ObjectiveTo investigate the liver-protecting and anti-liver fibrosis effects of astragaloside Ⅳ （AS-Ⅳ） in vitro and in vivo， as well as its mechanism of action in intervention against liver fibrosis. MethodsIn the animal experiment， C57BL/6J mice were divided into control group， model group， low-dose AS-Ⅳ （20 mg/kg） group， and high-dose AS-Ⅳ （80 mg/kg） group. The mice were given intraperitoneal injection of carbon tetrachloride for 6 weeks to induce liver fibrosis， and since week 3 of injection， the mice in the low-dose AS-Ⅳ group and the high-dose AS-Ⅳ group were given AS-Ⅳ by gavage at a dose of 20 mg/kg and 80 mg/kg， respectively. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured after 4 weeks of administration， as well as the serum levels of hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ N-terminal peptide （PⅢNP）， and collagen type Ⅳ （Col-Ⅳ）. HE staining， picrosirius red staining， and Masson staining were used to observe liver histopathology and collagen deposition； RT-qPCR was used to measure the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue， and Western blot was used to measure the protein expression levels of α-smooth muscle actin （α-SMA）， collagen type Ⅲ （Col-Ⅲ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated PI3K （pPI3K）， protein kinase B （Akt）， and phosphorylated AKT （p-Akt） in liver tissue； transcriptome sequencing was performed for liver tissue to identify differentially expressed genes and perform a bioinformatics analysis. In the cell experiment， transforming growth factor-β （TGF-β） was used to induce the activation of LX-2 cells， and the PI3K inhibitor LY294002 and the PI3K activator 740 Y-P were used for intervention. The cells were divided into control group， model group， AS-Ⅳ group， LY294002 group， and AS-Ⅳ+740 Y-P group， and the cells were harvested after 36 hours of intervention. Changes in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K/PI3K， and pAkt/Akt in LX-2 cells were measured， as well as changes in the relative mRNA expression levels of Acta2， Col1a1， and Col3a1. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the animal experiment， compared with the model group， the AS-Ⅳ treatment group had significant reductions in the serum levels of ALT， AST， HA， LN， PⅢNP， and Col-Ⅳ （all P<0.01）， the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue （all P<0.05）， and the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） in liver tissue （all P<0.05）. In the cell experiment， compared with the control group， the model group had significant increases in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） after TGF-β induction （all P<0.05）； compared with the model group， the AS-Ⅳ group had significant reductions in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） （all P<0.05）， and both the AS-Ⅳ group and the LY294002 group had significant reductions in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， Col1a1， and Col3a1 （all P<0.05）. Compared with the AS-Ⅳ group， there were significant increases in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， col1a1， and Col3a1 after 740 Y-P intervention （all P<0.05）. ConclusionAS-Ⅳ can inhibit hepatic stellate cell activation and improve liver fibrosis， possibly by inhibiting the PI3K/Akt signaling pathway.

Objective:To evaluate the accuracy of a self-developed extraoral scanning system based on photogrammetry technology, and to provide evidence for advancing the development and clinical application evaluation of domestically produced scanning devices.Methods:This research group developed a photogrammetry-based implant extraoral scanning system with customized scan bodies. Two distinct edentulous implant resin models were designed and three-dimensional (3D)-printed by Center of Digital Dentistry, Peking University School and Hospital of Stomatology, containing 6 (Model 1) and 8 (Model 2) abutment analogs respectively. Reference data acquisition was performed using a high-precision denture 3D scanner with scan caps mounted on the analogs. Specialized scan bodies were then mounted on the analogs for 3D positional data acquisition using both the self-developed system (experimental group) and the clinically established system (control group). Each system conducted 10 repeated scans per model. Trueness was assessed through root mean square error (RMSE), linear deviation (LD), and angular deviation (AD) relative to reference data, while precision was determined through intra-group RMSE analysis. Systematic comparisons included inter-group performance on identical models and intra-group variability across different models.Results:For Model 1, the experimental group showed statistically significant advantages over controls in intra-group RMSE [(3.10±0.71) μm vs (4.61±1.51) μm, P<0.001], reference-data RMSE [(21.48±0.60) μm vs (32.50±0.63) μm, P<0.001], linear deviation [23.64 (32.35) μm vs 44.86 (55.73) μm, P<0.001], and angular deviation [0.29° (0.29°) vs 0.23° (0.33°), P<0.001]. In Model 2, significant improvements were observed in intra-group RMSE [(4.47±1.58) μm vs (6.21±2.07) μm, P<0.001], reference-data RMSE [(38.84±0.86) μm vs (43.69±1.34) μm, P<0.001], and linear deviation [37.95 (50.68) μm vs 49.71 (58.89) μm, P<0.001]. Both groups exhibited model-dependent variability, with RMSE of precision and trueness of both groups, linear deviation of experimental group, angular deviation of control group showing statistically significant increases (all P<0.001) corresponding to abutment analog quantity. Conclusions:The self-developed scanning system demonstrates superior accuracy in 3D positional acquisition of abutment analogs compared to the contral group system, with implant number identified as a critical determinant of extraoral scanning accuracy.

AIM:This study aims to investigate the mechanisms underlying skeletal muscle mitochondrial damage associated with decline in exercise function during high-altitude de-adaptation,using a mouse model.METHODS:Twen-ty-four healthy male C57BL/6J mice were randomly assigned to two groups:a high-altitude de-adaptation group and a plain control group.The model group was exposed to a low-pressure,low-oxygen chamber simulating an altitude of 7 000 meters for two weeks,followed by eight days of rearing in a plain environment.The control group was maintained in a plain envi-ronment for the same duration.Grip strength and pole-climbing tests were conducted on the 1st,3rd,and 5th days post-re-turn to assess muscle strength and motor coordination.Treadmill exercises were performed on the 4th and 8th days to eval-uate exercise endurance.After the treadmill exercise on the 8th day,serum,liver,and skeletal muscle tissues were col-lected.Levels of lactic acid(LA),glucose(GLU),creatine kinase(CK),lactate dehydrogenase(LDH),alanine trans-aminase(ALT),and aspartate aminotransferase(AST)in serum,as well as glycogen levels in the liver and muscle,were analyzed.Additionally,the expression of proteins related to mitochondrial biogenesis,fission,fusion,and oxidative phos-phorylation in muscle tissues was assessed using Western blot.RESULTS:(1)The model group exhibited significant re-ductions in grip strength,increased pole-climbing T-turn and total times,and decreased total time and distance in the ex-haustion running test.(2)Serum levels of LA,CK,LDH,ALT,and AST were elevated,while GLU levels decreased,and glycogen levels in both the liver and muscle were reduced in the model group following the treadmill exercise.(3)Ab-normal indicators in the model group did not return to normal by the end of the de-adaptation period.(4)Western blot analysis revealed decreased expression of mitochondrial oxidative phosphorylation proteins(ATP6V1A and Mt-CO2)and mitochondrial biogenesis proteins(PGC-1α and FGF21),increased levels of mitochondrial fusion proteins(OPA1 and MFN1),and no significant changes in fission protein expression(FIS1 and DRP1)in muscle tissue from the model group.CONCLUSION:Exercise capacity in mice during the high-altitude de-adaptation period significantly declined,particu-larly in terms of muscle strength,motor coordination,and endurance.This decline is closely associated with abnormal pro-tein expression related to skeletal muscle mitochondrial energy metabolism and production.

Objective:To compare the efficacy of dienogest (DNG) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of intrinsic and extrinsic subtypes of adenomyosis.Methods:Totally 232 patients were enrolled in the study who were diagnosed as adenomyosis by ultrasound or pelvic magnetic resonance imaging (MRI), and were classified into intrinsic and extrinsic subtypes according to different locations of lesions in MRI, treated with DNG (DNG group) or LNG-IUS (LNG-IUS group) in Peking University Third Hospital from July 2019 to December 2023. Clinical data of patients were retrospectively collected to analyze the clinical and imaging characteristics of different MRI subtypes of adenomyosis and whether there were differences in the therapeutic effects of DNG and LNG-IUS.Results:(1) Among the 232 patients enrolled, 129 were intrinsic subtype and 103 were extrinsic subtype. Among the 129 patients treated with DNG, the numbers of intrinsic and extrinsic subtype were 69 and 60, respectively. And among the 103 patients treated with LNG-IUS, the numbers of intrinsic and extrinsic subtype were 60 and 43, respectively. The mean age in DNG group [(37.5±5.6) years] was lower than that in LNG-IUS group [(40.3±4.3) years, P<0.001]. There were no significant differences in other clinical features (all P>0.05). (2) The visual analog scale (VAS) scores of dysmenorrhea and cancer antigen 125 (CA 125) levels in DNG group and LNG-IUS group were significantly decreased after treatment (all P<0.001), and hemoglobin levels were increased (both P<0.01). Compared between the two groups, the VAS score after treatment was lower in DNG group ( P<0.001), and the hemoglobin level was increased more significantly in DNG group ( P=0.016). The complete remission rates of dysmenorrhea in DNG group and LNG-IUS group were 73.0% (89/122) and 29.5% (28/95), respectively ( P=0.039). The incidence of irregular bleeding in DNG group was higher than LNG-IUS group, but there was no statistical significance [62.8% (81/129) vs 52.4% (54/103), P=0.112]. (3) Among patients with intrinsic adenomyosis, the incidence of menorrhagia was significantly higher than in those with extrinsic adenomyosis ( P<0.001), while the incidence and severity of dysmenorrhea were lower compared to extrinsic adenomyosis ( P=0.004, P=0.007, respectively). After treatment with DNG and LNG-IUS, there were no statistically significant differences in VAS scores between patients with intrinsic and extrinsic adenomyosis (all P>0.05). The incidence of irregular bleeding after DNG treatment was 78.3% (54/69) in intrinsic adenomyosis, which was higher than the 45.0% (27/60) observed in extrinsic adenomyosis ( P<0.01). Similarly, the incidence of irregular bleeding after LNG-IUS treatment was 63.3% (38/60) in intrinsic adenomyosis, higher than the 37.2% (16/43) in extrinsic adenomyosis ( P=0.009). (4) DNG treatment ( OR=19.163, 95% CI: 7.564-48.544; P<0.01) and duration of treatment ( OR=1.043, 95% CI: 1.012-1.075; P=0.007) were independent positive factors for complete remission of dysmenorrhea, while VAS score before treatment ( OR=0.654, 95% CI: 0.454-0.942; P=0.023) was negative factor. Intrinsic subtype was an independent risk factor for irregular bleeding ( OR=0.436, 95% CI: 0.235-0.811; P=0.009). Conclusions:DNG demonstrates greater advantages over LNG-IUS in terms of complete relief of dysmenorrhea and the degree of symptom alleviation. The incidence of irregular vaginal bleeding in patients with intrinsic adenomyosis is higher than in those with extrinsic adenomyosis. For patients with extrinsic adenomyosis, particularly those with prominent dysmenorrhea symptoms, DNG treatment offers greater benefits. However, for patients with intrinsic adenomyosis and those with significant menstrual disorders, a more cautious approach is required when selecting progestin therapy, along with enhanced monitoring and management.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a non-atherosclerotic, non-amyloidogenic inherited cerebral small vessel disease caused by mutations in the NOTCH3 gene, typically manifesting in middle age. The diagnosis can be confirmed through the detection of granular osmiophilic material in skin biopsies and NOTCH3 gene mutations identified by genetic testing. However, the pathogenesis of this disease remains unclear, and treatment options are limited. A major contributing factor is that currently available preclinical animal models fail to adequately recapitulate the characteristic pathological features and clinical phenotypes of the disease. Therefore, a comprehensive review of recent advances in CADASIL animal models was conducted, and the advantages and limitations of existing models were systematically analyzed, aiming to offer guidance for selecting appropriate animal models in fundamental research and to propose future directions for developing experimental models.

Objective:To study the preoperative predictors for lower extremity intermuscular venous thrombosis (IMVT) in patients with thoracolumbar fracture.Methods:A retrospective study was conducted to analyze the 421 spinal fracture patients who had been admitted to Department of Spinal Surgery, The Fourth Hospital of Wuhan from November 2023 to October 2024. The cohort included 110 males and 311 females, aged from 16 to 89 years. They were stratified into a thrombosis group (26 cases) and a control group (395 cases) based on the presence or absence of lower extremity IMVT. Univariate analysis was performed of the following variables: gender, age, body mass index, multisegmental spinal fractures, fracture location, Caprini thrombosis risk score, visual analogue scale (VAS) pain score, D-dimer level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen, coagulation factor activity assay, fibrinogen level, estimated fibrinolytic ratio, clotting time, 30-minute fibrinolytic ratio, coagulation comprehensive index, clot mechanical strength, platelet function, and fibrin generation rate. The variables with a significance level of P<0.05 in the univariate analysis were further analyzed using multivariate logistic regression to identify the independent risk factors for lower extremity IMVT. The predictive efficacy of these factors was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Comparisons between the 2 groups showed that age, multisegmental spinal fractures, Caprini thrombotic risk score, and D-dimer level were variables with P<0.05. Binary logistic regression analysis of the above variables showed that a high Caprini thrombotic risk score, a high D-dimer level, and multisegmental spinal fractures were independent risk factors for preoperative lower extremity IMVT ( P<0.05). The ROC plot suggested an optimal cutoff point: a Caprini thrombotic risk score of 5 and a D-dimer level of 2.57 mg/L. Combination of Caprini thrombotic risk score, D-dimer level, and multisegmental spinal fractures demonstrated a sensitivity of 88.5%, a specificity of 71.9%, and an area under the curve (AUC) of 0.881 for diagnosis of lower extremity IMVT. Conclusions:The Caprini thrombosis risk score and presence of multisegmental spinal fractures are critical indicators for the preoperative risk of lower extremity IMVT in patients with thoracolumbar fracture. For individuals with a low Caprini thrombosis risk score, a D-dimer test is necessary in combination to determine the necessity of color Doppler ultrasound examination.

AIM To optimize the cellulase-assisted ultrasound extraction process for total flavonoids from Plumbago zeylanica L.,and to evaluate their anti-oxidant activity.METHODS With extraction time,liquid-solid ratio,cellulase addition amount,extraction temperature and ultrasonic power as influencing factors,extraction rate of total flavonoids as an evaluation index,the extraction process was optimized by response surface method on the basis of single factor test.Subsequently,The scavenging rates of extract on DPPH,ABTS and OH free radicals were determined.RESULTS The optimal conditions were determined to be 34∶1 for liquid-solid ratio,3％for cellulase addition amount,51 ℃ for extraction temperature,38 min for extraction time,and 400 W for ultrasonic power,the extraction rate of total flavonoids was(33.411±0.97)％.The IC50 values of three free radicals were 0.13,0.042,3.29 mg/mL,respectively.CONCLUSION This reasonable and reliable method can be used for the cellulase-assisted ultrasound extraction of total flavonoids from P.zeylanica with strong anti-oxidant activity.

Objective To determine the effects of cardiac resynchronization therapy at different pacing sites on electrocardiogram(ECG),left ventricular(LV)function and adverse events in elderly patients with heart failure(HF).Methods A total of 214 elderly HF patients admitted to our department between July 2021 and July 2024 were retrospectively recruited.According to different pacing sites in cardiac resynchronization therapy,they were divided into His bundle group(102 cases)and left bundle branch group(112 cases).Their grades of New York Heart Association(NYHA)cardiac function,duration of QRS complex,pacing parameters(pacing threshold,pacing perception,pacing resistance),cardiac function indicators,LV function,LV systolic synchrony[standard deviation of time to peak longitudinal strain,to peak radial strain and to peak circumferential strain(Tls-SD,Trs-SD and Tcs-SD)],and incidence of adverse events were compared between the two groups before and at 6 months after cardiac pacemaker implantation.Results In 6 months after surgery the left bundle branch group had significantly lower N-terminal pro-B-type natriuretic peptide level,smaller LV end-diastolic diameter and LV end-systolic diameter,decreased Tls-SD,Trs-SD and Tcs-SD,and shorter duration of QRS complex,but higher LV ejection fraction,cardiac index and cardiac output when compared with the His bundle group(P＜0.01).The incidence of adverse events was obviously lower in the left bundle branch group than the His bundle group(6.25％vs 15.69％,P＜0.05).Conclusion Left bundle branch pacing shows significant improvement for cardiac function in elderly HF patients,and can effectively maintain ECG stability and improve LV function.It is a safe and effective cardiac resynchronization therapy.

