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Biomedical subjects

Kai Xu

Publications and source records attributed to Kai Xu.

At least 19 recordsLinked to original sources

Identification and evaluation of glutamine-related gene characteristics based on multi-omics to predict the prognosis of patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), a prevalent malignancy of the gastrointestinal tract, ranks among the leading causes of cancer-related morbidity and mortality. Its clinical course is marked by high fatality and poor prognosis. Elucidating the mechanisms underlying CRC initiation and recurrence is therefore critical for identifying novel therapeutic targets. METHODS: This study incorporated two datasets, TCGA-CRC and GSE17537. A total of 84 glutamine metabolism-related genes (GMRGs) were identified, and differential expression analysis was conducted using the TCGA-CRC dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to determine gene modules most strongly associated with GMRG scores. Single-cell RNA sequencing (scRNA-seq) was utilized to characterize key cellular clusters and to identify differentially expressed genes (DEGs) between high and low glutamine metabolism (GM) groups. Overlapping GMRGs were visualized using the ggVennDiagram package in R. A CRC risk prediction model was developed through Cox proportional hazards and LASSO regression analyses, with performance evaluated by ROC curves. Cell type enrichment across 64 immune and stromal populations was assessed via xCell, and intergroup differences were tested using the Wilcoxon rank-sum test. TIDE scores were used to estimate immunotherapy responsiveness, while oncoPredict facilitated drug sensitivity profiling. PCOLCE2 expression in CRC was validated by RT-qPCR and Western blotting. Its functional role was examined through CCK-8 assays, invasion and migration tests, flow cytometry, and glutamate quantification. RESULTS: ScRNA-seq analysis identified two key cell populations and 437 DEGs associated with GM status. WGCNA pinpointed the MEgreen module as most significantly correlated with GMRG scores, encompassing 1075 genes. Integration of DEGs, module genes, and GM-related DEGs yielded 60 candidate genes for downstream analysis. A GMRG-based prognostic model comprising six genes (SRPX, CXCL1, GPX3, PCOLCE2, CLU, SEMA3E) demonstrated strong predictive performance. Prognostic gene expression correlated with immune and stromal infiltration patterns, as indicated by Spearman correlation analysis. The high-risk group exhibited diminished predicted response to immunotherapy (TIDE scores). Drug sensitivity analysis identified four compounds—Dasatinib-51, WH-4-023-56, TWS-119-366, and LDN-193189-478—with elevated efficacy in high-risk CRC cases. PCOLCE2 expression was significantly reduced in CRC tissues. Functional assays revealed that PCOLCE2 knockdown did not substantially affect cell proliferation but significantly impaired invasion and migration in CRC cells, increased apoptosis, and suppressed both glutamine uptake and glutamate production—highlighting its oncogenic role. CONCLUSION: Six GMRGs—SRPX, CXCL1, GPX3, PCOLCE2, CLU, and SEMA3E—were identified as key components of a robust prognostic model for CRC. These findings offer valuable insights into CRC pathogenesis and potential therapeutic strategies. Notably, this study provides the first evidence implicating PCOLCE2 as a tumor-promoting factor in CRC.

Glutamine↗

Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals.

Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source-embryos from same-sex parents-aiming to establish a stable, maintainable imprinting pattern de novo in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate. The findings provide strong evidence that imprinting abnormalities are a primary barrier to unisexual reproduction in mammals. Moreover, this approach can significantly improve developmental outcomes for embryonic stem cells and cloned animals, opening promising avenues for advancements in regenerative medicine.

Animals↗

Retrospective comparison of retroperitoneal laparoscopic versus open dismembered pyeloplasty for ureteropelvic junction obstruction.

