Hybrid argon plasma coagulation for the treatment of Barrett's esophagus: A prospective, multicenter study.

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

Biological characteristics and metabolic phenotypes of different anastomosis groups of Rhizoctonia solani strains.

BACKGROUND: Rhizoctonia solani is an important plant pathogen worldwide, and causes serious tobacco target spot in tobacco in the last five years. This research studied the biological characteristics of four different anastomosis groups strains (AG-3, AG-5, AG-6, AG-1-IB) of R. solani from tobacco. Using metabolic phenotype technology analyzed the metabolic phenotype differences of these strains. RESULTS: The results showed that the suitable temperature for mycelial growth of four anastomosis group strains were from 20 to 30oC, and for sclerotia formation were from 20 to 25oC. Under different lighting conditions, R. solani AG-6 strains produced the most sclerotium, followed by R. solani AG-3, R. solani AG-5 and R. solani AG-1-IB. All strains had strong oligotrophic survivability, and can grow on water agar medium without any nitrutions. They exhibited three types of sclerotia distribution form, including dispersed type (R. solani AG-5 and AG-6), peripheral type (R. solani AG-1-IB), and central type (R. solani AG-3). They all presented different pathogenicities in tobacco leaves, with the most virulent was noted by R. solani AG-6, followed by R. solani AG-5 and AG-1-IB, finally was R. solani AG-3. R. solani AG-1-IB strains firstly present symptom after inoculation. Metabolic fingerprints of four anastomosis groups were different to each other. R. solani AG-3, AG-6, AG-5 and AG-1-IB strains efficiently metabolized 88, 94, 71 and 92 carbon substrates, respectively. Nitrogen substrates of amino acids and peptides were the significant utilization patterns for R. solani AG-3. R. solani AG-3 and AG-6 showed a large range of adaptabilities and were still able to metabolize substrates in the presence of the osmolytes, including up to 8% sodium lactate. Four anastomosis groups all showed active metabolism in environments with pH values from 4 to 6 and exhibited decarboxylase activities. CONCLUSIONS: The biological characteristics of different anastomosis group strains varies, and there were significant differences in the metabolic phenotype characteristics of different anastomosis group strains towards carbon source, nitrogen source, pH, and osmotic pressure.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Tuning the Electrolyte and Interphasial Chemistry for All-Climate Sodium-ion Batteries.

Sodium-ion batteries (SIBs) present a promising avenue for next-generation grid-scale energy storage. However, realizing all-climate SIBs operating across a wide temperature range remains a challenge due to the poor electrolyte conductivity and instable electrode interphases at extreme temperatures. Here, we propose a comprehensively balanced electrolyte by pairing carbonates with a low-freezing-point and low-polarity ethyl propionate solvent which enhances ion diffusion and Na+-desolvation kinetics at sub-zero temperatures. Furthermore, the electrolyte leverages a combinatorial borate- and nitrile-based additive strategy to facilitate uniform and inorganic-rich electrode interphases, ensuring excellent rate performance and cycle stability over a wide temperature range from -45 °C to 60 °C. Notably, the Na||sodium vanadyl phosphate cell delivers a remarkable capacity of 105 mAh g-1 with a high rate of 2 C at -25 °C. In addition, the cells exhibit excellent cycling stability over a wide temperature range, maintaining a high capacity retention of 84.7 % over 3,000 cycles at 60 °C and of 95.1 % at -25 °C over 500 cycles. The full cell also exhibits impressive cycling performance over a wide temperature range. This study highlights the critical role of electrolyte and interphase engineering for enabling SIBs that function optimally under diverse and extreme climatic environments.

Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Molecular classification of small cell lung cancer subtypes: Characteristics, prognostic factors, and clinical translation / 中华医学杂志(英文版)

Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

Electrolyte Engineering with Tamed Electrode Interphases for High-Voltage Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) hold great promise for next-generation grid-scale energy storage. However, the highly instable electrolyte/electrode interphases threaten the long-term cycling of high-energy SIBs. In particular, the instable cathode electrolyte interphase (CEI) at high voltage causes persistent electrolyte decomposition, transition metal dissolution, and fast capacity fade. Here, this work proposes a balanced principle for the molecular design of SIB electrolytes that enables an ultra-thin, homogeneous, and robust CEI layer by coupling an intrinsically oxidation-stable succinonitrile solvent with moderately solvating carbonates. The proposed electrolyte not only shows limited anodic decomposition thus leading to a thin CEI, but also suppresses dissolution of CEI components at high voltage. Consequently, the tamed electrolyte/electrode interphases enable extremely stable cycling of Na3V2O2(PO4)2F (NVOPF) cathodes with outstanding capacity retention (>90%) over 3000 cycles (8 months) at 1 C with a high charging voltage of 4.3 V. Further, the NVOPF||hard carbon full cell shows stable cycling over 500 cycles at 1 C with a high average Coulombic efficiency (CE) of 99.6%. The electrolyte also endows high-voltage operation of SIBs with great temperature adaptability from -25 to 60 °C, shedding light on the essence of fundamental electrolyte design for SIBs operating under harsh conditions.

SpyGlass in Diagnosis of Hepatocellular Carcinoma with Right Hepatic Duct Tumor Thrombus Hemorrhage: A Case Report.

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.

Multifactor artificial intelligence model assists axillary lymph node surgery in breast cancer after neoadjuvant chemotherapy: multicenter retrospective cohort study.

BACKGROUND: The high false negative rate (FNR) associated with sentinel lymph node biopsy often leads to unnecessary axillary lymph node dissection following neoadjuvant chemotherapy (NAC) in breast cancer. The authors aimed to develop a multifactor artificial intelligence (AI) model to aid in axillary lymph node surgery. MATERIALS AND METHODS: A total of 1038 patients were enrolled, comprising 234 patients in the primary cohort, 723 patients in three external validation cohorts, and 81 patients in the prospective cohort. For predicting axillary lymph node response to NAC, robust longitudinal radiomics features were extracted from pre-NAC and post-NAC magnetic resonance images. The U test, the least absolute shrinkage and selection operator, and the spearman analysis were used to select the most significant features. A machine learning stacking model was constructed to detect ALN metastasis after NAC. By integrating the significant predictors, we developed a multifactor AI-assisted surgery pipeline and compared its performance and false negative rate with that of sentinel lymph node biopsy alone. RESULTS: The machine learning stacking model achieved excellent performance in detecting ALN metastasis, with an area under the curve (AUC) of 0.958 in the primary cohort, 0.881 in the external validation cohorts, and 0.882 in the prospective cohort. Furthermore, the introduction of AI-assisted surgery reduced the FNRs from 14.88 (18/121) to 4.13% (5/121) in the primary cohort, from 16.55 (49/296) to 4.05% (12/296) in the external validation cohorts, and from 13.64 (3/22) to 4.55% (1/22) in the prospective cohort. Notably, when more than two SLNs were removed, the FNRs further decreased to 2.78% (2/72) in the primary cohort, 2.38% (4/168) in the external validation cohorts, and 0% (0/15) in the prospective cohort. CONCLUSION: Our study highlights the potential of AI-assisted surgery as a valuable tool for evaluating ALN response to NAC, leading to a reduction in unnecessary axillary lymph node dissection procedures.

Clinical outcomes and risk factors of non-curative endoscopic submucosal dissection for early gastric cancer: a retrospective multicenter study in Zhejiang, China.

Background: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the "eCura system" is reliable for the risk stratification of LNM after non-curative ESD. Methods: We conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the "eCura system". Results: Among 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively). Conclusion: Clinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the "eCura system", additional surgery should be performed in patients with intermediate/high risk of LNM.

[Analysis of the causes of soft tissue complications after volar locking plate for the treatment of dorsal displaced distal radius fractures].

