BMSCs promote M2 macrophage polarization to attenuate acute radiation-induced lung injury / 中国辐射卫生

Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) for radiation-induced lung injury (RILI) and the underlying mechanism. Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control, model, and BMSCs groups. The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest, while the control group did not receive X-ray irradiation. For the BMSCs group, an injection of 1 × 106 BMSCs cells was administered via the tail vein within 6 h after irradiation. In the 5th week, the lung tissue was taken to observe pathological changes with HE staining; examine the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with immunohistochemical staining; observe the polarization of macrophages with immunofluorescence staining; and measure the expression of the epithelial-mesenchymal transition markers E-cadherin, N-cadherin, and vimentin proteins by Western blot. Results After radiation, the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration, and these changes were markedly reduced in the BMSCs group. The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with significantly increased levels in the model group (P < 0.01, P < 0.05). Treatment with BMSCs significantly increased the polarization of lung macrophages towards the M2 type, while significantly decreasing the abnormally increased N-cadherin and vimentin levels in RILI mice (P < 0.05, P < 0.01). Conclusion BMSCs have therapeutic effects for RILI mice, which may be through promoting macrophage polarization from M1 to M2.

Hydrogen therapy promotes macrophage polarization to the M2 subtype by inhibiting the NF-κB signaling pathway / 中国辐射卫生

Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.

Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52 / 药物分析学报

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Comparative Study on Analgesic Efficacy and Early Knee Function of Femoral Nerve Block and Adductor Canal Block after Tibial Tuberosity Osteotomy Combined with Medial Patellofemoral Ligament Reconstruction / 中国运动医学杂志

Objective To compare the analgesic effect and early function of adductor canal block(ACB)and femoral nerve block(FNB)after tibial tuberosity osteotomy and medial patellofemoral liga-ment reconstruction.Methods Forty-two recurrent patellar dislocation patients to undergo tibial tuberosi-ty osteotomy and medial patellofemoral ligament reconstruction in Beijing Jishuitan Hospital between February 2019 and September 2021 were selected and randomly divided into an ACB group and an FNB group,each of 21,according to a random number table.The ACB group underwent adductor ca-nal block,while the FNB group received femoral nerve block.Then the postoperative analgesic effect,joint range of motion,quadriceps muscle strength and functional recovery were evaluated and com-pared between the two groups.Results The average visual analogue scale scores of the ACB group at rest and exercise were 5.5±1.6 and 6.1±1.6,significantly better than the corresponding values of the FNB group(6.3±1.8 and 6.9±1.8)48 hours after surgery(P<0.05).However,no significant dif-ferences were found between the two groups in this value 12 and 24 hours after surgery.Moreover,12 and 24 hours after surgery,the quadriceps muscle strength of the ACB group was significantly bet-ter than the FNB group(P<0.05),while there were no significant differences between the two groups 48 hours after the surgery.The time required for the maximum knee flexion angle to reach 90° was 2.8±0.5 days in the ACB group,significantly shorter than 4.2±0.6 days of the FNB group(P= 0.018).Conclusion For recurrent patellar dislocation patients undergoing tibial tuberosity osteotomy com-bined with medial patellofemoral ligament reconstruction,adductor canal block may be superior to femo-ral nerve block in terms of preserving quadriceps muscle strength and early restoration of knee joint range of motion.

Analysis of risk factors for the occurrence and in-hospital prognosis in patients with peripartum cardiomyopathy / 中国医师进修杂志

