group were significantly higher than those in the control group(both P<0.05).Group analysis showed that in patients with CPS≥5,the 3-year DFS(91.5%vs.67.0%)and OS(95.7%vs.71.6%)rates within the experimental group were significantly better than those in the control group(both P<0.05).Intra-group analysis within the experimental group showed that the 3-year DFS rate(91.5%vs.55.6%)and OS rate(95.7%vs.55.6%)of patients with CPS≥5 were significantly better than those of patients with CPS<5(both P<0.05).The overall and grade≥3 incidences of liver and kidney function damage,thyroid dysfunction,colitis,pneumonia,and rash in the experimental group were higher than those in the control group(all P<0.05),while the differences in other adverse reactions,including leukopenia were not statistic-ally significant(all P>0.05).Conclusions:Sintilimab combined with the SOX regimen can significantly improve 3-year DFS and OS rates in pa-tients with stage Ⅲ gastric cancer after surgery,especially in the CPS≥5 subgroup,with significant benefits and controllable safety.

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.

Objectives:This study aims to explore the causal relationships between immune cells and serum metabolites in the development of coronary heart disease(CHD)using Mendelian randomization(MR)methods.Methods:We conducted a two-sample MR analysis utilizing data from the FinnGen Project's genome-wide association study(GWAS)on CHD,alongside data on metabolites and immune cells from the GWAS catalog.For the identified associated metabolites,we further employed mediation MR methods to evaluate their mediating roles in the influence of immune cells on CHD.Results:The MR analysis indicated that three immune cells(IgD-CD24-%B cell,CD11b on CD14+monocyte,HLA DR on DC)had stable causal relationship with CHD(under the premise of inverse variance weighted[IVW]method P<0.05,both MR-Egger and weighted median methods also showed P<0.05).Furthermore,these immune cells were associated with CHD through four metabolites(N-acetylneuraminic acid levels,the ratio of desmethyltaurine to taurine,X-24801 and X-18779).Conclusions:This study reveals the causal relationships between immune cells and serum metabolites in the pathogenesis of CHD,providing new biomarkers for early prediction and risk assessment of CHD.

Objective:To observe the effectiveness of extracorporeal counterpulsation therapy in patients with heart failure in ischaemic cardiomyopathy.Methods:A total of 112 patients with ischemic cardiomyopathy and heart failure admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2020 to June 2023 were prospectively selected and divided into two groups by random number table method. The control group was treated with conventional drugs and conventional cardiac rehabilitation program, and the observation group was combined with external counterbeating therapy on the basis of the control group. The levels of N-terminal B-type brain natriuretic peptide (NTproBNP), soluble growth stimulation-expression gene-2 protein (sST2), neutrophil gelatinase-associated lipid carrier protein (NGAL), galactin-3 (Gal-3), cardiopulmonary exercise test (CPET) parameters and cardiac ultrasound indexes were compared between the two groups before and after treatment. The curative effect and the rate of re-hospitalization within 6 months were compared between the two groups.Results:After treatment, the levels of NTproBNP, sST2, NGAL and Gal-3 in the observation group were lower than those in the control group: (1941.36 ± 312.59) ng/L vs. (2674.22 ± 404.64) ng/L, (44.78 ± 3.97) ng/L vs. (52.45 ± 4.13) ng/L, (22.63 ± 3.65) μg/L vs. (26.41 ± 3.77) μg/L, (4.63 ± 1.29) ng/L vs. (6.11 ± 1.78) ng/L, there were statistical differences ( P<0.05); the maximum kilogram oxygen uptake (VO 2max/kg), maximum kilogram oxygen uptake as a percentage of predicted value (VO 2max/kg%pred), maximum minute ventilation as a percentage of predicted value (VEmax%pred) in the observation group were higher than those in the control group: (22.41 ± 2.23) ml/(min·kg) vs. (21.35 ± 2.09) ml/(min·kg), (83.79 ± 11.04)% vs. (78.74 ± 10.14)%, (88.95 ± 12.74)% vs. (75.45 ± 11.14)%, there were statistical differences ( P<0.05 or <0.01); the left ventricular ejection fraction (LVEF) in the observation group was higher than that in the control group and the left ventricular posterior wall thickness (LVPWT) and left ventricular posterior wall end-systolic thickness (PWS) were lower than those in the control group: (50.12 ± 3.87)% vs. (48.63 ± 3.74)%, (8.77 ± 1.58) mm vs. (9.63 ± 1.97) mm, (9.34 ± 1.54) mm vs. (10.14 ± 1.79) mm, there were statistical differences ( P<0.05). There was no statistical difference in the total effective rate between the two groups ( P>0.05). The patient readmission rate within 6 months of follow-up in the observation group was lower than that in the control group: 5.45%(3/55) vs. 20.00%(11/55), there was statistical difference( χ2 = 5.24, P<0.05). Conclusions:Extracorporeal counterpulsation therapy for the treatment of heart failure in ischaemic cardiomyopathy can improve the cardiorespiratory function, reduce the expression of NTproBNP, sST2, NGAL and Gal-3, and decrease the patient readmission rate.

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system in China. With the progress of immunotherapy research, programmed death receptor-1 (PD-1) inhibitor-based combinatory therapy offers new ideas for the treatment of advanced gastric cancer. In recent years, with the increasing status of immunotherapy in the treatment of advanced gastric cancer, a growing number of domestic and international clinical studies shown that immunotherapy could achieve better efficacy in the neoadjuvant therapy and conversion therapy for patients with advanced gastric cancer. This paper reviews the current research progress on the application of PD-1 inhibitors in the neoadjuvant therapy and conversion therapy of gastric cancer.

IMPG2 gene variations can cause inherited retinal dystrophy (IRD).The clinical phenotypes of IMPG2 related IRD are heterogeneous, including retinitis pigmentosa, vitelliform macular dystrophy and occasionally Stargardt-like macular dystrophy.There is a certain correlation between the variation type and the clinical phenotype.The compound heterozygous/homozygous IMPG2 variations predominantly cause autosomal recessive retinitis pigmentosa, while heterozygous mutations is typically associated with autosomal dominant vitelliform macular dystrophy showing incomplete dominance.IMPG2 expressed by retinal photoreceptors encodes interphotoreceptor matrix, though its pathogenesis remains unclear.Studies suggest variations may cause mislocalization of matrix components, aberrant energy metabolism and impaired autophagy in the retina.This review summarizes IMPG2-related IRD phenotypes and advances in pathogenic mechanisms, providing theoretical support for clinical diagnosis, therapy and research.