Predictive value of spectral computed tomography parameters for EGFR gene mutation in non-small-cell lung cancer.

AIM: To explore the predictive value of morphological signs and quantitative parameters from spectral CT for EGFR gene mutations in intermediate and advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective observational study included patients with intermediate or advanced NSCLC at Xinjiang Medical University Affiliated Tumor Hospital between January 2017 and December 2019. The patients were divided into the EGFR gene mutation-positive and -negative groups. RESULTS: Seventy-nine patients aged 60.75 ± 9.66 years old were included: 32 were EGFR mutation-positive, and 47 were negative. There were significant differences in pathological stage (P<0.001), tumor diameter (P=0.019), lobulation sign, intrapulmonary metastasis, mediastinal lymph node metastasis, distant metastasis (P<0.001), bone metastasis (P<0.001), arterial phase normalized iodine concentration (NIC) (P=0.001), venous phase NIC (P=0.001), slope of the energy spectrum curve (λ) (P<0.001), and CT value at 70 keV in arterial phase (P=0.004) and venous phase (P=0.003) between the EGFR mutation-positive and -negative patients. The multivariable logistic regression analysis showed that intrapulmonary metastasis, distant metastasis, venous phase NIC, venous phase λ, and pathological stage were independent factors predicting EGFR gene mutations, with high diagnostic power (AUC = 0.975, 91.5% sensitivity, and 90.6% specificity). CONCLUSION: The pathological stage and the spectral CT parameters of intrapulmonary metastasis, distant metastasis, venous phase NIC, and venous phase λ might pre-operatively predict EGFR gene mutations in intermediate and advanced NSCLC.

Predictive effect of net water uptake on futile recanalisation in patients with acute large-vessel occlusion stroke.

AIM: To determine whether net water uptake (NWU) based on automated software evaluation could predict futile recanalisation in patients with acute anterior circulation large-vessel occlusion (LVO). MATERIALS AND METHODS: Patients with acute anterior circulation LVO undergoing mechanical thrombectomy in Jinling Hospital were evaluated retrospectively. NWU and other baseline data were evaluated by performing univariate and multivariate analyses. The primary endpoint was 90-day modified Rankin scale score ≥3. A nomogram to predict poor clinical outcomes was developed based on multivariate logistic regression analysis. RESULTS: Overall, 135 patients who underwent thrombectomy with a TICI grade ≥2b were enrolled. In multivariate logistic regression analysis, the following factors were identified as independent predictors of futile recanalisation: age (odds ratio [OR]: 1.055, 95 % confidence interval [CI]: 1.004-1.110, p=0.035), female (OR: 0.289, 95 % CI: 0.098-0.850, p=0.024), hypertension (OR: 3.182, 95 % CI: 1.160-8.728, p=0.025), high blood glucose level (OR: 1.36, 95 % CI: 1.087-1.701, p=0.007), admission National Institutes of Health Stroke Scale score (OR: 1.082, 95 % CI: 1.003-1.168, p=0.043), and NWU (OR: 1.312, 95 % CI: 1.038-1.659, p=0.023). CONCLUSIONS: NWU based on Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) could be used to predict the occurrence of futile recanalisation in patients with acute anterior circulation LVO ischaemic stroke.

Development of a machine learning interatomic potential for exploring pressure-dependent kinetics of phase transitions in germanium.

We introduce a data-driven potential aimed at the investigation of pressure-dependent phase transitions in bulk germanium, including the estimate of kinetic barriers. This is achieved by suitably building a database including several configurations along minimum energy paths, as computed using the solid-state nudged elastic band method. After training the model based on density functional theory (DFT)-computed energies, forces, and stresses, we provide validation and rigorously test the potential on unexplored paths. The resulting agreement with the DFT calculations is remarkable in a wide range of pressures. The potential is exploited in large-scale isothermal-isobaric simulations, displaying local nucleation in the R8 to ß-Sn pressure-induced phase transformation, taken here as an illustrative example.

[Long-term efficacy and prognostic factors of Beijing Children's Hospital-2009-lymphoblastic lymphoma in the treatment of T-lymphoblastic lymphoma in children and adolescents].

