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.

Epilepsy surgery is the main treatment method for medically intractable epilepsy，but at present，its clinical application is significantly limited by medical costs，which is also an important reason for the gap in treatment，and cost-effectiveness analysis can help to narrow this gap. This article analyzes the impact of cost-effectiveness on epilepsy surgery，the cost-effectiveness of preoperative evaluations，and cost-effectiveness across different age groups and surgical procedures，in order to promote the allocation of healthcare resources and provide appropriate surgical treatment options for patients. Preoperative evaluations，epilepsy surgery for both adults and children，and surgical methods such as resection or neuromodulation have shown favorable cost-effectiveness，particularly in the long term. However，further studies are needed to investigate the cost-effectiveness of ablative therapies.

OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

【Objective】 To establish a risk model for predicting spontaneous rupture bleeding of renal angiomyolipoma (RAML) in order to better assess and deal with the risk. 【Methods】 The information of 436 RAML patients diagnosed during Jan.2018 and Dec.2022 was retrospectively analyzed.According to the inclusion and exclusion criteria, 216 patients were included and divided into the rupture bleeding group (n=35) and non-rupture bleeding group (n=181).The factors influencing spontaneous rupture bleeding were identified using univariate and multivariate analysis, and a nomogram was constructed accordingly with R language.The nomogram was evaluated using Calibration curve and area under the receiver operator characteristic curve (AUC). 【Results】 It was found that clinical manifestations, tumor diameter, tumor convexity, tumor blood supply, and tuberous sclerosis complex (TSC) were significantly correlated with rupture bleeding.The Calibration curve fitted well with the nomogram.The AUC was 0.956 (95%CI: 0.856-0.943), indicating that the nomogram had good statistical performance. 【Conclusion】 The model can effectively predict the risk of spontaneous rupture bleeding of renal angiomyolipoma.

Objective : To study the effect and mechanism of action of Silibinin on the differentiation of 3T3-F442A preadipocytes in murine． Methods : The effects of 0－400 μmol / L Silibinin on the proliferation of 3T3-F442A adi- pocytes at 24，48 and 72 h were detected by 3-(4，5-dimethylthiazol-2) -2，5-diphenyltetrazolium bromide ( MTT) assay，and the effects of Silibinin on the adipogenesis of 3T3-F442A adipocytes were visualized by Oil Red O stai- ning ; RT-qPCR , Western blot and ELISA assays were used to detect the effects of Silibinin on 3T3-F442A adipo- cyte differentiation-associated transcription factor CCAAT / enhancer binding protein ( C / EBP) α , C / EBP β , per- oxisome proliferator-activated receptor γ cular endothelial growth factor (VEGF) -α and VEGF receptor 2 (VEGFR-2) ，matrix metalloproteinase (MMP) -2 and MMP-9，mitogen-activated protein kinase (MEK) and phosphorylated MEK (p-MEK) ，and extracellular regu- lated protein kinase (ERK) and phosphorylated ERK (p-ERK) expression. (PPARγ) ，adipocyte protein 2 (aP2) ，adipose generation-associated vas Results : MTT assay showed that the cell proliferation rate of 3T3-F442A preadipocytes decreased after 100，200，and 400 μmol /L Silibinin treatment compared with the control group (P＜0. 001) ; Oil Red O staining assay showed that the accumulation of red lipid droplets of the cells in the 160 μmol /L Silibinin assay group significantly decreased ; RT-qPCR assay showed that mRNA expression of C/EBPα , C/EBPβ , PPARγ , aP2，VEGF-α , VEGFR-2，MMP-2，and MMP-9 was down-reg- ulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin compared with the control group (P＜0. 001) ; Western blot assay showed that protein expression of C /EBPα , C /EBPβ , PPARγ and aP2 was down-regulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin (P＜0. 001) ，and the phosphorylation level of p-MEK/ MEK and p-ERK/ ERK proteins was down-regulated compared with the control group (P ＜0. 001) ; ELISA assay showed that the protein concentrations of MMP-2 and MMP-9 in the cell supernatant were down-regulated (P < 0. 001) in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin． Conclusion Silibinin inhibited 3T3-F442A adipocyte differentiation and adipogenesis through inhibition of the MEK/ ERK pathway and matrix metalloproteinase activity.

