BPI-28592 as a novel second generation inhibitor for NTRK fusion tumors.

Aberrant activation of tropomyosin receptor kinases (TRKs) is a well-defined oncogenic driver for neurotrophic tropomyosin receptor kinase (NTRK)-fusion cancers, and acquired resistant mutations have emerged with clinical use of the first-generation TRK inhibitors. Here we present BPI-28592, a novel second-generation TRK inhibitor with efficacy against TRK fusion-positive cancers, including those with resistant mutations. Docking simulations indicated no steric hindrance between BPI-28592 and TRK mutants, suggesting its potential to overcome drug resistance. Biochemical assays showed strong inhibition and high selectivity against TRKA, TRKB, and TRKC. The inhibitor significantly reduced cell proliferation and blocked TRK signaling. In vivo studies demonstrated effective tumor suppression in xenograft models harboring TRK fusions with or without resistant mutations. Clinically, BPI-28592 achieved a complete response in a patient with malignant melanoma carrying an AP3S2-NTRK3 fusion (Clinicaltrials. gov identifier: NCT05302843).

Clinical significance of preoperative nutritional status in elderly gastric cancer patients undergoing radical gastrectomy: A single-center retrospective study.

BACKGROUND: The population of elderly patients with gastric cancer is increasing, which is a major public health issue in China. Malnutrition is one of the greatest risk factors for adverse clinical outcomes in elderly patients with gastric cancer. AIM: To investigate the preoperative nutritional status and its association with delayed discharge of elderly gastric cancer patients following radical gastrectomy. METHODS: A total of 783 patients aged 65 years and older harboring gastric adenocarcinoma and following radical gastrectomy were retrospectively analyzed from the prospectively collected database of Zhongshan Hospital of Fudan University between January 2018 and May 2020. RESULTS: The overall rate of malnutrition was 31.8%. The incidence of postoperative complications was significantly higher in the malnourished group compared to the well-nourished group (P < 0.001). Nutritional characteristics in the malnourished group, including body mass index, prognostic nutritional index (PNI), albumin, prealbumin, and hemoglobin, were all significantly lower than those in the well-nourished group. The percentage of patients who received postoperative total nutrient admixture was lower in the malnourished group compared to the well-nourished group (22.1% vs 33.5%, P = 0.001). Age ≥ 70 years (HR = 1.216, 95%CI: 1.048-1.411), PNI < 44.5 (HR = 1.792, 95%CI: 1.058-3.032), operation time ≥ 160 minutes (HR = 1.431, 95%CI: 1.237-1.656), and postoperative complications grade III or higher (HR = 2.191, 95%CI: 1.604-2.991) were all recognized as independent risk factors associated with delayed discharge. CONCLUSION: Malnutrition is relatively common in elderly patients undergoing gastrectomy. Low PNI is an independent risk factor associated with delay discharge. More strategies are needed to improve the clinical outcome of these patients.

Tislelizumab combined with GT chemotherapy for intimal sarcoma of inferior vena cava: A case report.

RATIONALE: Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack of standardized treatment and methods. PATIENT CONCERNS: A 54-year-old female patient presented to Fenghua District People's Hospital with a post-active cough and hemoptysis and was subsequently referred to our hospital. DIAGNOSES: The patient was pathologically diagnosed as intimal sarcoma of IVC complicating multiple intrapulmonary metastases. Chest CT revealed left lung malignant tumor with multiple intrapulmonary metastases; while enhanced upper abdominal CT showed cancer embolus of IVC with extension to right atrium and bilateral renal veins. Besides, hematoxylin and eosin staining suggested intimal sarcoma of veins. Immunohistochemical staining showed positivity for PD-L1, Ki-67, CD31, Desmin and ERG. INTERVENTIONS: The patient initially received GT chemotherapy (gemcitabine injection + docetaxel). Then, immunotherapy (tislelizumab) was added based on the results of genetic testing (TP53 gene mutation). OUTCOMES: The disease was stabilized after receiving the treatment. LESSONS: Given the lack of characteristic clinical manifestations in patients with intimal sarcoma of IVC, imaging examination combined with immunohistochemical index were helpful for diagnosis of intimal sarcoma of IVC. Furthermore, the combination of tislelizumab and GT chemotherapy was feasible in such patients with positive PD-L1 expression and TP53 mutation.

