Association of statin use and increase in lipoprotein(a): a real-world database research.

BACKGROUND: There is an increased concern that statins may have an unintended effect of elevated lipoprotein(a) [Lp(a)]. We conducted a large sample real-world study to test the association. METHODS: This retrospective cohort study was conducted using data from an integrated SuValue database, which includes 221 hospitals across China covering more than 200,000 of population with longitudinal follow-up to 10 years. Propensity score matching was applied to identify two comparable cohorts with statin users and non-statin users. Detailed follow-up information such as Lp(a) levels were extracted. The hazard ratio was calculated on Lp(a) changes based on the statin usage cohorts. Detailed subgroup and different characteristic cohorts' analyses were also conducted. RESULTS: After baseline propensity score matching, a total of 42,166 patients were included in a 1:1 matched ratio between statin users and non-statin users. In the case of no difference in low density lipoprotein (LDL-C), Lp(a) was increased significantly with the use of statins (adjusted HR 1.47; 95% confidence interval [CI] 1.43-1.50). Lp(a) increase was observed in various subgroup analyses and different cohorts. The dose intensity of statin was positively associated with the evaluated Lp(a) level. CONCLUSION: The use of statins was associated with an increased risk of Lp(a) elevation compared with non-statin use counterparts. The clinical relevance of these increases needs to be addressed in surrogate marker trials and/or large, cardiovascular outcomes trials.

Natural Products and Gastric Cancer: Cellular Mechanisms and Effects to Change Cancer Progression.

Gastric cancer is a severe malignant tumor with high morbidity and mortality, which seriously affects people's health. At present, the most common treatment for gastric cancer is chemotherapy. However, chemotherapy is very harmful to the human body, and some of the injuries caused by chemotherapy are irreversible. Natural products have low toxicity and anti-cancer activity, so they are currently widely studied at present. Natural products are a large variety of compounds naturally found in fruits, vegetables, spices, and medicinal plants. It is reported that natural products have different anti-cancer properties. This review has summarized the study of natural products in inducing gastric cancer cell apoptosis, inhibiting gastric cancer cell metastasis, and inhibiting gastric cancer cell proliferation. The relevant references on gastric cancer and natural products were obtained from scientific databases, including Pub- Med, Web of Science, and Science Direct. This paper records dozens of natural products with anti-gastric tumor activity and describes the potential living anti-cancer chemical compounds, their element targets, and their underlying mechanism. This review may lay the foundation for future researchers to treat gastric cancer.

Herpud1 deficiency alleviates homocysteine-induced aortic valve calcification.

OBJECTIVES: To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD). BACKGROUND: The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited. METHODS: In vivo, we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice and used high methionine diet (HMD) to assess of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). In vitro, the role of Herpud1 in the Hcy-related osteogenic differentiation of AVICs was investigated by manipulating of Herpud1 expression. RESULTS: Herpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in HMD-fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis. CONCLUSIONS: These findings identify a previously unknown mechanism of Herpud1 upregulation in Hcy-related CAVD, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression. HIGHLIGHTS: • Herpud1 is upregulated in the leaflets of Hcy-treated mice and patients with CAVD. • In mice, global knockout of Herpud1 alleviates aortic valve calcification and Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of AVICs induced by Hcy. • 4-PBA suppressed Herpud1 expression to alleviate AVIC calcification in Hcy treated AVICs and to mitigate aortic valve calcification in mice.

Machine learning algorithms identifying the risk of new-onset ACS in patients with type 2 diabetes mellitus: A retrospective cohort study.

Background: In recent years, the prevalence of type 2 diabetes mellitus (T2DM) has increased annually. The major complication of T2DM is cardiovascular disease (CVD). CVD is the main cause of death in T2DM patients, particularly those with comorbid acute coronary syndrome (ACS). Although risk prediction models using multivariate logistic regression are available to assess the probability of new-onset ACS development in T2DM patients, none have been established using machine learning (ML). Methods: Between January 2019 and January 2020, we enrolled 521 T2DM patients with new-onset ACS or no ACS from our institution's medical information recording system and divided them into a training dataset and a testing dataset. Seven ML algorithms were used to establish models to assess the probability of ACS coupled with 5-cross validation. Results: We established a nomogram to assess the probability of newly diagnosed ACS in T2DM patients with an area under the curve (AUC) of 0.80 in the testing dataset and identified some key features: family history of CVD, history of smoking and drinking, aspartate aminotransferase level, age, neutrophil count, and Killip grade, which accelerated the development of ACS in patients with T2DM. The AUC values of the seven ML models were 0.70-0.96, and random forest model had the best performance (accuracy, 0.89; AUC, 0.96; recall, 0.83; precision, 0.91; F1 score, 0.87). Conclusion: ML algorithms, especially random forest model (AUC, 0.961), had higher performance than conventional logistic regression (AUC, 0.801) for assessing new-onset ACS probability in T2DM patients with excellent clinical and diagnostic value.

Improved ClickTags enable live-cell barcoding for highly multiplexed single cell sequencing.

Click chemistry-enabled DNA barcoding of cells provides a universal strategy for sample multiplexing in single-cell RNA-seq (scRNA-seq). However, current ClickTags are limited to fixed samples as they only label cells efficiently in methanol. Herein, we report the development of a new protocol for barcoding live cells with improved ClickTags. The optimized reactions barcoded live cells without perturbing their physiological states, which allowed sample multiplexing of live cells in scRNA-seq. The general applicability of this protocol is demonstrated in diversified types of samples, including murine and human primary samples. Up to 16 samples across these two species are successfully multiplexed and demultiplexed with high consistency. The wide applications of this method could help to increase throughput, reduce cost and remove the batch effect in scRNA-seq, which is especially valuable for studying clinical samples from a large cohort.

Mesenchymal Stem Cell-Derived Extracellular Vesicle-Shuttled microRNA-302d-3p Represses Inflammation and Cardiac Remodeling Following Acute Myocardial Infarction.

Our research intended to investigate the roles of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in acute myocardial infarction (AMI) via delivery of microRNA (miR)-302d-3p. AMI mouse models were established. EVs isolated from MSCs with miR-302d-3p mimic were injected near the infarct area or co-cultured with hypoxic cardiomyocytes to evaluate their effects. The expression of NF-κB pathway-related genes and inflammatory factors was determined. AMI mice exhibited downregulated miR-302d-3p and elevated MD2 and BCL6 levels. BCL6 was negatively targeted by miR-302d-3p and could bind to MD2 promoter to upregulate MD2 expression. MSCs-EVs, MSCs-EVs carrying miR-302d-3p, or BCL6 or MD2 silencing inactivated the NF-κB pathway and alleviated infarcted area, myocardial fibrosis, inflammation, apoptosis, and cardiac dysfunction in AMI mice. Besides, MSCs-EVs, MSCs-EVs carrying miR-302d-3p, or BCL6 or MD2 silencing diminished viability and inflammation but augmented apoptosis of hypoxic cardiomyocytes. Conclusively, MSCs-EVs carrying miR-302d-3p repressed inflammation and cardiac remodeling after AMI via BCL6/MD2/NF-κB axis.

Yellow Wine Polyphenolic Compound Protects Against Doxorubicin-Induced Cardiotoxicity by Modulating the Composition and Metabolic Function of the Gut Microbiota.

BACKGROUND: Dietary polyphenols help to prevent cardiovascular diseases, and interactions between polyphenols and gut microbiota are known to exist. In this study, we speculated that gut microbiota-mediated metabolite regulation might contribute to the anticardiotoxic effects of yellow wine polyphenolic compound (YWPC) in doxorubicin (DOX)-treated rats. METHODS: 16S-rDNA sequencing was performed to analyze the effects of YWPC on the gut microbiota in DOX-treated rats (n=6). Antibiotics were used to investigate the contribution of the altered microbiome to the role of YWPC (n=6). Plasma metabolomics were also analyzed by untargeted gas chromatography-mass spectrometry systems. RESULTS: YWPC ameliorated DOX-mediated cardiotoxicity, as evidenced by increased cardiac and mitochondrial function and reduced levels of inflammation and myocardial apoptosis (P<0.05 for all). The low abundance of Escherichia-Shigella, Dubosiella, and Allobaculum, along with enrichment of Muribaculaceae_unclassified, Ralstonia, and Rikenellaceae_RC9_gut_group in the gut, suggested that YWPC ameliorated DOX-induced microbial dysbiosis. YWPC also influenced the levels of metabolites altered by DOX, resulting in lower arachidonic acid and linoleic acid metabolism and higher tryptophan metabolite levels (P<0.05 for all). Correlational studies indicated that YWPC alleviated DOX-induced inflammation and mitochondrial dysfunction by modulating the gut microbial community and its associated metabolites. Antibiotic treatment exacerbated cardiotoxicity in DOX-treated rats, and its effect on the gut microbiota partly abolished the anticardiotoxic effects of YWPC, suggesting that the microbiota is required for the cardioprotective role of YWPC. CONCLUSIONS: YWPC protected against DOX-induced cardiotoxicity in a gut microbiota-dependent manner. This supports the use of dietary polyphenols as a therapeutic approach for the treatment of cardiovascular diseases via microbiota regulation.

Construction of Persistent Luminescence-Plastic Antibody Hybrid Nanoprobe for In Vivo Recognition and Clearance of Pesticide Using Background-Free Nanobioimaging.

We prepared a specific adsorptive nanocarrier for pesticide due to its challenge to cleanup and low detoxification in the treatment after intake, whether intentional or by mistake. We modified the plastic antibody (molecularly imprinted polymer (MIP)) on the surface of persistent luminescence nanoparticle (La3Ga5GeO14: Cr3+, Zn2+, LGGO) as the specific adsorptive nanocarrier for toxic molecules and realized the nanocarrier was widely distributed for absorbing pesticide and real-time in vivo bioimaging. We used LGGO as the core and trichlorphon as the template to prepare the plastic antibody nanocarrier. After in vivo bioimaging and biodistribution of mice, LGGO@MIP could be distributed evenly in the gastrointestinal tract, circulated in the blood for a long time, and finally excreted to achieve the adsorption and removal of pesticide in the body. The LGGO@MIP nanocarrier prepared in this study opens a new way for the treatment of poisoning.

Clinical study of serum procalcitonin level in patients with myocardial infarction complicated by pulmonary infection.

This study determined the serum procalcitonin (PCT) levels in patients with myocardial infarction complicated by pulmonary infection and explore its clinical significance and diagnostic value. A total of 473 patients who were admitted to the Third Affiliated Hospital of Qiqihar Medical University from January 2016 to June 2017 were enrolled as research subjects. Patients were divided into four groups based on their symptom status in myocardial infarction and pulmonary infection. There were 109 patients in normal control group who did not experience symptoms of either myocardial infarction or pulmonary infection. Blood samples were collected from each patient, and PCT levels were measured. The data were analyzed. The serum PCT levels prior to treatment were compared with each other. The PCT levels in the myocardial infarction and the pulmonary infection group were all higher than that in the normal control group (0.040±0.015) (p<0.05). On the contrary, the serum PCT level in the myocardial infarction complicated by pulmonary infection group was higher than that in the normal control group (p<0.001). The serum PCT level after treatment was compared with that before treatment within the same group. The serum PCT levels in the three disease groups were comparable after treatment. The differences in PCT levels before and after treatment were all statistically significant within all three groups (p<0.05). A patient's serum PCT level was correlated with myocardial infarction complicated by pulmonary infection, which suggested it can be used as an important diagnostic marker for this complication. This finding has important clinical value for predicting and evaluating the complicated condition of myocardial infarction and pulmonary infection by providing a more accurate, sensitive, and specific method for early diagnosis of the disease.

[Study on anatomic measurement of oropharynx dimensions between OSAHS and the healthy adults].

