AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

OBJECTIVE To establish the characteristic chromatogram of the volatile oil in the standard decoction of Qingshang juantong decoction， and preliminarily infer the main active components of volatile oil that affect the clinical therapeutic effect. METHODS The volatile oil in the standard decoction of Qingshang juantong decoction was extracted by steam distillation. The ultra-high performance liquid chromatography （UPLC） characteristic chromatograms of 15 batches of samples were established by the Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）， and the similarity evaluation was carried out. The volatile oil of standard decoction was identified by UPLC coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. Then the volatile oil components were analyzed by GC-MS. RESULTS The similarities of UPLC characteristic chromatograms for volatile oil of 15 batches of Qingshang juantong decoction were between 0.949 and 0.997. A total of 12 common peaks were obtained. According to the UPLC-Q-TOF/MS， the main components were methyl eugenol， E-ligustilide， E-butylidenephthalide and so on. A total of 23 components were identified by GC-MS， which were mainly 3，4，5-trimethoxy- methylbenzene， patchouli alcohol， Z-ligustilide and so on. CONCLUSIONS The characteristic chromatograms of the volatile oil in the standard decoction of Qingshang juantong decoction is established， and it is inferred that methyl eugenol， ligustilide， E- butylidenephthalide， patchouli alcohol， 3，4，5-trimethoxy-methylbenzene might be the main active components affecting the clinical therapeutic effect of the volatile oil of Qingshang juantong decoction.

Objective:To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD).Methods:This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm 2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results:A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm 2 vs. (47.9±23.8) cm 2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group ( P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group ( P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition ( P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score ( r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score ( r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95% CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95% CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95% CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95% CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence ( OR=6.616, 95% CI: 1.383-31.656, P=0.018; OR=5.548, 95% CI: 1.062-28.973, P=0.042). Conclusion:Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.

Objective:To explore the clinical characteristics of superior mesenteric artery ischemic diseases.Methods:The clinical and followup data of 141 hospitalized patients with ischemic disease of superior mesenteric artery in the Affiliated Hospital of Southwest Medical University from 1999 to 2021 were reviewed.Results:There were 99 males (70.2%) and 42 females (29.8%). The average age of the patients was (63.75±13.16) years; 127 patients (90.1%) complained abdominal pain.The number of all-cause deaths in the perioperative period was 27 (19.1%). ROC curve analysis showed that the optimal cutoff value of the age with predictive value was 64.5 years. The results of multivariate COX regression analysis showed that age ≥65 years old ( HR=3.855, 95% CI: 1.739-8.545), neutrophil count ( HR=1.072, 95% CI: 1.018-1.130), heart failure ( HR=2.863, 95% CI: 1.332-6.154), creatinine ( HR=1.009, 95% CI: 1.003-1.015), D-Dimer ( HR=1.112, 95% CI: 1.025-1.205) was an independent risk factor for all-cause death from superior mesenteric artery ischemic disease. Long-term survival rate of SMAD group was significantly higher than that of other SMAID; By comparing the clinical characteristics of different SMAID, neutrophil count, neutrophil ratio, D-dimer of SMAE group and SMAT group were significantly higher than that of SMAD group and ASSMA group. Conclusions:SMAID usually occurs in elderly men over 65 years old, with abdominal pain as the main symptom and often accompanied by hypertension. Risk factors included age, increased WBC count and D-dimer; The neutrophil count, neutrophil ratio, D-dimer in SMAE and SMAT group were significantly higher than that of SMAD and ASSMA group.

Objective:To understand the changes of brucellosis prevention and control knowledge awareness among breeders in Chunhua County, Xianyang City, Shaanxi Province before and after the publicity intervention.Methods:A multi-stage cluster sampling method was adopted to select 10 townships with more reported cases of human brucellosis in Chunhua County from January 2019 to June 2020, and each township was given priority to select the administrative village with the largest number of reported cases for investigation. At least 20 breeders aged 20 years old and over in each administrative village were selected, and if the number was insufficient, supplementary surveys would be conducted in other administrative villages with the larger number of breeders in the township. Questionnaire survey was conducted on all subjects, including general demographic characteristics, brucellosis prevention and control knowledge and related protective behaviors. After the baseline investigation, 6 months of brucellosis prevention and control knowledge publicity was carried out in the administrative villages included in the investigation, and the awareness rate of brucellosis prevention and control knowledge before and after the publicity intervention was compared to evaluate the effect of publicity intervention.Results:After the publicity intervention, a total of 240 breeders were investigated, and 176 people were aware of brucellosis prevention and control knowledge, with an overall awareness rate of 73.33% (176/240), which was significantly higher than that before the publicity intervention (57.50%, 115/200), and the difference was statistically significant (χ 2 = 12.21, P = 0.005). After the publicity intervention, the awareness rates of breeders on "can cattle and sheep transmit diseases to humans" and "do you know that cattle and sheep can only be purchased after passing the quarantine inspection" were relatively high, they were 95.83% (230/240) and 95.00% (228/240), respectively, and the differences were statistically significant (χ 2 = 50.04, 112.64, P < 0.001) compared with that before the publicity intervention [71.50% (143/200) and 51.00% (102/200)]. The awareness rate of breeders on "how brucellosis is transmitted from livestock to humans" was the lowest, it was 53.33% (128/240), which was not significantly different (χ 2 = 0.82, P = 0.370) from that before the publicity intervention (49.00%, 98/200). Conclusions:After the publicity intervention, the overall awareness rate of brucellosis prevention and control knowledge of breeders in Chunhua County has improved, but the awareness rate of some individual issues is still low. It is suggested to strengthen the pertinence of publicity and education.