Rare SMARCA4-deficient thoracic tumor: Insights into molecular characterization and optimal therapeutics methods.

INTRODUCTIONS: The 2021 WHO Classification of Thoracic Tumors recognized SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) as a distinct entity that shows a striking overlap in demographic and molecular profiles with SMARCA4-deficient non-small lung cancer (SMARCA4-dNSCLC). The implications of SMARCA4 deficiency based on immunohistochemistry remain unclear. We aimed to investigate molecular characteristics of SMARCA4-deficient thoracic tumors (SDTT) and explore optimal therapeutics. METHODS: From June.15, 2018, to Nov.15, 2023, a large cohort including patients diagnosed with SMARCA4-deficient (N = 196) and SMARCA4-intact (N = 438) thoracic tumors confirmed by immunohistochemistry at SYSUCC were screened. Clinicopathologic and molecular characteristics were identified and compared. External SRRSH cohort (N = 34) was combined into a pooled cohort to compare clinical outcome of first-line therapy efficacy. RESULTS: SDTT is male predominance with smoking history, high tumor burden, and adrenal metastases. The relationship between SMARCA4 mutation and protein expression is not completely parallel. The majority of SMARCA4-deficient patients harbor truncating (Class-I) SMARCA4 mutations, whereas class-II alterations and wild-type also exist. Compared with SMARCA4-intact thoracic tumors, patients with SDTT displayed a higher tumor mutation burden (TMB) and associated with a shorter median OS (16.8 months vs. Not reached; P < 0.001). Notably, SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in these differences. SDTT is generally resistant to chemotherapy, while sensitive to chemoimmunotherapy (median PFS: 7.5 vs. 3.5 months, P < 0.001). In particular, patients with SMARCA4 deficient thoracic tumors treated with paclitaxel-based chemoimmunotherapy achieved a longer median PFS than those with pemetrexed-based chemoimmunotherapy (10.0 vs. 7.3 months, P = 0.028). CONCLUSIONS: SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in its characteristics of higher TMB and poor prognosis. Chemoimmunotherapy serves as the optimal option in the current treatment regimen. Paclitaxel-based chemoimmunotherapy performed better than those with pemetrexed-based chemoimmunotherapy.

Effects of oral probiotics on inflammation and intestinal function in adult patients after appendectomy: Randomized controlled trial.

BACKGROUND: Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation. Oral probiotics are one of the postoperative treatments for rapid rehabilitation. However, there is a lack of prospective studies on this topic after appendectomy. AIM: To investigate whether the postoperative probiotics can modulate the inflammatory response and restore intestinal function in patients following appendectomy. METHODS: This was a prospective, randomized trial. A total of 60 emergency patients were randomly divided into a control group (n = 30) and a probiotic group (n = 30). Patients in the control group started to drink some water the first day after surgery, and those in the probiotic group were given water supplemented with Bacillus licheniformis capsules for 5 consecutive days postsurgery. The indices of inflammation and postoperative conditions were recorded, and the data were analyzed with RStudio 4.3.2 software. RESULTS: A total of 60 participants were included. Compared with those in the control group, the C-reactive protein (CRP), interleukin 6 and procalcitonin (PCT) levels were significantly lower in the probiotic group at 2 d after surgery (P = 2.224e-05, P = 0.037, and P = 0.002, respectively, all P < 0.05). This trend persisted at day 5 post-surgery, with CRP and PCT levels remaining significantly lower in the probiotic group (P = 0.001 and P = 0.043, both P < 0.05). Furthermore, probiotics resulted in a shorter time to first flatus and a greater percentage of gram-negative bacilli in the feces (P = 0.035, P = 0.028, both P < 0.05). CONCLUSION: Postoperative oral administration of probiotics may modulate the gut microbiota, benefit the recovery of the early inflammatory response, and subsequently enhance recovery after appendectomy.

Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer.

BACKGROUND: Baseline corticosteroids exposure is associated with inferior clinical outcomes in patients with non-small-cell lung cancer (NSCLC) treated with programmed cell death-1 (PD-1) axis blockade. Dexamethasone is a potent corticosteroid used in the prevention of chemotherapy-associated adverse events (CAAEs). OBJECTIVE: Since dexamethasone has immunosuppressive properties, this study attempted to elucidate its effects on the efficacy of immunotherapy plus chemotherapy in patients with non-squamous NSCLC. METHODS: The study retrospectively analyzed the medical records of 254 advanced non-squamous NSCLC patients who received front-line treatment with a PD-1 pathway inhibitor and platinum-based chemotherapy at three academic institutions. The average dosage of prophylactic dexamethasone per chemotherapy cycle was calculated. Patients were divided into three groups based on the dose of dexamethasone: High-d (≥24 mg), Moderate-d (12-24 mg), and Low-d (<12 mg). Spearman's rank correlation was used to assess the correlation between the dosage of dexamethasone and progression-free survival (PFS). Logistic regression was used to assess the correlation between dexamethasone dosage and the occurrence of immune related adverse effects (irAE). Univariate and multivariate Cox proportional hazards regression models were used to analyze the differences in survival among the different dexamethasone dosage groups. RESULT: The dosage of prophylactic dexamethasone was not significantly correlated with PFS (Spearman's rho = -0.103, P = 0.098). Results from the univariate [hazard ratio (HR)Low-d/High-d, 1.00; P = 0.997; HRModerate-d/High-d, 0.85; P = 0.438] and multivariate (HRLow-d/High-d, 0.71; P = 0.174; HRModerate-d/High-d, 0.87; P = 0.512) analyses showed no significant association between dexamethasone and PFS. Dexamethasone did not have significant effect on the objective response rate, disease control rate or overall survival. The toxicity profiles of irAE were similar across all three groups. CONCLUSION: The results of this study suggest that the use of prophylactic dexamethasone does not have an adverse effect on the clinical outcomes of non-squamous NSCLC patients treated with PD-1 blockade therapy and chemotherapy. Routine use of dexamethasone for preventing CAAEs should be recommended for patients undergoing combined immunotherapy and chemotherapy.

Complete mitochondrial genomic sequence of Auricularia delicata (Auriculariaceae), an edible Chinese mushroom.

Auricularia delicata (Mont.) Henn. 1893 is an edible and medicinal jelly mushroom popular in China. Here, we report the assembly and annotation of a complete A. delicata mitochondrial genome based on data sequenced using an Illumina NovaSeq 6000 platform. The length of the complete circular A. delicata mitochondrial genome is 189,696 bp, with a GC content of 34.1%. The A. delicata mitochondrial genome contains 60 genes, including 32 protein-coding genes, 26 tRNA genes, and two rRNA genes. Phylogenetic analysis indicated that A. delicata clustered with the Auricularia group, alongside A. auricula-judae and A. heimuer. Additionally, A. delicata was found to be genetically distant from other species of Polyporales, Russulales, and Agaricales. This genome will provide an invaluable reference for the continued study and utilization of A. delicata and other Auricularia species.

Integrated Analysis Identifies DPP7 as a Prognostic Biomarker in Colorectal Cancer.

Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand-receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target.

Immunochemotherapy achieved a complete response for metastatic adenocarcinoma of unknown primary based on gene expression profiling: a case report and review of the literature.