OBJECTIVE: One was to study on anatomic measurement of oropharynx dimensions between OSAHS and healthy adults, the other was to determine the normal value range of the healthy adults oropharyngeal cavity. METHOD: Six anatomic measurement of oropharynx dimensions were were measured among 200 healthy adults and 93 adult patients with OSAHS,and were compared with that of healthy adults, and to determine the normal value range of healthy adults oropharyngeal cavity. RESULT: The oropharyngeal cavity size of OSAHS patients and healthy adults were significantly different, P <0. 01. CONCLUSION: Nearly all OSAHS patients have anatomic obstructive factors at oropharyngeal cavity, The normal valve range of the oropharynx size can help to judge the oropharyngeal obstruction of OSAHS patients, and to provide the standard date for the operation of UPPP.

[Study of pharyngeal anatomical diameter in patients with obstructive sleep apnea-hypopnea syndrome before and after uvulopalatopharyngoplasty].

OBJECTIVE: To explore the changes of oropharynx in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS) before and after long-term uvulopalatopharyngoplasty with uvula reserved completely. METHOD: Thirty-one patients with OSAHS were studied. The following indexes were measured before and after uvulopalatopharyngoplasty: length of uvula, width of uvula base, distance between two-side pillars (DBTP), distance between uvula and posterior pharyngeal wall(DBUP), length of soft palate, perimeter of neck and body mass index (BMI). RESULT: The postoperative length of uvula, width of uvula base, DBTP, DBUP changed significantly after uvulopalatopharyngoplasty( P <0.05). The postoperative length of soft palate was significantly less than that before uvulopalatopharyngoplasty( P <0.05). There was no significance difference in BMI and perimeter of neck between preoperative and postoperative patients( P >0.05). CONCLUSION: The uvulopalatopharyngoplasty with uvula reserved completely is an effective method to solve the airway constriction, especially the oropharynx constriction. Transverse diameter could be enlarged to the length of normal adults.

[Determination of isosorbide-5-nitrate in human plasma by reversed-phase high performance liquid chromatography].

The method was established to determine the level of isosorbide-5-nitrate in human plasma by reversed-phase high performance liquid chromatography (RP-HPLC). The sample preparation was carried by alkalizing the plasma sample followed by extraction with dichloromethane. The HPLC analysis was performed under the conditions as follows: a mixture of an aqueous buffer (pH adjusted to 7.8 by 0. 03 mol/L ammonia water) and acetonitrile (80: 20, v/v) as mobile phase, paracetamol as the internal standard, and the detection at 230 nm. The linear range was 20 - 1 000 microg/L using the ratio of peak areas; the detection limit was 12 microg/L; the average recovery was (97.11 +/- 2.45)% - (104.34 +/- 2.17)%, the intra-day relative standard deviations (RSDs) were less than 2.52%, and inter-day RSDs were less than 5.21%.

[Necessity of preservation of uvulain uvulopaloto-pharyngoplasty].

OBJECTIVE: To explore the necessity and feasibility of the modified uvulopalotopharyngoplasty (UPPP) with uvula reserved completely, and to improve the traditional UPPP. METHODS: Sixty patients with the obstructive sleep apnea-hypopnea syndrome (59 men, 1 women) were diagnosed by polysomnography. The patients were operated under general anesthesia and the uvula was preserved completely in UPPP. Cut the fat from the velopharyngeal space so as to enlarge the the oropharyngeal cavitity. RESULTS: Most of patients reported improvement of main symptoms. The sleeping patients' oxygen saturation was determined 8 days after operation, the oxygen saturation of the patients lying on the side is 90% or even more, and 87% or even more for the ones lying on the back. The judging criterion is that the AHI(apnea-hypopnea index) decrease to 50% of its original level, the validity ratio is 83% 6 months after operation. 2 weeks after operation, the completely preserved uvula began to contract. 3 months after operation, the uvula contracted to the normal length and the anatomical shape of the pharyngeal cavity became normal. This approach avoids velopalatal insufficiency. CONCLUSION: Completely preserving the uvula in the UPPP is feasible and imperative.