BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

Objective To analyze the caregiver presence needs and their influencing factors among hospitalized elderly non-surgical patients and provide a basis for formulating relevant policies.Methods A descriptive qualitative study method was adopted.Through purposive sampling,semi-structured interviews were conducted on elderly non-surgical patients and their families and medical staff in Peking Union Medical College Hospital from September to October 2023.MAXQDA 2020 and the 7-step phenomenological analysis method of Colaizzi were used to classify and code the interview contents and identify themes.Results The categories of caregiver presence needs of elderly non-surgical patients included basic living assistance needs,disease monitoring needs,psychological support needs,as well as the needs for family members to provide economic support and participate in treatment decision-making.The influencing factors included advanced age,frailty,the lack of self-care ability in patients with comorbidities,the susceptibility of patients to sudden situations during the disease exacerbation period,the increased risk of unexpected events in patients with psychological distress,and patients' concerns about social support and medical decision-making.Conclusion The caregiver presence needs of elderly non-surgical patients during hospitalization are high and influenced by multiple factors.
Humans ; Caregivers/psychology* ; Aged ; Hospitalization ; Social Support ; Male ; Qualitative Research ; Female

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Pulmonary hypertension(PH)is a type of progressive cardiovascular disease or clinical syndrome. Its pathological mechanism is complex. The existing clinical drugs cannot well inhibit the progression of the disease. Traditional Chinese Medicine(TCM)has unique advantages in the treatment of PH due to its synergistic effect of multiple components and multiple targets. Recent studies have found that the TCM of promoting blood circulation and removing blood stasis can play a significant role in the treatment of PH, such as dilating pulmonary blood vessels, improving endothelial function, and relieving right heart failure. This article briefly summarizes and discusses the therapeutic effect and mechanism of TCM that can promote blood circulation and remove blood stasis in treatment of PH.

OBJECTIVE: To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients. METHODS: We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells. RESULTS: The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells. CONCLUSION As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.
Aldehyde Oxidoreductases ; CA-19-9 Antigen ; Carcinoembryonic Antigen ; Gastrectomy ; Humans ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/pathology*

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*

OBJECTIVE: To analyze the expression of centromere protein U (CENPU) in colorectal cancer and its predictive value for long-term prognosis of the patients. METHODS: We retrospectively analyzed the data of 102 patients with colorectal cancer undergoing radical resection in our hospital between January, 2005 and December, 2011. The expression level of CENPU in colorectal cancer tissue was detected immunohistochemically, and its association with clinicopathological characteristics of the patients were analyzed. The patients were divided into low expression group (n=51) and high expression group (n=51) based on the median CENPU expression level for analysis the value of CENPU for predicting long-term prognosis of the patients after radical resection of the tumors. In the in vitro study, we constructed colorectal cancer cell lines with CENPU interference and CENPU overexpression by lentiviral transfection and assessed the changes in the proliferation, migration and invasion of the cells using CCK-8 assay and Transwell assay. RESULTS: The protein expression level of CENPU was significantly higher in colorectal cancer tissues than in the adjacent tissues (P < 0.05) and was positively correlated with the expressions levels of Ki67 (r=0.569, P < 0.05) and VEGF-C (r=0.629, P < 0.05). CENPU expression level in colorectal cancer tissue was closely related with tumor progression and clinicopathological stage of the tumor (P < 0.05). Kaplan-Meier survival analysis showed that the patients with high CENPU expression had significantly decreased postoperative overall survival (χ²=11.155, P < 0.05); Cox multivariate regression analysis suggested that CENPU expression level was an independent risk factor affecting the overall survival of the patients after radical resection (HR=1.848, P < 0.05). The results of cell experiments demonstrated that high CENPU expression significantly promoted the proliferation, migration and invasion of the tumor cells. CONCLUSION CENPU is highly expressed in colorectal cancer tissues in closely correlation with tumor progression and may serve as a potential biomarker for evaluating the long-term prognosis of colorectal cancer patients.
Centromere/pathology* ; Colorectal Neoplasms/pathology* ; Humans ; Kaplan-Meier Estimate ; Prognosis ; Retrospective Studies