ELABELA-APJ Axis Enhances Mesenchymal Stem Cell Proliferation and Migration via the METTL3/PI3K/AKT Pathway.

Mesenchymal stem cells (MSCs) possess a strong therapeutic potential in regenerative medicine. ELABELA (ELA) is a 32 amino acid peptide that binds to the apelin peptide jejunum receptor (APJ) to regulate cell proliferation and migration. The aim of this study was to investigate the function of ELA vis-a-vis the MSC proliferation and migration, and further explore the underlying mechanism. We demonstrated that the exogenous supplement of ELA boosts the proliferation and migration ability of MSCs, alongside improved in vitro cell viability. These capabilities were rendered moot upon APJ knockdown. In addition, ELA (5-20 µM) was shown to upregulate the expression of METTL3 in a concentrationdependent pattern, a capacity which was suppressed by APJ reduction, whereas the downregulation of METTL3 expression blocked the beneficial effects induced by ELA. ELA was also observed to upregulate the phosphorylation level of AKT. This ELA-induced activation of the PI3K/AKT pathway, however, is inhibited with knockdown of METTL3. Our data indicate that ELA could act as a promoter of MSC proliferation and migration in vitro through the APJ receptor, something which might be attributed to the activation of the METTL3/PI3K/AKT signaling pathway. Therefore, ELA is a candidate for optimizing MSC-based cell therapy, while METTL3 is a potential target for its promoting action on MSCs.

[Clinical study of 15 cases of primary non-immunodeficient central nervous system lymphoma in children].

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

Dynamic stabilization of ablative Rayleigh-Taylor instability in the presence of a temporally modulated laser pulse.

This paper presents a numeric study of the dynamic stabilization of the ablative Rayleigh-Taylor instability (ARTI) in the presence of a temporally modulated laser pulse. The results show that the specially modulated laser produces a dynamically stabilized configuration near the ablation front. The physical features of the relevant laser-driven parameters in the unperturbed ablative flows have been analyzed to reveal the inherent stability mechanism underlying the dynamically stabilized configuration. A single-mode ARTI for the modulated laser pulse is first compared with that of the unmodulated laser pulse. The results show that the modulated laser stabilizes the surface perturbations and reduces the linear growth rate and enhancement of the cutoff wavelength. For multimode perturbations, the dynamic stabilization effect of the modulated laser pulse contributes to suppress the small-scale structure and reduce the width of the mixing layer. Moreover, the results show that the stabilization effect of the modulated laser pulse decreases as the maximum wavelength increases.

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.

Subsurface hydrological connectivity controls nitrate export flux in a hilly catchment.

Subsurface runoff represents the main pathway of nitrate transport in hilly catchments. The magnitude of nitrate export from a source area is closely related to subsurface hydrological connectivity, which refers to the linkage of separate regions of a catchment via subsurface runoff. However, understanding of how subsurface hydrological connectivity regulates catchment nitrate export remains insufficient. This study conducted high-frequency monitoring of shallow groundwater in a hilly catchment over 17 months. Subsurface hydrological connectivity of the catchment over 38 rainfall events was analyzed by combining topography-based upscaling of shallow groundwater and graph theory. Moreover, cross-correlation analysis was used to evaluate the time-series similarity between subsurface hydrological connectivity and nitrate flux during rainfall events. The results showed that the maximum subsurface hydrological connectivity during 32 out of 38 rainfall events was below 0.5. Although subsurface flow paths (i.e., the pathways of lateral subsurface runoff) exhibited clear dynamic extension and contraction during rainfall events, most areas in the catchment did not establish subsurface hydrological connectivity with the stream. The primary pattern of nitrate export was flushing (44.7%), followed by dilution (34.2%), and chemostatic behavior (21.1%). A threshold relationship between subsurface hydrological connectivity and nitrate flux was identified, with nitrate flux rapidly increasing after the subsurface connectivity strength exceeded 0.121. Moreover, the median value of cross-correlation coefficients reached 0.67, which indicated subsurface hydrological connectivity exerts a strong control on nitrate flux. However, this control effect is not constant and it increases with rainfall amount and intensity as a power function. The results of this study provide comprehensive insights into the subsurface hydrological control of catchment nitrate export.

