The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic. The pathogen responsible for this disease is a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It belongs to coronavirus family, a pathogen similar to SARS and Middle East respiratory syndrome (MERS), and manifests strong infectivity and pathogenicity to progress into severe pneumonia. Till now, there is no specific therapeutic drug targeting against this virus. With the rapid spread and deterioration of the epidemic situation, vaccination has become an urgent need. This review introduces the immune defense mechanism of human body against coronavirus briefly, set forth the key viral spike protein for coronavirus vaccine development, and then summarize the recent advances/progresses and potential challenges in safety and efficacy of vaccine development for SARS-CoV-2.

Hypertension is a common complication of patient with chronic kidney diseases (CKD), and an important risk factor for the development of CKD. Therefore, controlling hypertension is one of the keys to block the progression of CKD. Since the release of 2012 edition "KDIGO clinical practice guideline for management of blood pressure (BP) in patient with chronic kidney disease", new clinical trials has been constantly emerging. Based on this, KDIGO has released a 2021 updated guide. The new guideline covers standardized BP measurements, lifestyle interventions without dialysis, BP management and medication recommendations, and for special CKD population, including kidney transplant patients and children, the corresponding BP management and medication recommendations are recommended. Compared with the previous guideline, standardized BP measurements in the clinic is a new addition. Furthermore, one of the most noteworthy is that the target BP of CKD patients without dialysis is systolic pressure <120 mmHg, which further demonstrates the benefits of intensive hypotensive therapy, but the recommendation level is only 2B. This article launches interpretation for the above several aspects in this new consensus.

Male breast cancer (MBC) is a rare disease for which almost no prospective studies have focused on its diagnosis and treatment. MBC is more likely to be positive for hormone receptor while the ratio of triple negative and human epidermal growth factor receptor 2 (HER2) positive is very low. Most men have undergone radical mastectomy and modified radical mastectomy after diagnosis of breast cancer during past decades and sentinel lymph node biopsy has been gradually used in recent years. The indications of postoperative adjuvant radiotherapy refer to female breast cancer (FBC). Tamoxifen is the first choice of adjuvant endocrine therapy for MBC and chemotherapy can also improve MBC patients' prognosis. Anti-HER2 therapy is recommended for patients with high risks, though there is no definite evidence for its application. Data for the use of new drugs in MBC are lacking,whereas it may be a reasonable approach for metastatic MBC. In general, the overall prognosis of MBC is worse than FBC, but a few studies showed that MBC and FBC had similar survival rates after adjustment for demographic characteristics, disease stage, and treatment. Most of published articles are retrospective studies including small cohorts of MBC patients, which have been reviewed in this article. The review summarizes current data on the epidemiology of MBC, pathological and clinical characteristics, prognosis and treatment, and data published in our country during the past decade.

Objective To explore the correlation between the components of immune cell subsets in tumor microenvironment of colorectal cancer and the progression of colorectal cancer disease, and to explore the differential regulatory effects of different CD4⁺ T cell subsets on the progression of colorectal cancer. Methods Using the single cell transcriptome sequencing data of colorectal cancer patients in GEO database, CIBERSORTx algorithm was used to assess the immune cell subsets score from the transcriptome sequencing data of colorectal cancer patients in The Cancer Genome Atlas (TCGA) database. The obtained immune cell subsets scores were combined with clinical data to analyze the correlation between metastasis and prognosis. Subsets related genes were calculated based on immune cell subsets scores, and functional enrichment scores performed by using DAVID analysis platform were used to compare the different regulatory function of immune cell subsets in colorectal cancer. Lasso algorithm/regression was used to screen immune cell subsets and Cox analysis was used to construct a risk prognosis model. Results The abundance of CD4-TCF7 was significantly increased in metastatic patients of colorectal cancer compared with non-metastatic patients (P<0.01), the abundance of CD4-CTLA4, CD8-LEF1, PLASMAB-IgG, and MACRO-IL1B decreased in metastatic patients(P<0.05). In the survival analysis, 15 of the 38 immune cell subsets were significantly associated with over survival based on the AUC curve (P<0.05). After analyzing the regulatory functions of CD4⁺ T cell subsets in colorectal cancer cells, we find the CD4-GNLY,CD4-ANXA1 and CD4-CXCR6 with more powerful regulation on the colorectal cancer angiogenesis related pathways compared to others, CD4-IL23R preferentially enriched in energy metabolism related pathways, CD4-GZMK compared to other subsets uniquely enriched in hypoxia stress related pathways, CD4-ANXA1, CD4-TCF7 and CD4-CTLA4 compared to other subsets preferentially enriched in the cell proliferation related pathways, CD4-ANXA1, CD4-TCF7, CD4-CTLA4, and CD4-CXCL13 preferentially enriched in the pathways of cell adhesion and cell migration compared to other subsets. Conclusions There are differences in the regulation of colorectal cancer cell function by immune cell subsets. The composition of immune cell subsets in colorectal cancer immune microenvironment affects the survival and prognosis of patients.

