Objective To analyze the atrioventricular synchronization rate after implantation of Micra AV leadless pacemaker,and the impact of postoperative programming optimization on atrioventricular synchronization rate.Methods A prospective cohort study was conducted to select patients with complete atrioventricular block who underwent Micra AV leadless pacemaker implantation at Beijing Anzhen Hospital from August 2022 to June 2023.Programming optimization were performed at 1 week,1 month,and 3 months postoperatively,and atrioventricular synchronization rate,electrical parameters,and echocardiography were recorded.Results A total of 68 patients with complete atrioventricular block implanted with Micra AV were selected,with an average age of(68.2±9.7)years,including 47 males(69.1％).All patients were successfully implanted with Micra AV,and there were no serious postoperative complications;The average threshold,sense,and impedance parameters were stable during 1 week,1 month,and 3 months after the procedure;There was no significant difference in the EF value of postoperative echocardiography(P=0.162);The average atrioventricular synchronization rates at 1 week,1 month,and 3 months postoperatively were(75.2％vs.83.8％vs.91.6％,P=0.001).Conclusions As an mechanical atrial sensing,Micra AV requires personalized adjustment of relevant parameters;Postoperative follow-up programming optimization plays an important role in the atrioventricular synchronization and comfort level in patients with complete atrioventricular block after implantation of Micra AV leadless pacemaker.

The objective of this study was to analyze the effects on cell viability, apoptosis, and cell cycle of non-small cell lung cancer (NSCLC) A549 cells after intervention with Agrimonia pilosa (AP) and investigate Agrimonia pilosa anti-tumor activity in vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) metabolomics technology was used to analyze the changes of cellular metabolites and metabolic pathways. The results of this study will provide a theoretical and experimental basis for investigating the mechanism of the effect of Agrimonia pilosa on non-small cell lung cancer A549 cells. The results showed that the cell nucleus of A549 cells crumpled and apoptosis occurred with the increase of drug concentration. The survival rate of the cells decreased, and the inhibition rate reached 21.5% and 91.74% under the low and high dose conditions, respectively. Lactate dehydrogenase (LDH) content increased (P < 0.05). Metabolomics results showed significant differences in metabolism between groups, thirty-three distinct metabolites including LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) were deduced. The pathway enrichment showed that the Agrimonia pilosa plays an anti-tumor role mainly by regulating the metabolism of glycerophosphate and purine in A549 cells, in which the effect on glycerophosphate metabolism pathway was most significant. The results of combined pharmacodynamics suggested that Agrimonia pilosa might induce apoptosis and inhibit the growth of A549 cells by regulating LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) metabolites in A549 cells.

Objective:To assess the deformation of the bladder-neck opening and the impact of the bladder-neck angle(BNA)on urination in male patients by fluid-structure interaction(FSI)analysis.Methods:We established geometric models of the blad-der,prostate and urethra were established,incorporating both normal and enlarged BNAs,and assessed the effects of BNA alteration on urinary flow by FSI simulation of the flow rate and pressure of the urine within the bladder,bladder neck and urethra,and that of pros-tate displacement as well.We retrospectively analyzed the clinical data on 145 male patients from the Second Hospital of Hebei Medical University between June 2020 and June 2023,39 with acute urine retention(the AUR group)and 106 without(the non-AUR group),and evaluate the impact of BNA on urination based on the urinary flow rate and prostate volume.Results:Comparative simulation a-nalysis showed significant differences in the total urethral pressure and flow rate between the normal and enlarged BNA models(P＜0.05).The maximum prostate displacement was found at the bladder neck,with moderate displacement and unchanged urethral diame-ter in the normal BNA model,but significant displacement and a reduced urethral opening diameter in the enlarged BNA model.FSI analysis confirmed an evident impact of enlarged BNA on urination,more significant in the AUR than in the non-AUR patients(P＜0.05).The BNAs in the patients with the maximum urinary flow rate(Qmax)of＜10,10-15 or＞15 ml/s were 83.7°±2.5°,67.5°±1.8° and 65.1°±4.8° respectively,with statistically significant difference between the former one and the latter two groups(P＜0.05).The BNAs in the patients with normal prostate volume or BPH of grade Ⅰ,Ⅱ,Ⅲ or Ⅳ were 65.0°±3.7°,67.2°±3.1°,71.5°±2.0°,82.8°±3.5° and 105.8°±6.0°,respectively(P＜0.05),with statistically significant difference between BPH grades Ⅲ and Ⅳ(P＜0.05)as well as between these two and the other three groups(P＜0.05),but not among the normal prostate volume,BPH grade Ⅰ and BPH grade Ⅱ groups(P＞0.05).Spearman correlation analysis indicated that BNA was strongly correlated with total prostate volume(TPV),transition zone volume(TZV),intravesical prostatic protrusion(IPP),prostatic urethral angle(PUA),IPSS,and Qmax(P＜0.05).Conclusion:Changes in BNA affect urination and are closely associated with the se-verity of prostate hyperplasia.The BNA may be an important anatomical factor for assessing the severity of lower urinary tract symptoms in BPH patients.

