Objective·To explore the causal relationship between air pollution and the risk of Alzheimer's disease(AD)by using two-sample Mendelian randomization(MR).Methods·Based on the data from the genome-wide association study(GWAS),a two-sample MR analysis was conducted to evaluate the causal relationship between air pollution and the risk of AD.Air pollution indicators,including particulate matter 2.5(PM2.5),particulate matter 2.5-10(PM2.5-10),particulate matter 10(PM10),nitrogen dioxide and nitrogen oxides,were used as exposure factors,and summarized data were aggregated from the UK Biobank database.The PM2.5 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 single nucleotide polymorphisms(SNPs);the PM2.5-10 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 SNPs;the PM10 dataset included 455 314 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen dioxide dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen oxides dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs.AD was used as the outcome factor,and data were obtained from the International Genomics of Alzheimer's Project(IGAP).The AD dataset included 25 580 cases and 48 466 controls,with correlation analysis of 7 067 513 SNPs.SNPs significantly associated with AD were used as instrumental variables.The main analysis was conducted by using the inverse variance weighted(IVW)method,and four methods including weighted median,MR-Egger regression,mode-based simple estimation and mode-based weighted estimation were used for quality control.Heterogeneity testing,gene pleiotropy testing and sensitivity analysis were conducted to assess the reliability of the study results.Results·Heterogeneity testing indicated no evidence of heterogeneity among SNPs associated with air pollution indicators and AD(both IVW and MR-Egger results,P＞0.05).Gene pleiotropy testing did not detect any pleiotropic effects(MR-Egger results,P＞0.05).Sensitivity analysis confirmed the stability of the PM2.5 results.IVW analysis revealed a statistically significant association between PM2.5 and AD in European populations(P＜0.001),while no statistically significant associations were observed between PM2.5-10(P=0.664),PM10(P=0.664),nitrogen dioxide(P=0.284),nitrogen oxides(P=0.567)and AD.Conclusion·There is a significant causal relationship between PM2.5 exposure and the risk of AD,with PM2.5 exposure increasing the incidence of AD.However,no evidence has been found to suggest that PM2.5-10,PM10,nitrogen dioxide or nitrogen oxides cause an increased risk of AD.

Objective:To explore the predictive value of miR-21 combined with high mobility group box-1 protein (HMGB1) for postoperative prognosis in patients with hypertensive intracerebral hemorrhage (HICH).Methods:A total of 137 HICH patients (HICH group) admitted to the Central Hospital of Yongzhou from March 2021 to March 2023 were retrospectively selected, and 60 healthy subjects undergoing physical examination in the same hospital during the same period were enrolled as the control group. Serum miR-21 and HMGB1 levels were compared between the two groups, and differences in serum miR-21 and HMGB1 levels among HICH patients with different disease severities and prognoses were analyzed. Univariate and multivariate logistic regression analyses were used to screen influencing factors for postoperative prognosis in HICH patients, and receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of miR-21 combined with HMGB1 for postoperative prognosis.Results:The relative expression level of serum miR-21 on postoperative day 1 in the HICH group was significantly lower than that in the control group ( P<0.05), while the HMGB1 level was significantly higher ( P<0.05). With the aggravation of HICH severity, the relative expression of serum miR-21 significantly decreased (all P<0.05), while the HMGB1 level significantly increased (all P<0.05). The relative expression of serum miR-21 in the good prognosis group was significantly higher than that in the poor prognosis group ( P<0.05), while the HMGB1 level was significantly lower ( P<0.05). Univariate and multivariate logistic regression analyses showed that miR-21, HMGB1, preoperative Glasgow Coma Scale (GCS) score, and preoperative hematoma volume were influencing factors for postoperative prognosis in HICH patients (all P<0.05). ROC curve showed that the areas under the curve (AUC) of miR-21 and HMGB1 for predicting poor postoperative prognosis in HICH patients were 0.925 and 0.913, respectively, while the AUC of miR-21 combined with HMGB1 was 0.950. Conclusions:Peripheral blood miR-21 is significantly decreased and HMGB1 level is significantly increased in HICH patients. miR-21 combined with HMGB1 has a good predictive value for poor postoperative prognosis in patients with hypertensive intracerebral hemorrhage.