PURPOSE: We evaluated the clinical value of retroperitoneal laparoscopic dismembered pyeloplasty for ureteropelvic junction obstruction compared with open surgery. MATERIALS AND METHODS: The clinical data of 56 patients who underwent retroperitoneal laparoscopic dismembered pyeloplasty were retrospectively compared with those of 40 patients who underwent open dismembered pyeloplasty through a retroperitoneal flank approach. The Student t test, Pearson chi-square test and Mann-Whitney rank sum test were applied for statistical analysis as appropriate. RESULTS: Patient demographic data were similar between the 2 groups. In the laparoscopic group operative time (80 vs 120 minutes), estimated blood loss (10 vs 150 ml), recovery of intestinal function (1 vs 2 days), analgesic requirements (diclofenac sodium suppository) (75 vs 150 mg), incision length (3.5 vs 21 cm) and postoperative hospital stay (7 vs 9 days) were better than in the open group (p <0.001 for all). No intraoperative complications occurred in either group. The incidence of postoperative complications (2 of 56, 3.6% vs 3 of 40, 7.5%, p = 0.729) and success rates (55 of 56, 98.2% vs 39 of 40, 97.5%, p = 0.058) were equivalent in the 2 groups. CONCLUSIONS: Retroperitoneal laparoscopic dismembered pyeloplasty is a minimally invasive, safe and effective therapy for ureteropelvic junction obstruction with low morbidity, shorter convalescence and excellent outcomes, and can be accomplished reasonably quickly in experienced hands.

Adult↗

[Effect of Selaginella combined with radiotherapy on nasopharyngeal carcinoma].

OBJECTIVE: To observe the Chinese herbal medicine Selaginella-induced radiosensitization of terminal nasopharyngeal carcinoma (NPC). METHODS: Totally 180 patients with NPC were divided equally into 3 groups with the same radiotherapeutic protocols. The patients in group A received radiotherapy alone, those in group B were given daily Selaginella (30 g) prepared into 50 ml decoction during the entire course of radiotherapy, and those in group C had Selaginella 30 g daily in the late course of radiotherapy. RESULTS: The complete remission rate of nasopharyngeal primary lesions in groups B and C was significantly higher than that in group A, with also significantly higher complete remission rates of the cervical lymph nodes. The acute toxicity of the skin and mucous membrane was milder in the latter two groups, but the differences were not significant. CONCLUSION: Selaginella may induce radiosensitization for terminal NPC and does not increase the acute toxicity of radiotherapy.

Adult↗

[Photosynthetic acclimation to elevated CO2 in strawberry leaves grown at different levels of nitrogen nutrition].

Photosynthetic characteristics of strawberry (Fragaria ananassa Duch cv. 'Toyonoka') leaves grown in either elevated CO(2) (700 microL/L) or ambient CO(2) (390 microL/L), and at three levels of nitrogen nutrition (12 mmol/L, 4 mmol/L, 0.4 mmol/L) were studied. The results showed that for strawberry grown in 12 mmol/L nitrogen, P(n), maximal carboxylation rate (V(c, max)), maximal linear electron flow through photosystem II (J(max)), electron flow to the photosynthetic carbon reduction cycle (J(c)) and q(P) were all significantly higher in plants grown and measured at elevated CO(2) than for plants grown and measured at ambient CO(2) (Table 1 and 2, Fig. 2), which were due to a significant increase in J(c) exceeding any suppression of electron flow to the photorespiratory carbon oxidation cycle (J(o)). This increase in photochemistrical quenching with decreased non-photochemistrical quenching (q(N) or NPQ) at elevated CO(2) alleviated photoinhibition by high light (Table 2, Fig. 3). For plants grown at 4 mmol/L and 0.4 mmol/L nitrogen, P(n), V(c, max), J(c) and q(P) were all significantly lower in plants grown and measured at elevated CO(2) than for plants grown and measured at ambient CO(2) (Table 1 and 2, Fig. 2). Consistent with decreased photochemistrical quenching and increased non-photochemistrical quenching (q(N) or NPQ), for leaves grown at 4 mmol/L and 0.4 mmol/L nitrogen, the photoinhibition was aggravated by elevated CO(2) (Table 2, Fig. 3). Elevated CO(2) suppressed J(o) in leaves of plants grown at 12 mmol/L, 4 mmol/L and 0.4 mmol/L nitrogen (Fig. 2). The results above suggested that deficient nitrogen (4 mmol/L and 0.4 mmol/L nitrogen) and elevated CO(2) result in an acclimatory decrease of photosynthesis in leaves of plant grown in elevated CO(2).