Objective:To investigate the risk factors for the occurrence and poor in-hospital prognosis in patients with peripartum cardiomyopathy (PPCM).Methods:The clinical data of 35 patients with PPCM and 35 healthy pregnant women in Xuanwu Hospital, Capital Medical University and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2003 to January 2022 were retrospectively analyzed. The personal histories, laboratory examination, imaging examination, cardiac function outcome, etc were collected. According to the left ventricular ejection fraction (LVEF) at discharge, the patients with PPCM were divided into in-hospital recovery group (LVEF≥50%, 18 cases) and prolonged disease group (LVEF<50%, 17 cases). Multivariate Logistic regression analysis was used to analyze independent risk factors of poor in-hospital prognosis in patients with PPCM.Results:Among 35 patients with PPCM, the age was (29.81 ± 5.37) years old, 17 cases (48.57%) complicated with gestational hypertension, 6 cases (17.14%) complicated with gestational diabetes mellitus, 24 cases (68.57%) of New York Heart Association (NYHA) cardiac function classification was Ⅲ to Ⅳ class, and 4 cases died (11.43%). The gestational age in patients with PPCM was significantly shorter than that in healthy pregnant women: (36.26 ± 4.27) weeks vs. (38.54 ± 4.59) weeks, the rates of multiple pregnancy and gestational hypertension were significantly higher than those in healthy pregnant women: 17.14% (6/35) vs. 2.86% (1/35) and 48.57% (17/35) vs. 11.43% (4/35), and there were statistical differences ( P<0.05 or <0.01). Compared with hospital recovery group, the patients in protracted disease group had shorter gestational age, larger left ventricular end-diastolic diameter, higher serum creatinine, C-reactive protein and amino-terminal pro-brain natriuretic peptide (NT-proBNP), worse NYHA cardiac function classification, and there were statistical differences ( P<0.05 or <0.01); but there were no statistical difference in LVEF at the first diagnosis and troponin I between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that elevated creatinine was an independent risk factor for poor in-hospital prognosis in patients with PPCM ( OR = 4.554, 95% CI 1.536 to 13.684, P = 0.018). Conclusions:The gestational hypertension may be a risk factor for PPCM. The gestational hypertension, earlier onset time, enlarged left ventricular end-diastolic diameter, high NT-proBNP, high C-reactive protein, high creatinine and high cardiac function NYHA classification may be risk factors for poor in-hospital prognosis in patients with PPCM; and elevated creatinine is an independent risk factor for poor in-hospital prognosis in patients with PPCM.

A mendelian randomization study of the causal association between gastroesophageal reflux and atrial fibrillation / 公共卫生与预防医学

Objective In this study，we performed two sampie Mendelian Randomization to infer a causal association between Gastroesophageal reflux(GERD) and Atrial fibrillation(AF)，it can effectively avoid the problems such as reverse causation and confounds in traditional epidemiology. Methods We used the Summary data of GERD and AF from published Genome wide association study(GWAS) of European Individuals. Single Nucleotide Polymorphisms (SNPs) were extracted as Instrumental Variables (IVs).The main MR methods include Inverse Variance [] Weighted(IVW)，Weighted Median(WME)，MR-Egger，Simple Mode，and Weighted Mode.In addition，we used the sensitivity analysis such as MR-PRESSO，Cochran's Q test etc. Results The IVW shows a causal association between GERD and AF(P<0.0001，OR=1.16，95%CI:1.10-1.23).The WME shows P＜0.0001，OR=1.20，95%CI:1.11-1.30；Simple Mode shows P=0.01，OR=1.34，95%CI:1.07-1.69；Weighted Mode shows P=0.02，OR=1.33，95%CI:1.06-1.66. Conclusion This study based on genetic data supports the causal association between GERD and AF. The occurrence of GERD could increase the risk of AF.

Periodic dynamic observation and analysis of cellular and humoral immunity indexes of adults infected with Omicron BA.1 / 中华预防医学杂志

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.

Research progress of necrotizing otitis externa / 临床耳鼻咽喉头颈外科杂志

Necrotizing otitis externa is a progressive infectious disease involving the external auditory canal and even the skull base, which can lead to serious complications and even death if not treated in time. In this paper, the latest advances in etiology, pathogenesis, clinical manifestations, diagnosis and treatment were reviewed based on previous literature, providing reference for clinical diagnosis, treatment and future research.

Periodic dynamic observation and analysis of cellular and humoral immunity indexes of adults infected with Omicron BA.1 / 中华预防医学杂志

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.

Risk factors for venoarterial-extracorporeal membrane oxygenation related nosocomial infection in children after cardiac surgery / 中南大学学报(医学版)