Background: Cancer of unknown primary (CUP) is a malignant and aggressive tumor whose primary origin is still unknown despite thorough evaluation. CUP can be life-threatening with a median overall survival of less than 1 year based on empirical chemotherapy. Gene detection technology advances the driver gene detection of malignant tumors and the appropriate precise therapy. Immunotherapy has ushered in a new era in cancer therapy, changing the way advanced tumors, including CUP, are treated. Combined with comprehensive clinical and pathological investigations, molecular analysis of the original tissue and detection of potential driver mutations may provide therapeutic recommendations for CUP. Case presentation: A 52-year-old female was admitted to hospital for dull abdominal pain, with peripancreatic lesions below the caudate lobe of the liver and posterior peritoneal lymph nodes enlargement. Conventional biopsy under endoscopic ultrasonography and laparoscopic biopsy both revealed poorly differentiated adenocarcinoma based on immunohistochemical series. To help identify tumor origin and molecular characteristics, 90-gene expression assay, tumor gene expression profiling with Next-generation sequencing (NGS) method and Immunohistochemical expression of PD-L1 were employed. Although no gastroesophageal lesions discovered by gastroenteroscopy, the 90-gene expression assay yielded a similarity score and prompted the most likely primary site was gastric/esophagus cancer. NGS revealed high TMB (19.3mutations/Mb) but no druggable driver genes identified. The Dako PD-L1 22C3 assay IHC assay for PD-L1 expression revealed a tumor proportion score (TPS) of 35%. Given the presence of negative predictive biomarkers for immunotherapy, including adenomatous polyposis coli (APC) c.646C>T mutation at exon 7 and Janus kinase 1(JAK1), the patient received immunochemotherapy instead of immunotherapy alone. She was successfully treated with nivolumab plus carboplatin and albumin-bound nanoparticle paclitaxel for six cycles and nivolumab maintenance, which achieved a complete response (CR) maintained for 2 years without severe adverse events. Conclusions: This case highlights the value of multidisciplinary diagnosis and individual precision treatment in CUP. Further investigation is needed as an individualized treatment approach combining immunotherapy and chemotherapy based on tumor molecular characteristics and immunotherapy predictors is expected to improve the outcome of CUP therapy.

Thoracic SMARCA4-Deficient Undifferentiated Tumor With ALK Fusion Treated With Alectinib Achieved Remarkable Tumor Regression: Case Report.

Recently, SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) has emerged as a distinct subset of lung cancer. Previous studies have suggested that SMARCA4-UT is often associated with smoking-related mutations, such as KRAS and STK11, rather than EGFR or ALK alterations. Nevertheless, no specific precision therapy has been identified for SMARCA4-UT. Here, we report the first case of concomitant ALK rearrangement and SMARCA4 (BRG1) deficiency in a nonsmoking female with thoracic cancer. Alectinib was given as the first-line therapy, and the patient achieved a remarkable complete response. Our case highlights the significance of ALK rearrangement identification for the precise therapeutic potential of SMARCA4-UT.

Circ0005654 as a new biomarker of thyroid cancer interacting with SP1 to influence the prognosis: A case-control study.

