Analysis laboratory results of three cases of COVID-19 complicated with falciparum malaria / 中国热带医学

@#Abstract: Objective　To analyze the laboratory indexes of patients infected with malaria patients and COVID-19, so as to provide reliable evidence for the diagnosis of mixed infection of both. Methods　The routine clinical laboratory items such as routine blood, biochemistry and lymphocyte subsets were tested in three cases of COVID-19 complicated with falciparum malaria who admitted to Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University from July to December 2020 were tested. Laboratory data were stage-wise analyzed in conjunction with changes in the course of disease. Results　Three patients confirmed COVID-19 infection recruited all had malaria infection history. Fever, headache, and other symptoms emerged on the 4rd to 11th day after admission. Malaria parasite was detected by malaria parasite antigen testing and blood smear testing, and all three patients had re-ignition of malaria after being confirmed COVID-19 infection. In the early stage of malaria relapse, lymphocytes decreased, CRP and SAA increased, and gradually returned to normal level after antimalarial treatment. Interestingly, we only found one patient at the initial stage of malaria detection showed PLT decreased, no other unnormal changes in other routine blood results (WBC, ESO) and liver function results (ALT, AST, GGT, TBIL, DBIL, CG) were found from the beginning to end course of the disease. Conclusion　COVID-19 infection may promote the resurgence of malaria, so the relapse of malaria should be monitored especially for the patient with malaria infection history who begin to develop fever and other symptoms a few days after the diagnosis of COVID-19. The inflammatory indicators would be worth able as an auxiliary judgment basis for the effective treatment of the two combined infection.

G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

Changes of T cell subsets in major immune organs during sepsis / 中国小儿急救医学

Objective:To explore the changes in the proportion and number of T cell subsets in different immune organs during sepsis.Methods:Eight-week-old female C57BL/6 mice were randomly divided into sepsis group and sham group.The experimental sepsis model was constructed through cecal ligation and puncture, and the sham group just underwent sham operation.Then we detected the changes in the total number of lymphocytes and in the ratio and absolute number of CD4 + T cells, CD8 + T cells, CD4 + CD25 high Foxp3 + regulatory T cells(Treg) and CD4 + CD25 low Foxp3 - effector T cells(Teff) in the mouse spleen, axillary and inguinal lymph nodes and bone marrow by cell counting and flow cytometry 24 h and 16 d after modeling. Results:In the spleens of septic mice, the ratio and absolute numbers of CD4 + T cells and Teff, as well as the absolute number of CD8 + T cells were significantly reduced 24 h and 16 d after modeling.There was no significant change in the number of Treg 24 h after modeling, but a significant increase occurred 16 d after modeling.During sepsis, the changes of CD4 + T cells, CD8 + T cells and Teff in mouse lymph nodes were basically the same as those in the spleen; but the changes in Treg were different, with no significant change in the early stage and a significant decrease in the late stage.In addition, the absolute numbers of CD4 + T cells, CD8 + T cells, and Teff in the bone marrow did not change significantly in the 24 h model, but decreased significantly in the 16 d model.The proportion and absolute number of Treg during sepsis were significantly reduced. Conclusion:During different periods of sepsis, there is a large consumption of lymphocytes in the spleen, lymph nodes and bone marrow.In most cases, the trend of Treg changes is inconsistent or even opposite to that of other T cell subsets.There are differences in the changes of T cells among major immune organs, suggesting that the responses of different immune organs to sepsis are heterogeneous.

Biomarkers of gastrointestinal dysfunction in children / 中国小儿急救医学

Due to incomplete function of gastrointestinal barrier, children are more likely to develop gastrointestinal dysfunction.The clinical application of related biomarkers helps early diagnosis and treatment of gastrointestinal dysfunction in children.By sorting out the studies in recent years, we explored the relationship between inflammatory indicators, intestinal epithelial barrier damage biomarkers, immunological biomarkers, gut microbiome and gastrointestinal dysfunction, and summarized the main problems and solutions faced in the research, which may help the screening, identification and clinical application of relevant biomarkers in subsequent research.

