Objective:To investigate the practicality and clinical significance of quantitative indicators related to wide QRS complex in the diagnosis of atrial fibrillation (AF) with wide QRS complex.Methods:A retrospective study was conducted to analyze the dynamic electrocardiogram data of 93 patients who visited Ankang People's Hospital from January 2021 to December 2023. Based on the type of arrhythmia, the patients were divided into two groups: AF with premature ventricular contraction (PVC) group ( n = 65) and AF with intraventricular conduction abnormality group ( n = 28). The traditional diagnostic indicators and newly introduced quantitative indicators were compared between the two groups to analyze the clinical significance of the new quantitative indicators in identifying AF with wide QRS complex. Results:There were statistically significant differences in the occurrence of cannon waves, QRS duration > 140 ms, QRS morphology in lead V1, the R wave or qR pattern, or the deepest point of R being greater than r or rS in lead V1 being > 60 ms, R/S ratio in lead V6 < 1 or displaying QS pattern, the presence of a notching, a slow decline, or a prominent R wave in the QRS beginning in lead aVR, Vi/Vt in lead aVR ≤ 1, and the data regarding the electrical axis in the no man's land between the two groups ( χ2 = 11.83, 37.59, 26.05, 27.33, 5.30, 49.46, 34.95, 4.90, all P < 0.05). The premature interval/coupling interval in the AF with PVC group was (1.38 ± 0.32), which was significantly lower than (1.84 ± 0.43) in the AF with intraventricular condection abnormality group ( t = -5.71, P < 0.001). The quasi-compensatory pause/coupling interval and quasi-compensatory pause/premature interval in the AF with PVC group were (1.71 ± 0.36) and (1.28 ± 0.25), respectively, which were significantly higher than those in the AF with intraventricular conduction abnormality group ( t = 5.48, 5.06, both P < 0.001). The areas under the curve for the premature interval/coupling interval, quasi-compensatory pause /coupling interval, and quasi-compensatory pause/premature interval, and the combined three indicators (using logistic regression) in distinguishing AF with wide QRS complex were 0.810, 0.788, 0.818, and 0.953, respectively. The area under the curve for the combined three indicators was significantly greater than that for each individual indicator ( Z = -3.10, -3.92, -3.09, all P < 0.05). Conclusions:Premature interval/coupling interval, quasi-compensatory pause/coupling interval, and quasi-compensatory pause/premature interval show good value in the diagnosis of AF with wide QRS complex, and the combined use of the three can significantly improve the diagnostic accuracy.

OBJECTIVE To investigate the vasodilatory effect of dimethyl sulfoxide(DMSO)on isolated aortic arteries and intrarenal arteries of rats and the mechanisms.METHODS ① Rat aortas and intrarenal arteries were pre-contracted with KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.Following equilibration,dimethyl sulfoxide(DMSO)was cumulatively administered at concentrations of 0.1%,0.3%,1.0%,3.0%and 10.0%.Changes in the vascular tension of aortic and intrarenal arterial rings were recorded using an isolated vessel tension measurement system.Rat intrarenal arteries were pre-contracted with KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.Cumulative additions of DMSO(3.0%and 10.0%)were administered as the control group.Following pre-contraction with each of the three stimulants,the voltage-gated potassium channel(Kv)inhibitor 4-AP(0.5 mmol·L-1)was incubated for 15 min.Cumulative additions of DMSO(3.0%and 10.0%)were then administered,and the vascular relaxation percentages induced by DMSO before and after treatment were calculated.Whole-cell patch-clamp recordings were performed on acutely isolated intrarenal arterial smooth muscle cells of rat to assess Kv currents during cumulative DMSO applications(0.1%,0.3%,1.0%and 3.0%).② Rat aortic smooth muscle cells(A7r5)were exposed to DMSO concentration of 0.0%(control),0.1%,0.3%,1.0%and 3.0%for 24 h.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Malondialdehyde(MDA)content,catalase(CAT)activity,and superoxide dismutase(SOD)activity in A7r5 cells were measured by chemical colorimetry.Mitochondrial membrane potential was evaluated using the JC-1 fluorescent probe.RESULTS ① DMSO(0.1%-10.0%)dose-dependently relaxed rats aortic and intrarenal arteries pre-contracted with either KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.The values of maximum relaxation were(42.3±9.7)%,(73.2±8.4)%,(99.2±4.7)%and(84.0±1.9)%,(80.5±6.1)%and(81.2±4.4)%,respectively.Compared with the control group,vasorelaxation of DMSO on IRAs precontracted with U46619 was significantly attenuated by Kv inhibitor 4-AP.② Low concentrations(0.1%and 0.3%)of DMSO significantly increased Kv currents,while high concentrations(1.0%and 3.0%)of DMSO significantly decreased Kv currents.High concentrations(1.0%and 3.0%)of DMSO remarkablely increased ROS and MDA levels,but significantly decreased CAT activity,SOD activity and mitochondrial membrane potential in A7r5 cells.CONCLUSION DMSO(0.1%-10.0%)can relax rats aortal and intrarenal arteries in a concentra-tion-dependent manner,and the mechanism may be related to Kv,oxidative stress and mitochondrial damage.