Objective To investigate the molecular mechanisms by which Rivularin regulates the occurrence and metastasis of lung squamous cell carcinoma.Methods The relative expression levels of target genes in different cell lines were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Animal experiments:Animals were randomly divided into two groups,with the Rivularin animal group received 50 mg·kg-1 Rivularin solution daily by gavage;and the model group received an equal volume of 0.9％NaCl daily.Tumor volume was measured.Cell experiments:Cells were divided into control group(no treatment),scutellarin group(3.0 g·L-1 scutellarin),scutellarin+oe-HOXA11-AS group(3.0 g·L-1scutellarin extract treatment and transfection of HOXA11-AS),scutellarin+oe-HOXA11-AS+XAV939 group(3.0 g·L-1 scutellarin extract treatment,transfection of HOXA11-AS and addition of 10 μmol·L-1 XAV939).5-ethynyl-2'-deoxyuridine(Edu)and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assays were used to detect the proliferation and apoptosis rates of cells,respectively;the Transwell assay was used to detect the migration number of NCI-H520 cells in each group.Results The relative expression levels of HOXA11-AS in each lung cancer cell line were significantly higher than those in normal lung epithelial cells(all P＜0.05).At 35 days,the tumor volumes of the model group and Rivularin animal group were(937.83±67.40)and(512.32±45.61)mm3,respectively;compared between two groups,the difference was statistically significant(P＜0.001).The number of cell migration in the control group,Rivularin group,Rivularin+oe-HOXA11-AS group,and Rivularin+oe-HOXA11-AS+XAV939 group were 127.26±8.92,23.76±3.31,131.28±9.49 and 27.69±3.57;the proliferation rates were(56.27±7.49)％,(28.68±4.33)％,(50.12±7.86)％and(13.62±3.54)％respectively;the apoptosis rates were(10.86±2.97)％,(43.23±6.78)％,(30.92±4.53)％and(41.77±7.02)％.The above indicators of the Rivularin group are compared with the control group;the above indicators of the Rivularin+oe-HOXA11-AS group are compared with the Rivularin group;Rivularin+oe-HOXA11-AS+XAV939 group compared with the Rivularin+oe-HOXA11-AS group,the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Rivularin regulates the occurrence and metastasis of lung squamous cell carcinoma by inhibiting the Wnt/β-catenin signaling pathway through HOXA11-AS.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Since the end of 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has swept the world,bringing great harm to human society and significantly increasing the health burden.Due to stron-ger infectivity,faster transmission,and higher reinfection rate of the Omicron variant,it has now replaced the Delta variant as the main epidemic strain for both imported and local outbreaks in China.Chinese Diagnosis and treatment protocol for SARS-CoV-2 infection(10th trial version)emphasizes"strengthening the protection of key popula-tions,"which includes the increasing number of immunocompromised population.These people have a high inci-dence of severe diseases and a high fatality rate after infected with SARS-CoV-2,and belong to the high-risk popula-tions of severe or critical diseases.Moreover,due to underlying diseases,these people take immunosuppressants and other related drugs chronically.The interactions between anti-SARS-CoV-2 infection treatment drugs and origi-nal drugs are complicated,thus bring significant challenges to the treatment after the SARS-CoV-2 infection.Cur-rently,there is a lack of guidelines or consensus on the diagnosis and treatment of SARS-CoV-2 infection among im-munocompromised population.Therefore,the Guangzhou Institute of Respiratory Health and National Center for Respiratory Medicine organized experts from multiple disciplines(respiratory and critical care medicine,organ transplantation,rheumatology and immunology,hematology,infection,critical care medicine,etc.)in China.Af-ter multiple rounds of discussions,13 items of recommendations are made as the reference for peers based on evi-dence-based medical evidence,so as to provide a theoretical and practical reference for the diagnosis and treatment strategies of this population.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes, and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis, protein-protein interaction (PPI) network, and survival analysis based on the Gene Expression Omnibus (GEO) database.Methods By screening with highly expressed genes, we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites. Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis, PPI network, and survival analysis. Several software and platforms including Prism 8, R language, Cytoscape, DAVID, STRING, and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma (ESCC) tissue. Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer. Four genes including ALDH3A1, C2, SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer. Keratinization may greatly impact the pathogenesis of esophageal cancer. Genes ALDH3A1, C2, SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.