Objective:To analyze the epidemic characteristics of human brucellosis in Xianyang City, Shaanxi Province, to grasp the epidemic trend and provide scientific basis for further prevention and control of human brucellosis.Methods:Descriptive epidemiological methods were used to statistically analyze the incidence data and epidemic data of human brucellosis in Xianyang City, Shaanxi Province from 2011 to 2020 in the "Infectious Disease Surveillance System of China Disease Control and Prevention Information System".Results:A total of 864 human brucellosis cases had been reported in Xianyang City from 2011 to 2020, and there was no dead case. The annual incidence began to increase rapidly from 2014, the highest annual incidence in 2019 was 5.79/10 5. There were statistical differences between the incidence of different years (χ 2 = 900.40, P < 0.001). Human brucellosis cases in Xianyang City were mainly concentrated in dairy goat breeding counties, with a total of 571 cases reported, accounting for 66.09%. Cases were reported in all months of the year, and the peak incidence of human brucellosis was from April to August, accounting for 64.35% (556/864). The age of cases was mainly concentrated in the 40 - 69 years old group, accounting for 68.29% (590/864); the ratio of male to female was 2.40 ∶ 1.00 (610 ∶ 254). The occupation was mainly farmers, accounting for 83.45% (721/864). There had been an increase in the proportion of scattered children, students and preschool children. The total serological positive rate was 3.14% (283/9 009) in Xianyang City, and pathogenic culture showed variant strains. The median of interval between onset time and diagnosis time was 8 days. Conclusion:The prevalence of human brucellosis in Xianyang City, Shaanxi Province shows an overall upward trend, which needs to be paid more attention to and control efforts should be strengthened.

Objective:To understand the prescription medications that may cause or exacerbate heart failure (HF-CEPMs) in elderly outpatients with HF and analyze its influencing factors.Methods:Prescriptions for elderly patients with HF in clinic of Xuanwu Hospital, Capital Medical University between January 2016 and August 2020 were collected. According to the list of HF-CEPMs published by the American Heart Association in 2016, HF-CEPMs in prescriptions were identified. The patient′s gender, age, disease diagnosis, medical insurance, therapeutic drugs, visiting departments, physician titles, and other information are extracted from the prescription, and the use of HF-CEPMs in the prescription was descriptively analyzed. The patients were divided into HF-CEPMs group and non-HF-CEPMs group according to whether the prescription included at least one drug in the list of HF-CEPMs. The clinical characteristics, number of drugs, medical insurance, visiting departments, and professional titles of prescription physicians in patients in the 2 groups were compared, and the influencing factors of prescription containing HF-CEPMs were analyzed by multivariate logistic regression.Results:A total of 2 418 patients were enrolled, including 1 264 males (52.27%) and 1 154 females (47.73%), with a median age of 80 (65, 99) years and a median number of comorbidities 1 (0, 5). The top 3 comorbidities requiring long-term medication were hypertension (1 233 patients, 50.99%), bronchial asthma (448 patients, 18.53%) and diabetes mellitus (385 patients, 15.92%), and the median number of drugs was 5 (1, 16). Among the 2 418 patients, 254 (10.50%) used HF-CEPMs, including 142 (55.91%) males and 112 (44.09%) females. Two hundred and twenty-four patients (88.19%), 26 patients (10.24%), and 4 patients (1.57%) were treated with 1, 2, and 3 kinds of HF-CEPMs, respectively. The top 5 HF-CEPMs in drug use rates were antihypertensive drugs [4.47% (108/2 418)], pulmonary drugs [2.52% (61/2 418)], antidiabetic drugs [1.99% (48/2 418)], urological drugs [1.12% (27/2 418)], antipyretic and analgesic drugs [1.03% (25/2 418)]. Multiple logistic regression analysis showed that the number of comorbidities ≥1 (1 kind of disease: OR=3.732, 95 %CI: 2.246-6.623, P<0.001; more than 2 kinds of diseases: OR=6.054, 95 %CI: 3.624-10.788, P<0.001) and the number of prescribed drugs ≥5 ( OR=4.003, 95 %CI: 2.874-5.693, P<0.001) were independent influencing factors for prescribing HF-CEPMs. Conclusions:Antihypertensive drugs, pulmonary drugs, antidiabetic drugs, urological drugs, and antipyretic and analgesics drugs were the most common HF-CEPMs in outpatient prescriptions of elderly HF patients. The number of comorbidities and polypharmacy therapy in elderly outpatients with HF were independent influencing factors for prescribing HF-CEPMs.

