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.

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 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.

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 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 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.

Objective To investigate the distribution of HLA-B27 subtypes in ankylosing spondylitis(AS) patients of Chinese Han population by using the updated HLA-B27 typing data. Methods One hundred AS subjects were randomly selected from spondyloarthritis patients data bank of the third affiliated hospital of Sun Yat-sen university. All subjects were independent individuals, and the duplicated samples in the same family were excluded. Salt fraction method was used to prepare genome DNA. Luminex liquid array combining PCR-SSOP was used to perform the low resolution HLA-B genotyping. PCR-SSP was applied to perform the high resolution HLA-B27 typing for HLA-B27 positive subjects. Results Ninety-eight independent AS patients were recruited randomily, of which, 93 were HLA-B27 positive, with positive rate 94.9%, and covered 96% patients with family history of AS. Three subtypes were detected in this population including B * 2704 (n=76, 81.7%), B * 2705 (n=12, 12.9%) and B * 2715 (n=5, 5.4%). Compared with the two reports about HLA-B27 subtype distribution in healthy HLA-B27 positive Han population there was no significant difference between AS patients and healthy controls. But no B * 2715 case was found in those two reports of healthy population. Three reports (including 1 report in Chinese) could found about B * 2715 subtype, but all positive cases were oriental people. Furthermore, all B * 2715 positive patients were AS patients. Conclusion B * 2704 is the predominant subtype ,in AS patients of Chinese Han population, and followed by B * 2705. We found five cases with positive B * 2715, a considerable rare allele. This may suggest association between B * 2715 and AS.

BACKGROUND: Human leukocyte antigen (HLA)-B27 is closely connected to the occurrence of some rheumatic diseases such as ankylosing spondylitis and can be used as an important factor for evaluating the diagnosis of ankylosing spondylitis. Immunomagnetic separation and enzymelinked immunosorbent assay (IMS-ELISA) has been applied to the detection of HLA-B27.OBJECTIVE: To explore the accuracy, sensitivity and specificity of IMSELISA for detecting HLA-B27 and its value in the auxiliary diagnosis of ankylosing spondylitis.DESIGN: A clinical trial in comparison with the gold standard.SETTING: Departments of Rheumatology and Clinical Laboratory, Third Affiliated Hospital of Sun Yat-sen University.PARTICIPANTS: Eighty-six patients suffering from low back pain and/or arthritis who were treated for the first time in Department of Rheumatology from December 2002 to April 2003. Inclusion criteria: ① Presence of manifestations of low back pain and/or arthritis; ② Thorough documentation of clinical and other examinations; ③ Informed consent to HLA-B27 examination; ④ Treatment for the first time in the Third Affiliated Hospital of Sun Yet-sen University. Those with other serious diseases or with incomplete record of clinical and/or accessory examinations were excluded. The 86 patients included 56 male and 30 female patients aged from 12 to 65 years.METHODS: Blood sample was detected for HLA-B27 by both IMS-ELISA and microlymphocytotoxicity test, and the latter was selected as the gold standard. The coincidence rate of the results detected by the two methods as well as the sensitivity, specificity, positive and negative predictive values of IMS-ELISA were calculated.MAIN OUTCOME MEASURES: ① The coincidence rate of the results of the two methods. ② The sensitivity and specificity of IMS-ELISA for detecting HLA-B27.RESULTS: None of the patients was lost. For the 33 patients with ankylosing spondylitis, the positivity rate of IMS-ELISA (90.9％) was higher than that of microlymphocytotoxicity test (87.9％), but the difference was not statistically significant (P＞0.05). The total coincidence rate of the two methods was 93.0％ in all the 86 patients. The sensitivity, specificity, positive and negative predictive values of IMS-ELISA were 90.0％, 95.7％,94.7％ and 91.7％ respectively.CONCLUSION: Both IMS-ELISA and microlymphocytotoxicity test are capable of reliable examination of HLA-B27 with high sensitivity and specificity.