Adaptation, Physiological↗

Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive B cell precursors despite expressing different antibody reactivity.

B cell chronic lymphocytic leukemia (CLL) is a disease of expanding monoclonal B cells whose B cell receptor (BCR) mutational status defines 2 subgroups; patients with mutated BCRs have a more favorable prognosis than those with unmutated BCRs. CLL B cells express a restricted BCR repertoire including antibodies with quasi-identical complementarity-determining region 3 (CDR3), which suggests specific antigen recognition. The antigens recognized by CLL antibodies may include autoantigens since about half of CLL B cells produce autoreactive antibodies. However, the distribution of autoreactive antibodies between Ig heavy-chain variable-unmutated (IgV-unmutated) CLL (UM-CLL) and IgV-mutated CLL (M-CLL) is unknown. To determine the role of antibody reactivity and the impact of somatic hypermutation (SHM) on CLL antibody specificity, we cloned and expressed in vitro recombinant antibodies from M- and UM-CLL B cells and tested their reactivity by ELISA. We found that UM-CLL B cells expressed highly polyreactive antibodies whereas most M-CLL B cells did not. When mutated nonautoreactive CLL antibody sequences were reverted in vitro to their germline counterparts, they encoded polyreactive and autoreactive antibodies. We concluded that both UM-CLLs and M-CLLs originate from self-reactive B cell precursors and that SHM plays an important role in the development of the disease by altering original BCR autoreactivity.

Autoantibodies↗

Renal pedicle lymphatic disconnection for chyluria via retroperitoneoscopy and open surgery: report of 53 cases with followup.

PURPOSE: We present our experience with retroperitoneoscopic renal pedicle lymphatic disconnection. We compared the clinical efficacy of this treatment for chyluria with that of open surgery. MATERIALS AND METHODS: From January 1998 to June 2004, 53 patients (55 renal units) with chyluria underwent renal pedicle lymphatic disconnection via the retroperitoneoscopic and conventional open approaches. The diagnosis of chyluria was confirmed by the ether test and the side of chylous reflux was determined by cystoscopy. Operative time, intraoperative blood loss, postoperative intestinal recovery and hospital stay were evaluated. Increases in hemoglobin and serum albumin were compared before and after surgery during followup. RESULTS: Retroperitoneoscopic renal pedicle lymphatic disconnection or open surgery was performed successfully in all patients. In terms of operative time, intraoperative blood loss, postoperative intestinal recovery and hospital stay retroperitoneoscopy was superior to conventional open surgery. During retroperitoneoscopy the inferior vena cava was injured in 1 case but repaired successfully by laparoscopy without conversion to open surgery. Postoperative gross hematuria in 1 case disappeared 4 days later. In the open surgery group the renal segmental artery was inadvertently injured in 1 case and anastomosis was performed successfully. Wound healing was delayed in 1 case due to hypoalbuminemia. Recurrence developed in 2 patients during the 6 to 84-month followup. CONCLUSIONS: Retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria has the advantages of minimal invasion and rapid recovery compared with open surgery.

Adult↗

[Qualitative evaluation on literatures related with treatment of lung cancer with combined use of chemotherapy and Chinese herbs].

OBJECTIVE: To evaluate the quality of clinical literatures related with treatment of lung cancer with combined use of chemotherapy and Chinese herbs in respect of the scientific research design adapted. METHODS: According to the "Scale for Quality and Information Evaluation of TCM Clinical Research Literature" formulated by the group of methodology of this article, the literatures related with lung cancer published between 1979 to 2000 were evaluated in respect of the randomization and controlling of the trial. RESULTS: The method of randomization was not described in 93.7% of the literatures; problems or mistakes of randomized allocation existed in 2.5%, with no record about the state of dropped out or absconded cases in follow-up study in 29.1%, also no record about case screening was found in all the literatures. Besides, the blind trial method was seldom used, also some problems of key links concerning samples homogeneity and conclusion reasoning presented. All these bugs could influence quality of the randomized control trial. CONCLUSION: Randomized control trial has been applied progressively in TCM clinical researches of lung cancer, however, there are still problems such as insufficiency of samples, and improving of the reliability and quality of the trial is needed.