OBJECTIVE: To investigate the causes of soft tissue complications in patients with dorsal displacement distal radius fractures (DRF) after volar locking plate surgery. METHODS: From July 2016 to May 2021, 112 patients with dorsal displacement DRF were treated with volar locking plate surgery, including 45 males and 67 females. The average age was (46.24±10.08) years old, ranging from 18 to 85 years old. According to whether there were soft tissue complications after operation, they were divided into complication group (40 cases) and non complication group (72 cases). Compared with preoperation, the radial metacarpal inclination and ulnar deflection angle, wrist flexion activity and dorsal extension activity, and grip strength of patients after operation were significantly improved (P<0.05). Compared with the non complication group, the proportion of patients in the complication group whose age was>60 years, body mass index (BMI) more than 30 kg·m-2, smoking, diabetes, fracture type C, open fracture and operation time more than 90 min was higher (P<0.05). The age, BMI, smoking, diabetes, fracture AO classification, fracture type and operation time were analyzed by multifactor Logistic regression to determine the independent risk factors affecting the occurrence of postoperative soft tissue complications of patients, establish a nomogram prediction model, and evaluate the model. RESULTS: At the latest follow-up, the excellent and good rate of wrist joint function recovery was 83.93% (94/112), and the excellent and good rate of fracture reduction was 84.82% (95/112). Multivariate Logistic regression analysis showed that age more than 60 years old, diabetes, fracture type C, open fracture and operation time more than 90 min were independent risk factors for postoperative soft tissue complications (P<0.05). The receiver operating characteristic (ROC), calibration curve and clinical decision curve of the nomogram prediction model showed discrimination, accuracy and validity were good. CONCLUSION: Age more than 60 years, diabetes mellitus, fracture type C, open fracture, and operation time more than 90 min are all independent risk factors for soft tissue complications after DRF volar plate fixation. In clinical treatment, perioperative soft tissue management should be done in such patients to prevent complications.

Fecal microbial biomarkers combined with multi-target stool DNA test improve diagnostic accuracy for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a major global health burden. The current diagnostic tests have shortcomings of being invasive and low accuracy. AIM: To explore the combination of intestinal microbiome composition and multi-target stool DNA (MT-sDNA) test in the diagnosis of CRC. METHODS: We assessed the performance of the MT-sDNA test based on a hospital clinical trial. The intestinal microbiota was tested using 16S rRNA gene sequencing. This case-control study enrolled 54 CRC patients and 51 healthy controls. We identified biomarkers of bacterial structure, analyzed the relationship between different tumor markers and the relative abundance of related flora components, and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size, redundancy analysis, and random forest analysis. RESULTS: MT-sDNA was associated with Bacteroides. MT-sDNA and carcinoembryonic antigen (CEA) were positively correlated with the existence of Parabacteroides, and alpha-fetoprotein (AFP) was positively associated with Faecalibacterium and Megamonas. In the random forest model, the existence of Streptococcus, Escherichia, Chitinophaga, Parasutterella, Lachnospira, and Romboutsia can distinguish CRC from health controls. The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%, with a sensitivity and specificity of 98.1% and 92.3%, respectively. CONCLUSION: There is a positive correlation of MT-sDNA, CEA, and AFP with intestinal microbiome. Eight biomarkers including six genera of gut microbiota, MT-sDNA, and CEA showed a prominent sensitivity and specificity for CRC prediction, which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.

Prediction of the potentially suitable areas of Ligularia virgaurea and Ligularia sagitta on the Qinghai-Tibet Plateau based on future climate change using the MaxEnt model.

