Role of inhibiting lncRNA TUG1 to down⁃regulate nucleotide binding oligomerization domain like receptor protein 1 inflammasome in delaying the progression of Alzheimer’s disease / 解剖学报

Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.

Advances in relationship between pyroptosis and pulmonary arterial hypertension and therapeutic drugs / 中国药理学通报

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Very-long chain acyl-coA dehydrogenase deficiency: report of a Chinese pedigree and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).@*METHODS@#A Chinese pedigree affected with VLCADD admitted at the First People's Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed.@*RESULTS@#The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14:1, C16:1, C16:2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c.664G>A (p.G222R) and c.1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14:1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c.1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120).@*CONCLUSION@#The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c.1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.

Inflammatory Bowel Disease and Neurodegenerative Diseases

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

Study on pharmaceutical care model for drug-related problems in elderly patients based on comprehensive medication management review / 中国药房

OBJECTIVE To explore the pharmaceutical care model for elderly patients with drug-related problems （DRPs） based on the comprehensive medication management review （CMMR）， and to observe the effect of pharmaceutical care under the model. METHODS The pharmaceutical care new model for elderly patients was established by concerning CMMR guidelines in Australia. In other words， clinical pharmacists receive medical care through referral by health practitioners and active consultation by patients or their caregivers. Visits were made by a combination of face-to-face and telephone interviews. Follow-up was carried out in the form of outpatient follow-up， telephone follow-up， appointment， and home guidance to know about the treatment of DRPs by healthcare practitioners or patients.Under this model， the occurrence status and classification of DRPs in elderly patients were studied through cross-sectional investigation. The effect of pharmaceutical care was evaluated from the aspects of hospitalization rate， adverse drug reaction （ADR） incidence，medication compliance， the number of medications， blood lipid level， etc.， through self-before-after comparison. RESULTS In this study， a patient-centered， evaluation-intervention-reevaluation closed-loop pharmaceutical care model was formed. Among 317 study subjects， the average number of DRPs was 1.03 （0-7） cases. Compared before and after the intervention， the number of drug types increased from 2.00（0.00，3.00） to 2.00（1.00，3.00）， but the level of low-density lipoprotein cholesterin in patients decreased from 3.48 （2.58， 4.29） mmol/L to 3.11 （2.29，3.81） mmol/L （P＜0.05）. There was no statistical significance in hospitalization rate， ADR incidence within or medication compliance. CONCLUSIONS CMMR-based pharmaceutical care model can effectively identify and manage the patients’ DRPs and reduce the level of blood lipid.

Portal vein aneurysm after liver transplantation: report of two cases and literature review / 器官移植

Objective To summarize the diagnosis and treatment experience of portal vein aneurysm after liver transplantation. Methods Clinical data of two recipients with portal vein aneurysm after liver transplantation were retrospectively analyzed. Clinical features, diagnosis, treatment and prognosis were summarized based on literature review. Results Both two cases were diagnosed with intrahepatic portal vein aneurysm complicated with portal vein thrombosis and portal hypertension after liver transplantation. Case 1 was given with targeted conservative treatment and he refused to undergo liver retransplantation. Physical condition was worsened after discharge, and the patient eventually died from liver graft failure, kidney failure, lung infection, and septic shock. Case 2 received high-dose glucocorticoid pulse therapy, whereas liver function was not improved, and the patient was recovered successfully after secondary liver transplantation. Conclusions Long-term complication of portal vein aneurysm (especially intrahepatic type) after liver transplantation probably indicates poor prognosis. Correct understanding, intimate follow-up and active treatment should be conducted. Liver retransplantation may be a potential treatment regimen.

Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy and adverse reactions of peginterferon-α2b for treatment of chronic myeloproliferative neoplasms (MPN).@*METHODS@#We retrospectively analyzed the data of 107 patients with MPN, including 95 with essential thrombocythemia (ET) and 12 with polycythemia vera (PV), who all received peginterferon-α2b treatment for at least 12 months. The clnical and follow-up data of the patients were analyzed to evaluate the efficacy and adverse reactions of the treatment.@*RESULTS@#After receiving peginterferon- α2b treatment, both ET and PV patients achieved high hematological remission rates, and the total remission rates did not differ significantly between the two groups (86% vs 78%, P>0.05). In the overall patients, the spleen index decreased by 13.5% (95%CI: 8.5%-18.5%) after the treatment. The patients with hematological remission showed a significantly greater reduction of the total symptom score than those without hematological remission (P < 0.01). The median percentage of JAK2V617F allele load of PV patients decreased from 67.23% (49.6%-84.86%) at baseline to 19.7% (0.57%-74.6%) after the treatment, and that of JAK2V617F-positive ET patients decreased from 48.97% (0.45%-74.24%) at baseline to 22.1% (0.33%-65.42%) after the treatment. Mild adverse reactions (grade 1-2) were observed in both ET and PV groups without significant differences between them. The overall incidence of thrombotic events during the treatment was 2.8% in these patients, and no serious adverse reactions were observed.@*CONCLUSION@#For patients with chronic myelodysplasia, peginterferon-α2b treatment can achieve a high peripheral blood cell remission rate and maintain a long-term stable state with good effect in relieving symptoms such as splenomegaly. Peginterferon- α2b treatment caused only mild adverse reactions, which can be tolerated by most of the patients.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Relationship between Hemoglobin Level Variability and Effect of Repeated Blood Transfusion Therapeutic in Patients with Renal Anemia / 中国实验血液学杂志