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To analyze the influencing factors of tumor-specific mortality in patients with advanced endometrial carcinoma and construct a risk prediction model.Methods A total of 150 patients with advanced endometrial carcinoma admitted to the Fourth Clinical College of Zhejiang Chinese Medical University,Hangzhou First People's Hospital from January 2020 to January 2023 were selected as subjects.Cox regression was employed to analyze factors influencing mortality in advanced endometrial carcinoma.A Logistic regression model was constructed,with receiver operating characteristic(ROC)curve used to evaluate model discrimination,calibration curve for precision assessment,and decision curve for net benefit evaluation.Results Overall 2-year survival rate of 150 patients was 58.67％.The univariate analysis demonstrated that histological grade,lymph node metastasis,tumor maximum diameter,and preoperative carcinoembryonic antigen 125(CA125)levels were all significant risk factors for mortality in advanced endometrial carcinoma(P＜0.05).Multivariate analysis confirmed these parameters as independent prognostic indicators(P＜0.05).A Logistic regression model established using multivariate Cox regression yielded a C index of 0.873(95％CI:0.792-0.951).ROC curve analysis revealed the model's area under the curve for predicting mortality risk factors in advanced endometrial carcinoma was 0.916(95％CI:0.872-0.960).Conclusion The linear chart prediction model constructed based on histological grading,lymph node metastasis,maximum tumor diameter and preoperative CA125 level in this study can effectively predict the death of advanced endometrial carcinoma.

Objective:To investigate the practicality and clinical significance of quantitative indicators related to wide QRS complex in the diagnosis of atrial fibrillation (AF) with wide QRS complex.Methods:A retrospective study was conducted to analyze the dynamic electrocardiogram data of 93 patients who visited Ankang People's Hospital from January 2021 to December 2023. Based on the type of arrhythmia, the patients were divided into two groups: AF with premature ventricular contraction (PVC) group ( n = 65) and AF with intraventricular conduction abnormality group ( n = 28). The traditional diagnostic indicators and newly introduced quantitative indicators were compared between the two groups to analyze the clinical significance of the new quantitative indicators in identifying AF with wide QRS complex. Results:There were statistically significant differences in the occurrence of cannon waves, QRS duration > 140 ms, QRS morphology in lead V1, the R wave or qR pattern, or the deepest point of R being greater than r or rS in lead V1 being > 60 ms, R/S ratio in lead V6 < 1 or displaying QS pattern, the presence of a notching, a slow decline, or a prominent R wave in the QRS beginning in lead aVR, Vi/Vt in lead aVR ≤ 1, and the data regarding the electrical axis in the no man's land between the two groups ( χ2 = 11.83, 37.59, 26.05, 27.33, 5.30, 49.46, 34.95, 4.90, all P < 0.05). The premature interval/coupling interval in the AF with PVC group was (1.38 ± 0.32), which was significantly lower than (1.84 ± 0.43) in the AF with intraventricular condection abnormality group ( t = -5.71, P < 0.001). The quasi-compensatory pause/coupling interval and quasi-compensatory pause/premature interval in the AF with PVC group were (1.71 ± 0.36) and (1.28 ± 0.25), respectively, which were significantly higher than those in the AF with intraventricular conduction abnormality group ( t = 5.48, 5.06, both P < 0.001). The areas under the curve for the premature interval/coupling interval, quasi-compensatory pause /coupling interval, and quasi-compensatory pause/premature interval, and the combined three indicators (using logistic regression) in distinguishing AF with wide QRS complex were 0.810, 0.788, 0.818, and 0.953, respectively. The area under the curve for the combined three indicators was significantly greater than that for each individual indicator ( Z = -3.10, -3.92, -3.09, all P < 0.05). Conclusions:Premature interval/coupling interval, quasi-compensatory pause/coupling interval, and quasi-compensatory pause/premature interval show good value in the diagnosis of AF with wide QRS complex, and the combined use of the three can significantly improve the diagnostic accuracy.

Objective To analyze the influencing factors of tumor-specific mortality in patients with advanced endometrial carcinoma and construct a risk prediction model.Methods A total of 150 patients with advanced endometrial carcinoma admitted to the Fourth Clinical College of Zhejiang Chinese Medical University,Hangzhou First People's Hospital from January 2020 to January 2023 were selected as subjects.Cox regression was employed to analyze factors influencing mortality in advanced endometrial carcinoma.A Logistic regression model was constructed,with receiver operating characteristic(ROC)curve used to evaluate model discrimination,calibration curve for precision assessment,and decision curve for net benefit evaluation.Results Overall 2-year survival rate of 150 patients was 58.67％.The univariate analysis demonstrated that histological grade,lymph node metastasis,tumor maximum diameter,and preoperative carcinoembryonic antigen 125(CA125)levels were all significant risk factors for mortality in advanced endometrial carcinoma(P＜0.05).Multivariate analysis confirmed these parameters as independent prognostic indicators(P＜0.05).A Logistic regression model established using multivariate Cox regression yielded a C index of 0.873(95％CI:0.792-0.951).ROC curve analysis revealed the model's area under the curve for predicting mortality risk factors in advanced endometrial carcinoma was 0.916(95％CI:0.872-0.960).Conclusion The linear chart prediction model constructed based on histological grading,lymph node metastasis,maximum tumor diameter and preoperative CA125 level in this study can effectively predict the death of advanced endometrial carcinoma.

