Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization (MR) method. Methods The genome-wide association study (GWAS) data on coffee intake (exposure) and prostate cancer (outcome) were obtained from two independent data sets in UK Biobank. The inverse variance weighted method (IVW), weighted median estimator method (WME), and MR-Egger method were used for MR analyses. The OR value and 95%CI were used to represent the association between coffee intake and prostate cancer. In addition, the MR-Egger method was performed for pleiotropic and heterogeneity tests, and the leave-one-out method was used for sensitivity analysis. Results A total of 38 SNP were selected as instrumental variables. The IVW method showed that coffee intake might reduce the risk of prostate cancer (OR=0.994; 95%CI: 0.990-0.999; P=0.009). The WME method obtained the same conclusions (OR=0.991; 95%CI: 0.985-0.999; P=0.018), but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer (OR=0.992; 95%CI: 0.983-1.000; P=0.084). The MR-Egger method showed no pleiotropy (intercept=4.2E-5; P=0.581) or heterogeneity (Q=27.20; P=0.854) among the instrumental variables. The sensitivity analysis indicated that the conclusion was robust. Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.

OBJECTIVE To explore the pharmacodynamic related substances and mechanism of Weining San(WNS) against gastric ulcer(GU) according to fingerprint and network pharmacology. METHODS Twelve batches of WNS fingerprints were established by HPLC, and methodological investigation was carried out. Combined with reference substances, characteristic peaks were identified, pharmacodynamic related substances were screened, and network pharmacological analysis was carried out. Using TCMIP and Swiss Target Prediction database to retrieve component targets; Using OMIM, GeneCards and Drugbank databases to retrieve GU disease targets, taking the intersection targets of components and diseases, using String database to construct protein-protein interaction network diagram, and analyzing topological parameters; Using Cytoscape 3.8.2 software to construct "component-disease-target" network diagram; GO and KEGG enrichment analysis of intersection targets were carried out by Metascape website. Then the alcoholic GU mouse model was established by intragastric administration of absolute ethanol to verify the results of network pharmacology prediction. RESUITS　The precision, stability and repeatability of HPLC fingerprint method were good. By comparison and comprehensive analysis of control substances, notoginsenoside R1, ginsenoside Rg1, militarine, ginsenoside Rb1, schisandrin, schisandrol B, deoxyschizandrin and schisantherin A were identified as pharmacodynamic related substances in WNS, which may play their role by regulating core targets such as AKT1, IL-6, STAT3, TNF, IL1B and key signal pathways such as PI3K-Akt and JAK-STAT. The gastric ulcer index, ulcer inhibition rate and HE staining showed that WNS could improve gastric mucosal injury in GU mice. The results of ELISA, WST-1 and TBA showed that WNS could decrease the levels of TNF-α, IL-6, IL-1β and MDA, and increase the levels of SOD and PGE2, suggesting that the anti-GU effect of WNS was related to the inhibition of inflammatory reaction and oxidative stress mechanism, which further verified the prediction of network pharmacology. CONCLUSION This study combines fingerprint analysis, network pharmacology, and animal experimental validation to explore the pharmacodynamic related substances and mechanisms of WNS anti-GU efficacy, providing reference for quality control and clinical research of WNS.

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

Objective:To investigate the clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients who underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis in Xinjiang Uiger Municipal People′s Hospital from October 2019 to July 2021 were collected. There were 3 males and 4 females, aged (43±12)years. Observation indicators: (1) surgical situations; (2) complications; (3) follow-up. Mea-surement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 7 patients underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis successfully, without conversion to laparotomy and laparoscopic surgery. None of the 7 patients underwent intraoperative blood transfusion and the operation time, volume of intraoperative blood loss, time to postoperative first and flatus, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, time to postoperative urethral catheter removal, duration of postoperative hospital stay of 7 patients was (225±45)minutes, 100(range, 50-200)mL, (1.9±0.7)days, (4.2±1.2)days, (7±4)days, (2.9±0.8)days, (7±4)days, respectively. (2) Complications. None of the 7 patients had postoperative complications such as bile leakage, abdominal hemorrhage, incision infection, hydatid cavity infection, secondary operation, intestinal obstruction, pulmonary infection and deep venous thrombosis of lower limbs. (3) Follow-up. All 7 patients were followed up for 7 (range, 3-12) months. None of the 7 patients had recurrence of hepatic echinococcosis or peritoneal implantation and incision implantation, and all patients survived during follow-up.Conclusion:da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis is safe and feasible.