Ligularia virgaurea and Ligularia sagitta are two species of poisonous plants with strong invasiveness in natural grasslands in China that have caused considerable harm to animal husbandry and the ecological environment. However, little is known about their suitable habitats and the key environmental factors affecting their distribution. Although some studies have reported the distributions of poisonous plants on the Qinghai-Tibet Plateau (QTP) and predicted their potential distributions at local scales in some regions under climate change, there have been few studies on the widespread distributions of L. virgaurea and L. sagitta. In this study, we recorded 276 and 118 occurrence points of L. virgaurea and L. sagitta on the QTP using GPS, and then used the MaxEnt model to predict the distribution of suitable habitats. Results showed that (1) under current climate conditions, L. virgaurea and L. sagitta are mainly distributed in southern Gansu, eastern Qinghai, northwestern Sichuan, eastern Tibet, and southwestern Yunnan, accounting for approximately 34.9% and 39.8% of the total area of the QTP, respectively; (2) the main environmental variables affecting the distribution of suitable habitats for L. virgaurea and L. sagitta are the Human Footprint Index (52.8%, 42.2%), elevation (11%, 4.4%), soil total nitrogen (18.9%, 4.2%), and precipitation seasonality (5.1%, 7.3%); and (3) in the future, in the 2050s and 2070s, the area of habitat of intermediate suitability for L. virgaurea will spread considerably in northwest Sichuan, while that of high suitability for L. sagitta will spread to eastern Tibet and western Sichuan.

Clinical significance and potential application of cuproptosis-related genes in gastric cancer.

BACKGROUND: Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis. AIM: To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy. METHODS: We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics. RESULTS: Our results revealed that FDX1, LIAS, and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1, LIAS, MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1, LIAS, and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map. CONCLUSION: In conclusion, FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy.

Nuclear transport maintenance of USP22-AR by Importin-7 promotes breast cancer progression.

The translocation of biological macromolecules between cytoplasm and nucleus is of great significance to maintain various life processes in both normal and cancer cells. Disturbance of transport function likely leads to an unbalanced state between tumor suppressors and tumor-promoting factors. In this study, based on the unbiased analysis of protein expression differences with a mass spectrometer between human breast malignant tumors and benign hyperplastic tissues, we identified that Importin-7, a nuclear transport factor, is highly expressed in breast cancer (BC) and predicts poor outcomes. Further studies showed that Importin-7 promotes cell cycle progression and proliferation. Mechanistically, through co-immunoprecipitation, immunofluorescence, and nuclear-cytoplasmic protein separation experiments, we discovered that AR and USP22 can bind to Importin-7 as cargoes to promote BC progression. In addition, this study provides a rationale for a therapeutic strategy to restream the malignant progression of AR-positive BC by inhibiting the high expression state of Importin-7. Moreover, the knockdown of Importin-7 increased the responsiveness of BC cells to the AR signaling inhibitor, enzalutamide, suggesting that targeting Importin-7 may be a potential therapeutic strategy.

Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague-Dawley rats via the P38 MAPK signaling pathway.

Background: Periodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process. Methods: We established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1ß, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), ß-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation. Results: We demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1ß, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes. Conclusion: Our findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.

Research on gear crack fault diagnosis model based on permanent magnet motor current signal.

To solve the problem that it is inconvenient to install additional sensors to detect fault signals on the gear of the shearer, the permanent magnet motor control model was first established, and the motor control parameters were determined. Then, the gear mesh stiffness is used as the main judgment basis for gear failure. The gear failure model and the system torsion dynamics model are established. The gear meshing stiffness curve under the crack fault is fitted. Finally, the transmission system overall dynamic model is proposed to obtain the motor current and gear fault information. The influence of different faults on the system electromechanical performance is studied. The mapping relationship between the crack fault and the current is established. The typical characteristics under fault conditions are extracted, which is an important reference for studying the health status of the cutting drive system in the shearer.

Clinical features and prognosis of juvenile myelomonocytic leukemia: an analysis of 63 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis.@*METHODS@#Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed.@*RESULTS@#A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×109/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05).@*CONCLUSIONS@#The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.

Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL).@*METHODS@#Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data.@*RESULTS@#Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days.@*CONCLUSIONS@#Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size.