Patients with polycystic ovary syndrome (PCOS) have impaired follicular development and maturation. Ovarian granulosa cells play an important regulatory role in the initiation, growth and development of primordial follicles, in which the mitochondria of granulosa cells are involved in the regulation of cell cycle, metabolism, and signal transduction, and provide energy support for oocyte meiosis, fertilization, and up to early embryonic development through energy metabolic pathways. Studying the mitochondrial function of granulosa cells is one of the best non-invasive methods to study the pathological mechanisms in PCOS patients and to evaluate oocyte quality and embryonic developmental potential. A large number of evidences have shown that PCOS is associated with mitochondrial dysfunction in ovarian granulosa cells by mechanisms including altered mitochondrial DNA(mtDNA) copy number and mutations in the mtDNA gene. Some studies have explored the improvement of mitochondrial function in PCOS granulosa cells to improve the impaired follicular development and maturation in PCOS. Therefore, the relevant research progress in recent years have been reviewed in present paper about mitochondrial dysfunction in PCOS granulosa cells, for exploring the mechanism of mitochondrial dysfunction in PCOS granulosa cells, and the ways and methods of improvement.

Renal cancer, as a common urinary system tumor, its occurrence and development involve a series of genetic events including changes in the level of epigenetics. Its etiology is complex and highly heterogeneous. Renal cell carcinoma is the chief type of kidney cancer, while the clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell carcinoma.Recently, exon sequencing revealed that the mutation rate of polybromo-1 (PBRM1) gene in CCRCC can be as high as 40%. BAF180 protein, which is encoded by PBRM1 gene, is one of the specific subunits of the chromatin remodeling complex PBAF (polybromo-associated BRG1-associated factor), a type of SWItch/sucrose nonfermentable (SWI/SNF) complexes. It not only participates in the formation of PBAF complex, but also mediates the binding of the complex to specific DNA regions, thus affecting the gene transcription and translation processes, so indicates that PBRM1 plays an important role in the occurrence and development of renal cell carcinoma. The research status, molecular mechanism and clinical transformation of the major cancer related genes in CCRCC,especially the tumor suppressor gene PBRM1, were reviewed in present paper, in order to provide reference for the basic and clinical transformation research of SWI/SNF in renal cell carcinoma and other related tumors.