Objective To investigate the effects of lncRNA SBF2-AS1 on the proliferation and invasion of hepatoma cells by regulating the miR-372-3p/CDK6 pathway. Methods Bel7402 and SK-hep1 cells were selected as research objects. The expression levels of SBF2-AS1, miR-372-3p, and CDK6 were up- or down-regulated according to different experimental stages, while the expression levels of miR-372-3p and CDK6 in cells were detected by real-time fluorescence quantitative PCR and Western blot. Dual luciferase reporter assay verified the targeting relationships between SBF2-AS1 and miR-372-3p as well as miR-372-3p and CDK6, respectively. CCK-8, colony formation assay, Transwell, cell cycle assay, and flow cytometry were used to analyze cell proliferation, colony formation, migration/invasion ability, cell cycle activity, and apoptosis. Results SBF2-AS1 was highly expressed in hepatocellular carcinoma cells (P<0.05). SBF2-AS1 knockdown resulted in decreased proliferation and invasion of Bel7402 and SK-hep1 cells (P<0.05). After miR-372-3p knockdown, the proliferation capacity and invasion number of Bel7402 cells were significantly increased. However, the above results were reversed after SBF2-AS1 knockdown (P<0.05). In addition, miR-372-3p targeted CDK6 and inhibited its expression, although over-expressing SFB2-AS1 could reverse the above results (P<0.05). Over-expressing CDK6 could reverse the inhibition of over-expressing miR-372-3p on the proliferation and invasion of Bel7402 cells. Conclusion LncRNA SBF2-AS1 can positively regulate the expression of CDK6 through miR-372-3p. It can also influence the distribution of cell cycle and affect the proliferation and invasion abilities of hepatocellular carcinoma cells.

Objective:To evaluate the specialty of the clinical features, treatment procedure, clinical outcome, and prognosis in the patients with "sandwich" atlantoaxial dislocation (AAD).Methods:From 2008 to 2018, 160 cases with "sandwich" AAD were retrospectively selected from the case series of AAD in Peking University Third Hospital. The case series had 80 males and 80 females. The mean age at the initial visit was 35.5±14.6 years (range, 5-77). The clinical courses, treatment methodology and prognosis were reviewed. And the surgical approach, posterior fixation segment and the recovery of neurological function were mainly summarized. The atlantodental interval (ADI), the distance by which the odontoid exceeded the Chamberlain line and the cervical-medullary angle were analyzed.Results:The most common symptoms included weakness or numbness of the limbs (67.5%, 108/160), unstable gait (30%, 48/160) and vertigo (20%, 32/160). Among all, 130 cases (81.3%, 130/160) had myelopathy, with the Japanese Orthopaedic Association (JOA) scores from 4 to 16 (mean JOA scores 13.5±2.5). Cranial neuropathy was involved in 20 cases (12.5%). Radiological findings showed brainstem and/or cervical-medullar in 130 cases (81.3%), syringomyelia in 37 cases (23.1%) and Chiari malformation in 30 cases (18.8%). Computed tomography angiography (CTA) was performed in 90 cases, which showed vertebral artery anomalies in 55 cases (61.0%) and excessive medialized internal carotid artery in 5 cases (5.6%). All cases had no spinal cord or vertebral artery injury. The surgery included posterior occipito-cervical fusion (reducible dislocation, 145 cases), and transoral release followed by posterior fusion (irreducible dislocation, 15 cases). Fifty-seven cases were treated using alternative fixation technique. The average follow-up time was 50.5±22.4 months (range, 24 to 120 months). All of 152 cases (95.0%) achieved solid atlantoaxial fusion; there was no obvious osseous fusion formation on postoperative images in 6 cases (3.8%), but no atlantoaxial instability was found on dynamic radiographs; screw loosening happened in 2 patients (1.2%). Nine patients (5.6%) suffered complications, including 4 cases with recurrent dislocation, 2 screw loosening, 2 cases with bulbar paralysis and 1 wound infection. The mean postoperative JOA was 15.1±1.8 (range, 5-17), and the mean neurological improvement rate was 42.9%±33.3% in the patients with myelopathy.Conclusion:"Sandwich" AAD, a subgroup of AAD, has unique clinical features: earlier onset age and more severe myelopathy. The incidence of bone and vascular malformation is higher. So alternative surgical plan and hybrid fixation should be prepared for this subgroup of AAD.