Objective To explore the effect of LIMK1 on the progression of cervical cancer(CC).Methods HeLa and C-33A human cervical cancer cells overexpressing LIMK1 were established and injected subcutaneously into nude mice.The tumor volume was measured and expression of NOX2,NOX4,p-Src,p-RUNX3,RUNX3,and MMP-9 proteins in tumor cells was detected by Western blot assays.LIMK1-overexpressing HeLa and C-33A cells were cultured in 5％O2 with antioxidants.The protein expression of LIMK1,NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 in the cells was detected by Western blot assays.Cell migration was assessed by a scratch assay.Transwell assays were used to assess cell migration and invasion.A monoclonal proliferation assay was used to assess cell proliferation.Results The tumor volume in nude mice injected with LIMK1-overexpressing HeLa cells was increased significantly,and NOX2,NOX4,p-Src,p-RUNX3 and MMP-9 protein levels were increased,while RUNX3 protein expression was decreased.In LIMK1-overexpressing HeLa and C-33A cells,the protein expression of LIMK1,NOX4,p-Src,p-RUNX3,and MMP-9 was increased,RUNX3 protein expression was decreased,and cell migration,invasion,and proliferation were increased.However,after adding antioxidants,the expression levels of NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 proteins,and cell migration,invasion,and proliferation were not different from those of control cells.Conclusions LIMK1 promotes the progression of cervical cancer by enhancing the ROS/Src pathway,thereby promoting the migration,invasion,and proliferation of cervical cancer cells.

Objective:To explore the adjunctive diagnostic value of transcranial sonography (TCS) combined with olfactory test in early Parkinson′s disease (PD) and the clinical value of both in the cognitive function of PD patients.Methods:TCS and olfactory test were performed in 157 early PD patients(PD group) and 157 healthy controls(control group) in the Second Affiliated Hospital of Soochow University from January 2018 to January 2022. The differences in clinical characteristics, TCS, and olfactory test results between the two groups were analyzed. The values of TCS, olfactory test, and their combination in diagnosing early PD were evaluated using clinical diagnosis as the gold standard. The correlations of the midbrain area, the midbrain substantia nigra hyperechoic area, and the third ventricle width in TCS examination with the cognitive score were analyzed in the PD group. According to the olfactory test scores, 157 patients with early PD were divided into two groups: 110 cases of PD with olfactory dysfunction (PD-OD) and 47 cases of PD without olfactory dysfunction (PD-NOD). The differences in clinical scores and TCS results between the two groups were compared.Results:The midbrain substantia nigra hyperechoic area, substantia nigra hyperechoic positivity rate, third ventricle width, and olfactory dysfunction rate were higher in the PD group compared to the control group, while the midbrain area and olfactory test scores were lower than those in the control group (all P<0.001). The sensitivity and the coincidence rate of TCS combined with the olfactory test for early PD diagnosis (90.0%, 77.1%) were higher than those of TCS alone (60.0%, 71.3%) and olfactory test alone (70.1%, 72.3%), but the specificity (63.7%) was lower than that of both alone (82.8% for TCS and 75.2% for olfactory test), (all P<0.001). MoCA score, visual space and executive ability, memory, attention, and language were positively correlated with the area of the midbrain ( rs=0.38, 0.32, 0.27, 0.25, 0.23; all P<0.05) and negatively correlated with the width of the third ventricle ( rs=-0.39, -0.22, -0.39, -0.22, -0.32; all P<0.05), and orientation was negatively correlated only with the width of the third ventricle ( rs=-0.24, P<0.05). The MoCA score of PD-OD group[22(18, 25)] was lower than that of PD-NOD group[24(20, 26)]( P=0.040). Conclusions:The combination of TCS and olfactory test can enhance the sensitivity and diagnostic agreement rate for early PD diagnosis, providing some auxiliary value. The cognitive function of PD patients is positively correlated with the midbrain area and negatively correlated with the width of the third ventricle. The cognitive function of PD patients with olfactory dysfunction is lower than that of PD patients without olfactory dysfunction. TCS and olfactory test may help assess cognitive function in PD patients.