Objective:To explore the predictive value of miR-21 combined with high mobility group box-1 protein (HMGB1) for postoperative prognosis in patients with hypertensive intracerebral hemorrhage (HICH).Methods:A total of 137 HICH patients (HICH group) admitted to the Central Hospital of Yongzhou from March 2021 to March 2023 were retrospectively selected, and 60 healthy subjects undergoing physical examination in the same hospital during the same period were enrolled as the control group. Serum miR-21 and HMGB1 levels were compared between the two groups, and differences in serum miR-21 and HMGB1 levels among HICH patients with different disease severities and prognoses were analyzed. Univariate and multivariate logistic regression analyses were used to screen influencing factors for postoperative prognosis in HICH patients, and receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of miR-21 combined with HMGB1 for postoperative prognosis.Results:The relative expression level of serum miR-21 on postoperative day 1 in the HICH group was significantly lower than that in the control group ( P<0.05), while the HMGB1 level was significantly higher ( P<0.05). With the aggravation of HICH severity, the relative expression of serum miR-21 significantly decreased (all P<0.05), while the HMGB1 level significantly increased (all P<0.05). The relative expression of serum miR-21 in the good prognosis group was significantly higher than that in the poor prognosis group ( P<0.05), while the HMGB1 level was significantly lower ( P<0.05). Univariate and multivariate logistic regression analyses showed that miR-21, HMGB1, preoperative Glasgow Coma Scale (GCS) score, and preoperative hematoma volume were influencing factors for postoperative prognosis in HICH patients (all P<0.05). ROC curve showed that the areas under the curve (AUC) of miR-21 and HMGB1 for predicting poor postoperative prognosis in HICH patients were 0.925 and 0.913, respectively, while the AUC of miR-21 combined with HMGB1 was 0.950. Conclusions:Peripheral blood miR-21 is significantly decreased and HMGB1 level is significantly increased in HICH patients. miR-21 combined with HMGB1 has a good predictive value for poor postoperative prognosis in patients with hypertensive intracerebral hemorrhage.

Objective·To explore the causal relationship between air pollution and the risk of Alzheimer's disease(AD)by using two-sample Mendelian randomization(MR).Methods·Based on the data from the genome-wide association study(GWAS),a two-sample MR analysis was conducted to evaluate the causal relationship between air pollution and the risk of AD.Air pollution indicators,including particulate matter 2.5(PM2.5),particulate matter 2.5-10(PM2.5-10),particulate matter 10(PM10),nitrogen dioxide and nitrogen oxides,were used as exposure factors,and summarized data were aggregated from the UK Biobank database.The PM2.5 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 single nucleotide polymorphisms(SNPs);the PM2.5-10 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 SNPs;the PM10 dataset included 455 314 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen dioxide dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen oxides dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs.AD was used as the outcome factor,and data were obtained from the International Genomics of Alzheimer's Project(IGAP).The AD dataset included 25 580 cases and 48 466 controls,with correlation analysis of 7 067 513 SNPs.SNPs significantly associated with AD were used as instrumental variables.The main analysis was conducted by using the inverse variance weighted(IVW)method,and four methods including weighted median,MR-Egger regression,mode-based simple estimation and mode-based weighted estimation were used for quality control.Heterogeneity testing,gene pleiotropy testing and sensitivity analysis were conducted to assess the reliability of the study results.Results·Heterogeneity testing indicated no evidence of heterogeneity among SNPs associated with air pollution indicators and AD(both IVW and MR-Egger results,P＞0.05).Gene pleiotropy testing did not detect any pleiotropic effects(MR-Egger results,P＞0.05).Sensitivity analysis confirmed the stability of the PM2.5 results.IVW analysis revealed a statistically significant association between PM2.5 and AD in European populations(P＜0.001),while no statistically significant associations were observed between PM2.5-10(P=0.664),PM10(P=0.664),nitrogen dioxide(P=0.284),nitrogen oxides(P=0.567)and AD.Conclusion·There is a significant causal relationship between PM2.5 exposure and the risk of AD,with PM2.5 exposure increasing the incidence of AD.However,no evidence has been found to suggest that PM2.5-10,PM10,nitrogen dioxide or nitrogen oxides cause an increased risk of AD.