Antineoplastic Combined Chemotherapy Protocols↗

[Response of strawberry leaves photosynthesis to strong light and its mechanism].

In this paper, PAM-2000 portable chlorophyll fluorometer and HCM-1000 photosynthesis measurement system were applied to measure the apparent quantum efficiency (AQY), initial fluorescence (Fo), maximal photochemical efficiency of PSII (Fv/Fm), maximal fluorescence (Fm), photochemical quenching (qP), non-photochemical quenching (qN), actual quantum yield of PS II electron transport (phiPSII), electron transport rate (ETR), amount of inactive PS II reaction centers (Fi-Fo), Q(A) reduction rate, proportion of Q(B)-non-reducing PS II reaction centers [(Fi-Fo)/(Fp-Fo)], and energy-dependent quenching (qE), photoinhibitory quenching (qI) and state-transition quenching (qT) of non-photochemical quenching of strawberry leaves. The results showed that the Fv/Fm, Fm, Fi-Fo and Q(A) reduction rate decreased in strong light and increased during subsequent dark recovery, but (Fi-Fo)/(Fp-Fo) was in reverse. They changed drastically within the first 10 minutes in strong light or in subsequent darkness. In strong light, phiPSII, ETR and qP increased firstly and then decreased, while qN decreased drastically firstly and then increased slightly. After exposure to strong light for 4 hours, the AQY of two varieties "Toyonoka" and "Houkouwase" decreased by 20.9% and 37.5%, respectively, and qE was 89.1% and 87.1%, respectively in NPQ (qE + qI + qT). In strong light, "Toyonoka" showed less changes than "Houkouwase" in Fo, Fv/Fm, Fm, ETR, phiPSII and AQY. After treated with DTT, the Fv/Fm and Fm were lower, but Fo was much higher than control. It is deduced that in strong light, xanthophyll cycle-dependent non-radiative energy dissipation and pH-dependent heat dissipation could play an important protective role against photo-damage to the photosynthetic apparatus in strawberry leaves.

Chlorophyll↗

[Clinical study on comprehensive treatment of primary liver cancer mainly with chinese medicinal perfusion/embolization].

OBJECTIVE: To study the clinical efficacy and adverse reaction of comprehensive therapy mainly with Chinese anti-cancer medicinal perfusion/embolization and assisted with Chinese drug-therapy based on TCM Syndrome Differentiation in treating primary liver cancer. METHODS: Forty-one patients with liver cancer were divided into the treated group and the control group. To the treated group turmeric oil microballoon, cinobufotalin, Aidi injection and iodized oil were given via hepatic artery perfusion/embolization, and to the control group chemotherapeutic agents and iodized oil were given for instead. Besides, both groups were given Chinese herbs according to TCM Syndrome Differentiation additionally. RESULTS: The tumor inhibitory rate in the treated group and the control group was 77.78% and 69.57% respectively, with insignificant difference between them. The improvement of fatigue and anorexia in the treated group was better than that in the control group (P < 0. 05). The 6-month, 12-month and 24-month survival rate in the treated group and control group was 61.11% vs 56.62%, 27.78% vs 30.43% and 22.22% vs 26.09%, respectively, the difference between the two groups was insignificant. The occurrence of adverse reactions such as decreasing of white blood cells, platelet and hemoglobin, nausea and vomiting were obviously lower in the treated group than those in the control group (P < 0.05). CONCLUSION: Chinese anti-cancer medicinal perfusion/embolization has affirmative short-term clinical effect in treating primary liver cancer with few adverse reactions, which was tolerable to patients, but its long-term clinical efficacy needs further observation.

Adult↗

Myristoylation of the fus1 protein is required for tumor suppression in human lung cancer cells.