Objective:To understand the prescription medications that may cause or exacerbate heart failure (HF-CEPMs) in elderly outpatients with HF and analyze its influencing factors.Methods:Prescriptions for elderly patients with HF in clinic of Xuanwu Hospital, Capital Medical University between January 2016 and August 2020 were collected. According to the list of HF-CEPMs published by the American Heart Association in 2016, HF-CEPMs in prescriptions were identified. The patient′s gender, age, disease diagnosis, medical insurance, therapeutic drugs, visiting departments, physician titles, and other information are extracted from the prescription, and the use of HF-CEPMs in the prescription was descriptively analyzed. The patients were divided into HF-CEPMs group and non-HF-CEPMs group according to whether the prescription included at least one drug in the list of HF-CEPMs. The clinical characteristics, number of drugs, medical insurance, visiting departments, and professional titles of prescription physicians in patients in the 2 groups were compared, and the influencing factors of prescription containing HF-CEPMs were analyzed by multivariate logistic regression.Results:A total of 2 418 patients were enrolled, including 1 264 males (52.27%) and 1 154 females (47.73%), with a median age of 80 (65, 99) years and a median number of comorbidities 1 (0, 5). The top 3 comorbidities requiring long-term medication were hypertension (1 233 patients, 50.99%), bronchial asthma (448 patients, 18.53%) and diabetes mellitus (385 patients, 15.92%), and the median number of drugs was 5 (1, 16). Among the 2 418 patients, 254 (10.50%) used HF-CEPMs, including 142 (55.91%) males and 112 (44.09%) females. Two hundred and twenty-four patients (88.19%), 26 patients (10.24%), and 4 patients (1.57%) were treated with 1, 2, and 3 kinds of HF-CEPMs, respectively. The top 5 HF-CEPMs in drug use rates were antihypertensive drugs [4.47% (108/2 418)], pulmonary drugs [2.52% (61/2 418)], antidiabetic drugs [1.99% (48/2 418)], urological drugs [1.12% (27/2 418)], antipyretic and analgesic drugs [1.03% (25/2 418)]. Multiple logistic regression analysis showed that the number of comorbidities ≥1 (1 kind of disease: OR=3.732, 95 %CI: 2.246-6.623, P<0.001; more than 2 kinds of diseases: OR=6.054, 95 %CI: 3.624-10.788, P<0.001) and the number of prescribed drugs ≥5 ( OR=4.003, 95 %CI: 2.874-5.693, P<0.001) were independent influencing factors for prescribing HF-CEPMs. Conclusions:Antihypertensive drugs, pulmonary drugs, antidiabetic drugs, urological drugs, and antipyretic and analgesics drugs were the most common HF-CEPMs in outpatient prescriptions of elderly HF patients. The number of comorbidities and polypharmacy therapy in elderly outpatients with HF were independent influencing factors for prescribing HF-CEPMs.

This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure (HF)-related stroke. HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes. Gene Ontology (GO) and pathway enrichment analyses were performed on genes in the key modules. Genes in HF-and stroke-related key modules were intersected to obtain common genes for HF-related stroke, which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke. Key genes were functionally annotated through GO in the Reactome and Cytoscape databases. Finally, key genes were validated in these two datasets and other datasets. HF-and stroke-related datasets each identified two key modules. Functional enrichment analysis indicated that protein ubiquitination, Wnt signaling, and exosomes were involved in both HF-and stroke-related key modules. Additionally, ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke. OTU deubiquitinase with linear linkage specificity (OTULIN) and nuclear factor interleukin 3-regulated (NFIL3) were determined to be the key genes in HF-related stroke. Through functional annotation, OTULIN was involved in protein ubiquitination and Wnt signaling, and NFIL3 was involved in DNA binding and transcription. Importantly, OTULIN and NFIL3 were also validated to be differentially expressed in all HF and stroke groups. Protein ubiquitination, Wnt signaling, and exosomes were involved in HF-related stroke. OTULIN and NFIL3 may play a key role in HF-related stroke through regulating these processes, and thus serve as promising intervention targets.