Objective:To study the effects of different calcium ion concentrations on epithelial mesenchymal transformation (EMT) of human peritoneal mesothelial cell (HPMC) via endoplasmic reticulum stress (ERS).Methods:HPMC cell line HMrSV5 was cultured in vitro and treated in groups. The cells in the control group, high calcium group 1, and high calcium group 2 were treated with medium containing calcium ion concentrations of 1.25, 1.75, and 2.25 mmol/L, respectively. The solvent control group was treated with medium containing 1.25 mmol/L physiological calcium ion concentration and 0.1% dimethyl sulfoxide (DMSO), the high calcium+solvent group was treated with medium containing 2.25 mmol/L calcium ion concentration and 0.1% DMSO, the high calcium+4-phenylbutyric acid (4-PBA) group was treated with medium containing 2.25 mmol/L calcium ion concentration and 1 mmol/L ERS inhibitor 4-PBA, and each group was treated for 48 hours. Morphological changes of cells in each group were observed under light microscope. The expressions of epithelial cell phenotype marker zonula occluden-1 (ZO-1) and mesenchymal cell phenotype marker α-smooth muscle actin (α-SMA) in the cells were observed by immunofluorescence staining. The expressions of EMT marker genes E-cadherin, ZO-1, α-SMA and Vimentin were detected by fluorescence quantitative polymerase chain reaction (PCR). The expressions of ERS marker proteins phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), transcription activating factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by Western blotting. Results:Compared with the control group, the morphology of HMrSV5 cells became slender and fibrotic, the fluorescence intensity of ZO-1 increased, and the fluorescence intensity of α-SMA decreased in high calcium 1 and high calcium 2 groups, indicating that the cells transformed from epithelial cells to mesenchyme cells. The mRNA expressions of E-cadherin and ZO-1 were significantly decreased, while the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly increased, moreover, the expressions of the above marker genes or proteins in the high calcium 2 group was more obvious than those in the high calcium 1 group [E-cadherin mRNA (2 -ΔΔCt): 0.53±0.05 vs. 0.75±0.09, ZO-1 mRNA (2 -ΔΔCt): 0.42±0.06 vs. 0.69±0.06, α-SMA mRNA (2 -ΔΔCt): 1.81±0.16 vs. 1.32±0.14, Vimentin mRNA (2 -ΔΔCt): 2.05±0.22 vs. 1.48±0.16, p-PERK protein (p-PERK/β-actin): 0.81±0.09 vs. 0.59±0.06, p-eIF2α protein (p-eIF2α/β-actin): 0.87±0.10 vs. 0.50±0.06, ATF4 protein (ATF4/β-actin): 0.93±0.10 vs. 0.72±0.06, CHOP protein (CHOP/β-actin): 0.79±0.09 vs. 0.46±0.04, all P < 0.05]. Compared with the solvent control group, the morphological changes of cells, the expressions of EMT marker genes and ERS marker proteins after high calcium ion concentration of 2.25 mmol/L were consistent with those in the high calcium 2 group than control group. Compared with the high calcium+solvent group, the cell morphology recovered the characteristics of polygonal and pebble-like epithelial cells in the high calcium+4-PBA group, the fluorescence intensity of ZO-1 increased, the fluorescence intensity of α-SMA decreased, and the mRNA expressions of E-cadherin and ZO-1 in the cells were significantly increased [E-cadherin mRNA (2 -ΔΔCt): 0.86±0.09 vs. 0.57±0.04, ZO-1 mRNA (2 -ΔΔCt): 0.81±0.06 vs. 0.48±0.05, both P < 0.05], the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly decreased [α-SMA mRNA (2 -ΔΔCt): 1.21±0.13 vs. 1.77±0.15, Vimentin mRNA (2 -ΔΔCt): 1.30±0.14 vs. 1.94±0.20, p-PERK protein (p-PERK/β-actin): 0.38±0.04 vs. 0.92±0.11, p-eIF2α protein (p-eIF2α/β-actin): 0.34±0.05 vs. 1.05±0.13, ATF4 protein (ATF4/β-actin): 0.57±0.06 vs. 0.97±0.11, CHOP protein (CHOP/β-actin): 0.51±0.04 vs. 0.90±0.12, all P < 0.05]. Conclusion:High calcium ion concentrations of 1.75 mmol/L and 2.25 mmol/L promote EMT of HPMC via activating ERS.

Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.

Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Crizotinib/therapeutic use* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology* ; Gene Frequency

Objective:To analyze the accuracy of a single-lead electrocardiogram (iECG) algorithm based on intelligent wristwatch in identifying sinus tachycardia and atrial fibrillation (AF) with rapid ventricular rate.Methods:In this non-randomized control trial, 642 patients aged ≥18 years were enrolled in the General Hospital of Chinese PLA between December 15, 2020 and May 30, 2022, with sinus tachycardia or rapid ventricular rate of AF (ranging from 111 to 145 beats/min for sinus tachycardia, from 110 to 150 beats/min for rapid ventricular rate of AF, respectively). The patients wore Huawei Watch GT2 Pro smartwatches on their left wrists, and the physiological signals detected by the smartwatches in a relaxed state were used as the measured data. The iECG algorithm developed by Huawei was used for identification. Simultaneously, 12-lead electrocardiograms (12L-ECG) were performed, and two cardiologists served as the gold standard for interpretation. Three participants who did not meet the inclusion criteria were excluded based on the detection results, and a total of 639 participants were included in the study. The accuracy of the algorithm in identifying sinus tachycardia and rapid ventricular rate AF was evaluated using metrics such as recall rate, precision rate, macro F1 score for multi-class classification.Results:Among 639 subjects, there were 469 males and 170 females. There were 389 cases of sinus tachycardia and 250 cases of rapid ventricular rate AF, with a mean age of (46.53±13.32) years. The recall rate, precision rate, and F1 value of iECG algorithm in identifying sinus tachycardia was 98.7%, 99.2% and 99.0%, respectively, while it was 98.8%, 98.0% and 98.4%, respectively for AF with rapid ventricular rate. The macro F1 of AF with rapid ventricular rate and sinus tachycardia was 98.7%. The iECG based on the intelligent wristwatch showed good consistency with the corresponding 12L-ECG waveforms.Conclusion:The intelligent wristwatch-based iECG algorithm can effectively identify sinus tachycardia and rapid ventricular rate AF, demonstrating good accuracy.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Early diagnosis and effective management are important to reduce atrial fibrillation-related adverse events. Photoplethysmography (PPG) is often used to assist wearables for continuous electrocardiograph monitoring, which shows its unique value. The development of PPG has provided an innovative solution to AF management. Serial studies of mobile health technology for improving screening and optimized integrated care in atrial fibrillation have explored the application of PPG in screening, diagnosing, early warning, and integrated management in patients with AF. This review summarizes the latest progress of PPG analysis based on artificial intelligence technology and mobile health in AF field in recent years, as well as the limitations of current research and the focus of future research.
Humans ; Atrial Fibrillation/therapy* ; Photoplethysmography ; Artificial Intelligence ; Electrocardiography ; Biomedical Technology

BACKGROUND: Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. METHODS: Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. RESULTS: There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. CONCLUSIONS At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mice ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins B-raf/genetics*