Circular RNAs (CircRNAs) have been reported to play key roles in the progression of various cancers, including thyroid cancer (TC). Transcription factor 1 (SP1) promotes the development of thyroid cancer. This study aims at investigating the expression level of Circ0005654 in combination with Transcription factor1 (SP1) in patients with TC for diagnostic and therapeutic purposes. A total of 76 patients with thyroid cancer underwent radical surgery. Intraoperatively, thyroid cancer tissues and paired adjacent tissues and the corresponding clinicopathological data were collected. The expression of SP1 and ß-catenin in thyroid cancer and adjacent tissues was determined by immunohistochemistry (IHC) while the Circ0005654 expression level was measured by semiquantitative real-time polymerase chain reaction (sqRT-PCR). Then, we compared the variability of Circ0005654, SP1, and Wnt/ß-catenin expression in cancerous and adjacent tissues and determined the relationship between the correlation analysis and the clinicopathological features of the thyroid cancer patients. The diagnostic value of Circ0005654 in thyroid cancer tissues was analyzed with the help of the receiver operating characteristic (ROC) curve, counting the 3-year postoperative survival rate, and analyzing the effect of Circ0005654 and SP1 protein levels on the 3-year survival rate of the patients. sqRT-PCR showed that the expression level of Circ0005654 in thyroid cancer tissue was significantly higher than that of adjacent tissues. The area under the ROC of Circ0005654 was 0.9553, 95% confidence interval: (0.9211-0.9895) with a cutoff value of 0.7895, a sensitivity of 92.11%, and a specificity of 86.84%. The IHC results showed that the expression level of SP1, ß-catenin, and Wnt was higher in cancer tissues than in adjacent tissues; Circ0005654, SP1, Wnt/ß-catenin expression levels were associated with tumor diameter, lymph node metastasis, TNM stage, and envelope invasion (all P < .05). According to the Circ0005654 expression level in thyroid cancer tissue, the 3-year survival rate of the high expression group was 77.5% and 94.4% in the low expression group with a statistically significant difference; the 3-year survival rate of SP1 positive and negative patients was 78.6% and 100%, respectively, with the data being significantly different. Circ0005654 may serve as a potential biomarker for thyroid cancer diagnosis and may be involved in the development of thyroid cancer.

The value of nonverbal intelligence in cochlear implant.

BACKGROUND: Congenital sensorineural hearing loss is a common congenital condition. OBJECTIVES: The purpose of this study was to assess the correlation between nonverbal mental development and the effect of post-cochlear implant in children. MATERIAL AND METHODS: The study is a retrospective analysis of the CI program implemented at the ENT in the Lanzhou University Second Hospital (China). We reviewed data of 225 children who received CI between 2015 and 2018. Finally, 115 children met the inclusion criteria. Our hospital used The Griffith mental development scales to evaluate the preoperative non-verbal intelligence. The outcome of CI was evaluated using the categories of IT-MAIS, MUSS, CAP and SIR at 2 years after surgery. The associations between the preoperative non-verbal development quotient (DQ) and the postoperative outcomes were analyzed. RESULTS: Preoperative non-verbal DQ correlates with the long-term postoperative result, especially the Eye-hand co-ordination and Performance DQ. CONCLUSIONS AND SIGNIFICANCE: Preoperative non-verbal intelligence would predict postoperative effect. The single postoperative scale does not fully reflect the postoperative result.

Radiomics signature for prediction of long-term survival and recurrence patterns in patients with gastric cancer after radical gastrectomy: A multicenter study.

Background: This study aimed to develop and validate a radiomics score to predict the long-term survival and patterns of recurrence of gastric cancer (GC). Methods: A total of 513 patients who underwent radical gastrectomy for GC after curative resection between 2008 and 2016 at two institutions were analyzed. A radiomics score was generated using the least absolute shrinkage and selection operator Cox regression model on 327 patients and was validated in 186 patients. A nomogram consisting of the radiomics score and clinicopathological factors was created and compared with the tumor-lymph node-metastasis (TNM) staging system. Model performance was assessed using calibration, discrimination, and clinical usefulness. Results: The radiomics score was established based on five selected features. A higher score was significantly associated with poorer recurrence-free survival (RFS) and overall survival (OS) rates, both in the training and validation cohorts (P < 0.05). Multivariate analysis demonstrated that the radiomics score was an independent prognostic factor for both RFS and OS (P < 0.05). A nomogram incorporating the radiomics score had a significantly better prognostic value than the TNM system alone. Moreover, a high score was significantly associated with an increased risk of distant recurrence, a medium score was significantly associated with an increased risk of peritoneal recurrence, and a low score was significantly associated with an increased risk of locoregional recurrence, in the entire cohort (P < 0.05). Conclusions: The newly proposed radiomics score may be a powerful predictor of long-term outcomes and recurrence patterns of GC. Further studies are warranted to confirm these findings.