OBJECTIVES@#Extracorporeal membrane oxygenation (ECMO) is an extracorporeal life support strategy for the treatment of critically ill children with reversible heart and lung failure, increasingly being used in patients with low cardiac output after cardiac surgery. However, the mortality of patients is closely related to the complications of ECMO, especially bleeding, thrombosis, and infection, ECMO-related nosocomial infection has become a challenge to the success of ECMO. This study aims to analyze the incidence and risk factors for venoarterial-ECMO (VA-ECMO)-related nosocomial infections in children after cardiac surgery.@*METHODS@#We retrospectively collected the data of patients who underwent VA-ECMO treatment after pediatric cardiac surgery in the Second Xiangya Hospital of Central South University from July 2015 to March 2021, and divided them into an infected group and a non-infected group. The clinical characteristics of the 2 groups of patients, VA-ECMO-related nosocomial infection factors, pathogenic microorganisms, and patient mortality were compared. Logistic regression was used to analyze the risk factors for nosocomial infection related to VA-ECMO after cardiac surgery.@*RESULTS@#Of the 38 pediatric patients, 18 patients (47.37%) had VA-ECMO related nosocomial infection, served as the infected group, including 7 patients with blood infections and 11 respiratory tract infections. Gram-negative pathogens (16 strains, 88.9%) were the main bacteria, such as Acinetobacter baumannii (6 strains), Klebsiella pneumoniae (3 strains), and Stenotrophomonas maltophilia (3 strains). Compared with the non-infected group (n=20), the infection group had longer time of cardiopulmonary bypass, time of myocardial block, and time of VA-ECMO assistance (All P<0.05). Multivariate logistic regression analysis showed that time of cardiopulmonary bypass (OR=1.012, 95% CI 1.002 to 1.022; P=0.021) was an independent risk factor for ECMO-related nosocomial infection. The number of surviving discharges in the infected group was less than that in the non-infected group (1 vs 11, P<0.05).@*CONCLUSIONS@#Cardiopulmonary bypass time is an independent risk factor for VA-ECMO-related nosocomial infection in children after cardiac surgery. Shortening the duration of extracorporeal circulation may reduce the incidence of VA-EMCO-related nosocomial infections in children after cardic surgery. The occurrence of VA-ECMO-related nosocomial infections affects the number of patient's discharge alive.

Retrospective Analysis of Hematological Phenotypes in Patients with Gene Mutation and Deletion α-Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia.@*METHODS@#By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed.@*RESULTS@#There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (α@*CONCLUSION@#The hematological phenotype changes caused by α

Composition and histopathological features of prostatic calculi in patients with benign prostatic hyperplasia / 中华男科学杂志

Objective@#To analyze the composition of prostatic calculus in patients with BPH and explore its pathogenic factors and histopathological characteristics.@*METHODS@#Strictly following the inclusion and exclusion criteria, we included in this retrospective study 580 cases of bipolar transurethral plasma kinetic prostatectomy (TUPKP) performed in our hospital from May 2015 to May 2019, analyzed the histopathological and calculus-composition features of the patients with BPH complicated by prostatic calculi (the BPH+PC group) and the histopathological data of those with BPH only (the BPH group). We compared the related factors between the two groups of patients and performed uni- and multivariate logistic regression analyses of the data on those in the BPH+PC group.@*RESULTS@#The incidence rate of chronic inflammation was significantly higher in the BPH+PC than in the BPH group (83.1% vs 61.1%, P 0.05). Logistic regression analyses showed that prostatic calculus was significantly correlated with chronic inflammation of the prostate, the patient's age and IPSS (P 0.05).@*CONCLUSIONS@#Prostatic calculus has a high incidence in BPH patients and varies widely in composition, chiefly consisting of calcium oxalate and carbonate apatite. The major factors contributing to prostatic calculi include chronic inflammation of the prostate (primarily the severe type), age and BPH. Prostate calculi may aggravate lower urinary tract symptoms, especially urinary storage symptoms, in patients with BPH, but not significantly affect the PSA level.？.

Clinical value of PCR-flow Fluorescence Hybridization in Prenatal Genetic Diagnosis of Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To explore the value of PCR-flow fluorenscence immunmicrobeads assay in prenatal gene diagnosis of thalassemia.@*METHODS@#A total of 1001 pregnant women and their couples checked in the First Affiliated Hospital of Sun Yat-Sen University from January 2016 to August 2019 were selected. Both pregnant women and their spouses were the carriers of thalassemia gene. Samples such as amniotic fluid, were used to extract genomic DNA at the right time. Parallel detection of α- and β- thalassemia genes to samples should be carried out by PCR-flow cytometric fluorescence hybridization and traditional multiple Gap-PCR and PCR-RDB techniques. The consistency of two methods in gene diagnosis of thalassemia was evaluated by analyzing the results of detection.@*RESULTS@#389 normal genotypes (38.86%, 389/1001) and 59 abnormal genotypes (61.14%, 612/1001) was cheked out by the two methods, including 416 cases of α-thalassemia, 162 cases of β-thalassemia and 34 cases of αβ- complex thalassemia. The main genotypes of α-thalassemia were --@*CONCLUSION@#Guangzhou is a area with high incidence of thalassemia, and the genetic types of thalassemia are complex and diverse. Prenatal diagnosis is the final barrier to the prevention of thalassemia. PCR flow-cytometric fluorescence hybridization, as a simple and fast technique, combined with traditional techniques in parallel contributed to the accuracy of prenatal gene diagnosis of thalassemia.