[Progress and prospects of liquid-liquid phase separation in developmental diseases].

Membrane-bound organelles as well as membrane-free compartments exist in eukaryotic cells, which divide the nucleus and cytoplasm into distinct subregions and allow specific biochemical reactions to occur. The physiological mechanisms of membrane-bound organelles have been extensively characterized, but the formation and function of membrane-free compartments have not been thoroughly studied. Over the past decade, significant progress had been made in the studies about the role of liquid-liquid phase separation (LLPS) in the formation of membrane-free organelles. LLPS which serves as an aggregated separation mechanism for cellular biochemical reactions, is associated with a variety of physiological processes such as signal transduction and gene transcriptional regulation; while aberrant LLPS may contribute to the occurrence of developmental diseases. The present review investigates the role of LLPS as a mechanism of aggregation and segregation of cellular biochemical responses. The mechanisms of LLPS development and recent advances in the relationships between aberrant LLPS and developmental diseases are forward discussed, as well as how these advances may aid in the development of LLPS-based therapies.

Post-operative vestibular and equilibrium evaluation in patients with cholesteatoma-induced labyrinthine fistulas.

OBJECTIVE: This study aimed to compare the pre- and post-operative vestibular and equilibrium functions of patients with cholesteatoma-induced labyrinthine fistulas who underwent different management methods. METHODS: Data from 49 patients with cholesteatoma-induced labyrinthine fistulas who underwent one of three surgical procedures were retrospectively analysed. The three management options were fistula repair, obliteration and canal occlusion. RESULTS: Patients underwent fistula repair (n = 8), canal occlusion (n = 18) or obliteration procedures (n = 23). Patients in the fistula repair and canal occlusion groups suffered from post-operative vertigo and imbalance, which persisted for longer than in those in the obliteration group. Despite receiving different management strategies, all patients achieved complete recovery of equilibrium functions through persistent efforts in rehabilitation exercises. CONCLUSION: Complete removal of the cholesteatoma matrix overlying the fistula is reliable for preventing iatrogenic hearing deterioration due to unremitting labyrinthitis. Thus, among the three fistula treatments, obliteration is the optimal method for preserving post-operative vestibular functions.

Risk factors in ICU patients with initial acquisition of carbapenemase-resistant Klebsiella Pneumoniae.

OBJECTIVE: To identify the risk factors associated with antimicrobial use on the initial acquisition of carbapenem-resistant Klebsiella pneumoniae (CRKP) in elderly intensive care unit (ICU) patients.METHODS: Respiratory secretion, blood, urine, anal swab and peritoneal drainage samples from all elderly patients with non-colonised CRKP who had been hospitalised from January 2021 to December 2022 were collected, and screened for CRKP colonisation using surveillance culture at the time of the first ICU admission and weekly thereafter in Zhejiang Provincial Hospital of Chinese Medicine, Zhejiang, China. Cumulative antibiotic variables included duration of antibiotic use, total amount of antimicrobials received in grams, total antibiotic consumption (defined daily dose) and the types of antimicrobial exposure. A time-dependent model based on Cox regression analysis was used to investigate the effect of each variable on the initial acquisition of CRKP infection or colonisation.RESULTS: Of 214 patients, 44 were infected or had CRKP colonies and death rate was 34.1%. males were the risk factor for acquiring CRKP in culture (HR 2.12, 95% CI 1.06-4.21; P = 0.033). It is notable that the hazard of acquiring CRKP increased by 9% with every single-point increase in the APACHE II score (HR 1.09, 95% CI 1.01-1.18; P = 0.025). The hazard of acquiring CRKP doubled when carbapenems were administered (HR 1.81, 95% CI 1.42-2.30; P < 0.001), In contrast, exposure to quinolone antimicrobials had a smaller effect on acquiring CRKP (HR 1.07; 95% CI 1.01-1.14; P = 0.024).CONCLUSION: This study found that male sex, APACHE II score and exposure to quinolones and carbapenems were independent risk factors for acquiring CRKP.

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.

An E-band multi-channel Doppler backscattering system on EAST.

An E-band (60-90 GHz) multi-channel Doppler backscattering (DBS) system with X-mode polarization has been installed on the Experimental Advanced Superconducting Tokamak (EAST), which can measure the turbulence at five different radial locations simultaneously. This system can launch 31 fixed microwave frequencies in the range of 60-90 GHz with a 1 GHz interval into the plasma, and five probing signals are selected by employing a reference signal and multiple filters. During experiments, the frequency of the reference signal is tunable in the E-band, and the selected probing signals can be changed as needed without any other adjustments, which can be performed in one shot or between shots. Furthermore, the incident angle can be adjusted from -10° to 20°, and the wavenumber range is 4-25 cm-1 with a wavenumber resolution of Δk/k ≤ 0.35. Ray tracing simulations are employed to calculate the scattering locations and the perpendicular wavenumber. In this article, the hardware design, ray tracing, and initial results obtained from the EAST plasma will be presented.

[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.

[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.

[Curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds].

Objective: To explore the curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds. Methods: A retrospective observational study was conducted. From October 2016 to June 2018, 20 patients with wounds on palms and multiple fingers who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 15 males and 5 females, aged 18 to 77 years. After debridement, the wound area was 8 cm×4 cm-17 cm×12 cm. The wound was repaired by ultrathin anterolateral femoral flap with area of 9 cm×5 cm to 19 cm×13 cm. According to the wound condition of finger, the finger division was performed in one stage, and the length-to-width ratio of the split-finger flap was 2.0:1.0-2.5:1.0. During the surgery, the descending branches of lateral circumflex femoral artery and accompanying vein of flap were anastomosed end-to-end to the radial artery and vein in the recipient area, respectively, and the anterolateral femoral cutaneous nerve of flap was bridged with the superficial branch of radial nerve in the recipient area. The wounds in the donor area of flap in 14 patients were sutured directly, the wounds in the donor area of flap in 3 patients were repaired by relay superficial iliac circumflex artery perforator flap, and the wounds in the donor area of flap in 3 patients were covered by free trunk medium-thick skin graft. The survival of flap, occurrence of vascular crisis and other complications, and healing of wounds in the donor area of flap were recorded. The appearance of flap, scar hyperplasia in the donor and recipient areas and the patients' satisfaction with the shape and function of the donor and recipient areas were followed up. In 1 year after surgery, the two-point discrimination distance of the flap was measured, and the recovery of hand function was evaluated by the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. Results: The flaps of 17 patients survived without vascular crisis or other complications after surgery. The flap of 1 patient had poor blood circulation and partial necrosis, and the wound was healed 14 days after dressing change and grafting of split-thickness skin graft from head. Two patients had mild cyanosis at the margin of flap after surgery, which disappeared spontaneously 5 days later. Incisions at donor site, relay flaps, and skin grafts of all patients survived well. After surgery, the color and texture of flap were basically the same as that of the normal skin of hand, and linear scars were observed in the donor and recipient areas. The patients were satisfied with the recovery of appearance and function of donor and recipient areas. After 1 year of follow-up, the patients' hand sensory function recovered well, the two-point discrimination distance of flap was 4-6 mm, and the recovery of hand function was evaluated as excellent in 18 cases and good in 2 cases. Conclusions: The ultrathin anterolateral femoral flap in repairing the palmar combined with multiple finger wounds in one-stage split-finger can significantly reduce the number of surgeries and improve the function and beauty of the hand, so it is worthy of clinical promotion.

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.

[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.

[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.

[One case of myocardial damage caused by carbamate pesticide poisoning].

The data of a patient with carbamate pesticide poisoning were analyzed. Cardiac arrest, oliguria, acute renal injury and pulmonary infection occurred during treatment. After cardiopulmonary resuscitation, tracheal intubation, CRRT, anti-infection and other symptomatic support treatment, the patient recovered and discharged. The myocardial damage caused by carbamate pesticide poisoning is easy to be ignored, and it often causes cardiac manifestations such as arrhythmia and cardiac insufficiency, and the related markers of cardiac injury, electrocardiogram and echocardiogram are also changed. Therefore, the awareness of cardiac damage caused by carbamate pesticide poisoning should be improved.

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.