Objective: To summarize the long-term efficacy of Beijing Children's Hospital-2009-lymphoblastic lymphoma (BCH-2009-LBL) in the treatment of T-lymphoblastic lymphoma (T-LBL) in children and adolescents and to explore the prognostic factors. Methods: T-LBL children admitted to Beijing Children's Hospital Affiliated to Capital Medical University from January 2009 to April 2017 were retrospectively included. According to clinical stage, prognostic genes and treatment response, the children were divided into low, intermediate and high risk groups, and stratified treatment was performed according to the BCH-2009-LBL protocol, with follow-up until December 31, 2023. The clinical characteristics and therapeutic effect of each group were compared. Survival curve was drawn by Kaplan-Meier method, and the difference in survival rate between groups was compared by log-rank test. Multivariate Cox regression model was used to analyze the prognostic factors. Results: A total of 146 patients were included, the age of disease onset [M(Q1, Q3)] was 8.0 (1.5, 14.0) years old. There were 107 (73.3%) males and 39 (26.7%) females. Clinical staging: 1 case in stage Ⅰ and 1 case in stage Ⅱ (0.7% each), 41 cases (28.1%) cases in stage Ⅲ and 103 cases(70.5%) in stage Ⅳ. There were 1 case (0.7%), 93 cases (63.7%), and 52 cases (35.6%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 121 (80, 180) months, and the 5-year and 10-year event-free survival (EFS) rates were 76.4% and 75.0%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 81.3% and 67.3%, respectively. There was significant difference in remission between the middle-risk group and the high-risk group on the 8th day of hormone pretreatment and at the end of induction (both P<0.05). Recurrence/progression occurred in 29 cases (recurrence rate 19.9%), and the recurrence time was 15 (3, 74) months, in which 26 cases died and only 3 cases survived. Infection-related death occurred in 6 cases (4.1%). The failure or progression of hormone pretreatment at d8 (HR=10.089, 95%CI: 1.266-80.387, P=0.029) and the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=7.638, 95%CI: 2.411-24.199, P=0.001) were the risk factors for EFS rate of intermediate risk group. The above indexes had no statistical significance on EFS rate in high-risk groups (all P>0.05). Conclusions: BCH-2009-LBL regimen shows good efficacy in the treatment of pediatric T-LBL. The failure or progression of hormone pretreatment at d8 and the failure to achieve complete remission at the end of induction (mid-term evaluation) were the risk factors for EFS rate.

[Analysis of the efficacy and safety of dual immunotherapy in patients with driver gene and programmed death ligand-1 double negative advanced non-small cell lung cancer].

Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage ⅢC and 47 cases (77.0%) classified as stage Ⅳ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.

[Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma].

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial.

BACKGROUND: IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here. PATIENT AND METHODS: The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1 : 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition). Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay). RESULTS: At a median of 45.3 months' follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified hazard ratio (HR) was 0.995 [95% confidence interval (CI) 0.78-1.28]. The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n = 882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 tumour cell (TC) ≥1% (n = 476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n = 229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis [grade 3/4 in 53 (10.7%) and grade 5 in 4 (0.8%) of 495 patients, respectively]. CONCLUSIONS: Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting.

Branching of High-Current Relativistic Electron Beam in Porous Materials.

Propagation of high-current relativistic electron beam (REB) in plasma is relevant to many high-energy astrophysical phenomena as well as applications based on high-intensity lasers and charged-particle beams. Here, we report a new regime of beam-plasma interaction arising from REB propagation in medium with fine structures. In this regime, the REB cascades into thin branches with local density a hundred times the initial value and deposits its energy 2 orders of magnitude more efficiently than that in homogeneous plasma, where REB branching does not occur, of similar average density. Such beam branching can be attributed to successive weak scatterings of the beam electrons by the unevenly distributed magnetic fields induced by the local return currents in the skeletons of the porous medium. Results from a model for the excitation conditions and location of the first branching point with respect to the medium and beam parameters agree well with that from pore-resolved particle-in-cell simulations.

Coherent Subcycle Optical Shock from a Superluminal Plasma Wake.

