Objective To investigate the impact of intergenerational caregiving on the brain structure and function of grandparents,and to analyze its correlation with caregiving factors.Methods Healthy adults(66 with grandchildren,24 without grandchildren)were recruited as study subjects,and clinical and MRI data were collected.Resting-state brain functional degree centrality(DC)and surface-based morphometry(SBM)methods were used to compare the differences in brain structure and function between the groups with and without grandchildren.The correlation between the differences in brain regions and △ values with grandchild's age,number,and time spent in childcare were assessed,respectively.Results Compared to the group without grandchildren,the group with grandchildren showed reduced surface area and cortical volume in the left middle temporal gyrus,as well as decreased DC values in the left medial superior frontal gyrus,bilateral orbital superior frontal gyrus,and left anterior cingulate and paracingulate gyrus(P＜0.05),respectively.In the grandchildren group,DC values and △ values in the left orbital superior frontal gyrus,left anterior cingulate and paracingulate gyrus were significantly positively correlated with time spent in childcare.Conclusion The brain structures and functions of grandparents related to empathy and motivation are changed in intergenerational caregiving,which may reveal the neuroplasticity after caring for their grandchildren.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network properties among patients with mild cognitive impairment (MCI) exhibiting different cognitive outcomes and normal controls (NCs), and to further evaluate the predictive value of these imaging indicators for cognitive deterioration in MCI patients.Methods:A total of 43 NCs, 65 stable MCI (sMCI), and 26 progressive MCI (pMCI) patients enrolled in the Alzheimer′s Disease Neuroimaging Initiative (ADNI) database between December 2012 and May 2016 were included in this study. Baseline demographic information and T 1-weighted magnetic resonance imaging scans were collected. Hippocampal subfield volumes were extracted using freesurfer software, and structural covariance networks of hippocampal subfields were constructed. Multivariate analysis of covariance was used to compare hippocampal subfield volumes among the 3 groups. A general linear model was applied to examine group differences in hippocampal subfield structural covariance network properties. Least absolute shrinkage and selection operator (LASSO)-Logistic regression was employed to identify imaging predictors associated with conversion to Alzheimer′s disease (AD), based on which structural, network-based, and combined predictive models were constructed. Model discrimination was evaluated using the area under the curve (AUC); internal validation was performed using Bootstrap resampling; model calibration was assessed with the Hosmer-Lemeshow test; and clinical utility was evaluated through decision curve analysis. Results:Significant differences in hippocampal subfield volumes (mm3) were observed among the 3 groups (all P<0.05, Bonferroni-corrected). Specifically, left parasubiculum (65.58±13.30, 61.96±17.56, 49.56±11.82, F=9.900), right parasubiculum (65.92±15.21, 59.45±16.65, 47.69±15.48, F=11.612), left presubiculum (277.09±39.85, 258.15±44.86, 224.05±45.05, F=14.513), right presubiculum (262.85±40.43, 247.41±43.27, 209.97±46.11, F=14.500), left subiculum (399.66±32.19, 374.25±55.83, 306.12±51.62, F=32.923), right subiculum (417.93±48.92, 376.59±51.01, 316.82±70.22, F=28.764), left cornu ammonis 1 (CA1) (592.10±83.87, 561.96±94.72, 490.06±86.89, F=13.352), right CA1 (632.15±100.09, 601.24±88.88, 531.05±110.29, F=10.579), left CA3 (191.58±30.08, 180.47±34.66, 155.08±37.82, F=12.182), right CA3 (210.42±28.92, 203.84±34.80, 176.69±41.47, F=9.597), left CA4 (224.61±28.94, 210.49±35.04, 183.98±36.89, F=16.521), right CA4 (238.49±28.14, 227.43±30.65, 200.23±42.74, F=13.702), left granule cell-molecular layer-dentate gyrus (GC-ML-DG) (259.96±36.76, 239.42±41.17, 207.61±41.84, F=19.831), right GC-ML-DG (273.98±35.12, 258.79±36.82, 227.81±49.07, F=14.204), left molecular layer (505.62±66.16, 468.58±75.17, 402.68±75.47, F=22.293), right molecular layer (527.39±72.39, 493.14±70.39, 423.81±88.09, F=19.588), left hippocampal amygdala transition area (HATA) (54.91±9.99, 49.52±9.93, 43.27±9.59, F=13.571), right HATA (58.43±9.83, 54.55±10.80, 47.12±12.54, F=10.037), left fimbria (69.94±25.04, 56.63±23.74, 40.58±19.83, F=14.846), right fimbria (68.61±26.24, 53.95±23.16, 45.25±17.04, F=10.424), left hippocampal tail (488.37±83.44, 463.54±80.33, 393.83±77.73, F=13.570), and right hippocampal tail (519.78±80.22, 498.84±81.68, 419.75±93.29, F=14.339) all showed significant group differences. Significant group differences were also observed in small-worldness metric γ (0.51±0.10, 0.51±0.08, 0.62±0.14, F=9.317), small-worldness metric λ (0.39±0.02, 0.39±0.02, 0.43±0.04, F=9.925), global efficiency (0.19±0.01, 0.20±0.01, 0.18±0.01, F=3.189), local efficiency (0.26±0.02, 0.26±0.01, 0.27±0.01, F=3.068), clustering coefficient (0.23±0.01, 0.23±0.01, 0.24±0.02, F=4.274), and characteristic path length (0.73±0.06, 0.72±0.06, 0.76±0.07, F=4.477) of the hippocampal subfield structural covariance network (all P<0.05). Specifically, the pMCI group exhibited higher γ ( t=3.773, P<0.001), λ ( t=4.060, P<0.001), local efficiency ( t=2.445, P=0.047), and clustering coefficient ( t=2.849, P=0.015) than the NCs group, and higher γ ( t=4.074, P<0.001), λ ( t=4.068, P<0.001), and characteristic path length ( t=2.986, P=0.010) but lower global efficiency ( t=-2.444, P=0.047) than the sMCI group. The AUC of the structural, network, and combined models based on LASSO-Logistic regression was 0.837, 0.861, and 0.899, respectively. After internal validation, the corrected AUC was 0.835, 0.855, and 0.889, respectively. All models demonstrated good calibration ( P>0.05), and decision curve analysis indicated favorable clinical net benefit across models. Conclusions:Both sMCI and pMCI patients exhibit widespread hippocampal subfield atrophy and altered global properties of hippocampal subfield structural covariance networks compared to NCs. The models constructed based on hippocampal subfield volumes and structural covariance networks show strong potential for predicting cognitive decline in MCI patients.