Background::Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.Methods::A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.Results::The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% ( P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis ( P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). Conclusion::Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

Objective:To observe and analyze the macular microvascular system changes in unilateral pediatric uveitis (PU) and healthy contralateral eyes.Methods:A cross-sectional case-control study. From January 2019 to July 2021, 21 eyes of 21 patients with PU diagnosed in one eye (PU group), 21 unaffected contralateral eyes (contralateral eye group), and 21 age-matched volunteers with 21 eyes (NC group) during the same period were examined in Peking Union Medical College Hospital. Optical coherence tomography angiography was used to scan the 6 mm × 6 mm fundus macular area in the three groups of selected eyes to measure the vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the retina, the area of the avascular zone (FAZ) in the fovea of the macula, the choroidal thickness under the fovea (SFCT), and the retinal thickness in the fovea of the macula (CRT). The device comes with a software choriocapillary flow measurement tool, which can obtain the macula's choriocapillary density (CCD) with the fovea as the center and the diameter of the annular area of 1.0 mm, 1.5 mm, and 3.0 mm, respectively. They were recorded as CCD-1.0, CCD-1.5, and CCD-3.0. The measurement data of multiple groups were compared by analysis of variance; if the variance of the three groups of data was not uniform, the Kruskal-Wallis test was used. Multiple linear regression analysis was used to evaluate the potentially related factors of CCD.Results:Compared with the contralateral eye group and the NC group, the vessel density of SCP ( H=-13.857,-25.500; P=0.043, P<0.001), DCP ( H=-15.333, -31.595; P=0.007, P<0.001) and CCD-1.0 ( H=-14.000,-16.214; P=0.040, 0.012) of the clinically quiescent PU group were significantly decreased. CRT and FAZ were not statistically different between PU and NC groups ( F=0.955; P=1.000, 0.661). Compared with the NC group, the mean vessel density of SCP and DCP in the contralateral eye group decreased, and the difference in DCP vessel density was statistically significant ( H=-16.262, P=0.004). There was no statistically significant difference between the CCD of two groups ( P=1.000). The SFCT of the PU group was significantly thicker than that of the NC group ( F=5.552, P=0.004), however, difference was not statistically significant from the fellow eye group ( F=5.552, P=0.270). The results of multiple linear regression analysis revealed that the CCD-1.0, CCD-1.5, and CCD-3.0 showed a linear correlation with the area of FAZ ( β=-0.494, -0.527, -0.566; P=0.015, 0.009, 0.010) and CRT ( β=-0.322, -0.466, -0.342; P=0.026, 0.002, 0.028). CCD-1.0 and CCD-1.5 showed a linear correlation with the vessel density of DCP ( β=0.277, 0.275; P=0.047, 0.045). Conclusion:Both retinal and choroidal microvasculature are abnormal in resting eyes with PU, and macular circulation disorders may be present in the unaffected fellow eye.

Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.