Objective To study the pharmacokinetic characteristics of etoricoxib tablets in healthy Chinese subjects and to evaluate the bioequivalence and safety of the test and reference formulations.Methods In a randomised,single-dose,two-period,two-sequence crossover trial,28 healthy subjects were enrolled under the fasting and fed conditions,respectively,who received a single oral dose of 60 mg of etoricoxib tablets in the test or reference formulation.The concentration of etoricoxib in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate bioequivalence and using WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:The fasting condition Cmax of etoricoxib were(1 176.96±287.95)and(1 164.93±189.65)ng·mL-1;AUC0-t were(18 651.95±6 100.27)and(19 241.39±6 107.48)ng·h·mL-1;and AUC0-∞ were(19 939.15±7 553.27)and(20 536.31±7 223.40)ng·h·mL-1.The fed condition Cmax of etoricoxib were(913.50±184.72)and(878.59±164.35)ng·mL-1;and AUC0-t were(19 085.22±5 155.01)and(18 669.54±4 508.21)ng·h·mL-1;AUC0-∞ were(20 103.77±5 567.02)and(19 528.05±4 989.74)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters in the fasting and fed conditions fell between 80.00％and 125.00％.The incidence of adverse events in the fasting and fed conditions were 28.57％and 21.43％,respectively.Conclusion Two kinds of etoricoxib tablets are bioequivalent,and have similar safety in healthy Chinese subjects.

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

Objective Current data are insufficient for comparisons of effectiveness between percutaneous coronary intervention(PCI)and coronary artery bypass grafting(CABG)among patients with coronary artery disease(CAD)and left ventricular dysfunction.Methods A total of 905 CAD patients with reduced left ventricular ejection fraction(LVEF≤35％)in single center of China who underwent either PCI or CABG were enrolled in a real-world cohort study.Clinical outcomes included short-and long-term all-cause mortality,rates of heart failure(HF)hospitalization and repeat revascularization.Propensity score matching was used to balance the 2 cohorts.Results PCI was associated with lower 30-day mortality rate(HR 0.29,95％CI 0.09-0.88,P=0.029).At a mean follow-up of 4.5 years,PCI and CABG had similar all-cause death(HR 1.00,95％CI 0.67-1.50,P=0.990)and HF hospitalization(HR 0.81,95％CI 0.40-1.64,P=0.561),but PCI had higher risk of repeat revascularization(HR 14.46,95％CI 3.43-60.98,P＜0.001).PCI was associated with more significant LVEF improvement than CABG(P=0.031 for interaction).Conclusions CAD patients with reduced LVEF who underwent PCI had lower short-term mortality rate and more LVEF improvement but higher risk of repeat revascularization during follow-up than patients who underwent CABG.PCI showed comparable long-term survival and HF hospitalization risk.