Chronic thromboembolic pulmonary hypertension is characterised by the persistent obstruction of the proximal pulmonary arteries by organized thrombi and peripheral microvascular disease,which can lead to right-sided heart failure and mortality.Pulmonary endarterectomy enables complete removal of visible obstructive elements within the pulmonary arteries and is recommended for operable patients.Nevertheless,over 40%of patients are precluded from pulmonary endarterectomy because of factors such as surgically inaccessible lesions,compromised general health status,or concurrent comorbidities or still with residual pulmonary hypertension after pulmonary endarterectomy.For inoperable patients or those with residual pulmonary hypertension after pulmonary endarterectomy,balloon pulmonary angioplasty is an effective therapeutic option,which could significantly improve the hemodynamic,exercise tolerance and outcome of the patients.With the emerging accumulation of clinical experience and evidence,2022 European Society of Cardiology/European Respiratory Society guidelines of pulmonary hypertension recommend balloon pulmonary angioplasty as an alternative therapeutic option for these patients.However,different types of lesions may have their own lesion characteristics,the strategy and device of balloon pulmonary angioplasty should thus be individually considered for different lesions,in fact,the success rate of treatment and the incidence rate of complications are varied significantly.Therefore,the aim of this review is to comprehensively summarize the existing studies on balloon pulmonary angioplasty treatment strategies for different types of lesions and the management of complications to provide guidance and reference for clinicians.

Objective:To explore the influencing factors of olfactory impairment in patients with obstructive sleep apnea（OSA） and establish a nomogram prediction model. Methods:A total of 100 OSA patients were enrolled. Snap&Sniff olfactory test was used to evaluate the olfactory identification function and olfactory threshold of the patients. According to the scoring criteria, either olfactory identification scores below 14 points or olfactory threshold scores below 3 points was defined as olfactory impairment. Multivariate logistic regression analysis was used to explore the influencing factors of olfactory impairment in OSA. The nomogram model was constructed by using the R 4.4.2 software package. ROC curve, calibration curve and decision curve were used to evaluate the predictive efficacy, consistency and clinical utility of the model. Results:A total of 55 of 100 OSA patients had olfactory impairment. The results of multivariate logistic regression analysis showed that age, ESS score, MoCA score, and apnea-hypopnea index（AHI） were the influencing factors of olfactory impairment in OSA. Based on the above parameters, a nomogram model was established. The ROC curve analysis showed that the AUC was 0.897（95%CI 0.834-0.961）, indicating that the model had good predictive ability. The calibration curve showed that the predicted probability of the model fits the actual probability well. Decision curve analysis showed that when the threshold probability was in the range of 0-0.9, the model had a high clinical net benefit rate. Conclusion:Age, ESS score, MoCA score and AHI are the influencing factors of olfactory impairment in patients with OSA. The nomogram model constructed based on the above factors has good predictive value, which is conducive to the clinical multi-angle understanding of OSA and the formulation of scientific prevention and treatment measures.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Nomograms ; Olfaction Disorders/etiology* ; Logistic Models ; Middle Aged ; Male ; Female ; ROC Curve ; Adult ; Aged