Background/Aims: Mean nocturnal baseline impedance (MNBI) is a new reflux metric for mucosal integrity. It remains unclear whether MNBI can help identify evidence against pathological reflux by the Lyon Consensus in patients with refractory gastroesophageal reflux disease (GERD) symptoms. Methods: Three hundred and forty-nine patients with refractory GERD symptoms enrolled in this study were subjected to high-resolution manometry, 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring, and endoscopy. Conventional indexes (ie, reflux events and acid exposure time) and the novel index (MNBI) of MII-pH monitoring were extracted and analyzed. The value of MNBI in diagnosing patients with evidence against pathologic reflux was evaluated by receiver-operating-characteristic analysis. Results: There were 102 (29.2%) patients with evidence against pathologic reflux, 149 (42.7%) with inconclusive or borderline evidence and 98 (28.1%) with conclusive evidence for pathologic reflux. The MNBI was significantly higher while the proportion of pathological MNBI was significantly lower in subjects with evidence against pathologic reflux than in patients with inconclusive or borderline evidence and in patients with conclusive evidence for pathologic reflux (2444.3 [1977.9-2997.4] vs 1992.8 [1615.5-2253.6] and vs 1772.3 [758.6-2161.3], both P < 0.001; 42.2% vs 79.7% and vs 80.0%, both P < 0.05). When identifying evidence against pathologic reflux in patients with refractory GERD symptoms, the MNBI yielded an area under the curve of 0.749 (P < 0.001) at a cutoff value of 1941.8 Ω. Conclusions The MNBI has a good diagnostic value for evidence against pathological reflux in patients with refractory GERD symptoms. For its simplicity and reproducibility, we believe that MNBI should be referred to in reports of impedance-pH tracings by physicians.

Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.

Objective:To construct a Nomogram model in predicting recurrence-free survival (RFS) and overall survival (OS) at six months, one year and two years after hepatocellular carcinoma (HCC) resection by using inflammatory markers combined with other routine clinical indicators.Methods:The data of 314 patients with HCC who underwent first time hepatectomy at Beijing Chaoyang Emergency Rescue Center and Air Force Characteristic Medical Center from January 2013 to January 2018 were analyzed. HCC patients who underwent hepatectomy at the First Medical Center of PLA General Hospital from January 2011 to January 2016 ( n=106) were used as the external validation group. Univariate and multivariate Cox proportional risk model was used to analyze independent risk factors of recurrence and death in HCC patients. A Nomogram model was constructed based on independent risk factors. Validation of the efficacy of the Nomogram model was done based on external data. Results:In the experimental group, 174 patients relapsed. The median RFS was 26 months. The 6 months, 1 year and 2 years RFS were 26.8%, 43.9%, and 68.8%, respectively. A total of 142 patients had died. The median survival time was 30 months. The 6 months, 1 year and 2 years OS were 5.9%, 23.6% and 63.1%, respectively. In the external validation group, 63 patients had developed recurrence, with a median RFS time of 28 months. The 6 months, 1 year and 2 years RFS were 26.4%, 45.3%, 54.7%, respectively. The median survival time was 31 months. The 6 months, 1 year and 2 years OS were 7.5%, 25.5%, 46.6%, respectively. Tumor size (>6.0 cm, HR: 1.447), vascular invasion ( HR: 1.408), TBil (>0.94 mg/dl, HR: 1.949), NLR (>2.54, HR: 2.843), AGR (≤0.88, HR: 2.447) were independent risk factors of HCC recurrence ( P<0.05). Tumor size (>6.0 cm, HR: 2.207), vascular invasion ( HR: 1.529), and NLR (>2.54, HR: 2.708) were independent risk factors of death for HCC patients ( P<0.05). The C-indexes of half-year, one-year and two-year RFS were 0.764 (95% CI: 0.677-0.854), 0.710 (95% CI: 0.615-0.824) and 0.673 (95% CI: 0.601-0.786), respectively. The C-indexes of half-year OS, one-year OS and two-year OS were 0.729 (95% CI: 0.648-0.841), 0.708 (95% CI: 0.608-0.813) and 0.664 (95% CI: 0.618-0.771), respectively. Conclusion:In this study, the construction of a Nomogram model in predicting prognosis of HCC patients was helpful to guide clinicians in improving preoperative treatment plans and in providing ideas for individualized treatment of patients.