OBJECTIVE@#To observe the variability of hemoglobin (HB) level in patients with renal anemia, and to analyze its relationship with effect of repeated blood transfusion therapeutic in patients.@*METHODS@#A retrospective cohort study and propensity score matching method were used, 60 patients with renal anemia who had effective treatment with repeated blood transfusion in Changzhou No.2 People's Hospital from May 2018 to May 2021 were retrospectively analyzed and set as the effective group; 153 patients with renal anemia who had ineffective treatment with repeated blood transfusion in the hospital in the same period were collected and set as the ineffective group, the propensity score matching method was used, the patients who were effective and ineffective in repeated blood transfusion were matched 1∶1 for analysis; the medical records and laboratory indexes of the two groups were checked; the Hb level of patients within 6 months (1/month) were recorded, the residual standard deviation (Res-SD) of Hb of patients was calculated according to the Hb level and evaluated the variability of Hb level; the relationship between HB variability level and therapeutic effect of repeated blood transfusion in patients with renal anemia was analyzed.@*RESULTS@#After propensity score matching, there was no statistical significant difference between the two groups in terms of baseline data such as age, sex, dialysis age and BMI (P>0.05). The levels of serum albumin and transferrin of patients in the ineffective group were significantly lower than those of patients in the effective group (P<0.05); at 1 and 2 months of the observation period, there was no statistical significant difference in Hb levels of patients in both groups (P>0.05); the Hb level of patients in the ineffective group was significantly lower than that of patients in the effective group at 3, 5 and 6 months, and significantly higher than that of patients in the effective group at 4 months (P<0.05); the Res-SD of male patients and female patients in the ineffective group were respectively significantly higher than that of male patients and female patients in the effective group (P<0.05). Logistic regression analysis results showed that high variability of Hb level (Res-SD) was a risk factor for the ineffective treatment of repeated blood transfusion in patients with renal anemia (OR>1, P<0.05); the decision curve results showed that, when the high-risk threshold was 0.0-1.0, Res-SD predicted the net benefit rates of male and female patients with renal anemia were greater than 0, which was clinically significant, the smaller the high-risk threshold in the above range, the greater the net benefit rate.@*CONCLUSION@#The therapeutic effect of repeated blood transfusion in patients with renal anemia may be related to the variability of Hb level.

Acute effects of NO2 on hospitalization risk of children with respiratory diseases in Foshan City / 公共卫生与预防医学

Objective To explore the acute effects of NO2 on children's respiratory hospitalization risk in Foshan City. Methods The daily average concentrations of six air pollutants such as NO2 and fine particulate matter, and meteorological data including average temperature and relative humidity in Foshan were collected from 2016 to 2019. Data on the daily number of children newly hospitalized for respiratory diseases (ECRH) in Foshan Women and Children Hospital were retrieved. Time series analysis was used to quantitatively evaluate the effect of daily NO2 concentration on the hospitalization risk of children with respiratory diseases. Results From 2016 to 2019, the average ECRH in the hospital was 10. The daily average concentrations of air pollutants NO2, PM2.5, PM10, and SO2 were 42.0 μg/m3, 35.3 μg/m3, 58.1 μg/m3, and 11.4 μg/m3, respectively. The air pressure, daily average temperature and relative humidity of atmosphere were 1008.4 Pa, 23.7℃ and 73.3%, respectively. ECRH was significantly correlated with the daily average concentration of NO2 (r=0.079, P3 increase of NO2 concentration in the single pollutant model, the excess risk of ECHR in the hospital increased by 1.22% (95% CI: 0.06%, 2.40%) and 1.37% (95% CI: 0.23%, 2.53%) in lag0 and Lag1 day, respectively. The strongest effect appeared in lag0:7 with the excess risk increasing by 1.70% (95% CI:0.12%, 3.31%). In the NO2 + SO2 + CO + O3_8h + PM2.5 and NO2 + SO2 + CO + O3_8h + PM10 multi-pollutant models, significance correlation still existed between the daily average NO2 concentration and ECHR in lag0, lag1 and lag0:1 to lag0:7. The strongest effect appeared in lag0:1, and the excess risks were 4.06% (95% CI: 1.83%, 6.34%) and 3.95% (95% CI: 1.85%, 6.09%), respectively. Dose-response relationship analysis showed a linear relationship between the daily average NO2 concentration and ECHR, and the excess risk of new hospitalization gradually increased with the increase of daily average NO2 concentration. Conclusion There was a significant correlation between NO2 concentration and hospitalization risk of children with respiratory diseases in Foshan City, which suggests that the government should further strengthen the prevention and control of air pollution.

