Hyperthyroidism （HT） is frequently complicated by atrial fibrillation （AF） in clinical practice. Based on traditional Chinese medicine （TCM） zang-xiang （藏象） theory and clinical experience， both HT and AF are closely associated with dysfunction of the liver. The pathogenesis is initiated by the liver failing to govern the free flow of qi， and liver constraint and qi stagnation， with the key turning points being liver constraint transforming into fire and the internal stirring of liver wind， ultimately leading to liver blood depletion and insufficient nourishment of the heart spirit. Thus， it is proposed to treat the disease from the liver， with stage-specific therapeutic approaches according to the evolution of the disease. In the early stage， the treatment should focus on soothing the liver and relieving constraint to reduce goiter and calm the heart， while in the progressive stage， the method of clearing liver and draining fire is suggested to subdue yang and stabilize palpitations. In the acute stage， the strategy is calming the liver and nourishing yin to subdue yang and extinguish wind. In the later stage， it is suggested to soften the liver and benefit qi， so as to nourish yin and restore pulse. These methods are sequentially applied to synergistically reduce goiter and stabilize palpitations， providing a therapeutic approach for HT complicated by AF.

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

OBJECTIVE: To explore the mechanism for the occurrence and phenotypic characteristics of Turner syndrome based on a prenatally diagnosed case of a mosaic karyotype containing double pseudo-isodicentric X chromosome and a review of relevant literature. METHODS: A fetus diagnosed with increased risk for trisomy 21 at the Provincial Hospital Affiliated to Shandong First Medical University in August 2023 was selected as the study subject. Clinical data of the fetus was collected. Following amniocentesis, chromosomal G-banding karyotype analysis and chromosomal microarray analysis (CMA) were carried out. This study has been approved by the Ethics Committee of the Hospital (Ethics No.: SWYX No. 2022-287). RESULTS: The early-trimester screening suggested a high risk of trisomy 21 (1/19), with free β-hCG of 116 ng/mL (MoM value 2.35), PAPP-A of 0.394 ng/mL (MoM value 0.12), and NT value of 1.3 mm, though no abnormality was found in the fetus at 19 weeks gestation. The karyotype of amniocyte was determined as 46,X,psu idic(X)(p11.21)[55]/45,X[27]/47,X,psu idic(X)(p11.21)×2[5]/46,XX[13]. CMA has yielded a result of arr[GRCh37] Xp22.33p11.21(168552_55585678)×1[0.67],Xp11.21q28(55703291_155233098)×3[0.5]. CONCLUSION Karyotypes of Turner syndrome are complex and diverse, and a rare 46,X,psu idic(X)(p11.21)[55]/45,X[27]/47,X,psu idic(X)(p11.21)×2[5]/46,XX[13] mosaic karyotype with double pseudo-isodicentric X chromosome has been identified. Literature review suggested that this karyotype may lead to phenotypic diversification and a risk of reduced sensitivity to hormone therapy.
Humans ; Turner Syndrome/diagnosis* ; Female ; Pregnancy ; Chromosomes, Human, X/genetics* ; Mosaicism ; Prenatal Diagnosis ; Karyotyping ; Adult ; Karyotype ; Amniocentesis

Objective:To explore the mechanism for the occurrence and phenotypic characteristics of Turner syndrome based on a prenatally diagnosed case of a mosaic karyotype containing double pseudo-isodicentric X chromosome and a review of relevant literature.Methods:A fetus who was diagnosed with increased risk of trisomy 21 at the Provincial Hospital Affiliated to Shandong First Medical University in August 2023 was selected as the study subject. Clinical data of the fetus was collected. Following amniocentesis, chromosomal G-banding karyotype analysis and chromosomal microarray analysis (CMA) were carried out. This study has been approved by the Ethics Committee of the Hospital (Ethics No.: SWYX No. 2022-287).Results:The early-trimester screening suggested a high risk of trisomy 21(1/19), with free β-hCG of 116 ng/mL (MoM value 2.35), PAPP-A of 0.394 ng/mL (MoM value 0.12), and NT value of 1.3 mm, though no abnormality was found in the fetus at 19 weeks gestation. The karyotype of amniocyte was determined as 46, X, psu idic(X)(p11.21)[55]/45, X[27]/47, X, psu idic(X)(p11.21)×2[5]/46, XX[13]. CMA has yielded a result of arr[GRCh37] Xp22.33p11.21(168552_55585678)×1[0.67], Xp11.21q28(55703291_155233098)×3[0.5].Conclusion:Karyotypes of Turner syndrome are complex and diverse, and a rare 46, X, psu idic(X)(p11.21)[55]/45, X[27]/47, X, psu idic(X)(p11.21)×2[5]/46, XX[13] mosaic karyotype with double pseudo-isodicentric X chromosome has been identified. Literature review suggested that this karyotype may lead to phenotypic diversification and a risk of reduced sensitivity to hormone therapy.

Objective To investigate the binding interaction between the calmodulin(CaM)mutant D130V and the IQ motif of the car-diac Cav1.2 channel.Methods The binding of mutant CaM-D130V to the IQ motif was predicted by fold recognition modeling,homology modeling,and protein docking.The plasmid was transformed into Escherichia coli BL-21 sensory cells via heat shock at 42 ℃ to induce the expression of glutathione S-transferase(GST)fusion protein.The protein was extracted by ultrasonic fragmentation and purified using GS-4B beads.PreScission protease was applied to remove the GST.SDS-PAGE was performed to detect the purity of protein.A GST pull-down assay was conducted to detect the interaction between CaM-D130V and IQ motif.Results Protein docking results showed that both CaM-WT and CaM-D130V could bind to the IQ motif of the cardiac Cav1.2 channel,but the binding sites of the mutant CaM-D130V to the IQ motif were reduced,and its binding conformation was changed compared with the CaM-WT,with decreased binding energy(|S|reduced from 48.086 6 kcal/mol to 47.309 5 kcal/mol).The GST pull-down assay indicated that the binding of CaM-D130V to IQ motif significantly decreased(P＜0.01),and the affinity was significantly reduced at 2 mmol/L Ca2+concentration compared with CaM-WT.Conclusion The reduced binding ability of CaM-D130V to the IQ motif of the cardiac Cav1.2 channel may contribute to functional alterations in the channel.These findings provide a theoretical basis for understanding the pathogenesis of CaM mutant-associated cardio-vascular diseases as well as targeted therapies.

Objective To investigate the binding interaction between the calmodulin(CaM)mutant D130V and the IQ motif of the car-diac Cav1.2 channel.Methods The binding of mutant CaM-D130V to the IQ motif was predicted by fold recognition modeling,homology modeling,and protein docking.The plasmid was transformed into Escherichia coli BL-21 sensory cells via heat shock at 42 ℃ to induce the expression of glutathione S-transferase(GST)fusion protein.The protein was extracted by ultrasonic fragmentation and purified using GS-4B beads.PreScission protease was applied to remove the GST.SDS-PAGE was performed to detect the purity of protein.A GST pull-down assay was conducted to detect the interaction between CaM-D130V and IQ motif.Results Protein docking results showed that both CaM-WT and CaM-D130V could bind to the IQ motif of the cardiac Cav1.2 channel,but the binding sites of the mutant CaM-D130V to the IQ motif were reduced,and its binding conformation was changed compared with the CaM-WT,with decreased binding energy(|S|reduced from 48.086 6 kcal/mol to 47.309 5 kcal/mol).The GST pull-down assay indicated that the binding of CaM-D130V to IQ motif significantly decreased(P＜0.01),and the affinity was significantly reduced at 2 mmol/L Ca2+concentration compared with CaM-WT.Conclusion The reduced binding ability of CaM-D130V to the IQ motif of the cardiac Cav1.2 channel may contribute to functional alterations in the channel.These findings provide a theoretical basis for understanding the pathogenesis of CaM mutant-associated cardio-vascular diseases as well as targeted therapies.

