Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment, memory decline and emotional loss, which is more common in middle-aged and elderly people. In recent years, studies have shown that chronic neuroinflammation is an important factor leading to AD development. As the core participant in neuroinflammation, microglia play a dual role in the pathological process of AD: on one hand, through M1 polarization, they exert a pro-inflammatory effect and exacerbate the neurotoxic response; on the other hand, through M2 polarization, they enhance the phagocytic ability of amyloid β-protein and exert a neuroprotective effect. Metabolic reprogramming is the key in determining the polarization of microglia M1/M2 type and exerting neurotoxicity/protection. Therefore, this article reviews the recent advance in role of metabolism reprogramming of microglia in AD, in order to provide new idea and direction for studing AD pathogenesis and treatment in the future.

Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.

Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment, memory decline and emotional loss, which is more common in middle-aged and elderly people. In recent years, studies have shown that chronic neuroinflammation is an important factor leading to AD development. As the core participant in neuroinflammation, microglia play a dual role in the pathological process of AD: on one hand, through M1 polarization, they exert a pro-inflammatory effect and exacerbate the neurotoxic response; on the other hand, through M2 polarization, they enhance the phagocytic ability of amyloid β-protein and exert a neuroprotective effect. Metabolic reprogramming is the key in determining the polarization of microglia M1/M2 type and exerting neurotoxicity/protection. Therefore, this article reviews the recent advance in role of metabolism reprogramming of microglia in AD, in order to provide new idea and direction for studing AD pathogenesis and treatment in the future.

Objective:To discuss the effects of moxibustion combined with acupuncture on nasal resistance and quality of life in allergic rhinitis (AR) patients with lung qi deficiency and cold syndrome.Methods:Randomized controlled trial was conducted. Totally 82 patients of AR were divided into two groups according to random number table method, with 41 cases in each group. The control group received routine intervention, and the observation group received moxibustion combined with acupuncture intervention on the basis of routine intervention. The treatment for both groups lasted for 4 weeks. The severity of nasal symptoms was evaluated using the Total Nasal Symptom Score (TNSS) before and after treatment. The Rhinoconjunctival Quality of Life Questionnaire (RQLQ) was used to evaluate the quality of life, patient nasal resistance was measured, and clinical efficacy was evaluated.Results:The total effective rate was 95.12% (39/41) in the observation group and 75.61% (31/41) in the control group, with statistical significance ( χ2=4.78, P=0.029). The scores and total scores of nasal itching, sneezing, runny nose and congestion in the observation group after treatment were lower than those in the control group ( t values were 4.45, 4.73, 4.64, 4.68, 9.09, respectively, P<0.01). The scores of daily activities, sleep, non-nasal/eye symptoms, behavioral problems, nasal symptoms, eye symptoms, and emotion were lower than those in the control group ( t values were 4.83, 4.63, 4.50, 5.32, 5.56, 5.29, 4.84, respectively, P<0.01). The nasal resistance of the observation group after treatment [(0.15±0.03) Pa/(cm?s) vs. (0.21±0.03) Pa/(cm?s), t=9.06] was lower than that of the control group ( P<0.001). Conclusion:Moxibustion combined with acupuncture in patients with AR can further reduce nasal resistance and improve their quality of life and clinical efficacy.

Objective:To compare the value of coronary CT angiography, congenital heart disease CT, and transthoracic echocardiography (TTE) in the diagnosis of sinus venosus atrial septal defect (SVASD), to summarize the CT image features of SVASD, and to explore its significance in guiding the selection of surgical procedures.Methods:A total of 443 patients of SVASD diagnosed by surgical procedures from January 2017 to December 2021 were retrospectively analyzed. All patients underwent coronary CT angiography or congenital heart disease CT examination and TTE before surgery. Using surgical results as the gold standard, McNemar test was used to analyze the differences between CT and TTE in distinguishing SVASD and pulmonary venous drainage. The difference of pulmonary venosus drainage was analyzed between superior sinus venosus atrial septal defect (ASD) and inferior sinus venosus ASD. The image features of SVASD were summarized and the corresponding surgical procedures were analyzed.Results:No significant difference was found between CT and TTE for the diagnostic accuracy of the SVASD (63.21%, 57.56%, P=0.065). There were 159 patients (35.89%) with PAPVC and 284 patients (64.11%) without PAPVC in the 443 SVASD patients. The diagnostic accuracy of CT and TTE in diagnosing pulmonary venous drainage was statistically significantly different (98.42%, 73.81%, P<0.001). Among 145 patients with superior sinus venosus ASD, 101 (69.66%) were associated with PAPVC; in contrast, among 298 patients with inferior sinus venosus ASD, 58 (19.46%) had PAPVC. The difference between the two groups was statistically significant ( χ 2=106.79, P<0.001), indicating a higher prevalence of PAPVC in patients with superior sinus venosus ASD. The CT imaging features of SVASD can be categorized into four types. The first type was SVASD alone without PAPVC, comprising 284 patients (64.11%). Surgical intervention for this type typically involved direct suturing or closure using a patch. The second type was SVASD with concomitant PAPVC, encompassing 151 patients (34.09%). This type included superior sinus venosus ASD with anomalous pulmonary venous low connection and inferior sinus venosus ASD with PAPVC. During the repair of the defect, it was necessary to redirect the anomalous pulmonary veins into the left atrium. The third type was superior sinus venosus ASD in 7 patients (1.58%). The position of pulmonary vein draining into superior vena cava was too high to be directly corrected to the left atrium, requiring Warden′s technique. The fourth type was rare (1 patient, 0.22%). The anomalous pulmonary vein drained into the coronary sinus. The surgery included incision of the roof of the coronary sinus to redirect pulmonary vein flow to the left atrium, reconstruction of the roof of the sinus to drain coronary vein back to the right atrium, and repair of the ASD. Conclusions:Both CT and TTE can diagnose the type of SVASD, and CT is more accurate than TTE in the diagnosis of PAPVC. CT image features of SVASD can provide valuable information for surgical procedures and guide the selection of surgical procedures.

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

Aggressive angiomyxoma (AAM) is a rare clinical entity. A case of AAM was reported in this paper. The patient presented with severe hydronephrosis of the left kidney and was diagnosed with a pelvic mass compressing the ureter. The patient underwent laparoscopic resection of the pelvic mass. The postoperative pathology and immunohistochemistry confirmed the diagnosis of AAM. The patient had no recurrence and metastasis after 9 months of follow-up.