Rosuvastatin acts on the lymphatic system to improve atherosclerosis / 中华心血管病杂志

Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.

Microvascular perfusion and cardiac function after revascularization assessed by myocardial contrast echocardiography in patients with acute ST-segment elevation myocardial infarction / 中华心血管病杂志

Objectives: To evaluate microvascular perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction after revascularization using myocardial contrast echocardiography (MCE), and to explore clinical influencing factors of abnormal microvascular perfusion in these patients. Methods: This is a cross-sectional study. The analysis was performed among patients admitted to Peking University People's Hospital for acute ST-segment elevation myocardial infarction (STEMI) from June 2018 to July 2021. All patients underwent percutaneous coronary intervention (PCI) and completed MCE within 48 hours after PCI. Patients were divided into normal myocardial perfusion group and abnormal perfusion group according to the myocardial perfusion score. The echocardiographic indexes within 48 hours after PCI, including peak mitral valve flow velocity (E), mean value of early diastolic velocity of left ventricular septum and lateral mitral annulus (Em), left ventricular global longitudinal strain (GLS) and so on, were analyzed and compared between the two groups. Multivariate logistic regression analysis was used to evaluate the influencing factors of myocardial perfusion abnormalities. Results: A total of 123 STEMI patients, aged 59±13 years with 93 (75.6%) males, were enrolled. There were 50 cases in the normal myocardial perfusion group, and 73 cases in the abnormal myocardial perfusion group. The incidence of abnormal myocardial perfusion was 59.3% (73/123). The left ventricular volume index ((62.3±18.4)ml/m2 vs. (55.1±15.2)ml/m2, P=0.018), wall motion score index (WMSI) (1.59 (1.44, 2.00) vs. 1.24(1.00, 1.47), P<0.001) and mitral E/Em (17.8(12.0, 24.3) vs. 12.2(9.2, 15.7), P<0.001) were significantly higher whereas left ventricular global longitudinal strain (GLS) ((-10.8±3.4)% vs. (-13.8±3.5)%, P<0.001) was significantly lower in the abnormal myocardial perfusion group than those in the normal myocardial perfusion group. Multivariate logistic regression analysis showed that left anterior descending (LAD) as culprit vessel (OR=3.733, 95%CI 1.282-10.873, P=0.016), intraoperative no/low-reflow (OR=6.125, 95%CI 1.299-28.872, P=0.022), and peak troponin I (TnI) (OR=1.018, 95%CI 1.008-1.029, P=0.001) were independent risk factors of abnormal myocardial perfusion. As for ultrasonic indexes, deceleration time of mitral E wave (OR=0.979, 95%CI 0.965-0.993, P=0.003), mitral E/Em (OR=1.100, 95%CI 1.014-1.194, P=0.022) and WMSI (OR=7.470, 95%CI 2.630-21.222, P<0.001) were independently related to abnormal myocardial perfusion. Conclusions: The incidence of abnormal myocardial perfusion after PCI is high in patients with acute STEMI. Abnormal myocardial perfusion is related to worse left ventricular systolic and diastolic function. LAD as culprit vessel, intraoperative no/low-reflow and peak TnI are independent risk factors of abnormal myocardial perfusion.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Analysis on the influencing factors for re-positive nucleic acid test result in discharged COVID-19 patients in Chengdu / 中国胸心血管外科临床杂志