Objective:To investigate the association between hepatic echinococcus granulosus infection and necrosis with gene polymorphism of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α), and to identify the related factors at the gene level.Methods:A total of 106 patients with hepatic echinococcosis who underwent surgical treatment in the department of hepatobiliary surgery, People′s Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2020 were selected. Patients with necrosis caused by hepatic echinococcus granulosus infection were selected as the observation group, and patients without necrosis caused by hepatic echinococcus granulosus infection were selected as the control group, with 53 cases in each group. The serum levels of IL-10 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-10 (-592, -1082) and TNF-α (rsl800630) were detected by polymerase chain reaction (PCR). The levels of IL-10 and TNF-α and their gene polymorphisms were analyzed.Results:The levels of serum IL-10 and TNF-α in the observation group were significantly higher than those in the control group (all P<0.05); There was significant difference in genotype and allele frequency of IL-10 (-592, -1082) and TNF-α (rsl800630) (all P<0.05). The serum IL-10 level of CC genotype patients with IL-10 gene -592C/A locus in the observation group was higher than that of CA+ AA genotype patients, with statistically significant difference ( P<0.05). The serum IL-10 level in patients with TT genotype at -1082T>A of IL-10 gene in the observation group was higher than that in patients with TA+ AA genotype, with statistically significant difference ( P<0.05). The serum TNF-α level in patients with CC genotype at rsl800630C/A locus of TNF-α gene in the observation group was higher than that in patients with CA+ AA genotype, with statistically significant difference ( P<0.05). Conclusions:The changes of IL-10 (-592, -1082) and TNF-α (rsl800630) gene polymorphisms may be associated with hepatic echinococcus granulosus infection and necrosis.

Objective:To validate the performance of cardiovascular risk prediction models based on the Sweden National Diabetes Register (NDR) and Diabetes Lifetime-perspective prediction (DIAL) model for assessing risks of 5-year and 10-year cardiovascular disease (CVD) among Chinese patients with type 2 diabetes.Methods:Based on the Chinese Electronic Health Records Research in Yinzhou study, 83 503 patients with type 2 diabetes aged 30-75 years without a history of CVD at baseline were included from January 1, 2010 to December 31, 2020. Recalibrated NDR model was used to estimate 5-year risk, while the recalibrated DIAL model was used to predict 5-year and 10-year risks. The competing events adjusted Kaplan-Meier analysis was used to obtain the observed cardiovascular events. Discrimination C statistics evaluated model accuracy, calibration χ2 value, and calibration plots. Results:Through a median follow-up of 7.0 years, 7 326 cardiovascular events, and 2 937 non-vascular deaths were identified among a total of 83 503 subjects. The recalibrated NDR model overestimated 5-year risk by 39.4% in men and 8.6% in women, whereas the overestimation for the recalibrated DIAL model was 14.6% in men and 50.1% in women. The DIAL model had a better discriminative ability ( C-statistic=0.681, 95% CI: 0.672-0.690) than NDR model ( C-statistic=0.667, 95% CI: 0.657-0.677) in 5-year risk prediction for men, and the models had a similar ability for women ( C-statistic=0.699, 95% CI: 0.690-0.708 for NDR and C-statistic=0.698, 95% CI: 0.689-0.706 for DIAL). The prediction accuracy of the DIAL model was improved in the 10-year risk, with the underestimation being 1.6% for men and the overestimation being 12.8% for women. Conclusions:Both recalibrated NDR and DIAL models overestimated 5-year cardiovascular risk in Chinese patients with type 2 diabetes, while the higher overestimation was shown using the DIAL model. However, the improvement was found in predicting 10-year CVD risk using the DIAL model, which suggested the value of lifetime risk prediction and indicated the need for research on the lifetime risk prediction model for cardiovascular risk assessment in Chinese patients with type 2 diabetes.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult