A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension.

Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily.Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

BACKGROUND: While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. HYPOTHESIS: This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. METHODS: A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event-free survival, and all-cause survival were assessed and analyzed at baseline and posttreatment. RESULTS: Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low-risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6-minute walking distance (6MWD), pulmonary arterial systolic pressure, pulmonary arterial pressure, right ventricle, and eccentricity index, and significant decreases in N-terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6-month event-free survival and all-cause survival between two groups. CONCLUSIONS: Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH.

Value of preoperative evaluation of FEV1 in patients with destroyed lung undergoing pneumonectomy - a 20-year real-world study.

BACKGROUND: Clinical guidelines recommend a preoperative forced expiratory volume in one second (FEV1) of > 2 L as an indication for left or right pneumonectomy. This study compares the safety and long-term prognosis of pneumonectomy for destroyed lung (DL) patients with FEV1 ≤ 2 L or > 2 L. METHODS: A total of 123 DL patients who underwent pneumonectomy between November 2002 and February 2023 at the Department of Thoracic Surgery, Beijing Chest Hospital were included. Patients were sorted into two groups: the FEV1 > 2 L group (n = 30) or the FEV1 ≤ 2 L group (n = 96). Clinical characteristics and rates of mortality, complications within 30 days after surgery, long-term mortality, occurrence of residual lung infection/tuberculosis (TB), bronchopleural fistula/empyema, readmission by last follow-up visit, and modified Medical Research Council (mMRC) dyspnea scores were compared between groups. RESULTS: A total of 96.7% (119/123) of patients were successfully discharged, with 75.6% (93/123) in the FEV1 ≤ 2 L group. As compared to the FEV1 > 2 L group, the FEV1 ≤ 2 L group exhibited significantly lower proportions of males, patients with smoking histories, patients with lung cavities as revealed by chest imaging findings, and patients with lower forced vital capacity as a percentage of predicted values (FVC%pred) (P values of 0.001, 0.027, and 0.023, 0.003, respectively). No significant intergroup differences were observed in rates of mortality within 30 days after surgery, incidence of postoperative complications, long-term mortality, occurrence of residual lung infection/TB, bronchopleural fistula/empyema, mMRC ≥ 1 at the last follow-up visit, and postoperative readmission (P > 0.05). CONCLUSIONS: As most DL patients planning to undergo left/right pneumonectomy have a preoperative FEV1 ≤ 2 L, the procedure is generally safe with favourable short- and long-term prognoses for these patients. Consequently, the results of this study suggest that DL patient preoperative FEV1 > 2 L should not be utilised as an exclusion criterion for pneumonectomy.

Immunoassay with Novel Paired Antibodies for Detection of Lipoarabinomannan in the Pleural Fluid and Plasma of Patients with Tuberculous Pleurisy.

Tuberculous pleurisy (TP) is one of the most common forms of extrapulmonary tuberculosis, but its diagnosis is challenging. Lipoarabinomannan (LAM) antigen is a biomarker for Mycobacterium tuberculosis (Mtb) infection. LAM detection has potential as an auxiliary diagnostic method for TP. We have successfully generated five rabbit anti-LAM monoclonal antibodies (BJRbL01, BJRbL03, BJRbL20, BJRbL52, and BJRbL76). Here, anti-LAM antibodies were tested to detect LAM in the pleural fluid and plasma of patients with TP by sandwich enzyme-linked immunosorbent assays (ELISAs). The results revealed that all of the anti-LAM antibodies were successfully used as capture and detection antibodies in sandwich ELISAs. The BJRbL01/BJRbL01-Bio pair showed better performance than the other antibody pairs for detecting mycobacterial clinical isolates and had a limit of detection of 62.5 pg/mL for purified LAM. LAM levels were significantly higher in the pleural fluid and plasma of patients with TP than in those of patients with malignant pleural effusion or the plasma of non-TB, and LAM levels in the pleural fluid and plasma were positively correlated. Moreover, LAM levels in the pleural fluid sample were significantly higher in confirmed TP patients than in clinically diagnosed TP patients. Our studies provide novel LAM detection choices in the pleural fluid and plasma of TP patients and indicate that LAM detection assay has an auxiliary diagnostic value for TP, which may help to improve the diagnosis of TP.

Lysine succinylation, the metabolic bridge between cancer and immunity.

