ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

The gene encoding regulatory subunit 15 A of protein phosphatase 1 produces a protein that is a universally present protein phosphatase in eukaryotic cells.In this study,genomic DNAs were extracted from the blood of 89 Chinese Holstein cows and were used as templates for PCR amplification of the target fragment of the PPP1R15A gene.The product was tested and a polymor-phic site,E3-250T＞A was found.The polymorphism of this side and its correlation with milk pro-duction traits in Chinese Holstein cattle were statistically analyzed using SPSS 23.0 software.The findings revealed three genotypes at this site:AA,AT and TT.Cows possessing the AT and TT genotypes exhibited significant differences(P＜0.01)in milk fat and solid non-fat content com-pared to those with the AA genotype.While no significant differences were noted for other milk production traits,including milk yield,protein,lactose,somatic cell count,blood urea nitrogen,and corrected milk.The identification of functional SNPs in the PPP1R15A gene provides a theoretical basis for further research and identification of causal variations in the cow PPP1R15A gene.

Objective To investigate the association between dipstick hematuria and chronic kidney disease(CKD)in patients with diabetes mellitus(DM).Methods DM patients who underwent the first health examination among the working and retired employees of Kailuan General Hospital and 11 affiliated hospitals in Tangshan City,Hebei Province from 2006 to 2007 were included as the study objects.Test dipstick hematuria is defined by the level of urine occult blood on the test paper:negative dipstick hematuria(NH)<10 erythrocytes/μl,moderate dipstick hematuria(MH)trace～1+(10～49 erythrocytes/μl),severe dipstick hematuria(SH)2+～3+(≥50 erythrocytes/μl).CKD is diagnosed based on eGFR and urinary protein levels.Logistic regression model was used to analyze the association between paper hematuria and CKD in DM patients.Results A total of 8958 DM patients were included,including 2390 patients(26.68%)in the CKD group and 6568 patients(73.32%)in the DM group.The detection rates of moderate dipstick hematuria and severe dipstick hematuria in CKD group were 9.00%and 4.64%,respectively,higher than those in DM group(7.20%and 2.33%).The risk of CKD in MH and SH patients was 1.560(95%CI 1.260～1.940)and 3.080(95%CI 2.220～4.270)times that in NH patients,respectively.The odds ratios were 1.960(95%CI 1.530～2.510)and 3.430(95%CI 2.270～5.200)in males and 0.910(95%CI 0.580～1.430)and 2.760(95%CI 1.570～4.880)in females.The odds ratios were 1.650(95%CI 1.150～2.350)and 4.070(95%CI 2.240～7.400)in patients aged≥60 years,and 1.550(95%CI 1.170～2.040)and 2.860(95%CI 1.920～4.240)in patients aged<60 years.Conclusions Dipstick hematuria is a risk factor for CKD in DM patients.The association between dipstick hematuria and CKD in DM patients is not only independent of traditional risk factors,but also affected by age and gender.

Objective:To investigate the efficacy of 99Tc m-pyrophosphate (PYP) SPECT imaging for the differential diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA) and hypertrophic cardiomyopathy (HCM). Methods:Data of patients who were definitively diagnosed with ATTR-CA (35 patients (28 males, 7 females); age 62.5(58.6, 64.3) years) or HCM (14 patients (13 males, 1 female); age 60.5(57.3, 68.7) years) by extracardiac biopsy and echocardiography in the Second Xiangya Hospital of Central South University between June 2020 and March 2023 were retrospectively analyzed. All patients underwent planar and SPECT imaging 1 h after injection of 370-720 MBq 99Tc m-PYP. Visual scoring was performed (0-1 was negative, 2-3 was positive), and heart-to-contralateral lung uptake ratio (H/CL) was calculated based on planar images. The χ2 test was used to compare the difference in visual scores between ATTR-CA and HCM groups, and the diagnostic efficacy of the visual score was calculated. The H/CL differences between ATTR and HCM groups were compared with Mann-Whitney U test, and the ROC curve was used to analyze the efficacy of H/CL for the differential diagnosis of ATTR-CA and HCM. Results:There were 34 patients with visual scores≥2 and 1 patient with visual score<2 in the ATTR-CA group, 6 patients with visual scores =2 and 8 patients with visual scores <2 in HCM group, and there were significant differences between the 2 groups ( χ2=16.20, P<0.001). The diagnostic sensitivity of the visual score was 97.1%(34/35), and the specificity was 8/14. The H/CL in the ATTR-CA group was significantly higher than that in the HCM group (2.08(1.97, 2.20) vs 1.26 (1.17, 1.35), z=-5.09, P<0.001). The ROC curve analysis suggested that the optimal cut-off value was 1.45 (AUC: 0.980, 95% CI: 0.946-1.000; P<0.001); the sensitivity of H/CL differential diagnosis between HCM and ATTR-CA was 97.1%(34/35), and the specificity was 14/14. Conclusion:99Tc m-PYP SPECT imaging is useful in differentiation of ATTR-CA and HCM, and the optimal cut-off value of H/CL for differential diagnosis of these 2 diseases is 1.45.

Objective To construct a risk assessment scale for postoperative delirium(POD)in elderly patients undergoing hip and knee joint replacement and evaluate the effect.Methods A total of 474 elderly patients undergoing hip and knee arthroplasty from March 2021 to May 2022 were collected as the training set,and a total of 153 the homogeneous patients from January 2022 to May 2022 were collected as the validation set.The patients were divided into two groups based on whether or not POD occurred:non-POD group and POD group.Risk factors of POD in the training set were analyzed by univariate analysis and multifactorial logistic regression.The consistency of the model was evaluated by Homser-Lemeshow goodness of fit test.The postoperative delirium risk assessment scale was established after the selected variables as-signed value according to OR value,and the predictive efficacy of the scale was evaluated by receiver oper-ating characteristic(ROC)curve.The patients in the training set and the validation set were divided into two groups according to the cut-off value:high-risk and low-risk.The incidence rate of POD with different risk stratification was calculated and the applicability of the risk assessment scale was evaluated.Results Fifty-eight patients(12.2%)with POD in the training set,and nineteen patients(12.4%)with POD in the validation set.Multifactor logistic regression showed that age≥85 years,ASA physical status Ⅲ or Ⅳ,the mini-mental state examination(MMSE)score≤24 points,preoperative sleep disorder,comorbid neu-rological disorders,use of general anesthesia,and non-use of dexmedetomidine were independent risk factors of POD.The POD risk assessment scale was then published based the seven risk factors.The ROC curve showed that the area under the curve(AUC)for this scale to predict the risk of POD was 0.956(95%CI 0.937-0.975),and the risk stratification was performed with a cut-off value of 44.5 points,which divided the patients into low-risk and high-risk.Compared with low-risk,the incidence rate of POD in high-risk patients group was significantly increased(P＜0.001).Conclusion A risk assessment scale based on the seven risk factors:age≥85 years,ASA physical status Ⅲ or Ⅳ,MMSE score≤24 points,preoperative sleep disorder,combined neurological disease,use of general anesthetic modality,and non-use of dexmedetomidine,can effectively identify elderly patients undergoing hip and knee replacement who are at high risk of developing POD.

Objective:To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia.Methods:This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded.Results:Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%.Conclusions:Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.

Objective:To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement.Methods:This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve.Results:Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time ( M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95% CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95% CI:61.8% to 92.8%). Conclusions:TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.

Objective To construct a TCM Zhengsu differentiation model for type 2 diabetes based on deep learning and multimodal fusion,thus providing algorithmic support for full intelligence in TCM Zhengsu differentiation.Methods A total of 2585 patients with type 2 diabetes were recruited.Three experts were invited to perform the Zhengsu differentiation separately.Deep fully connected neural networks,U2-Net and ResNet34 networks were applied to construct the symptom-based differentiation model(S-Model)and the tongue image-based differentiation model(T-Model),respectively,while multimodal fusion techniques were employed to build the multimodal fusion model(TS-Model)with the above two as co-inputs.Finally,the prediction performance of the above models was compared by F1 value,accuracy,and recall.Results The predicted F1 values of the T-Model fluctuated from 0.000%to 86.726%,while those in the S-Model and TS-Model fluctuated from 0.000%to 97.826%and from 55.556%to 99.065%,respectively.A stable and high F1 value was found in the TS-Model.Conclusion The multimodal fusion technique was demonstrated to be applicable in the TCM Zhengsu differentiation model,which provided methodological support for developingof a fully intelligent Zhengsu differentiation model with high objective four diagnostic information.

Objective To investigate the clinical significance of serum S100 calcium binding protein(S100 A4)and S100A12 in patients with severe traumatic brain injury(sTBI).Methods A total of 147 sTBI pa-tients admitted to Handan Central Hospital from March 2021 to March 2023 were selected as the sTBI group,and 50 healthy subjects who underwent physical examination in Handan Central Hospital during the same pe-riod were selected as the control group.The correlation between S100A4,S100A12 levels and brain injury markers and the influencing factors of early death in sTBI patients were analyzed,and the predictive value of serum S100A4 and S100A12 for early death in sTBI patients was studied.Results The serum levels of S100A4,S100A12,myelin basic protein(MBP),S100B and neuron specific enolase(NSE)in sTBI group were significantly higher than those in control group(P＜0.05).The serum levels of S100A4 and S100A12 were positively correlated with MBP,NSE and S100B in sTBI patients(P＜0.05).Multivariate Logistic regression analysis showed that decreased Glasgow coma scale(GCS)score on admission and increased serum levels of S100A4,S100A12,MBP,NSE and S100B were risk factors for early death in sTBI patients(P＜0.05).Receiv-er operating characteristic curve showed that the combination of serum S100A4 and S100A12 with GCS score,MBP,NSE and S100B was superior to any single detection in predicting early death in sTBI patients.Conclu-sion The serum levels of S100A4 and S100A12 are increased in sTBI patients,which are related to the aggra-vations of brain injury and early death.The combined detection of S100A4 and S100A12 has a good predictive value for early death in sTBI patients.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.