eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

ObjectiveTo investigate the application of endoscopy in obtaining the great saphenous vein （GSV） during coronary artery bypass grafting （CABG） and explore the learning curve， with a particular focus on common challenges encountered during the learning process and their impact on early clinical outcomes. MethodsA retrospective analysis was conducted on clinical data from 83 patients who underwent off-pump CABG with endoscopic GSV harvesting at the First Affiliated Hospital of Zhengzhou University from July 2013 to April 2014. Patients were categorized into four groups based on the chronological order of their hospitalization： Group A （novice group， n=20）， Group B （proficient group， n=20）， Group C （progressive group， n=20）， and Group D （mature group， n=23）. Differences in perioperative and midterm follow-up outcomes among the groups were analyzed to determine the learning curve period. ResultsThe study population had a mean age of （60.22±8.06） years and a mean body weight of （69.77±11.66） kg. Comorbidities included hypertension （24 cases）， diabetes （26 cases）， and subacute cerebral infarction （14 cases）. The novice group exhibited significantly shorter GSV length-to-harvest time ratio relative to the other three groups （P<0.001） and a significantly higher incidence of main vein damage （P=0.006）. However， there was no statistically significant difference in graft patency at the 1-year follow-up. ConclusionThorough and reliable technical training in endoscopic GSV harvesting is essential to minimize vascular injury caused by novice operators. Approximately 20 cases of hands-on experience and a careful self-analysis of procedural challenges are likely required to achieve proficiency in GSV harvesting.

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

Objective To explore some reasonable ways of anticoagulation for pregnant women with mechanical prosthetic valves.Methods Retrospective analysis was conducted for 27 women with mechanical prosthetic valves who have born children after their cardiac surgeries.Numbers of pregnancies,ages,ways of anticoagulation during pregnancy,ways of anticoagulation before pregnancy,valve thrombosis events,thromboembolism events,bleeding events,outcomes of pregnancy and ways of delivery were collected and studied.Comparing adverse events and outcomes of different ways of anticoagulation which those women used during their pregnancies.Results 27 women with mechanical prosthetic valves experienced 41 pregnancies,and bore 28 children.24 pregnancies used oral low does warfarin(＜ 5 mg/day) to anticoagulate,2 minor bleeding events and 10 early abortion occurred,no abnormal neonates were found,14 healthy neonates were born.6 pregnancies used low-molecularweight heparin to anticoagnlate from 6th week to 12th week,they used oral warfarin to anticoagulate in rest weeks of pregnancy.1 late abortion occurred,1 fetus with hydrocephalus was found at 20th week,then induced labour was conducted.4 healthy neonates were born.11 pregnancies used low-molecular-weight heparin to anticoagulate until delivery,1 early abortion,2 minor bleeding events and 1 valve thrombosis occurred.10 neonates were born,and 1 of them has hypoxic-ischemic encephalopathy,the other 9 neonates were healthy.Conclusion For pregnant women with mechanical prosthetic valves,using oral low does warfarin throughout pregnancy is a reasonable way of anicoagnlation with low risk of maternal and fetal adverse events except high risk of abortion.Low-molecular-weight heparin is hopeful anticoagulant agent for pregnant women with mechanical prosthetic valves,but more studies about its safety and effectiveness should be conducted.

Breast cancer is a common malignancy for women.Since 21st century,the incidence of breast cancer has been increasing all over the world and ranked first among all the female malignancies in the developed regions of Europe and America.With the increase of the morbidity of breast cancer,experts have paid more and more attention to the study of the susceptibility genes of breast cancer.The research of breast cancer susceptibility genes will help to understand the causes of breast cancer,find out available preventive measures,diagnose and treat patients with breast cancer in the early period.Specially,susceptibility genes also play an important role in the screening,early diagnosis and preventive treatment for those with family history of breast cancer or the carriers of the susceptibility genes mutation.The susceptibility genes of breast cancer include the high-penetrance susceptibility genes,the moderate-penetrance susceptibility genes,and the low-penetrance susceptibility genes.Nowadays,there are plenty of studies of BRCA1 and BRCA2,two of the high-penetrance susceptibility genes of breast cancer.The review summarizes the current study progress of the common susceptibility genes of breast cancer.

The transient receptor potential (TRP) family is a superfamily of cation channels located on the cell membrane. Transient receptor potential melastatin (TRPM) 7, a member of the TRPM subgroup of TRP channels, and was the most representative biofunctional membrane protein. It conducts calcium and monovalent cations to depolarize cells and increase intracellular calcium. It is capable of phosphorylating TRPM7 and other substrates. TRPM7 can mediate sensory transmission, regulate cellular Ca2+ and Mg2+ homeostasis and affect embryonic development. Abnormal expression and/or activity of the TRPM7 channel kinase is involved in a variety of diseases, particularly the development and progression of cancer. TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration.
Calcium ; Cell Differentiation ; Humans ; Neoplasms ; Protein-Serine-Threonine Kinases ; TRPM Cation Channels