Objective To investigate the role of membrane-associated tyrosine/threonine-protein ki-nase 1(PKMYT1)in glucocorticoid(GC)-induced osteoblast(OB)apoptosis,providing a theoretical basis and potential therapeutic targets for early-stage steroid-induced avascular necrosis of the femoral head(SANFH).Methods(1)Mouse calvarial osteoblastic cells(MC3T3-E1)were selected for the study.The control group was cultured in standard medium,while the experimental group was subject-ed to osteogenic induction culture,with osteogenic capacity verified by alkaline phosphatase(ALP)and Alizarin Red S(ARS)staining.Then,mouse osteoblasts(mOB)were treated with different con-centrations of GC.After that,apoptosis was detected by using Annexin V-FITC/PI double staining as-say,while cell proliferation was assessed by using Cell Counting Kit-8(CCK8).Moreover,the expres-sions of anti-apoptotic protein B-cell lymphoma/leukemia-2(BCL-2),pro-apoptotic proteins cleaved caspase-3andcleavedcaspase-9(cleavedcaspase 3/9)weredetectedbyusing Westernblotting(WB).Meanwhile,proteomic analysis was employed to identify molecules potentially regulating GC-in-duced apoptosis in mOBs.What's more,quantitative real-time PCR(qPCR)and WB were used to further analyze PKMYT1 expression.(2)mOBs were treated with PKMYT1 inhibitor GSK-1520489A of different concentrations to screen the optimal one,and all subjects were then further divided into a control,a GC,a GSK-1520489A,and a GC+GSK-1520489A group.Later,the expression of PK-MYT1 and apoptosis-related proteins BCL-2 and cleaved caspase 3/9 of all groups were detected us-ing WB,and cell viability and cytotoxicity were evaluated by CCK8 assay,with cell proliferation by using 5-ethynyl-2'-deoxyuridine(EDU)assay and apoptosis by cell live/dead staining and Annexin V-FITC/PI double staining.(3)mOBs were infected with PKMYT1 overexpression lentiviral vectors,and its efficiency was verified by using immunofluorescence,qPCR,and WB.After successful overexpres-sion of PKMYT1,all cells were divided into the control,GC,PKMYT1 overexpression(OE),and OE+GC groups,whose cell proliferation was detected by EDU assay,and apoptosis was assessed by Annexin V-FITC/PI double staining and cell live/dead staining.(4)To verify the changes in PKMYT1 expression in human osteoblasts(hOB),hOBs extracted from human femoral heads of healthy individu-als were chosen into the control group,while those from patients with hormone-induced avascular ne-crosis of the femoral head(hSANFH)were selected into the hSANFH group.Then,PKMYT1 expres-sion in both groups was detected by using qPCR and WB.Results(1)After inducing the differentia-tion of mouse calvarial osteoblastic cells(MC3T3-E1)into mature osteoblasts,under the action of GC,compared with the control group,with the increase of GC concentration,the experimental group showed increased mOB apoptosis(P<0.01)and expression of cleaved caspase 3/9(P<0.01),but de-creased cell viability(P<0.01)and expressionof apoptosis-relatedprotein BCL-2(P<0.01).More-over,according to the proteomic sequencing,significant decrease was observed in the PKMYT1 expres-sion in mature mOBs treated with GC.(2)As to treatment of mOBs with different concentrations of PKMYT1 inhibitor GSK-1520489A,with the increase of concentration,cell viability decreased and cy-totoxicity increased(P<0.001).Moreover,compared with the control group,mOBs proliferation de-creased(P<0.001)and apoptosis increased(P<0.001)in the GSK-1520489A group.Meanwhile,com-pared with the GC group,mOB proliferation decreased(P<0.05)and apoptosis increased significantly(P<0.01)in the GC+GSK-1520489A group.(3)After overexpression of PKMYT1,in comparison with the control group,mOB proliferation increased(P<0.001)but apoptosis did not increase significantly(P>0.05)in the OE group.Moreover,compared with the GC group,mOB proliferation increased(P<0.001)but apoptosis decreased(P<0.001)significantly in the OE+GC group.(4)In hOBs extracted from human femoral head tissues,qPCR and WB results showed that PKMYT1 expression of the hSANFH group was significantly lower than the control group(P<0.001).Conclusion Down regulation of PKMYT1 expression promotes GC-induced apoptosis of mOBs.Conversely,over expression of PK-MYT1 inhibits GC-induced apoptosis of mOBs.Therefore,PKMYT1 may serve as a potential target for the early treatment of SANFH.