Lysine succinylation is a naturally occurring post-translational modification (PTM) that regulates the stability and function of proteins. It can be regulated by enzymes such as SIRT5 and SIRT7. Recently, the effect and significance of lysine succinylation in cancer and its implication in immunity have been extensively explored. Lysine succinylation is involved in the malignant phenotype of cancer cells. Abnormal regulation of lysine succinylation occurs in different cancers, and inhibitors targeting lysine succinylation regulatory enzymes can be used as potential anti-cancer strategies. Therefore, this review focused on the target protein lysine succinylation and its functions in cancer and immunity, in order to provide a reference for finding more potential clinical cancer targets in the future.

Acquired resistance to EGFR-TKIs in NSCLC mediates epigenetic downregulation of MUC17 by facilitating NF-κB activity via UHRF1/DNMT1 complex.

Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has brought significant benefits to non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, most patients eventually develop acquired resistance after treatment. This study investigated the epigenetic effects of mucin 17 (MUC17) in acquired drug-resistant cells of EGFR-TKIs. We found that GR/OR (gefitinib/osimertinib-resistance) cells enhance genome-wide DNA hypermethylation, mainly in 5-UTR associated with multiple oncogenic pathways, in which GR/OR cells exerted a pro-oncogenic effect by downregulating mucin 17 (MUC17) expression in a dose- and time-dependent manner. Gefitinib/osimertinib acquired resistance mediated down-regulation of MUC17 by promoting DNMT1/UHRF1 complex-dependent promoter methylation, thereby activating NF-κB activity. MUC17 increased the generation of IκB-α and inhibit NF-κB activity by promoting the expression of MZF1. In vivo results also showed that DNMT1 inhibitor (5-Aza) in combination with gefitinib/osimertinib restored sensitivity to OR/GR cells. Acquired drug resistance of gefitinib/osimertinib promoted UHRF1/DNMT1 complex to inhibit the expression of MUC17. MUC17 in GR/OR cells may act as an epigenetic sensor for biomonitoring the resistance to EGFR-TKIs.

Analysis of Pulmonary Function in Thymoma Subjects: A 20-Year Retrospective Cohort Study.

BACKGROUND: Thymoma is the most common tumor of the anterior mediastinum. However, the correlation between thymoma stage and pulmonary function was not assessed. Our objective in this study was to describe the pulmonary function in thymoma subjects stratified with different staging systems. METHODS: A total of 143 subjects with a diagnosis of thymoma who underwent extended thymectomy for thymoma between January 2001 and December 2019 were reviewed retrospectively. All the subjects experienced pulmonary function tests (PFTs) using Master Screen PFT system and total respiratory resistance measurement. RESULTS: We evaluated 143 subjects with a diagnosis of thymoma; the significant differences were observed in mean values of vital capacity, inspiratory volume (IC), total lung capacity (TLC), ratio of residual volume to total lung capacity (RV/TLC), forced vital capacity, forced expiratory volume in 1 second, ratio of forced expiratory volume in 1 second to forced vital capacity, peak expiratory flow, peak inspiratory flow, maximum ventilation volume, total airway resistance, and diffusing capacity for carbon monoxide (DLCO) across upper airway obstruction classification. PFTs of subjects with varying Masaoka stages are different. RV and RV/TLC of subjects in stages III and IV were higher than those of normal level, while DLCO of subjects in stage IV was lower than the normal level, and the mean level of IC showed significant difference between stage II and stage III. DISCUSSION: The pulmonary function patterns of thymoma subjects significantly correlate with tumor location and size rather than clinical Masaoka stage.

Enhanced Serum IgG Detection Potential Using 38KD-MPT32-MPT64, CFP10-Mtb81-EspC Fusion Protein and Lipoarabinomannan (LAM) for Human Tuberculosis.

