In recent years， the research method of Mendelian randomization based on genome-wide association studies has been widely used for etiological exploration in the medical field， which can effectively overcome the confounding biases and interference of reverse causalities in traditional observational researches with its unique advantages of the distributive randomness and timing priority of genetic variants. This article reviews the method of Mendelian randomization and its application in liver cancer， in order to provide new ideas for the research on causal association in liver cancer.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Operation duration has consistently been regarded as a important factor influencing the outcome of total knee arthroplasty(TKA).Prolonged operation time can give rise to an array of adverse events,ultimately leading to surgical failure,escalated healthcare expenses,and even jeopardizing patient survival.Numerous studies have demonstrated that prolonged operation time is linked with an augmented risk of postoperative complications.Recent investigations have revealed that extended operation duration can heighten the likelihood of postoperative pain,wound dehiscence,anemia and blood transfusion requirements,surgical site infection,sepsis,prolonged hospitalization and readmission rates;impact prosthetic longevity and patient survival rate.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Cerebral hemorrhage accounts for about 10%-15% of all strokes， and its pathogenesis is complex. Currently， the main clinical treatment is mainly medical symptomatic treatment， including the use of antihypertensive drugs， hypoglycemic drugs， and hemostatic drugs， and surgical treatment is required in some cases， but there is still a lack of effective treatment. In recent years， traditional Chinese medicine and proprietary Chinese medicine have been widely accepted for their stable efficacy， high safety， and low cost. Rhei Radix et Rhizoma is one of the most commonly used herbal medicines for the treatment of cerebral hemorrhage. This paper summarizes the relevant literature on the treatment of cerebral hemorrhage with Rhei Radix et Rhizoma and finds that its active ingredients are mainly anthraquinones， such as emodin， Rhei Radix et Rhizoma acid， and Rhei Radix et Rhizoma phenol. The herbal formulas are Da Chengqitang， Shengdi Dahuangtang， Liangxue Tongyufang， and Naoxueshu oral liquid. The effects involve protecting the blood-brain barrier， promoting hematoma absorption， reducing inflammation levels， decreasing lactic acid accumulation at the bleeding site， and increasing the expression of brain-derived neurotrophic factors. The pathways involved include aquaporin 4 （AQP4）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， Toll-like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB）， nuclear factor E₂-related factor 2 （Nrf2）， and Wnt3a/β-linked protein pathway. This paper summarizes the progress of clinical studies and animal experiments on the treatment of cerebral hemorrhage with active ingredients of Rhei Radix et Rhizoma and herbal compounds containing Rhei Radix et Rhizoma， so as to provide a reference for the treatment protocol of cerebral hemorrhage.

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological com-ponents of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the meta-bolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the in-flammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

Coronary artery diseases (CAD) have always been serious threats to human health. The measurement, constitutive modeling, and analysis of mechanical properties of the blood vessel wall can provide a tool for disease diagnosis, stent implantation, and artificial artery design. The vessel wall has both active and passive mechanical properties. The passive mechanical properties are mainly determined by elastic and collagen fibers, and the active mechanical properties are determined by the contraction of vascular smooth muscle cells (VSMC). Substantial studies have shown that, the two-layer model of the vessel wall can feature the mechanical properties well, and the circumferential, axial and radial strain and stress are of great significance in arterial wall mechanics. This study reviewed recent investigations of mechanical properties of the vessel wall. Challenges and opportunities in this area are discussed relevant to the clinical treatment of coronary artery diseases.
Biomechanical Phenomena ; Coronary Vessels ; Humans ; Models, Cardiovascular ; Myocytes, Smooth Muscle ; Stress, Mechanical

Long-term follow-up for end point is an extremely important and arduous task in large population-based cohort studies, which is also the key to the success of large cohort studies. Thus, the fundamental question of the achievements above is how to construct a large population- based cohort in a standardized way. The Chinese Preventive Medicine Association coordinated experienced researchers from Zhejiang Provincial Center for Disease Control and Prevention and other professional institutes to write up the group standard entitled Technical specification of long-term follow-up for end point in large population-based cohort study (T/CPMA 002-2019). The standard is drafted with principles of emphasizing the scientific, normative, applicability, and feasible nature. This group standard recommended the follow-up target population, time, content, methods, quality control, and indicators assessment. The standard aims to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence, to improve domestic scientific research level and the international influence, and to support decision-making and practice of disease prevention and control.

Objective: To compare the outcome of radiofrequency catheter ablation under local anesthesia/sedation (S) or general anesthesia(GA) in atrial fibrillation patients. Methods: Data of 498 patients with atrial fibrillation undergoing radiofrequency catheter ablation in our departmentfrom January 2014 to December 2015 were retrospectively analyzed. Two hundred and twenty patients assigned to the GA group, the other 278 patients to the S group. Patients were followed clinically every 3 months within one year after procedure. Immediate electrocardiogram was performed in patients with palpitation or choking sensation in chest. The end point of the study was recurrence of any atrial tachyarrhythmia lasting >30 seconds in device interrogation, 24-hour Holter monitoring or 12-lead electrocardiogram after a single procedure. After the ablation procedure, a blanking period of 3 months was allowed according to the guidelines. Procedure time, radiofrequency time, fluoroscopy time, the detection of paroxysmal supraventricular tachycardia, the success rate and the complications were compared between the two groups. Results: There was no difference in the baseline characteristics between the two groups, such as age, gender, BMI, complications, LVEF, LAD (all P>0.05). The duration of procedure ((117.8±51.7)minutes vs.(115.4±36.9)minutes, P=0.79), duration of fluoroscopy((12.5±11.2)minutes vs. (10.4±10.2)minutes, P=0.35), duration of radiofrequency((40.1±12.9)minutes vs. (48.6±44.3)minutes, P=0.48) were similar between the two groups (P>0.05). Compared with S group, discovery of the frequency of atrioventricular node reentrant tachycardia (AVNRT) was significantly lower in GA group (0 vs. 3.6%(10/278), P<0.01), but the difference disappeared with repeat electrophysiological examination when patients become conscious from GA(3.2%(7/220) vs. 3.6%(10/278), P=0.311). The difference of atrioventricular reentrant tachycardia (AVRT) was similar between the two groups(0.9%(2/220) vs. 0.7%(2/278), P=0.841). Compared with S group, reflection of vagus nerve was less in GA group (1.4%(3/220) vs. 8.6%(24/278), P=0.026). After following up of (356±92) days, freedom from atrial fibrillation/atrial flutter/atrial tachyarrhythmia was similar between the two groups(77.9%(162/208) vs. 79.9%(215/269), P=0.818). Conclusion General anesthesia is a promising method to atrial fibrillation ablation, in view of stable patient status and safety for the procedure. There is no difference in complications, recurrence of arrhythmia between the two groups, but detection rate of AVNRT is lower in GA group.