PX-12 Promoting Apoptosis of Multiple Myeloma Cell Line H929 Induced by Bortezomib / 中国实验血液学杂志

OBJECTIVE@#To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib.@*METHODS@#MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H@*RESULTS@#MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G@*CONCLUSION@#PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.

Rituximab combined with ABVD regimen in treatment of Hodgkin lymphoma with autoimmune hemolytic anemia: report of one case and review of literature / 白血病·淋巴瘤

Objective:To explore the efficacy of rituximab combined with ABVD (epirubicin+ bleomycin+ vindesine +dacarbazine) regimen in treatment of Hodgkin lymphoma (HL) complicated with autoimmune hemolytic anemia (AIHA).Methods:The clinical data of 1 HL patient complicated with AIHA in November 2019 in Henan Cancer Hospital were retrospectively analyzed, and literatures were reviewed.Results:The patient received left cervical lymph node biopsy and bone marrow biopsy, and then lymphoma-related gene mutations and whole genetic genome detection were performed. The patient was diagnosed as HL (tuberous sclerosis in stage Ⅳ) complicated with AIHA. After 6 cycles of rituximab combined with ABVD regimen, the efficacy was evaluated. This patient's anemia was recovered, and HL also achieved complete remission.Conclusions:Rituximab combined with ABVD regimen is effective in treatment of HL patients complicated with AIHA.

Bioequivalence of rosuvastatin calcium tablets in Chinese healthy subjects / 中国临床药理学与治疗学

AIM: To study the bioequivalence of rosuvastatin calcium tablets produced by two different manufacturers on a fasting and postprandial basis in Chinese healthy subjects. METHODS: A single-center, randomized, balanced, open, two-sequence, two-cycle, double-crossover, and single-dose trial design was used in this study. Each of the fasting group and the postprandial group was enrolled in 52 healthy subjects. Fasting/postprandial oral rosuvastatin calcium tablets 10 mg test preparation or reference preparation, the validated LC-MS/MS method was used to determine the concentration of rosuvastatin calcium tablets in plasma, and the pharmacokinetic parameters were calculated. Human bioequivalence and safety evaluation of two rosuvastatin calcium tablets were evaluated. RESULTS: The t

Spectrum of thalassemia mutations in fetuses of Han and Li ethinicities in Hainan province, China

To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China. Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all - and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of -thalassemia and 41/42 (-CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.

Review on correction methods related to the pleiotropic effect in Mendelian randomization / 中华流行病学杂志

Mendelian randomization is an approach using the genetic variants as instrumental variable to estimate and assess the casual relationship between exposure of interest and outcomes. As a valid instrument, genetic variants have to meet the assumptions of strong correlation with exposure but without pleiotropic effect with the outcomes. However, pleiotropy of the variants is usually inevitable, owing to the existence of complex biological effects. Thus, correction methods related to pleiotropic bias are introduced in this paper regarding the selection of instrumental variables, testing of invalid instrumental variables, construction of pleiotropic effect correction models and sensitivity analysis of the robust results. For practical application, investigators should take consideration on the following areas including the types of data, sample size and other relative aspects, thereby selecting the suitable method for the inference of consistent and robust casual estimation.