For the rapid, reliable, and cost-effective methods of tuberculosis (TB) auxiliary diagnosis, antibody (Ab) detection to multiple antigens of Mycobacterium tuberculosis (Mtb) has great potential; however, this methodology requires optimization. We constructed 38KD-MPT32-MPT64, CFP10-Mtb81-EspC, and Ag85B-HBHA fusion proteins and evaluated the serum Ab response to these fusion proteins and to lipoarabinomannan (LAM) by ELISA in 50 TB patients and 17 non-TB subjects. IgG responses to the three fusion proteins and to LAM were significantly higher in TB patients, especially in Xpert Mtb-positive TB patients (TB-Xpert+), than in non-TB subjects. Only the anti-38KD-MPT32-MPT64 Ab showed higher levels in the Xpert Mtb-negative TB patients (TB-Xpert-) than in the non-TB, and only the anti-LAM Ab showed higher levels in the TB-Xpert+ group than in the TB-Xpert- group. Anti-Ag85B-HBHA Ab-positive samples could be accurately identified using 38KD-MPT32-MPT64. The combination of 38KD-MPT32-MPT64, CFP10-Mtb81-EspC, and LAM conferred definite complementarity for the serum IgG detection of TB, with relatively high sensitivity (74.0%) and specificity (88.2%). These data suggest that the combination of 38KD-MPT32-MPT64, CFP10-Mtb81-EspC, and LAM antigens provided a basis for IgG detection and for evaluation of the humoral immune response in patients with TB.

Identification of Six Small Heat Shock Protein Genes in Ostrinia furnacalis (Lepidoptera: Pyralidae) and Analysis of Their Expression Patterns in Response to Environmental Stressors.

Ostrinia furnacalis (Guenée) is a major insect pest in maize production that is highly adaptable to the environment. Small heat shock proteins (sHsps) are a class of chaperone proteins that play an important role in insect responses to various environmental stresses. The present study aimed to clarify the responses of six O. furnacalis sHsps to environmental stressors. In particular, we cloned six sHsp genes, namely, OfHsp24.2, OfHsp21.3, OfHsp20.7, OfHsp21.8, OfHsp29.7, and OfHsp19.9, from O. furnacalis. The putative proteins encoded by these genes contained a typical α-crystallin domain. Real-time quantitative polymerase chain reaction was used to analyze the differences in the expression of these genes at different developmental stages, in different tissues of male and female adults, and in O. furnacalis under UV-A and extreme temperature stresses. The six OfsHsp genes were expressed at significantly different levels based on the developmental stage and tissue type in male and female adults. Furthermore, all OfsHsp genes were significantly upregulated in both male and female adults under extreme temperature and UV-A stresses. Thus, O. furnacalis OfsHsp genes play important and unique regulatory roles in the developmental stages of the insect and in response to various environmental stressors.

Risk factors for respiratory failure after tuberculosis-destroyed lung surgery and increased dyspnea score at 1-year follow-up.

Background: Although pneumonectomy is an important surgical treatment for tuberculosis-destroyed lung (TDL), few studies have investigated long-term postoperative TDL prognosis. Here, risk factors were determined for postoperative secondary respiratory failure and modified British Medical Research Council (mMRC ≥1) at discharge and at 1-year post-surgical follow-up. Methods: A two-way cohort study was conducted of 116 patients admitted to our thoracic surgery department for surgical TDL treatment from January 2001 to June 2020. General clinical data were collected then patient postoperative mMRC scores were monitored for 1 year. Dyspnea-associated factors (mMRC ≥1) were identified then risk factors for postoperative respiratory failure and compromised long-term respiratory function were identified using multivariate adjusted logistic regression analysis. Results: Of 116 patients, 27.6% (32/116) developed respiratory failure secondary to surgery. Multifactorial logistic regression analysis revealed that preoperative serum albumin of <30 g/L [adjusted odds ratios (aOR) 6.613, 95% confidence intervals (CI): 1.064-41.086] and intraoperative bleeding of >1,000 mL (aOR 6.876, 95% CI: 1.236-38.243) were risk factors for subsequent respiratory failure only in patients experiencing postoperative secondary respiratory failure. Sorting of patient mMRC dyspnea index scores into two groups (mMRC =0, mMRC ≥1) followed by logistic regression analysis revealed that risk factors for 1-year postoperative dyspnea included mMRC score ≥1 at discharge (aOR 14.446, 95% CI: 1.102-189.361) and postoperative respiratory failure occurrence (aOR 9.946, 95% CI: 1.063-93.034). Conclusions: TDL patient preoperative hypoalbuminemia and extensive intraoperative bleeding were risk factors for postoperative secondary respiratory failure. Postoperative secondary respiratory failure and high mMRC (≥1) at discharge were associated with reduced postoperative long-term recovery of respiratory function.

Long-term follow-up of tuberculosis-destroyed lung patients after surgical treatment.