Objective:To explore the mechanism for the occurrence and phenotypic characteristics of Turner syndrome based on a prenatally diagnosed case of a mosaic karyotype containing double pseudo-isodicentric X chromosome and a review of relevant literature.Methods:A fetus who was diagnosed with increased risk of trisomy 21 at the Provincial Hospital Affiliated to Shandong First Medical University in August 2023 was selected as the study subject. Clinical data of the fetus was collected. Following amniocentesis, chromosomal G-banding karyotype analysis and chromosomal microarray analysis (CMA) were carried out. This study has been approved by the Ethics Committee of the Hospital (Ethics No.: SWYX No. 2022-287).Results:The early-trimester screening suggested a high risk of trisomy 21(1/19), with free β-hCG of 116 ng/mL (MoM value 2.35), PAPP-A of 0.394 ng/mL (MoM value 0.12), and NT value of 1.3 mm, though no abnormality was found in the fetus at 19 weeks gestation. The karyotype of amniocyte was determined as 46, X, psu idic(X)(p11.21)[55]/45, X[27]/47, X, psu idic(X)(p11.21)×2[5]/46, XX[13]. CMA has yielded a result of arr[GRCh37] Xp22.33p11.21(168552_55585678)×1[0.67], Xp11.21q28(55703291_155233098)×3[0.5].Conclusion:Karyotypes of Turner syndrome are complex and diverse, and a rare 46, X, psu idic(X)(p11.21)[55]/45, X[27]/47, X, psu idic(X)(p11.21)×2[5]/46, XX[13] mosaic karyotype with double pseudo-isodicentric X chromosome has been identified. Literature review suggested that this karyotype may lead to phenotypic diversification and a risk of reduced sensitivity to hormone therapy.

Objective To investigate the distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Lüliang City, Shanxi Province, so as to provide insights into assessment of the visceral leishmaniasis transmission risk and formulation of visceral leishmaniasis control measures. Methods A total of 12 natural villages were sampled from Shilou County, Lishi District, Lanxian County, Linxian County and Wenshui County in Lüliang City, Shanxi Province from June to September, 2023, and sandflies were captured using light traps from 7 breeding habitats, including farmers’ houses, sheep pens, cattle pens, chicken coops, pig pens, mule and horse pens, and loess-cave dwellings. Following morphological identification of the sandfly species, the distribution of sandflies and the seasonal fluctuations of the sandfly density were analyzed. In addition, the Leishmania was detected in sandflies using a real-time fluorescence quantitative PCR assay. Results A total of 2 831 sandflies were captured with 156 light traps in Lüliang City from June to September, 2023, including 2 638 female sandflies (93.18%) and 193 male sandflies (6.82%), and the average density was 16.91 sandflies/(light-night). The seasonal fluctuations of the sandfly density all appeared a unimodal distribution in all survey sites, and the sandfly density peaked in July and then declined rapidly. Among all types of breeding habitats, the greatest sandfly density was found in sheep pens [39.04 sandflies/(light-night)]. In addition, 4.08% (2/49) of the sandfly samples were tested positive for Leishmania nucleic acid as revealed by the real-time fluorescence quantitative PCR assay. Conclusions Sandflies were widely distributed in Lüliang City, Shanxi Province in 2023, and the peak of the sandfly density was observed in July, which had a visceral leishmaniasis transmission risk. Intensified surveillance of visceral leishmaniasis and sandfly vectors is required and targeted vector control is recommended.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Myocardial ischemia-reperfusion injury(MIRI)is one of the reasons for the high mortality in patients with acute myocardial infarction after percutaneous coronary intervention,which is regulated by several cell death pathways including apoptosis,autophagy,and pyroptosis.Recently,it has been found that ferroptosis,a unique programmed cell death,appears to be a therapeutic target for MIRI.However,the mechanisms remain incompletely elucidated.This re-view summarizes the latest research progress on the role of ferroptosis in MIRI,including mitochondrial dysfunction,endo-plasmic reticulum stress(ERS),oxidative stress,calcium overload,epigenetic modification,apoptosis,autophagy,etc.Moreover,the signaling pathways between ferroptosis and MIRI are elaborated,which will provide new insights for the prevention and treatment of MIRI.