We propose exploiting the superluminal plasma wake for coherent Cherenkov radiation by injecting a relativistic electron beam (REB) into a plasma with a slowly varying density up-ramp. Using three-dimensional particle-in-cell and far-field time-domain radiation simulations, we show that an isolated subcycle pulse is coherently emitted towards the Cherenkov angle by bubble-sheath electrons successively at the rear of the REB-induced superluminal plasma wake. A theoretical model based on a superluminal current dipole has been developed to interpret such coherent radiation, and agrees well with the simulation results. This radiation has ultrashort attosecond-scale duration and high intensity, and exhibits excellent directionality with ultralow angular divergence and stable carrier envelope phase. Its intensity increases with the square of the propagation length and its central frequency can be easily tuned over a wide range, from the far infrared to the ultraviolet.

Silicon nanowire FET biosensor and its application in acute myocardial infarction.

Over the last two decades, silicon nanowire field-effect transistors (SiNW-FETs) with prominent merits of high surface-to-volume ratio, excellent biocompatibility and mature fabrication with standard silicon technology, have been widely studied as ultrahigh sensitive biosensors for the detection of target biomolecules, such as proteins, nucleic acids, cells and viruses so on. Herein we present a comprehensive review of the fundamental aspects of SiNW-FET biosensors, involving the working principle and the device fabrication, surface functionalization, and system integration with fluid exchange and electrical detection. Futhermore, we emphatically discuss the electrical detection of cardiac-specific biomarkers related to acute myocardial infarction disease. SiNW-FET biosensors are being increasingly exploited as promising diagnostic devices, which provide high sensitivity, high integration density, high speed sampling, strong specificity, and real-time and label-free detection for simple and cheap clinical testing.

Endovascular treatment for acute ischaemic stroke caused by isolated internal carotid artery occlusion: treatment strategies, outcomes, and prognostic factors.

AIM: To describe the experience of endovascular treatment (EVT) of acute ischaemic stroke caused by isolated internal carotid artery (ICA) occlusion, with emphasis on treatment strategies, outcomes, and prognostic factors. MATERIALS AND METHODS: A retrospective examination was performed of 66 consecutive patients with acute moderate-to-severe stroke who underwent EVT for isolated ICA occlusion from July 2016 to June 2021. The modified thrombolysis in cerebral ischaemia (mTICI) score was used to evaluate reperfusion outcomes. A multivariate analysis was performed to identify risk factors associated with poor 90-day outcome (modified Rankin Scale [mRS] 3-6). RESULTS: The National Institutes of Health Stroke Scale (NIHSS) median score of the 66 patients at admission was 15. Twelve patients (18.2%) showed thrombus migration to the M1 segment or proximal M2 during EVT and underwent additional intracranial thrombectomy. Successful reperfusion (mTICI 2b-3) was achieved in 60 patients (90.9%) and complete reperfusion (mTICI 3) in 42 (63.6%). A poor functional outcome was seen in 27 patients (40.9%). The rate of 90-day mortality was 9.1% (6/66). Higher NIHSS scores and a lower Alberta Stroke Program Early CT Score (ASPECTS) were independently associated with poor outcomes. Complete reperfusion was the only treatment factor with a significant predictive value (adjusted odds ratio [OR] 0.03; 95% CI = 0.01 to 0.25; p=0.001). CONCLUSION: Endovascular therapy is safe and effective in patients with acute ischaemic stroke due to isolated ICA occlusion. Prevention of thrombus migration and complete reperfusion should be the aim of EVT.

[Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma].

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

[IL-8 Links NF-κB and Wnt/ß-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection].

Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and ß-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/ß-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/ß-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.

[Clinicopathological characteristics and prognosis of non-Hodgkin lymphoma in oral and maxillofacial regions: An analysis of 369 cases].