Hemorrhagic, hypovolemic shock resuscitated with Ringer's solution using bicarbonate versus lactate: A CONSORT-randomized controlled study comparing patient outcomes and blood inflammatory factors.

BACKGROUND: Isotonic crystalloids are the preferred solution for the initial clinical management of patients with multiple trauma, among which lactated Ringer's solution and normal saline are the most widely used, but both have clinical limitations. Bicarbonated Ringer's solution (BRS), which provides physiological levels of bicarbonate ions and electrolyte ions, can be used to supplement missing extracellular fluid and correct metabolic acidosis. METHODS: A prospective, randomized controlled study enrolled 63 patients with traumatic hepatic rupture and hemorrhagic shock. They were randomly assigned to the Bicarbonated group (n = 33) or the Control group (n = 30), which received restrictive fluid resuscitation with sodium bicarbonate Ringer's solution or sodium lactate Ringer's solution, respectively. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, arterial blood lactic acid and potential of hydrogen (pH) were measured prior to, 1, 3, 24, and 72 hours following resuscitation. The primary outcomes were patient survival, shock-related complications, and comparison of the inflammatory factors. RESULTS: The incidence of complications in the Bicarbonated group was significantly lower than in the Control group (15.15% vs 40.0%; P < .05). The intensive care unit length of stay and mechanical ventilation time in the Bicarbonated group were significantly shorter than in the Control group (all P < .01). The levels of IL-6 and TNF-α in the Bicarbonated group were significantly lower 1 hour following resuscitation than prior to resuscitation (P < .01), whereas these levels in the Control group were increased following 1h of resuscitation as compared with before resuscitation (P < .01). Following resuscitation, the levels of IL-6, TNF-α and lactate in the Bicarbonated group were significantly lower than in the Control group (P < .01). Moreover, in the Bicarbonated group, the lactic acid level decreased and the pH value increased significantly following resuscitation, whereas there was no difference in lactic acid levels and pH value between pre- and 1 hour post-resuscitation in the Control group (P > .05). CONCLUSION: The shock-related complications were dramatically reduced from using BRS in these patients. Additionally, the BRS was found to better inhibit the expression of inflammatory factors in their peripheral blood and could correct acidosis.

A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma.

Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab (200 mg, q2w) and apatinib (250 mg, once daily) before surgery. The primary endpoints are safety and major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score (CPS, defined as the number of PD-L1-stained cells divided by the total number of viable tumour cells, multiplied by 100) and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%-24.3%) and 95% (95% CI: 85.4%-100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC.

Underlying mechanisms of saphenous vein graft stenosis after coronary artery bypass caused by clipping of the side branches: an experimental study.

Background: Saphenous veins are regular bypass conduits selected in non-left anterior descending artery (LAD) coronary artery bypass graft (CABG) surgery. Despite the technical errors, acute thrombosis, intimal hyperplasia and arteriosclerosis which could lead to saphenous vein graft (SVG) failure, the metal-clipping-related SVG failure is unique and rare. This study was conducted to investigate the clinical and underlying mechanisms of the metal-clipping-related SVG failure. Methods: We collected 6 typical cases of the metal-clipping-related SVG failure in 41 patients who were diagnosed graft stenosis by coronary angiograph after CABG in the Department of Cardiology, Beijing Anzhen Hospital, from January 2020 to September 2021. Furthermore, we built an in vitro model to verify the identical intravascular ultrasound (IVUS) pattern of metal clip. Results: There were 6 in 41 cases of SVG stenosis caused by clipping of the side branches. We found that the stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. In this situation, great resistance could be felt when pushing the instruments through the stenosis and crystallized cholesterol was rarely caught by the distal protection device. We verified the similar IVUS pattern of metal clip at the side-branches of SVG in vitro. Conclusions: The metal-clipping-related stenosis may lead to SVG failure. The stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. IVUS showed great modality for clarification.

CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer.

The crucial role of CD4+ and CD8+ T cells in shaping and controlling immune responses during immune disease and cancer development has been well established and used to achieve marked clinical benefits. CD3+CD4-CD8- double-negative (DN) T cells, although constituting a rare subset of peripheral T cells, are gaining interest for their roles in inflammation, immune disease and cancer. Herein, we comprehensively review the origin, distribution and functions of this unique T cell subgroup. First, we focused on characterizing multifunctional DN T cells in various immune responses. DN regulatory T cells have the capacity to prevent graft-versus-host disease and have therapeutic value for autoimmune disease. T helper-like DN T cells protect against or promote inflammation and virus infection depending on the specific settings and promote certain autoimmune disease. Notably, we clarified the role of DN tumor-infiltrating lymphocytes and outlined the potential for malignant proliferation of DN T cells. Finally, we reviewed the recent advances in the applications of DN T cell-based therapy for cancer. In conclusion, a better understanding of the heterogeneity and functions of DN T cells may help to develop DN T cells as a potential therapeutic tool for inflammation, immune disorders and cancer.

Intentional Replantation for a Right Mandibular Premolar.

The present study reports a case of intentional replantation (IR) for a right mandibular second premolar (#45). For the present case, root canal retreatment was first considered after removal of the metal post and core. When the metal post and core could not be removed from #45, micro-apical surgery or intentional tooth replantation was performed. Six-month postoperative evaluation revealed that the right mandibular second premolar had no obvious symptoms of discomfort, and the clinical follow-up revealed uneventful healing and good bone regeneration. The short-term clinical efficacy was acceptable. For cases with root canal treatment failure, when the apical surgical access could not be established due to the adjacent important anatomical structures, IR may be employed as an accepted endodontic treatment procedure. Key Words: Root canal treatment failure, Post-core crown, Root canal retreatment, Intentional replantation.

[Metabonomics research on lung tissue of rats with acute exacerbation of chronic obstructive pulmonary disease treated with mineral Chinese medicine Chloriti Lapis].

To study the effect of mineral Chloriti Lapis on pulmonary metabolites and metabolic pathways in lung tissues of rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). The AECOPD rat model of phlegm heat syndrome was replicated by the method of smoking combined with Klebsiella pneumoniae infection. Except for using UPLC-Q-TOF-MS analysis, SPSS 18.0, SIMCA 13.0 and other software were also used for statistical analysis. Through literature search and online database comparison, the differential metabolites were identified, and the possible metabolic pathways were analyzed. After 15 days of administration, PLS-DA analysis was carried out on lung tissue samples of rats in each group. The results showed that the metabolic profiles of lung tissues of rats in each group could be well separated, which indicated that Chloriti Lapis and aminophylline had significant intervention effect on the lung metabolic profile of rats with AECOPD. Moreover, the metabolic profile of Chloriti Lapis group was closer to that of control group, and the intervention effect was better than that of aminophylline group. As a result, 15 potential differential metabolites were identified: phytosphingosine, sphinganine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], lysoPC(18∶0), stearic acid, lysoPC(15∶0), arachidonic acid, docosapentaenoic acid, linoleic acid and palmitic acid. Among them, Chloriti Lapis could significantly improve the levels of 10 differential metabolites of phytosphingosine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], stearic acid, lysoPC(15∶0), and palmitic acid(P<0.05). The intervention effect of Chloriti Lapis group was better than that of aminophylline group. Analysis of metabolic pathways showed that there were 8 possible metabolic pathways that could be affected, and three of the most important metabolic pathways(pathway impact>0.1) were involved: linoleic acid metabolism, arachidonic acid metabolism, and sphingolipid metabolism. Chloriti Lapis had obvious intervention effects on lung tissue-related metabolites and metabolic pathways in rats with AECOPD, and the effect was better than that of aminophyllinne.