Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

Objective To compare the clinical efficacy and safety of catheter-directed intra-arterial thrombolysis(CDT)and percutaneous mechanical thrombectomy(PMT)in treating long-segment occlusion of lower extremity artery complicated by thrombosis.Methods The clinical data of 21 patients with long-segment occlusion of lower extremity artery complicated by thrombosis,who were admitted to the Ningbo Municipal Medical Center Lihuili Hospital from January 2021 to June 2024,were retrospectively analyzed.According to the treatment methods,the patients were divided into CDT group(n=10)and PMT group(n=11).SPSS statistical software was used to analyze the patient's general data,intraoperative condition,postoperative short-term complications,average hospital stay,and used dose of urokinase.The clinical efficacy and safety of the two treatment methods were compared between the two groups.Results No statistically significant differences in the surgical success rate,perioperative bleeding,ischemia-reperfusion injury,intraoperative thrombus falling off,operation time,and hospitalization days existed between the two groups(all P＞0.05).During hospital stay the total used dose of urokinase in CDT group was obviously higher than that in PMT group(P＜0.05).Conclusion For long-segment occlusion of lower extremity artery complicated by thrombosis,both CDT and PMT are effective thrombus clearance regimen.However,in CDT treatment the total used amount of urokinase is higher,which carries certain risk for patients with abnormal coagulation function and for patients having a higher risk of bleeding,therefore,the clinicians should seriously take this point into account when making treatment decisions.

Objective To explore the influencing factors for poor prognosis in patients with acute myocardial infarction(AMI)complicated by heart failure(HF),construct a nomogram prediction model,and validate its performance.Methods A total of 252 patients with AMI complicated by HF were selected as training set and divided into poor prognosis group(60 patients)and good prognosis group(192 patients)based on 1-year follow-up results.Additionally,86 patients with AMI compli-cated by HF,with a ratio approximately 1∶3 to the training set,were selected as validation set.Cox regression models were used to analyze the influencing factors for poor prognosis.A nomogram model was constructed based on the screening results and underwent internal and external validation[Hos-mer-Lemeshow test was used to assess goodness of fit,calibration curves were plotted to evaluate cali-bration,receiver operating characteristic(ROC)curves were drawn to analyze discriminative ability,and decision curve analysis(DCA)was conducted to assess clinical utility].Results There were no statistically significant differences in clinical data between the training set and validation set(P＞0.05).The poor prognosis group had higher levels of serum creatinine and cardiac troponin T(cTnT),higher proportions of patients aged≥60 years,with time from onset to admission ≥4 hours,with heart function grades Ⅲ to Ⅳ,and a lower left ventricular ejection fraction(LVEF)compared with the good prognosis group(P＜0.05).Multivariate Cox regression analysis showed that time from onset to admission,heart function grade,serum creatinine,cTnT,and LVEF were independent influen-cing factors for poor prognosis in patients with AMI complicated by HF(P＜0.05).Based on these results,a nomogram model was constructed.Internal validation results showed that the model had good goodness of fit(x2=13.966,P=0.083),excellent calibration,and good discriminative abili-ty[area under the curve(AUC)was 0.831].External validation results also showed that the model had good goodness of fit(x2=6.465,P=0.136),excellent calibration,and good discriminative a-bility(AUC was 0.884).DCA results indicated that the nomogram model had good clinical net benefit within a high-risk threshold range of 0.02 to 0.98.Conclusion Influencing factors for poor prognosis in patients with AMI complicated by HF include time from onset to admission,heart func-tion grade,serum creatinine,cTnT,and LVEF.The constructed nomogram model has high predic-tive value for poor prognosis in these patients.

Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P＜0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P＜0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.