@#Objective    To analyze the influencing factors for re-positive nucleic acid test in discharged corona-virus disease 2019 (COVID-19) patients in Chengdu, Sichuan Province, and to provide data support for the epidemics prevention and control. Methods    The clinical data of 660 discharged COVID-19 patients from January 23, 2020 to February 28, 2021 in our center were retrospectively analyzed. The patients were divided into two groups according to the reexamination of virus nucleic acid, including a negative group [549 patients, including 428 males and 121 females with a median age of 33.0 (28.0, 48.0) years] and a positive group [111 patients, including 76 males and 35 females with a median age of 39.0 (28.0, 51.0) years]. The clinical data of the two groups were compared. Results     The re-positive rate of the discharged patients was 16.82%. Univariate analysis showed that the re-positive rate of females was higher than that of males (χ2=4.608, P=0.032). The re-positive rate of confirmed patients was higher than that of asymptomatic infected patients (χ2=8.140, P=0.004). The re-positive rate of domestic patients was higher than that of imported patients (χ2=9.178, P=0.002). The counts of CD3+ (P=0.038), CD4+ (P=0.048) and CD8+ (P=0.040) T lymphocytes in the negative group were higher than those in the positive group. The binary logistic regression analysis showed that the clinical classification and CD8+ T lymphocyte count were independent risk factors affecting the recurrence of virility. Conclusion    The gender, origin, T lymphocyte subsets count and clinical type are the influencing factors for re-positive result, and clinical type and CD8+ T lymphocyte count are the independent influencing factors for re-positive result. Therefore, improving the immunity of infected patients, as well as early detection and timely treatment are effective means to reduce the re-positive occurrence.

The research of liver-targeted drugs based on asialoglycoprotein receptor / 药学学报

Asialoglycoprotein receptor (ASGPR) is highly expressed on the surface of parenchymal liver cells. It can specifically recognize and bind to desialylated glycoproteins which contain terminal galactose or N-acetylgalactosamine residues, and endocytosed by clathrin-mediated endocytosis, transported and then degraded in lysosome. Based on this character, ASGPR mediated liver-targeted drug delivery is likely to increase drug distribution, reduce potential side effects and lower dose. This article reviewed the expression, structure, ligand binding and endocytosis of ASGPR, and summarized the design and optimization of ASGPR ligands and the release strategies. Finally, we put forward some expects about the clinical drug development for ASGPR.

Co-load of silybin and doxorubicin by MoS2 nanosheets for synergetic chemotherapy and photothermal therapy of lung cancer / 药学学报

The active ingredient of traditional Chinese medicine, silybin (SBN), can inhibit the proliferation of cancer cells and enhance the anticancer effect of doxorubicin (DOX). However, due to non-targeting and short half-life of SBN and DOX, as well as different administration routes and pharmacokinetic processes, this combination drug cannot act on the tumor in the set order, seriously eliminating the synergistic effect between them and limiting the effect in vivo. Therefore, we intended to construct a nano-delivery system based on molybdenum disulfide (MoS2), modified by polyethylene glycol (PEG) and sialic acid (SA), and co-loaded with SBN and DOX. The system induced the release of combined drugs under the dual-stimulation of pH and near infra-red (NIR), increased the free concentration of intracellular drugs, so as to achieve the synergistic effect between them. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Fujian University of Traditional Chinese Medicine. MoS2-PEG-SA-SBN/DOX circulated in vivo, and effectively accumulated at tumor sites through enhanced permeability and retention effect (EPR) and SA-mediated active targeting. Under near infrared light irradiation, MoS2-PEG-SA-SBN/DOX realized the combination of synergistic chemotherapy and photothermal therapy for tumor, thus achieving excellent anti-tumor effect in vivo. This study can provide a new idea and strategy for the clinical treatment of lung cancer. Taken together, MoS2-PEG-SA-SBN/DOX can offer a new idea and strategy for the clinical treatment of lung cancer.

The screening model for dopamine receptor agonists by a dopamine sensor / 药学学报

Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×104, and the effective concentration of the positive drug was 1-100 µmol·L-1. In addition, pretreated with 10 µmol·L-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.

Research advances in immune checkpoint inhibitor-related cholangitis / 临床肝胆病杂志

Immune checkpoint inhibitors (ICIs) have ushered in a new era of tumor treatment; however, immunotherapy-related adverse events are critical issues that restrict the clinical application of ICIs and have attracted wide attention. The liver is one of the target organs that is easily affected. With the progress in research, scholars have found that besides hepatocytes, intrahepatic and extrahepatic bile ducts can also be attacked by the immune system, leading to the disease known as immune-related cholangitis. This article reviews the research advances in ICI-related cholangitis by summarizing related articles, in order to preliminarily reveal its clinical, pathological, and imaging features and provide clues for early identification, standard treatment, and subsequent research.