Objective:To investigate the anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics of patients with warfarin-related major bleeding in the emergency department of a general hospital.Methods:In a registry study from January 2017 to February 2020, 114 cases of warfarin-related major bleeding patients admitted to Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University were enrolled. The descriptive methods were used to analyze anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics. Patients were divided into the international normalized ratio (INR) overrange group and the INR non-overrange group according to INR value during bleeding. The Chi-square test, Student’s t test, and Wilcoxon rank sum test were used to compare the differences between the INR overrange group and the INR non-overrange group. The Wilcoxon rank sum test and Student’s t test were used to analyze the characteristics of gastrointestinal tract bleeding and cerebral hemorrhage. Results:Warfarin-related major bleeding accounted for 0.36% (114/32 040) of first aid cases and 9.84% (114/1 158) of warfarin-taking cases, respectively. Seventy-seven cases (67.5%) of anticoagulant causes were related to atrial fibrillation (AF) and 32 cases (28.1%) were related to post-operative cardiac valve replacement. Of the bleeding susceptibility factors, HAS-BLED scored at 4.0 (3.0, 5.0), 84 cases (73.7%) had a history of drug use, 77 cases (67.5%) aged older than 65 years old, 65 cases (57.0%) had irregular INR monitoring, and 29 cases (25.4%) had recent increase in dose. Forty cases (35.1%) were gastrointestinal tract bleeding with the lowest hemoglobin (Hb) value and the highest score of HAS-BLED. Twenty-one cases (18.4%) were cerebral hemorrhage with the shortest prothrombin time (PT), the lowest INR value, the highest Hb, and the lowest score of HAS-BLED. Twelve cases (10.5%) died or gave up treatment in critical condition, including 6 cases of cerebral hemorrhage, 5 cases of gastrointestinal tract bleeding, and 1 case of hemoptysis. There were statistically significant differences in previous history of antiplatelet therapy, recent increase in dose, HAS-BLED score and bleeding site between the INR overrange group and the INR non-overrange group (all P<0.05). Conclusions:Among patients with warfarin-related major bleeding, AF and post-operative cardiac valve replacement are the main causes of warfarin anticoagulation. INR overrange is related to the previous history of antiplatelet therapy, recent increase in dose, and the high score of HAS-BLED. The gastrointestinal tract bleeding is the most common, with the lowest Hb value and the highest score of HAS-BLED. Cerebral hemorrhage is the second common, with the shortest PT, the lowest INR value, and the highest Hb. The incidence and mortality rates of warfarin-related major bleeding are relatively high.

Multi-disciplinary team(MDT)mode is regarded as the key to standardized diagnosis and treatment of malignant tumors. The model, however, encounters such roadblocks in the current form of MDT organization, as costly clinical resources and time consumption, low efficiency, poor management of participating experts in MDT, and lack of enforceability of the therapeutic decisions made. This paper summarized the practical MDT experiences of the Affiliated Cancer Hospital of Shandong First Medical University. It introduced the construction of an intranet-based MDT system covering a large proportion of newly diagnosed malignant tumor patients, and the practices and achievements of such MDT management system under hospital administrative guidance. The authors proposed to use reporting ratio as the main assessment indicator in promoting MDT, and that to define the performance, responsibilities and rights in MDT practice. These measures aim at to upgrading individual behaviors of doctors to organizational behaviors of hospitals, and providing cancer patients with more standardized, comprehensive and personalized diagnosis and treatment decisions.

Objective A three-dimensional （3D） printing precise pressure device was designed specifically targeted at cambered limbs according to the requirement of postoperative rehabilitation of total knee replacement(TKR), and its effectiveness and safety was verified by finite element analysis. Methods Based on gastrocnemius muscle of lower limbs as the pressurized objects, the precise pressure device was designed, which contained an air pressure generating module, an inflatable airbag and a 3D printing brace. Through the closed loop control algorithm, the device stably supplied different pressures in the airbag. Distributed pressure data of the airbag-skin within contact surface were collected under different experimental conditions and imported into biomechanical simulation software which combined CT images to reconstruct 3D model of the lower limb mechanics. Finally, the effective compression area fraction and the joint micro-motion angle under each condition were obtained, to verify the effectiveness and safety of the system. Results Using generally preferred 4 cm-size offset and 4-barrel airbag configurations, under different intracapsular pressure of 5.32，6.65，7.98，9.31，10.64 kPa, the simulated knee joint micro-motion angles were 5.3°, 6.1°, 7.2°, 9.5°, 10.6°， respectively, and the effective compression area fraction could be up to 90-8%-95-2%. Conclusions For the optimized scheme, the dynamic range of joint micro-motion angle and the effective compression area fraction caused by different airbag pressure values were the best and met the design requirements of effectiveness and safety. The research findings can contribute to analyzing the influence of compression system on limb biomechanics, which are of great significance for effective and safe rehabilitation training after TKR.