OBJECTIVE: To summarize the outcome of tricuspid valve replacement.
 METHODS: A total of 28 patients (15 males and 13 females) underwent tricuspid valve replacement from March 2000 to February 2015 in the First Affiliated Hospital of Zhengzhou University were recruited. Among them, 16 patients were Ebstein's anomaly, 7 had rheumatic valve heart disease, 3 and 2 suffered from infective endocarditis and degenerative tricuspid lesions, respectively.
 RESULTS: One patient died of multiple organ failure. Four patients were implanted permanent cardiac pacemaker because of third degree atrioventricular block occurring in the 5th day (2 patients) and in the 9th day (2 patients) after the operation, respectively. Twenty-seven patients were followed up from 1 month to 15 years. The prosthetic valves and permanent pacemakers worked well.
 CONCLUSION Third degree of atrioventricular block, mostly appearing in early postoperative period, is the most common and severe complication of tricuspid valve replacement. The key point for prevention of damage is to accurately identify the anatomical relationship among the tricuspid valve, atrioventricular node, and conduction bundle.
Ebstein Anomaly ; surgery ; Female ; Heart Valve Diseases ; surgery ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Pacemaker, Artificial ; Rheumatic Heart Disease ; surgery ; Tricuspid Valve ; pathology ; surgery

Atherosclerosis is a leading cause of death worldwide and is characterized by lipid-laden foam cell formation. Recently, pycnogenol (PYC) has drawn much attention because of its prominent effect on cardiovascular disease (CVD). However, its protective effect against atherosclerosis and the underlying mechanism remains undefined. Here PYC treatment reduced areas of plaque and lipid deposition in atherosclerotic mice, concomitant with decreases in total cholesterol and triglyceride levels and increases in HDL cholesterol levels, indicating a potential antiatherosclerotic effect of PYC through the regulation of lipid levels. Additionally, PYC preconditioning markedly decreased foam cell formation and lipid accumulation in lipopolysaccharide (LPS)-stimulated human THP-1 monocytes. A mechanistic analysis indicated that PYC decreased the lipid-related protein expression of adipose differentiation-related protein (ADRP) and adipocyte lipid-binding protein (ALBP/aP2) in a dose-dependent manner. Further analysis confirmed that PYC attenuated LPS-induced lipid droplet formation via ADRP and ALBP expression through the Toll-like receptor 4 (TLR4) and nuclear factor-kappaB (NF-kappaB) pathway, because pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-kappaB (PDTC) strikingly mitigated the LPS-induced increase in ADRP and ALBP. Together, our results provide insight into the ability of PYC to attenuate bacterial infection-triggered pathological processes associated with atherosclerosis. Thus PYC may be a potential lead compound for the future development of antiatherosclerotic CVD therapy.
Animals ; Anti-Inflammatory Agents/*therapeutic use ; Atherosclerosis/*drug therapy/immunology/metabolism/pathology ; Cell Line ; Flavonoids/*therapeutic use ; Foam Cells/drug effects/immunology/pathology ; Humans ; Lipid Metabolism/*drug effects ; Male ; Mice ; NF-kappa B/*immunology ; Signal Transduction/drug effects ; Toll-Like Receptor 4/*immunology

Objective: To investigate the correlation between eukaryotic translation initiation factor 3, subunit A (eIF3a) and human epididymis protein 4 (HE4) expression and ovarian cancer. Methods: RT-PCR or immunohistochemistry was used to examine eIF3a and HE4 mRNA or protein expression in ovarian tissues from patients with ovarian cancer (n=181) or benign ovariantumors, or from the healthy women. Results: hTere were signiifcant differences in mRNA and protein expression of eIF3a and HE4 among normal ovarian tissues, benign ovarian tumor tissues, and ovarian cancer tissues (P<0.05). hTere were signiifcant differences in mRNA expression of eIF3a and HE4 between the normal tissues and the ovarian cancer tissues, or between the benign ovarian tumor tissues and the normal tissues (P<0.001). hTe mRNA expression of eIF3a in the normal ovarian tissues was signiifcantly higher than that in the benign ovarian tumor tissues or that in the ovarian cancer tissues. hTe mRNA expression of HE4 was gradually increased from the normal ovarian tissues, the benign ovarian tumor tissues to the ovarian cancer tissues. hTe mRNA expression of HE4 in the ovarian cancer tissues was signiifcantly higher than that in the benign ovarian tumor tissues (P<0.001). Positive expression rates for eIF3a or HE4 protein in normal, benign tumor, and cancer tissues were 0, 66.7%, and 81.0% or 0, 27.8%, and 56.2%, respectively. hTere were signiifcant differences in positive expression rates of eIF3a protein and HE4 protein between the ovarian tumor tissues and benign ovarian tumor tissues, between the ovarian cancer tissues and the normal ovarian tissues, or between the benign ovarian tumor tissues and the normal ovarian tissues (P<0.001). hTe eIF3a protein expression was positively correlated with HE4 protein expression (r=0.575,P<0.05). Conclusion: The expressions of eIF3a and HE4 are associated with ovarian cancer, and extracellular regulated protein kinases may play a role in the interaction between eIF3a and HE4.

In kidney, the role of cell proliferation, differentiation, apoptosis, inflammatory mediators and cytokines expression is closely related with cell signaling pathways, including tyrosine kinase pathway, transforming growth factor-beta/Smad pathway, Rho/Rho-associated coiled-coil forming protein kinase pathway, phosphoinositol pathway, cyclic nucleotide pathway, nuclear factor kappaB pathway and so on. Some Chinese herbs and their extracts, such as rhubarb and triptolide, as well as some Chinese herbal prescriptions, such as astragalus-angelica mixture and Chailing decoction, not only could ameliorate proliferation, differentiation and apoptosis of renal cell by regulating cell signaling pathways, but also could control target gene transcription, expression and its biological effects through inhibiting the phosphorylation of key signaling molecules.
Animals ; Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Kidney ; cytology ; drug effects ; metabolism ; Signal Transduction ; drug effects