BACKGROUND: To monitor dypsnea and mortality at 5 and 10 years, respectively, after surgical treatment of tuberculosis-destroyed lung (TDL) patients. METHODS: TDL patients treated surgically at Beijing Chest Hospital from November 2007 to June 2019 were monitored in this observational study. Follow-up assessments of respiratory function indicators and survival conducted 5 and 10 years post-surgery led to patient grouping based on mMRC score into a dyspnea group (mMRC ≥ 1) and a non-dyspnea group (mMRC = 0). Cox regression analysis detected effects of patient demographics, clinical characteristics, surgical factors and respiratory function on 5 year post-surgical survival. RESULTS: By study completion (June 30, 2020), 32 of 104 patients were lost and 72 completed follow-up for a study total of 258.9 person-years. 45 patients (62.5%, 45/72) had mMRC scores of 0, while 12 (16.7%, 12/72), 21 (36.2%, 21/58) and 27 (60.0%, 27/45) patients exhibited dyspnea by 1, 3 and 5 years post-surgery, respectively. Low lung carbon monoxide diffusion score (DLCO% pred) and scoliosis contributed to dyspnea occurrence. CONCLUSIONS: Most TDL patients lacked subjective dyspnea signs post-surgery, while dyspnea rates increased with time. Preoperative low lung diffusion function and Scoliosis were associated with factors for postoperative dyspnea. Surgical treatment increased TDL patient survival overall.

Key Factors Associated With Administration of Ventilator Support After Thymoma Resection.

INTRODUCTION: In clinical practice, some patients undergoing surgery for thymoma require post-surgical ventilator support, although, factors associated with administration of ventilator support are unclear. This study aimed to explore factors associated with incidence of post-surgical severe respiratory failure requiring ventilator support after thymoma resection. METHODS: Clinical data of patients who underwent thymoma re-section in our thoracic surgery department between January 2001 and February 2020 was retrospectively analyzed. Multiple logistic regression analysis was used to identify factors associated with patient need for post-surgical ventilator support after thymoma resection. RESULTS: Among 157 patients who underwent thymoma resection, 17.8% (28/157) required post-surgical ventilator support. Results of univariate analysis revealed that gender, myasthenia gravis (MG) grade, anti-MG medication use (neostigmine or prednisone), Masaoka thymoma stage, pulmonary function test index values, surgical approach, and intraoperative blood loss were associated with increased incidence of severe respiratory failure requiring post-operative ventilator support (P < 0.05). Results of multivariable logistic regression analysis revealed that median sternotomy, MG grade three status, and patient use of anti-MG drug treatments before thymoma resection surgery were associated with greater need for post-surgical ventilator support. CONCLUSIONS: Our data suggest that median sternotomy, MG grade three status, and preoperative use of anti-MG drugs are associated with greater incidence of severe respiratory failure requiring respiratory support after thymoma surgery. Therefore, patients with these risk factors should be closely monitored to reduce the incidence of severe postoperative respiratory failure.

Incidence and risk factors of postoperative complications in patients with tuberculosis-destroyed lung.

BACKGROUND: The purpose of this study was to determine risk factors of postoperative complications in tuberculosis-destroyed lung (TDL) patients. METHODS: We retrospectively analyzed the data from all consecutive TDL patients undergoing surgical treatment at the Beijing Chest Hospital from January 2001 to September 2019. RESULTS: Of 113 TDL cases experiencing surgery, 33 (29.2%) experienced postoperative complications. The patients with low BMI were more likely to have postoperative complications compared to those with normal BMI, whereas a significant lower rate of postoperative complications was noted in patients with BMI ≥ 25 kg/m2. In addition, significant increased risk was observed in patients with smoking history. We found that the patients with underlying infection, including aspergillus and nontuberculous mycobacteria (NTM), had significantly higher odds of having postoperative complications compared with those without underlying infection. The anaemia was another important independent factor associated with postoperative complication. Patients with blood transfusion above 1000 mL had a strongly increased frequency of postoperative complications than patients with blood transfusion below 1000 mL. CONCLUSION: In conclusion, our data demonstrate that approximate one third of TDL patients experience postoperative complications in our cohort. Patients with low BMI, anaemia, tobacco smoking, and coinfected aspergillus or NTM are at markedly higher risk to experience postoperative complications after pneumonectomy.

Expression stability of candidate RT-qPCR housekeeping genes in Spodoptera frugiperda (Lepidoptera: Noctuidae).

Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) is commonly used to quantify gene expression. For normalization, the expression of each gene is compared with a reference "housekeeping" gene that is stably expressed under relevant stress. Unfortunately, there have been no reports on the stability of such reference genes under various treatments of the Spodoptera frugiperda. In this study, we used five tools (RefFinder, GeNorm, NormFinder, BestKeeper, and ΔCt methods) to evaluate the stability of 12 candidate reference genes (RPS18, ß-tubulin, GAPDH, RPS7, RPS15, RPL7, RPL32, Actin-5C, EF1-α, EF1-γ, RPL27, and ACE) in different instars, tissues, and treatments (high and low temperature, UV-A, and emamectin benzoate). Several ribosomal proteins (RPS7, RPS15, RPL32, RPS18, and RPL7), GAPDH, Actin-5C, and ß-tubulin, were relatively stable, suggesting that they are ideal housekeeping genes for various treatments. ACE was extremely unstable under various experimental treatments, rendering it unsuitable as an internal reference. This study identified the reference housekeeping genes stably expressed by S. frugiperda under different treatments, thus setting a foundation for further exploration of the physiological and biochemical mechanisms.

Risk factors associated with postoperative respiratory failure in tuberculous empyema patients.

ABSTRACT: Our objective was to identify independent risk factors for predicting which patients in the Chinese population would likely develop respiratory failure.A descriptive analysis was conducted of demographic and clinical data of patients with tuberculous empyema (TE) admitted to the Beijing Chest Hospital, Capital Medical University between January 2001 and January 2020. Risk factors associated with postsurgical respiratory failure in TE patients were identified based on results of analyses based on univariable and multivariable logistic regression models.A total of 139 TE patients who underwent surgical treatment in the Beijing Chest Hospital, Capital Medical University from January 2001 to January 2020 were enrolled in this study. Cases included 109 male and 30 female patients, with an overall mean age (range 17-73) of 39.3 years. Of 139 TE patients, 26 (18.7%) experienced respiratory failure after surgery. Among significant risk factors for postsurgical respiratory failure, intraoperative blood loss volume greater than 1000 mL had the highest odds ratio value of 6.452. In addition, a pathologic preoperative pulmonary function test result showing a high partial pressure of carbon dioxide level was an independent risk factor for respiratory failure. Moreover, the presence of tuberculosis lesions in the contralateral lung was another significant risk factor for respiratory failure, as determined using multivariate analysis.Respiratory failure is a predominant complication experienced by TE patients undergoing surgery. High intraoperative blood loss, high preoperative high partial pressure of carbon dioxide level, and tuberculosis lesion(s) in the contralateral lung of TE patients were associated with increased risk of postoperative respiratory failure.

The Efficacy and Safety of Surgical Treatment for Patients With Tuberculosis Destroyed Lung With or Without Chronic Pulmonary Aspergillosis.

BACKGROUND: To evaluate the efficacy and safety of surgical treatment of tuberculosis destroyed lung (TDL), and the influence of chronic pulmonary aspergillosis (CPA) on the outcomes of surgical treatment of TDL. METHODS: We performed a retrospective analysis of 113 patients with TDL who underwent surgical treatment from January 2005 to December 2019. Among them, 30 of these cases were complicated with CPA. The patients were divided into two groups: TDL group and TDL + CPA group. We analyzed the effectiveness and safety of surgical treatment of TDL, and further compared the effectiveness and safety of surgical treatment of TDL with or withoutthe presence of CPA. RESULTS: The TDL + CPA group had a significantly higher age (P=0.003), symptoms of hemoptysis (P=0.000), and a higher proportion of patients with preoperative serum albumin <30 g/L (P=0.014) as compared with TDL group. For all enrolled patients, the incidence of severe postoperative complications was 12.4% (14/113) and the postoperative mortality within 30 days after discharge was 4.4% (5/113). 86.7% (98/113) of the patients recovered and discharged, the incidence of severe postoperative complications in the TDA + CPA group was higher than that of TDL group (23.3% vs 8.4%, P = 0.034), although there was no difference in mortality between the two groups (P = 1.000). A binary logistic regression analysis showed that the independent risk factors for severe postoperative complications were male (OR 25.24, 95% CI 2.31-275.64; P = 0.008) and age ≥ 40 years (OR 10.34, 95% CI 1.56-68.65; P = 0.016). CONCLUSION: Surgical treatment for patients with TDL is effective with an acceptable mortality rate whether or not the disease is complicated with CPA. The independent risk factors identified for severe postoperative complications in patients with TDL were male and ≥ 40 years old. It implies that when treating patients with TDA + CPA, particular attention should be paid to these patients who have these independent risk factors to avoid a poor outcome.