Objective To construct a complete chemical culture system based on small molecule compounds and study its role in promoting the reversal of senescence of mesenchymal stem cells (MSCs). Methods MSCs were transmitted to 20 generations (P20) continuously. The model of the replicative aging cells (P20-MSCs) was established, then divided into aging model group and small molecule treatment group, and the fifth generation of umbilical cord MSCs (P5-MSCs) was set as control group. The aging model group and control group were cultured in the whole chemical culture system for 7 days, and small molecular treatment group was cultured in the whole chemical culture system containing valproate and Repsox for 7 days. β-galactosidase staining was used to detect cell senescence, immunofluorescence staining was used to detect the protein expression levels of Ki-67, OCT4, Nanog,P16, and P21; RT-qPCR to detect the mRNA expression levels of OCT4, Nanog, P16 and P21. Flow cytometry was used to detect the anti-apoptotic ability of cells. Migration experiments, Transwell invasion experiments and clone formation experiments to detect small molecules effects on migration, invasion and self-cloning functions of senescent MSCs. Results The cell bodies of senescent mesenchymal stem cells were enlarged and presented dendritic processes. After incubation in the full chemical culture system, the cells return to a spindle shape or irregular triangle similar to young MSCs. SA-β-gal staining results showed that compared with aging model group, the positive rate of galactosidase in cells treated with small molecules was significantly reduced, and the difference was statistically significant (45.00%±1.23% vs. 84.80%±1.50%, P<0.001). The immunofluorescence results showed that compared with aging model group, the proportion of positive cells expressing Ki-67, OCT4 and Nanog increased (Ki-67: 89.00%±1.50%vs. 25.00%±2.00%, P<0.001; OCT4: 88.40%±0.80% vs. 25.40%±1.20%, P<0.001; Nanog: 76.30%±1.70% vs. 10.50%±0.60%,P<0.001), the proportion of positive cells expressing P16, P21 decreased (P16: 64.00%±3.20% vs. 98.00%±1.50%, P<0.05; P21:45.00%±1.10% vs. 82.00%±2.00%, P<0.05) in small molecule treatment group. RT-qPCR results showed that compared with aging model group, small molecule compounds could up-regulate the mRNA expression levels of OCT4 and Nanog in aging MSCs(P<0.001), down-regulate the mRNA expression levels of P16 and P21 (P<0.05). Compared with aging model group, the abilities of anti-apoptosis (21.60%±1.20% vs. 31.40%±0.80%), migration (49.30%±3.30% vs. 30.60%±4.40%), invasion [(90.00±12.00)cells vs. (34.00±9.00) cells] and self-cloning abilities [(144.00±10.00) cells vs. (68.00±7.00) cells] in small molecule treatment group were significantly increased, and the differences were statistically significant (P<0.05 or P<0.01). Conclusion The constructed small molecule full chemical culture system can inhibit and partially reverse the aging process of long-term cultured MSCs in vitro.

Trauma-induced hypercoagulopathy is a hypercoagulable phenotype of trauma-induced coagulopathy (TIC) characterized by vascular endothelial injury, excessive release of procoagulants, hyperfibrinogenemia, platelet hyperactivity, anticoagulant pathways impairment and fibrinolysis shutdown. Recent studies have found that the incidence, mortality and disability rate of trauma-induced hypercoagulopathy increased significantly with the severity of trauma. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and China Medical Education Association Professional Committee of Thrombosis, Hemostasis and Critical Care Medicine jointly formulated Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy published in Military Medical Research in April, 2021. In present paper, the main contents of the consensus were interpreted from the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.