FUS1 is a novel tumor suppressor gene identified in the human chromosome 3p21.3 region that is deleted in many cancers. Using surface-enhanced laser desorption/ionization mass spectrometric analysis on an anti-Fus1-antibody-capture ProteinChip array, we identified wild-type Fus1 as an N-myristoylated protein. N-myristoylation is a protein modification process in which a 14-carbon myristoyl group is cotranslationally and covalently added to the NH2-terminal glycine residue of the nascent polypeptide. Loss of expression or a defect of myristoylation of the Fus1 protein was observed in human primary lung cancer and cancer cell lines. A myristoylation-deficient mutant of the Fus1 protein abrogated its ability to inhibit tumor cell-induced clonogenicity in vitro, to induce apoptosis in lung tumor cells, and to suppress the growth of tumor xenografts and lung metastases in vivo and rendered it susceptible to rapid proteasome-dependent degradation. Our results show that myristoylation is required for Fus1-mediated tumor-suppressing activity and suggest a novel mechanism for the inactivation of tumor suppressors in lung cancer and a role for deficient posttranslational modification in tumor suppressor-gene-mediated carcinogenesis.

Animals↗

Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo.

Lung cancer is one of the leading causes of death in the world. The underlying cause for lung cancer has been attributed to various factors that include alteration and mutation in the tumor suppressor genes. Restoration of normal function of the tumor suppressor gene is a potential therapeutic strategy. Recent studies have identified a group of candidate tumor suppressor genes on human chromosome 3p21.3 that are frequently deleted in human lung and breast cancers. Among the various genes identified in the 3p21.3 region, we tested the antitumor activity of the FUS1 gene in two human non-small-cell lung cancer (NSCLC) xenografts in vivo. Intratumoral administration of FUS1 gene complexed to DOTAP:cholesterol (DOTAP:Chol) liposome into subcutaneous H1299 and A549 lung tumor xenograft resulted in significant (P = .02) inhibition of tumor growth. Furthermore, intravenous injections of DOTAP:Chol-FUS1 complex into mice bearing experimental A549 lung metastasis demonstrated significant (P = .001) decrease in the number of metastatic tumor nodules. Finally, lung tumor-bearing animals when treated with DOTAP:Chol-FUS1 complex demonstrate prolonged survival (median survival time: 80 days, P = .01) compared to control animals. This result demonstrates the potent tumor suppressive activity of the FUS1 gene and is a promising therapeutic agent for treatment of primary and disseminated human lung cancer.

Carcinoma, Non-Small-Cell Lung↗

[Advance of fast magnetic resonance spectroscopic imaging].

The required time of conventional magnetic resonance spectroscopic imaging technique is too long to be applied to clinic. It is necessary to develop the fast methods for magnetic resonance spectroscopic imaging. Nowadays there are 7 kinds of methods presented, which come from MRI techniques. In this contribution the conventional spectroscopic imaging and 7 sorts of fast spectroscopic imaging are elaborated. It is envisaged that more rapid imaging techniques will be designed, if these arbitrary trajectory reconstruction methods in MRI are applied to spectroscopic imaging.

Magnetic Resonance Imaging↗

[Neural stem cell transplantation and postoperative management: report of 70 cases].

OBJECTIVE: To review the operations of neural stem cells transplantation in patients with brain trauma or spinal cord injury and their postoperative management. METHODS: A retrospective analysis was conducted in 70 cases of brain trauma or paraplegia treated with neural stem cell transplantation in the recent two years. RESULTS: All patients were smoothly discharged except for 3 who developed intracranial infection corrected with antibiotics via the vertebral canal. Another 3 patients with total loss of sexual function after spinal cord injury for over 1 year recovered sexual function after neural stem cell transplantation. CONCLUSION: Neural stem cell transplantation can promote the functional recovery of the brain and spinal cord in patients with brain trauma or spinal cord injury. Proper postoperative management for the patients is crucial to ensure favorable prognosis.

Adolescent↗

[Changes of light energy distribution in reaction centers of Citrus unshiu leaf photosystem under different light intensities].