Protective effects of Salidroside on cardiac function in mice with myocardial infarction.

Salidroside (SAL) is the major ingredient of Rhodiola rosea, and has been traditionally used in Chinese medicine for decades. Numerous studies have demonstrated the protective effects of SAL for myocardial ischemia. However, it is yet to be deciphered whether SAL has cardioprotective effects after myocardial infarction (MI) in vivo. In the present study, we established a mouse MI model via coronary artery ligation. The aim was to investigate whether SAL treatment could reduce mortality, improve cardiac function and attenuate myocardial remodeling in MI mice. Post-surgery, mice were randomly administered SAL or normal saline. After 21 days, SAL was found to significantly reduce mortality, improve cardiac function, reduce fibrosis and infarct size compared to normal saline. In addition, oral administration of SAL could attenuate myocardial inflammation and apoptosis and promote angiogenesis. SAL down-regulated the expression levels of TNF-α, TGF-ß1, IL-1ß, Bax and up-regulate the expression of Bcl-2, VEGF, Akt and eNOS. These results indicated that SAL could alleviate the pathological processes of myocardial remodeling in MI mice, and may be a potentially effective therapeutic approach for the management of clinical ischemic cardiovascular diseases.

The acute effects of 30 mg vs 60 mg of intravenous Fasudil on patients with congenital heart defects and severe pulmonary arterial hypertension.

OBJECTIVE: The optimal dose of Fasudil is still controversial in congenital heart disease accompanied with severe pulmonary hypertension (CHD-PAH). This study aimed to compare acute hemodynamic changes after different doses of Fasudil in 60 consecutive adult patients with CHD-PAH. DESIGN: Prospective randomized controlled trial. SETTING: Tertiary cardiology center. PATIENTS: Adult patients with CHD-PAH. INTERVENTIONS: Patients were randomized to Fasudil 30 or 60 mg. OUTCOME MEASURES: The hemodynamic parameters were measured at baseline and after 30 minutes of Fasudil through right cardiac catheterization. Blood gas results were obtained from the pulmonary artery, right ventricle, right atrium, superior and inferior vena cava, and femoral artery. Pulmonary vascular resistance (PVR) and systemic arterial resistance (SVR) were calculated. RESULTS: The changes in systolic pulmonary artery pressure (sPAP) (-13.1% vs -9.3%, P < .05), diastolic PAP (dPAP) (-17.6% vs -14.5%, P < .05), mean PAP (mPAP) (-12.4% vs -8.5%, P < .05), and PVR (-35.8% vs -22.2%, P < .05) were more pronounced in the 60-mg group than in the 30-mg group. All patients had no obvious adverse reactions related to peripheral blood pressure. CONCLUSIONS: Fasudil could improve the hemodynamics of patients with CHD-PAH, especially with the 60-mg dose. There were no serious adverse reactions.

Obesity and hypertension.

The imbalance between energy intake and expenditure is the main cause of excessive overweight and obesity. Technically, obesity is defined as the abnormal accumulation of ≥20% of body fat, over the individual's ideal body weight. The latter constitutes the maximal healthful value for an individual that is calculated based chiefly on the height, age, build and degree of muscular development. However, obesity is diagnosed by measuring the weight in relation to the height of an individual, thereby determining or calculating the body mass index. The National Institutes of Health have defined 30 kg/m2 as the limit over which an individual is qualified as obese. Accordingly, the prevalence of obesity in on the increase in children and adults worldwide, despite World Health Organization warnings. The growth of obesity and the scale of associated health issues induce serious consequences for individuals and governmental health systems. Excessive overweight remains among the most neglected public health issues worldwide, while obesity is associated with increasing risks of disability, illness and death. Cardiovascular diseases, the leading cause of mortality worldwide, particularly hypertension and diabetes, are the main illnesses associated with obesity. Nevertheless, the mechanisms underlying obesity-associated hypertension or other associated metabolic diseases remains to be adequately investigated. In the present review, we addressed the association between obesity and cardiovascular disease, particularly the biological mechanisms linking obesity and hypertension.