ObjectiveTo observe the effect of Scutellariae Radix-Coptidis Rhizoma on plaque stability in atherosclerotic （AS） mice and to explore its possible mechanism of action based on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa B （NF-κB） signaling pathway. MethodTen normal C57BL/6J mice were used as the normal group， and the same strain of ApoE knockout （ApoE^-/-） mice were fed with a high-fat diet for 12 weeks to construct an atherosclerosis model. Mice were randomly divided into five groups， namely the model group， the atorvastatin group， and the Scutellariae Radix-Coptidis Rhizoma low-， medium-， and high-dose groups， with ten mice in each group. Then normal and model groups were given equal volume of saline gavage， and the low-， medium-， high-dose Scutellariae Radix-Coptidis Rhizoma groups were given 1.95， 3.9， 7.8 g·kg^-1 of the drug by gavage for 8 weeks， respectively. The general state of mice was observed. Hematoxylin-eosin staining was utilized to observe the pathology of aortic root plaques and calculate the percentage of plaque area. Masson staining and oil red O staining combined with immunohistochemistry of F4/80 and α-SMA were used to detect the plaque components of aortic root plaques and calculate the plaque vulnerability index. Enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was applied to detect the protein expression levels of matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， TLR4， MyD88， NF-κB p65， and phosphorylation （p） -NF-κB p65 in the aortic tissues of mice in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） assay was employed to detect the expression levels of MMP-2， MMP-9， TLR4， and MyD88， NF-κB p65 mRNA. ResultCompared with the model group， the general state of the mice in each medication group was improved， and no obvious side effects were observed. Compared with the model group， the percentage of plaque area in the aortic root of AS mice was significantly reduced in the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The content of collagen fibers and smooth muscle cells in the plaques of the high-dose Scutellariae Radix-Coptidis Rhizoma group was significantly increased （P<0.01）， and the content of lipids and macrophages was significantly reduced （P<0.05）， the plaque vulnerability index of each dose group of Scutellariae Radix-Coptidis Rhizoma was significantly reduced， with significant reduction of the medium- and high-dose groups （P<0.01）. MMP-2 and MMP-9 protein and mRNA expression levels in aortic tissues were significantly reduced in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The serum levels of TNF-α and IL-6 were significantly reduced in AS mice in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. In the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups， the levels of TLR4， MyD88 protein， and mRNA expression in aortic tissues were significantly reduced （P<0.05）， and the level of NF-κB p65 phosphorylation in aortic tissues was significantly reduced （P<0.05）. ConclusionScutellariae Radix-Coptidis Rhizoma may play an anti-inflammatory and stabilizing role by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma （SRCR） on atherosclerosis （AS） in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasomes. MethodApoE^-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model， atorvastatin （5 mg·kg^-1）， and low-， medium-， and high-dose （1.95， 3.9， 7.8 g·kg^-1， respectively） SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration， hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 （EMR1）/NLRP3 and EMR1/gasdermin D （GSDMD）. The serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1， cleaved Caspase-1， GSDMD， N-terminus of GSDMD （GSDMD-NT）， pro-IL-1β， IL-1β， and IL-18 were determined by Western blot， and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed obvious plaques， elevated serum levels of TG， TC， LDL-C， IL-1β， and IL-18 （P<0.01）， lowered serum level of HDL-C （P<0.01）， and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques （P<0.01）. Compared with the model group， SRCR， especially at the medium and high doses， alleviated the plaque pathology， reduced the lipid content in plaques （P<0.05， P<0.01）， recovered the serum lipid levels （P<0.05）， reduced the macrophage recruitment （P<0.01）， activation of NLRP3 inflammasomes， and pyroptosis in aortic root plaques （P<0.05）， lowered the serum IL-1β and IL-18 levels （P<0.01）， and down-regulated the protein levels of NLRP3， ASC， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-NT， pro-IL-1β， IL-1β， and IL-18 （P<0.05） and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 in the aortic tissue （P<0.05）. ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.