In order to further understand the light energy distribution in photochemical reaction centers of fruit trees, this paper employed modulated fluorescence technique to study the state transition of photosystem in Citrus unshiu leaves under high and low light intensities. The results indicated that under low light intensity of 100 micromol x m(-2) s(-1), the PQ pool was in reduction state due to Q(A) reduction, which made the light energy distribution in photosystem changed from PS II to PS I; while under high light intensity of 1000 micromol x m(-2) s(-1), the PQ pool could not get electron and was in oxidation state, making light energy distribution changed from state 2 to state 1. When the leaves were treated by a phosphatase inhibitor NaF, the state 2 to state 1 transition of photosystem was inhibited under high light intensity, and the excessive light energy distribution from PS I to PS II caused damage to PS II. These findings would be helpful to understand the mechanisms of the photoinhibition of photosynthesis and the photodamage of photosynthetic apparatus of fruit trees.

Chlorophyll↗

CACNA2D2-mediated apoptosis in NSCLC cells is associated with alterations of the intracellular calcium signaling and disruption of mitochondria membrane integrity.

The CACNA2D2 gene, a new subunit of the Ca(2+)-channel complex, was identified in the homozygous deletion region of chromosome 3p21.3 in human lung and breast cancers. Expression deficiency of the CACNA2D2 in cancer cells suggests a possible link of it to Ca(2+) signaling in the pathogenesis of lung cancer and other cancers. We investigated the effects of overexpression of CACNA2D2 on intracellular Ca(2+) contents, mitochondria homeostasis, cell proliferation, and apoptosis by adenoviral vector-mediated wild-type CACNA2D2 gene transfer in 3p21.3-deficient nonsmall cell lung cancer cell lines. Exogenous expression of CACNA2D2 significantly inhibited tumor cell growth compared with the controls. Overexpression of CACNA2D2 induced apoptosis in H1299 (12.5%), H358 (13.7%), H460 (22.3%), and A549 (50.1%) cell lines. Levels of intracellular free Ca(2+) were elevated in AdCACNA2D2-transduced cells compared with the controls. Mitochondria membrane depolarization was observed prior to apoptosis in Ad-CACNA2D2 and Adp53-transduced H460 and A549 cells. Release of cyt c into the cytosol, caspase 3 activation, and PARP cleavage were also detected in these cells. Together, these results suggest that one of the pathways in CACNA2D2-induced apoptosis is mediated through disruption of mitochondria membrane integrity, the release of cyt c, and the activation of caspases, a process that is associated with regulation of cytosolic free Ca(2+) contents.

Animals↗

[Protective mechanism in photoinhibition of photosynthesis in Citrus unshiu leaves].

By using a portable PAM-2000 fluorometer and a spectrophotometer (722 Model), the diurnal variation in main chlorophyll fluorescence parameters such as initial fluorescence (F0), maximal fluorescence (Fm), ratio of variable fluorescence to maximal fluorescence (Fv/Fm), non-photochemical quenching (qN), fast-phase (qNf) and slow-phase (qNs) of non-photochemical quenching, electron transport rate (ETR), and relative content of xeaxanthin in Citrus unshiu leaves were observed on fine days. The results showed that ETR, qN, qNf, qNs and relative content of xeaxanthin increased with increasing light intensity, but Fm, F0, photo-chemical efficiency of PS II (Fv/Fm) decreased. After treated by DTT, qNs was much lower, but F0 was much higher than control. These results indicated that xanthophyll cycle and delta pH existed, and played an important protective role against photo-damage to the photosynthetic apparatus in Citrus unshiu leaves during diurnal variation of photosynthetic efficiency.

Chlorophyll↗

[Software for MR image reconstruction from data acquired on an irregular k-space trajectory].

A PC-based software was developed and programmed with VC++6 for reconstructing MR images from the data acquired on an irregular k-space trajectory. It can read clinical MRI raw data and image data, create numerical phantoms, design k-space trajectories, generate k-space data from numerical phantom, calculate weighting functions, reconstruct images, and carry out error analysis for the reconstructed images. It is helpful to the investigations of new k-space trajectories and new reconstruction algorithms.

Algorithms↗