Objectives:To investigate the clinical characteristics of patients with idiopathic pulmonary arterial hypertension(IPAH)with cardiovascular comorbidities.Methods:A total of 150 patients with IPAH admitted to Fuwai Hospital,Chinese Academy of Medical Sciences from October 2014 to June 2024 were enrolled in this retrospective study.The clinical variables,cardiac structure and hemodynamic characteristics were analyzed and compared between IPAH patients with or without cardiovascular comorbidities.Results:The mean age of the 150 patients was(35.9±12.5)years,73.3%of whom were female.There were 88(58.7%)IPAH patients with cardiovascular comorbidities.Compared to those without cardiovascular comorbidities(n=62),patients with cardiovascular comorbidities were older([38.9±12.3]years vs.[31.7±11.9]years,P=0.001),and N-terminal pro-B-type natriuretic peptide level was higher(1 469.0[656.8,2 615.8]pg/ml vs.923.5[304.4,1 958.8]pg/ml,P=0.006).The hemodynamic examination indicated that patients with cardiovascular comorbidities were featured with higher mean right atrial pressure(6.0[3.3,9.0]mmHg[1 mmHg=0.133 kPa]vs.4.0[3.0,6.3]mmHg,P=0.006),but lower mixed venous oxygen saturation([67.0±7.0]%vs.[70.3±6.9]%,P=0.010)and cardiac index(2.4[1.9,2.9]L/[min·m2]vs.2.8[2.3,3.8]L/[min·m2],P=0.013).Among IPAH patients with cardiovascular comorbidities,compared to patients with 1 comorbidity,patients with≥2 comorbidities were older(51.0[40.0,63.3]years vs.35.0[29.3,43.8]years,P<0.001),left atrial anteroposterior diameter([35.6±4.8]mm vs.[30.4±4.4]mm,P<0.001)and left end-diastolic anteroposterior diameter([40.8±7.5]mm vs.[35.8±5.5]mm,P=0.006)were larger.In patients with cardiovascular comorbidities,hypertension was the most common comorbidity(48.9%).Conclusions:Patients with IPAH and cardiovascular comorbidities exhibit aging characteristics.A series of cardiovascular comorbidities,including hypertension,significantly impact the clinical features,cardiac structural parameters,and hemodynamic status of IPAH.The assessment and management of comorbidities in IPAH patients should be prioritized in the future clinical practice.

Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.

To enhance the standardization and management of diagnosis and treatment for pulmonary arterial hypertension in Chinese adults,Working Group on Pulmonary Hypertension,National Center for Cardiovascular Quality Improvement,National Center for Cardiovascular Diseases,China Specialized Alliance of Pulmonary Hypertension and National Expert Committee for Cardiovascular Diseases,Professional Committee of Right Heart and Pulmonary Vascular Diseases established a working group.Guided by the"structure-process-outcome"theoretical framework,the group established a medical quality control indicator system for pulmonary arterial hypertension in Chinese adults through literature review,expert discussions,and Delphi expert consultation.The system ultimately comprises 32 primary indicators and 6 secondary indicators.It encompasses three categories of indicators:structure,process,and outcome,with the process indicators further covering diagnosis and risk stratification,initial treatment,and follow-up.This quality control indicator system has laid the theoretical foundation for improving the medical quality of care for Chinese adult patients with pulmonary arterial hypertension,though it still requires validation and refinement during clinical practice.

Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.

With the passage of time,the disease spectrum of comorbidities in patients with arterial pulmonary arterial hypertension has gradually become more diversified,posing significant challenges to the diagnosis,differential diagnosis,and management of the disease.This article introduces the key points of differential diagnosis and the precautions for treatment of patients with arterial pulmonary arterial hypertension complicated by cardiopulmonary diseases,aiming to further improve the individualized diagnosis and treatment of pulmonary arterial hypertension.