Humans ; Esophageal Neoplasms/metabolism* ; Esophageal Squamous Cell Carcinoma/metabolism* ; Epithelial Cell Adhesion Molecule/metabolism* ; Gene Expression Profiling/methods* ; Gene Regulatory Networks ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Intracellular Signaling Peptides and Proteins

OBJECTIVE: To develop a method for R-peak detection of ECG data from wearable devices to allow accurate estimation of the physiological parameters including heart rate and heart rate variability. METHODS: A fully convolutional neural network was applied to predict the R-peak heatmap of ECG data and locate the R-peak positions. The heartbeat-aware (HA) module was introduced to enable the model to learn to predict the heartbeat number and R-peak heatmap simultaneously, thereby improving the capability of the model for extraction of the global context. The R-R interval estimated by the predicted heartbeat number was adopted to calculate the minimum horizontal distance for peak positioning. To achieve real-time R-peak detection on mobile devices, the deep separable convolution was adopted to reduce the number of parameters and the computational complexity of the model. RESULTS: The proposed model was trained only with ECG data from wearable devices. At a tolerance window interval of 150 ms, the proposed method achieved R peak detection sensitivities of 100% for both wearable device ECG dataset and a public dataset (i.e. LUDB), and the true positivity rates exceeded 99.9%. As for the ECG signal of a 10 s duration, the CPU time of the proposed method for R-peak detection was about 23.2 ms. CONCLUSION The proposed method has good performance for R-peak detection of both wearable device ECG data and routine ECG data and also allows real-time R-peak detection of the ECG data.
Algorithms ; Electrocardiography ; Heart Rate ; Neural Networks, Computer ; Signal Processing, Computer-Assisted ; Wearable Electronic Devices

Alveolar bone is an important anatomic basis for implant-supported denture restoration, and its different degrees of defects determine the choices of bone augmentation surgeries. Therefore, the reconstruction of alveolar bone defects is an important technology in the clinical practice of implant restoration. However, the final reconstructive effect of bone quality, bone quantity and bone morphology is affected by many factors. Clinicians need to master the standardized diagnosis and treatment principles and methods to improve the treatment effect and achieve the goal of both aesthetic and functional reconstruction of both jaws. Based on the current clinical experience of domestic experts and the relevant academic guidelines of foreign counterparts, this expert consensus systematically and comprehensively summarized the augmentation strategies of alveolar bone defects from two aspects: the classification of alveolar bone defects and the appropriate selection of bone augmentation surgeries. The following consensus are reached: alveolar bone defects can be divided into five types (Ⅰ-0, Ⅰ-Ⅰ, Ⅱ-0, Ⅱ-Ⅰ and Ⅱ-Ⅱ) according to the relationship between alveolar bone defects and the expected position of dental implants. A typeⅠ-0 bone defect is a bone defect on one side of the alveolar bone that does not exceed 50% of the expected implant length, and there is no obvious defect on the other side; guided bone regeneration with simultaneous implant implantation is preferred. Type Ⅰ-Ⅰ bone defects refer to bone defects on both sides of alveolar bone those do not exceed 50% of the expected implant length; the first choice is autologous bone block onlay grafting for bone increments with staged implant placement or transcrestal sinus floor elevation with simultaneous implant implantation. Type Ⅱ-0 bone defects show that the bone defect on one side of alveolar bone exceeds 50% of the expected implant length, and there’s no obvious defect on the other side; autologous bone block onlay grafting (thickness ≤ 4 mm) or alveolar ridge splitting (thickness > 4 mm) is preferred for bone augmentation with staged implant placement. Type Ⅱ-Ⅰ bone defects indicate that the bone plate defect on one side exceeds 50% of the expected implant length and the bone defect on the other side does not exceed 50% of the expected implant length; autologous bone block onlay grafting or tenting techniques is preferred for bone increments with staged implant implantation. Type Ⅱ-Ⅱ bone defects are bone plates on both sides of alveolar bone those exceed 50% of the expected implant length; guided bone regeneration with rigid mesh or maxillary sinus floor elevation or cortical autologous bone tenting is preferred for bone increments with staged implant implantation. This consensus will provide clinical physicians with appropriate augmentation strategies for alveolar bone defects.