Childhood obesity and coronary artery disease: a Mendelian randomization study / 中华流行病学杂志

Objective@#To assess the casual effect of childhood obesity on adulthood coronary artery disease (CAD) using Mendelian randomization (MR) method.@*Methods@#Data on BMI of children aged 2-10 years in 2015 were downloaded from Early Growth Genetics Consortium and Genetic Investigation of Anthropometric Traits Consortium. Twenty-seven genetic variants related to children’s BMI were selected as instrumental variables (IVs), and the associations between IVs and CAD were extracted from a Meta-analysis of the genome-wide association study of CAD cases published in UK Biobank 2015. We used MR-Egger regression to test whether there was the pleiotropy of the selected SNPs. In the present MR methods, we conducted MR analyses by using mode-based estimate method as primary method for summary-level of associations to estimate the causal association between childhood obesity and CAD.@*Results@#The intercept term estimated for CAD from MR-Egger method suggested that the selected SNPs don’t exert pleiotropy with a 95%CI including the null (-0.008-0.018). In addition, we found evidence that support the effect of childhood obesity on CAD risk: a 1 s increase in children BMI (kg/m2), and the risk of suffering from CAD in adulthood increased by an average of 37% (OR=1.37, 95%CI: 1.09-1.72).@*Conclusion@#This study provides a causal association between childhood obesity and CAD risk.

Correlations of expressions of peripheral blood regulatory T cells and related inflammatory factors with TOAST subtypes and infection risk in patients with acute cerebral infarction / 中华神经医学杂志

Objective To explore the differences of degrees of immune inflammatory response in patients with different TOAST subtypes of acute cerebral infarction and their relations with infection risk after cerebral infarction.MethodsOne hundred and fifty-four patients with acute cerebral infarction who were free of detectable infection on admission, admitted to our hospital from October 2017 to June 2018, were recruited as patient group; according to TOAST subtypes, these patients were divided into large-artery atherosclerosis group (LAA,n=72), cardioembolic group (CE,n=38), and small-artery occlusion group (SAO,n=44); 45 healthy subjects enrolled at the same period were selected as control group. Fasting blood samples were taken on the next day of admission or during physical examination. Treg％ (percentage of CD4+CD25+CD127[low] regulatory T cells [Treg] in CD4+ lymphocytes) was measured by flow cytometry. Interleukin (IL)-6, IL-10, and hypersensitive C-reactive protein (hsCRP) levels were measured by ELISA or Turbidimetric inhibition immuno assay. Spearman correlation analysis was performed to investigate the relations of Treg％ and related inflammatory factors with TOAST subtypes of acute cerebral infarction and post-stroke infection risk. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of Treg％ and inflammatory factors in post-stroke infection. Univariate Logistic regression analysis and multivariate Logistic regression analysis were used to screen the risk factors of infection after cerebral infarction.Results(1) Treg％ in LAA group was significantly lower than that in control group (P<0.05), and Treg％ in CE group was statistically higher than that in control group (P<0.05); patients in the LAA and CE groups had significantly higher IL-6 and hsCRP levels as compared with those in the control group (P<0.05); patients in the LAA, CE and SAO groups had significantly lower IL-10 level than those in the control group (P<0.05); patients in the LAA and SAO groups had significantly decreased IL-6 and IL-10 levels as compared with those in the CE group (P<0.05); patients in the SAO group had significantly lower hsCRP level as compared with those in the CE group (P<0.05). Spearman correlation analysis showed that Treg％ was negatively correlated with LAA (rs=-0.488,P=0.000) and positively correlated with CE and SAO (rs=0.355,P=0.000;rs=0.200,P= 0.013); the levels of IL-6, IL-10 and hsCRP were positively correlated with CE (rs=0.578,P=0.000;rs= 0.508,P=0.000;rs=0.299,P=0.015), and negatively correlated with SAO (rs=-0.404,P=0.001;rs=0.394, P=0.001;rs=0.308,P=0.012). (2) There were 36 patients who developed infection associated with cerebral infarction in the patient group; as compared with those in the non-infection group, Treg％, IL-6, IL-10 and hsCRP levels in the infection group were significantly increased (P<0.05); Spearman correlation analysis showed that Treg％ and hsCRP were positively correlated with infection after cerebral infarction (rs= 0.305,P= 0.007;rs=0.653,P=0.000). The area under the curve of hsCRP for prediction of post-stroke infection was 0.943 (95％ confidence interval [CI]: 0.895-0.992,P=0.000), that of Treg％ was 0.707 (95％CI: 0.548-0.866,P=0.008), and that of combination of hsCRP and Treg％ was 0.958 (95％CI: 0.918-0.998,P=0.000). (3) Multivariate Logistic regression analysis showed that hsCRP was an independent risk factor for post-infarction infection (P<0.05).ConclusionsThere are differences in the degrees of immune inflammatory response among patients with different TOAST subtypes of acute cerebral infarction. Treg％ and hsCRP can be used as early warning markers of infection after cerebral infarction.