Objective To study the effects of chronic manganism on hearing and cochlear cells in rats by using animal model of chronic manganism .Methods Sixty adult SD rats were randomly divided into Mn - exposed and controlgroups.RatsweretreatedwithMnCl24H2O(100mg·kg -1·d-1)ordeionizedwaterbygastricperfusion, lasted for 12 weeks .The Mn concentration in peripheral blood was measured respectively at 4 weeks ,8 weeks and 12 weeks after treatment .At 12 weeks after treatment ,the auditory brainstem response was recorded ,the hair cells morphology and counting were examined by stretched preparation of basilar membrane stained with FITC -phalloi-din ,and the spiral ganglion cells morphology and counting were studied by HE staining ,the ultrastructure changes of hair cells and spiral ganglion cells were detected by transmission electron microscopy .Results The blood Mn concentration increased gradually with time after treatment .ABR thresholds at 4 ,8 ,16 ,24 and 32 kHz were sig-nificantly increased at 12 weeks after treatment ,especially in the high-frequency range .Morphological study at 12 weeks after treatment showed loss of outer hair cells ,mainly in the basal turn of the cochlea ,and decreased number of spiral ganglion cells .The ultrastructure changes of outer hair cells and spiral ganglion cells included the break -ups ,disappearance or vacuolar change of mitochondria cristas .Conclusion Our data demonstrate that chronic man-ganism can cause loss of outer hair cells and spiral ganglion cells in cochlear in rats ,leading to hearing loss .

Objective To evaluate the efficacy and safety of CT-guided percutaneous celiac plexus block (NCPB) using 25 G controllable curved needle together with 22 G straight needle in treating refractory carcinomatous upper abdominal pain. Methods A total of 18 patients with advanced refractory carcinomatous upper abdominal pain were enrolled in this study. The carcinomatous upper abdominal pain failed to the three-step analgesic therapy. Guided by CT scan, percutaneous injection of ethanol with a 25 G controllable curved needle to destroy celiac plexus was carried out in all patients. According to WHO pain relief standards, the relieving degree of pain was evaluated before NCPB and 2 weeks, one, 2, 3 and 6 months after NCPB. The results were analyzed. Results The technical success rate was 100%. The short-term (within 2 weeks) efficacy rate was 88.8%and the complete remission rate was 38.8%. The long-term (over 3 months) efficacy rate was 50% and the complete remission rate was 20%. No severe complications occurred. Conclusion For refractory carcinomatous upper abdominal pain, CT-guided percutaneous celiac plexus block is a simple, safe and effective treatment.

Objective To evaluate the urodynamic and functional characteristics of 26 patients who had underwent orthotopic contient globular ileal neobladder. Methods The clinical date of 26patients who underwent radical cystectomy were reviewed. The neobladder pressure, capacity, urethral pressure and urinary flow rate were collected at 3-12 months after operation. Results The neobladders average pressure was less than 15 cm H2O when the volume was 400 ml. The pressure was 22.4 cm H2O at 100% capacity. The mean pressure of contractions was less than 40 cm H2O. The mean filling pressure after operation was relative stable while the difference between 3 months and 6 months was statistically significant. The difference between 6 and 9 and 12 month showed no statistical significance. The mean post-void residual was 42 ml. A mean voiding flow rate of 19. 6 ml/s could be obtained by Valsalva. Conclusion The neobladder not only could offer adequate capacity at low pressures but also could give a satisfied continent.

Objective To search for the genetic and molecular immunity basis of CXCR-1 associated pathogenesis in ankylosing spondylitis (AS) patients. Methods Sequencing analysis was used to detect mutation in the exonic, junctional and promoter sequences of CXCR-1 which might be related with ankylosing spondylitis; the hydrophobicity, conservation and evolutionary distance of the mutated amino acids were also analyzed. Results Six affected individuals in the family were detected with a novel mutation Arg192Gly. The glycine at 192 codon was highly conserved in different species. Arginine and glycine had quite distinct hydrophobicity and BLOSUM score. Conclusion The mutation CXCR-1 (Arg192Gly) detected in these patients might be involved in genetic and molecular immunity mechnisms of ankylosing spondylitis.