Objective To explore the effect and mechanism of ivermectin (Ive) in enhancing oxaliplatin (L-OHP) against colon cancer HCT116/L-OHP cells. Methods In vitro establishment of colon cancer HCT116/L-OHP cells model with L-OHP low-concentration gradient increasing and low-concentration L-OHP (4 μmol/L) continuous culture. Set control group, L-OHP 25 μmol/L group, and L-OHP 25 μmol/L combined with 1, 2, 4, and 8 μmol/L Ive groups, and used MTT assay to detect cell viability. Set control group, L-OHP 25 μmol/L group, L-OHP+Ive 2 μmol/L group, and L-OHP+Ive 4 μmol/L group, and use cloning experiment to detect cell clone formation ability and flow cytometry apoptosis and cell cycle distribution, Western blotting was used to detect the expression levels of nuclear factor κB p65 (NF-κB p65), pregnane X receptor (PXR) and P-glycoprotein (P-gp). The colon cancer HCT116/L-OHP cells model with high expression of NF-κB p65 was constructed by LPS induction(setting control group, LPS group, LPS+L-OHP group, LPS+L-OHP+Ive 2 μmol/L group and LPS+L-OHP+Ive 4 μmol/L group), using lentiviral transfection to construct a colon cancer HCT116/L-OHP cells model with high PXR expression (setting control group, Ad-PXR group, Ad-PXR+L-OHP group, Ad-PXR+L-OHP+Ive 2 μmol/L group and Ad-PXR+L-OHP+Ive 4 μmol/L group), Western blotting was used to detect the expressions of NF-κB p65, PXR and P-gp protein levels. Twenty nude mice were injected subcutaneously with HCT116/L-OHP cells to establish a colon cancer drug-resistant cell transplantation tumor model and were divided into control group, L-OHP group, Ive group and Ive+L-OHP group, 5 mice in each group, and the tumor volume was calculated, the tumor weight was measured, and use immunohistochemistry to detect the expression of NF-κB p65, PXR and P-gp protein in the tumor tissues. Results Ive can potentiate L-OHP to inhibit colon cancer HCT116/L-OHP cells proliferation and clone formation (P<0.05), and promote colon cancer HCT116/L-OHP cells apoptosis and cell cycle S phase block (P<0.05).Western blotting showed that, in colon cancer HCT116/L-OHP cells, the expression levels of NF-κB p65, PXR and P-gp proteins in L-OHP+Ive 2 μmol/L group and L-OHP+Ive 4 μmol/L group were lower than those in control group, those in L-OHP+Ive 4 μmol/L group were lower than in L-OHP group (P<0.05). In the HCT116/L-OHP cells model with high NF-κB p65 expression, the expression levels of the NF-κB p65, PXR and P-gp protein in LPS+L-OHP+Ive 2 μmol/L group and the LPS+L-OHP+Ive 4 μmol/L group were lower than those in LPS group (P<0.05). In HCT116/L-OHP cells model with high PXR expression, the expression levels of the NF-κB p65, PXR and P-gp protein in Ad-PXR+L-OHP+Ive 2 μmol/L group and Ad-PXR+L-OHP+Ive 4 μmol/L group were lower than those in Ad-PXR group and Ad-PXR+L-OHP group, those in Ad-PXR+L-OHP+Ive 4 μmol/L group were lower than those in Ad-PXR+L-OHP+Ive 2 μmol/L group (P<0.05). In vivo experimental results showed that Ive can cooperate with L-OHP to inhibit the growth of HCT116/L-OHP cells xenograft tumors (P<0.05). The results of immunohistochemistry showed that the relative expression density of NF-κB p65, PXR and P-gp protein in the tumor tissues of Ive group, L-OHP group and Ive+L-OHP group was lower than that of control group. The L-OHP group and Ive+L-OHP group were lower than those in Ive group, and the Ive+L-OHP group were lower than those in L-OHP group (P<0.05). Conclusion Ive can enhance the effect of L-OHP against colon cancer HCT116/L-OHP cells, and its potential mechanism of action is to reduce the mediating effect of P-gp protein on L-OHP resistance by inhibiting the expression of NF-κB p65/PXR signaling pathway.

Atherosclerosis is the basis of a variety of cardiovascular and cerebrovascular diseases, which may further lead to myocardial infarction, cerebral infarction and other life-threatening diseases. At present, the main therapy for atherosclerosis is to control the levels of cholesterol and low density lipoprotein. High density lipoprotein (HDL) is one of the main protective factors of cardiovascular disease. In recent years, more and more studies have revealed the relationship among atherosclerosis, HDL and immune system. The inhibitory effect of HDL on immuno-inflammatory responses could be one of the targets for treatment of atherosclerosis. The mechanism of HDL involved in the regulation of immuno-inflammatory responses of atherosclerosis was summarized in present paper for providing a new idea on treatment of atherosclerosis