OBJECTIVE To investigate the vasodilatory effect of dimethyl sulfoxide(DMSO)on isolated aortic arteries and intrarenal arteries of rats and the mechanisms.METHODS ① Rat aortas and intrarenal arteries were pre-contracted with KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.Following equilibration,dimethyl sulfoxide(DMSO)was cumulatively administered at concentrations of 0.1%,0.3%,1.0%,3.0%and 10.0%.Changes in the vascular tension of aortic and intrarenal arterial rings were recorded using an isolated vessel tension measurement system.Rat intrarenal arteries were pre-contracted with KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.Cumulative additions of DMSO(3.0%and 10.0%)were administered as the control group.Following pre-contraction with each of the three stimulants,the voltage-gated potassium channel(Kv)inhibitor 4-AP(0.5 mmol·L-1)was incubated for 15 min.Cumulative additions of DMSO(3.0%and 10.0%)were then administered,and the vascular relaxation percentages induced by DMSO before and after treatment were calculated.Whole-cell patch-clamp recordings were performed on acutely isolated intrarenal arterial smooth muscle cells of rat to assess Kv currents during cumulative DMSO applications(0.1%,0.3%,1.0%and 3.0%).② Rat aortic smooth muscle cells(A7r5)were exposed to DMSO concentration of 0.0%(control),0.1%,0.3%,1.0%and 3.0%for 24 h.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Malondialdehyde(MDA)content,catalase(CAT)activity,and superoxide dismutase(SOD)activity in A7r5 cells were measured by chemical colorimetry.Mitochondrial membrane potential was evaluated using the JC-1 fluorescent probe.RESULTS ① DMSO(0.1%-10.0%)dose-dependently relaxed rats aortic and intrarenal arteries pre-contracted with either KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.The values of maximum relaxation were(42.3±9.7)%,(73.2±8.4)%,(99.2±4.7)%and(84.0±1.9)%,(80.5±6.1)%and(81.2±4.4)%,respectively.Compared with the control group,vasorelaxation of DMSO on IRAs precontracted with U46619 was significantly attenuated by Kv inhibitor 4-AP.② Low concentrations(0.1%and 0.3%)of DMSO significantly increased Kv currents,while high concentrations(1.0%and 3.0%)of DMSO significantly decreased Kv currents.High concentrations(1.0%and 3.0%)of DMSO remarkablely increased ROS and MDA levels,but significantly decreased CAT activity,SOD activity and mitochondrial membrane potential in A7r5 cells.CONCLUSION DMSO(0.1%-10.0%)can relax rats aortal and intrarenal arteries in a concentra-tion-dependent manner,and the mechanism may be related to Kv,oxidative stress and mitochondrial damage.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To investigate the immediate brain effect of acupuncture at Fengchi using amplitude of low-frequency fluctuation(ALFF)and functional connectivity by the resting-state functional magnetic resonance imaging(rs-fMRI)in patients with posterior circulation ischemia vertigo(PCIV).Methods Twenty patients with PCIV were enrolled.The dizziness handicap inventory(DHI)was used to evaluate the severity of vertigo.The patients were randomly divided into acupuncture group and sham acupoint acupuncture group.Rs-fMRI scan was performed before and after acupuncture.MATLAB-based DPABI 6.1 software was used to analyze rs-fMRI data.Correlation analysis was used between the altered ALFF values and DHI scores.The regions of altered ALFF were taken as seeds to analyze functional connectivity.Results Compared with the sham acupoint acupuncture group,the increased ALFF values were mainly located on the left precuneus,left superior frontal gyrus and left caudate nucleus after acupuncture in the acupuncture group;the decreased ALFF values were mainly located on the left cerebellum and right inferior occipital gyrus.The ALFF value of the left superior frontal gyrus was negatively correlated with the DHI score(P=0.04).The increased functional connectivity was mainly found between left precuneus and the right middle frontal gyrus,the right superior frontal gyrus,the decreased functional connectivity was mainly found between left precuneus and the bilateral paracentral lobule and right cerebellum.Conclusion The ALFF value and functional connectivity are different before and after acupuncture,indicating that the vestibular network,visual and motor brain regions functional activities are changed after needling at Fengchi,which may be the brain functional basis of Fengchi for vertigo in PCIV.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.