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*

Animals ; Rats ; Diabetes Mellitus ; Vascular Endothelial Growth Factor A

Objective: To investigate the potential risk factors for occult lateral cervical lymph node metastasis (LNM) to levels Ⅲ and Ⅳ in patients with papillary thyroid carcinoma (PTC) and the necessity of super-selective lateral lymph node dissection for patients harboring these metastases. Methods: This prospective study included PTC patients who were operated by the same surgeon in the Department of Head and Neck Surgery of Cancer Hospital, Chinese Academy of Medical Sciences from October 2015 through October 2019. Preoperative ultrasound and enhanced Computer Tomography (CT) did not denote suspected enlarged lymph nodes in the lateral neck. All patients underwent lymph node dissection in levels Ⅲ and Ⅳ on the basis of original thyroid collar incision after LNM to level Ⅵ was confirmed by preoperative fine needlebiopsy or intraoperative frozen pathology. Results: Of all 143 patients, 74 (51.7%) had occult LNM in levels Ⅲ and Ⅳ confirmed by postoperative pathology. The average number of metastasized lymph nodes in levels Ⅲ and Ⅳ was 2.64±1.80, and that in level Ⅵ was 3.77±3.27. There was a significant linear positive correlation between the number of metastasized lymph nodes in level Ⅵ and that in levels Ⅲ and Ⅳ (r=0.341, P<0.001). That the metastasized lymph nodes in level Ⅵ equals three was the best predictor of occult lateral LNM to levels Ⅲ and Ⅳ. Univariate analysis showed that age <55 years, tumor size ≥2.0 cm, number of metastasized lymph nodes in level Ⅵ ≥3, and percentage of metastasized lymph nodes in the total number of dissected lymph nodes in level Ⅵ >50% were associated with occult LNM in levels Ⅲ and Ⅳ (P<0.05). Multivariate analysis showed that number of metastasized lymph nodes in level Ⅵ≥3 was an independent risk factor for occult LNM in levels Ⅲ and Ⅳ (P=0.006). Conclusions: Age, tumor size and LNM in level Ⅵ were associated with occult lateral LNM in PTC patients. Lymph node dissection in levels Ⅲ and Ⅳ could be considered for selective patients, since it will help to avoid secondary operation for residual tumor or recurrence resulted from insufficient treatment without increasing the incidence of complications or affecting patients' appearances.

Objective: To investigate the potential risk factors for occult lateral cervical lymph node metastasis (LNM) to levels Ⅲ and Ⅳ in patients with papillary thyroid carcinoma (PTC) and the necessity of super-selective lateral lymph node dissection for patients harboring these metastases. Methods: This prospective study included PTC patients who were operated by the same surgeon in the Department of Head and Neck Surgery of Cancer Hospital, Chinese Academy of Medical Sciences from October 2015 through October 2019. Preoperative ultrasound and enhanced Computer Tomography (CT) did not denote suspected enlarged lymph nodes in the lateral neck. All patients underwent lymph node dissection in levels Ⅲ and Ⅳ on the basis of original thyroid collar incision after LNM to level Ⅵ was confirmed by preoperative fine needlebiopsy or intraoperative frozen pathology. Results: Of all 143 patients, 74 (51.7%) had occult LNM in levels Ⅲ and Ⅳ confirmed by postoperative pathology. The average number of metastasized lymph nodes in levels Ⅲ and Ⅳ was 2.64±1.80, and that in level Ⅵ was 3.77±3.27. There was a significant linear positive correlation between the number of metastasized lymph nodes in level Ⅵ and that in levels Ⅲ and Ⅳ (r=0.341, P<0.001). That the metastasized lymph nodes in level Ⅵ equals three was the best predictor of occult lateral LNM to levels Ⅲ and Ⅳ. Univariate analysis showed that age <55 years, tumor size ≥2.0 cm, number of metastasized lymph nodes in level Ⅵ ≥3, and percentage of metastasized lymph nodes in the total number of dissected lymph nodes in level Ⅵ >50% were associated with occult LNM in levels Ⅲ and Ⅳ (P<0.05). Multivariate analysis showed that number of metastasized lymph nodes in level Ⅵ≥3 was an independent risk factor for occult LNM in levels Ⅲ and Ⅳ (P=0.006). Conclusions: Age, tumor size and LNM in level Ⅵ were associated with occult lateral LNM in PTC patients. Lymph node dissection in levels Ⅲ and Ⅳ could be considered for selective patients, since it will help to avoid secondary operation for residual tumor or recurrence resulted from insufficient treatment without increasing the incidence of complications or affecting patients' appearances.