OBJECTIVE To explore the effects of pterostilbene （PTE） on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group； after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back， model rats were randomly divided into model group， PTE low-dose group （40 mg/kg）， PTE high-dose group （80 mg/kg）， PTE high-dose+PP2 group （80 mg/kg PTE+2 mg/kg SRC inhibitor PP2）， with 10 rats in each group. On the second day after modeling， the rats in each drug group were intraperitoneally injected with corresponding drug solutions， while the rats in control group and model group were intraperitoneally injected with normal saline， once a day， for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration； the contents of interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α） and vascular endothelial growth factor （VEGF） in the serum of rats were detected； the pathological changes of wound granulation tissue were observed， and the expressions of SRC/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group， the wound healing rate， serum content of VEGF， the phosphorylation levels of SRC， MEK1/2 and ERK1/2 were decreased significantly （P＜0.05）， while serum contents of IL- 1β， IL-6 and TNF-α were increased significantly （P＜0.05）； there was obvious infiltration of inflammatory cells in the wound granulation tissue， and the number of new blood vessels decreased. Compared with model group， above indexes of PTE low-dose and high-dose groups were improved significantly （P＜0.05）， and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes （P＜0.05）. CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats， the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.

Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality. How to effectively control fungal infection is a thorny problem faced by clinicians. During the treatment of ECMO, the patient's physiological status, ECMO oxygenation membrane, circulation pipeline and other factors may change the pharmacokinetic profiles of antifungal drugs, thereby affect the clinical efficacy of drugs. This artical reviews the pharmacokinetic characteristics of antifungal drugs during ECMO support, in order to provide references for clinical antifungal treatment.

Objective:To investigate the postnatal grading, surgical intervention and prognosis in fetal hydronephrosis.Methods:The clinical data of 243 children who were prenatally diagnosed with fetal hydronephrosis and first seen at Dalian Children′s Hospital after birth from November 2014 to November 2017 were retrospectively analyzed. All cases were followed up by routine ultrasound after birth and were assessed and graded according to the postnatal urinary tract dilation (UTD) system. The children with clinical indication for surgery underwent surgical treatment (operation group), and the children without clinical indication were closely followed up (non-operation group).Results:Among 243 children, 182 were male and 61 were female; the gestational age at first diagnosis was (27.5±3.2) weeks, and the maternal age was (29 ± 6) years; 212 cases were unilateral, and 31 cases were bilateral. The results of the first ultrasound examination result showed UTD low-risk was in 117 cases, medium-risk in 67 cases, high-risk in 59 cases. All the children were followed up from 14 to 50 months, with a mean of 26.4 months. During the follow-up period, 117 cases with UTD low-risk did not undergo surgical treatment; 62 cases of 67 with UTD medium-risk did not receive operation, and 5 were operated; while operation were performed on 56 cases of 59 with UTD high-risk, and 3 children with stable hydronephrosis were not treated surgically. The non-operation group had 182 cases, and operation group had 61 cases. The UTD high-risk rate and renal pelvis anteroposterior diameter of first ultrasound examination in operation group were significantly higher than those in non-operation group: 91.80% (56/61) vs. 1.65% (3/182) and 1.9 (1.6, 2.4) mm vs. 0.7 (0.3, 1.5) mm, the thickness of renal parenchyma was significantly lower than that in non-operation group: 3.0 (1.3, 4.1) mm vs. 6.0 (5.1, 7.2) mm, and there were statistical differences ( P<0.01 or <0.05). The result of follow-up in operation group showed that the renal pelvis anteroposterior diameter and the ratio of renal pelvis anteroposterior diameter to renal parenchyma thickness 1 year after operation were significantly lower than those before operation: (1.6 ± 0.7) cm vs. (3.5 ± 1.5) cm and 0.3 ± 0.2 vs. 1.1 ± 1.0, the thickness of renal parenchyma and differentiated renal function were significantly higher than those before operation: (5.8 ± 2.4) mm vs. (3.2 ± 3.1) mm and (45.4 ± 1.9)% vs. (39.5 ± 2.3)%, and there were statistical differences ( P<0.05). Conclusions:UTD grading system is required after birth. Children with hydronephrosis in UTD low-risk and most of the UTD medium-risk have relatively satisfactory prognosis. The hydronephrosis children with UTD high-risk should undergo early surgery if progressive worsening appears and decline in differentiated renal function is detected.