OBJECTIVE: To investigate the clinicopathological characteristics and factors influencing the prognosis of non-Hodgkin lymphoma (NHL) in oral and maxillofacial regions. METHODS: Clinicopathological data of 369 patients with oral and maxillofacial NHL initially diagnosed in Peking University Hospital of Stomatology from 2008 to 2020 were collected and analyzed retrospectively. RESULTS: There were 180 males and 189 females. The median age of the patients was 56 years (3 months to 92 years), and the median duration was three months. Clinically, 283 cases manifested as mass, 38 cases as ulcerative necrotizing lesions, and 48 cases as diffuse soft tissue swelling. The lesions of 90 cases located in face and neck (75 cases neck, 20.3%), 99 cases were of major salivary glands (79 cases parotid glands, 20.9%), 103 cases of oral cavity, 50 cases of maxillofacial bones, 20 cases of Waldeyer's ring, and 7 cases of infratemporal fossa. In the study, 247 of the 369 patients had cervical lymphadenopathy, only 40 cases had B symptoms, and 23 cases had the bulky disease. Of the 369 NHLs, 299 (81%) were B-cell NHL, and 70(19%) were T-cell NHL. Diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, follicular lymphoma, and extranodal natural killer (NK)/T-cell lymphoma nasal type were the most common pathological subtypes. According to Ann Arbor staging, 87, 138, 106, and 38 cases were classified as staged Ⅰ, Ⅱ, Ⅲ, Ⅳ, respectively. The me-dian follow-up time was 48 months, 164 patients died during the follow-up period. The overall survival rates for one year, two years, and five years were 90.1%, 82.4%, and 59.9%, respectively, and the median survival was (86.00±7.98) months. Multivariate analysis showed that age (P < 0.001), Ann Arbor staging (P < 0.001), elevated lactate dehydrogenase (P=0.014), and pathological subtype (P=0.049) were the independent factors influencing the overall survival rate of NHL patients. CONCLUSION: Oral and maxillofacial NHL has unique clinical characteristics and distribution patterns of pathological subtypes. Fewer patients had systemic symptoms. Neck and parotid glands were the most common sites invaded by NHL. Advanced age, Ann Arbor stage Ⅲ-Ⅳ, B symptoms, and T-cell NHL may predict a poor prognosis in oral and maxillofacial NHL patients.

[Pre-operative prognostic nutritional index as a predictive factor for prognosis in non-metastatic renal cell carcinoma treated with surgery].

OBJECTIVE: To evaluate the implications of the prognostic nutrition index (PNI) in non-metastatic renal cell carcinoma (RCC) patients treated with surgery and to compare it with other hematological biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII). METHODS: A cohort of 328 non-metastatic RCC patients who received surgical treatment between 2010 and 2012 at Peking University First Hospital was analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of the hematological biomarkers. The Youden index was maximum for PNI was value of 47.3. So we divided the patients into two groups (PNI≤ 47. 3 and >47. 3) for further analysis. Categorical variables [age, gender, body mass index (BMI), surgery type, histological subtype, necrosis, pathological T stage and tumor grade] were compared using the Chi-square test and Student' s t test. The association of the biomarkers with overall survival (OS) and disease-free survival (DFS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model. RESULTS: According to the maximum Youden index of ROC curve, the best cut-off value of PNI is 47. 3. Low level of PNI was significantly associated with older age, lower BMI and higher tumor pathological T stage (P < 0.05). Kaplan-Meier univariate analysis showed that lower PNI was significantly correlated with poor OS and DFS (P < 0.05). In addition, older age, lower BMI, tumor necrosis, higher tumor pathological T stage and Fuhrman grade were significantly correlated with poor OS (P < 0.05). Cox multivariate analysis showed that among the four hematological indexes, only PNI was an independent factor significantly associated with OS, whether as a continuous variable (HR=0.9, 95%CI=0.828-0.978, P=0.013) or a classified variable (HR=2.397, 95%CI=1.061-5.418, P=0.036). CONCLUSION: Low PNI was a significant predictor for advanced pathological T stage, decreased OS, or DFS in non-metastatic RCC patients treated with surgery. In addition, PNI was superior to the other hematological biomar-kers as a useful tool for predicting prognosis of RCC in our study. It should be externally validated in future research before the PNI can be used widely as a predictor of RCC patients undergoing nephrectomy.

[Association between extracellular water/body cell mass ratio and cognitive impairment in patients on maintenance hemodialysis].