Aim To study the regulatory effect of acupuncture pretreatment on ferroptosis of nerve cells in rats with ischemic stroke.Methods Sixty SD rats were randomly divided into sham middle cerebral artery occlusion(MCAO)group,MCAO group,and acupuncture+MCAO group.In the acupuncture+MCAO group,the acupuncture points of DU26,PC6,and SP6,were selected for acupuncture pretreatment,once a day for a total of 5 days.After pre-treatment,MCAO or sham MCAO models were prepared.The Zausinger sextintegral method was used to score the neuro-logical function of rats,and the infarct volume of brain tissue was calculated by TTC staining.Electron microscopy was used to observe the pathomorphological changes of brain tissue.The iron content was detected by colorimetric method,the content of malondialdehyde(MDA)and glutathione(GSH)was determined by ELISA,and the expression of glutathione peroxidase 4(GPX4)was detected by immunofluorescence.Results Compared with the sham MCAO group,the MCAO group had a decrease in neurological function scores,a significant increase in infarct volume,a decrease in the number of mitochondria under electron microscopy,a rupture and vacuolization of the inner mitochondrial cristae,an in-crease in the contents of iron and MDA in brain tissue,and a decrease in GSH content and GPX4 expression.Compared with the MCAO group,the acupuncture+MCAO group had an increase in neurological function scores,a decrease in infarct volume,a large number of mitochondria under electron microscopy,a clear structure,a decrease or disordered arrangement of some mitochondrial crest structures,a decrease in the contents of iron and MDA in brain tissue,and an increase in GSH content and GPX4 expression.Conclusion Acupuncture pretreatment can alleviate neurological damage in rats,and its mechanism may be related to regulating iron,GSH and MDA contents in brain tissue,and GPX4 expression,improving cell antioxidant capacity and inhibiting nerve cell ferroptosis.

Objective:To investigatetheclinicalefficacy and satetyoflaparoscopic abdominoperineal resection with pelvicperitoneum colsure for low rectal cancer.Methods:A comprehesive search was conducted across multiple da-tabases,including the Cochrane Library、PubMed、Embase、CBM、VIP、CNKI、and WanFang Data,focusing on studies re-lated to pelvic peritoneum colsure(PPC)-oriented laparoscopic abdominoperineal resection from database inception to July,2024.Then,meta-analysis was performed using RevMan 5.3 software.Results:A total of 12 studies involving 999 patients were included.The results showed that there was no significant difference in intraoperative blood loss.The laparoscopic pelvicperitoneum colsure takes a longer time,with a statistically significant difference(WMD=12.37,95%CI=2.27～22.46,P=0.02),but the postoperative exhaust time and hospitalization time are shorter,with a statistically significant difference(WMD=0.40,95%CI=0.07～0.72,P=0.02;WMD=-2.36,95%CI=-3.33～-1.38,P＜0.00001).In terms of postoperative complications,the overall complication rate was higher in the group that did not undergo pelvic-peritoneum colsure,with a statistically significant difference(OR=0.12,95%CI=0.08～0.18,P＜0.00001).The incidence of postoperative intestinal obstruction,perineal incisional hernia,pelvic effusion infection,and radiation enteritis was higher,and the differences were statistically significant(OR=0.24,95%CI=0.13～0.45,P＜0.00001,OR=0.23,95%CI=0.11～0.49,P=0.0001,OR=0.27,95%CI=0.14～0.51,P＜0.0001,OR=0.24,95%CI:0.07～0.81,P=0.03).Conclusion:In lapa-roscopic abdominoperineal resection,closing the pelvicperitoneum has lower postoperative complications,shorter post-operative exhaust time and hospitalization time,and longer operation time,which has better clinical efficacy and safety.