Objective: To explore the correlation between extracellular water/body cell mass (ECW/BCM) ratio and cognitive impairment (CI) in patients on maintenance hemodialysis (MHD). Methods: A multicenter, cross-sectional study was conducted in Guizhou Province. All adult MHD patients in hemodialysis centers of 18 hospitals in Guizhou Province between June and October 2020 were included. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) score. The ECW and BCM was derived from bioelectrical impedance, and the ECW/BCM ratio was calculated. The patients were divided into four groups based on the quartile of ECW/BCM ratio. Multivariate logistic regression analysis and subgroup analysis were conducted. Results: A total of 3 160 patients were included in the final analysis, of which 761 (24.1%) developed CI. There were 1 868 males (59.1%) and 1 292 females (40.9%), and the mean age was (55±15) years. Multivariate logistic regression analysis showed that the risk of CI in ECW/BCM Q3 group was 1.55 times (95%CI: 1.03-2.34, P=0.035) of that in group Q1, while the risk of CI in Q4 group was 1.62 times of that in group Q1 (95%CI: 1.05-2.51, P=0.029). Subgroup analysis showed that there was an interaction between previous cerebrovascular event and ECW/BCM on CI (P for interaction=0.04). Patients with a previous history of cerebrovascular events had a higher risk of CI than those without. Among those with no previous cerebrovascular events, the risk of CI in group Q4 was 1.62 times of that in group Q1 (95%CI: 1.19-2.20), while the risk of CI in group Q4 was 7.17 times of that in group Q1 (95%CI: 1.59-32.35) in those with previous cerebrovascular events. Conclusion: Increased ECW/BCM ratio is associated with increased CI risk in patients with MHD, and the risk was more obvious in those with previous history of cerebrovascular events.

[Comparison of the therapeutic effects of optic nerve sheath fenestration and medication on papilledema due to cerebral venous thrombosis].

Objective: To compare the therapeutic effects of optic nerve sheath fenestration (ONSF) and medication on papilledema induced by cerebral venous thrombosis (CVT). Methods: Patients with papilledema induced by CVT in Beijing Tiantan Hospital and Xuanwu Hospital from January 2017 to July 2022 were retrospectively enrolled and were divided into two groups according to the treatment strategies they underwent, with 76 cases (107 eyes) in ONSF group and 35 cases (69 eyes) in medication group. The degree of papilledema was evaluated by the modified Frisén's grading (grade 0-1 was defined as mild, grade 2-3 was moderate, and grade 4-5 was severe edema). The mean defect (MD) of visual field, the degree of papilledema, and the mean retinal nerve fiber layer (RNFL) thickness in different subgroups were compared between baseline versus 1 month after ONSF or medication. Results: There were 76 cases in ONSF group (26 males and 50 females), and aged (35.3±11.4) years. Meanwhile, there were 35 cases in medication group (22 males and 13 females), and aged (35.2±11.0) years. Compared with baseline, MD were improved in both moderate [(-8.4±6.6) vs (-11.8±8.6) db, P=0.021] and severe [(-8.1±5.3) vs (-11.4±6.9) db, P<0.001] papilledema subgroups after ONSF, while there was an improvement in mild papilledema subgroup [(-1.5±5.3) vs (-3.4±5.1) db, P<0.001] after medication. The papilledema (Frisén's scores) in both ONSF group (P<0.001) and medication group (P=0.010) was improved. Compared with baseline, the mean RNFL decreased in mild [(78.5±13.5) vs (91.0±17.4) µm, P=0.002], moderate [(126.6±67.6) vs (154.8±77.9) µm, P=0.011] and severe [(179.0±70.9) vs (230.6±89.7) µm, P=0.001] papilledema subgroups after ONSF, while the mean RNFL decreased [(142.0±29.3) vs (158.8±22.7) µm, P=0.020] in moderate papilledema subgroup after medication. Conclusions: ONSF might attenuate CVT-mediated papilledema, and improve the visual function in patients with moderate and severe papilledema. Likewise, patients with mild papilledema could also get benefit from medication.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

[Report content and prenatal diagnosis of non-invasive prenatal testing for sex chromosome aneuploidy].

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ2=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.

[Bioinformatics analysis of primary biliary cholangitis key genes and molecular mechanisms].

Objective: To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism. Methods: The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method. Results:: A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference. Conclusion:: Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.