Changes of bone marrow vascular system and endothelial cells in the early stage of sepsis / 中国小儿急救医学

Objective:To clarify the changes in the bone marrow vascular system in the early stage of sepsis in animal model.Methods:A sepsis mouse model was established by cecal ligation and puncture (CLP), and HE staining, immunofluorescence staining, flow cytometry and real-time quantitative PCR were used to comprehensively analyze the varieties of bone marrow vascular system in structure, the relative proportion of vascular endothelial cells and the expressions of damage-related genes at mRNA level.Results:A series of adaptive changes occurred in the bone marrow vascular system in the early stage of sepsis.Histological analysis showed that the bone marrow vascular structure was significantly remodeled.The average density of bone marrow sinusoids in the CLP group was (410.43±72.63)counts/mm 2, which was significantly higher than that in the sham group[(294.43±68.94)counts /mm 2, P<0.01]. The area of luminal pixels accounted for (43.46±3.21)%, which was significantly higher than that in the sham group[(30.28±4.44)%, P<0.001]. The exudation amount of evans blue in the bone marrow tissue of the CLP group was (0.42±0.12)ng/mg tissue, which was significantly higher than that in the sham group[(0.24±0.09)ng/mg tissue, P<0.05], suggesting increased vascular permeability.The results of flow cytometry analysis showed that the EC in bone marrow of the CLP group mice was in a proliferative state, with the proportion of Ki67 + endothelial cell increasing[(1.91±0.65)% vs.(5.06±1.10)%, P<0.01]. The mRNA levels of some genes related to the activation of vascular endothelial cells were up-regulated. Conclusion:Sepsis changes the structure and function of the bone marrow vascular system, and has a significant impact on the bone marrow microenvironment.

Research progress of Sodium-glucose cotransporter 2 inhibitors on treatment of diabetic nephropathy / 医学研究生学报

Diabetic nephropathy(DN) is one of the most common microvascular complications of Diabetes mellitu. It is one of the leading causes of End-stage renal diseae(ESRD). The pathogenesis of DN is complex and difficult to treat. In recent years, Sodium-glucose cotransport 2 (SGLT-2) inhibitors have become a research hotspot in the treatment of DN. They could effectively lower blood glucose, improve renal hyperfiltration and hypoxia, reduce urinary protein, weight, blood pressure and uric acid. In addition, SGLT2 is also anti-inflammatory and antioxidative, etc. This article reviews the progress of SGLT-2 inhibitors in 3 aspects, including the hypoglycemic characteristics, the protective effects of SGLT-2 inhibitors on the kidney, as well as the adverse reactions of SGLT-2 inhibitors.

Research progress of regulatory T cells in sepsis / 中国小儿急救医学

Sepsis is a common critical illness in clinic and a worldwide serious public health issue.Regulatory T cell(Treg) is a type of negative immune-regulatory cell that can affect the organism immune status through various pathways to inhibit inflammation.Mastering the research progress in related fields of Treg is of great significance for further understanding the pathogenesis of sepsis and exploring new diagnostic and therapeutic methods for sepsis.This review provided the recent research progress of Treg cells in sepsis.

The Ability of Baseline Triglycerides and Total Cholesterol Concentrations to Predict Incidence of Type 2 Diabetes Mellitus in Chinese Men and Women: A Longitudinal Study in Qingdao, China / 生物医学与环境科学（英文）

OBJECTIVE@#The purpose of this study was to assess the association between triglycerides (TG), total cholesterol (TC) at baseline, and type 2 diabetes mellitus (T2DM) incidence in a general Chinese population. Further, it aimed to evaluate the ability of TG and TC to predict T2DM incidence.@*METHODS@#Qingdao Diabetes Prevention Program participants recruited between 2006 and 2009 were followed up in 2012-2015. TG, TC, and T2DM status were measured. Cox proportional hazards models were used to estimate the association between TG, TC, and T2DM incidence. The receiver operating characteristic (ROC) curve was used to evaluate the ability of TG and TC to identify T2DM participants.@*RESULTS@#The incidence of T2DM significantly increased with TG in women and TC in both men and women (Ptrend 1.15 and > 1.23 mmol/L in men and women, respectively. For TC, they were > 5.17 and > 5.77 mmol/L in men and women, respectively. The area under the ROCs of TG and TC were 0.54 (0.51-0.57) and 0.55 (0.52-0.58), respectively, in men, and 0.60 (0.58-0.62) and 0.59 (0.56-0.61), respectively, in women.@*CONCLUSION@#Elevated TG and TC were risk factors for T2DM incidence. However, no predictive capacity was found for both factors to identify T2DM incidence in Chinese men and women. Hence, TG and TC levels in both Chinese men and women might be used for decreasing the incidence of T2DM but no clinical predictive capacity for T2DM.

Effect of flufenamic acid on solubility, dissolution andpharmacokinetic behavior of sorafenib in MSNM@SFN / 药学学报

The aim of this study is to investigate the influence of flufenamic acid (FFA) on the solubility, dissolution and bioavailability of sorafenib (SFN) in the combined administration of the MSNM@SFN and FFA. The MSNM@SFN&FFA was prepared by mixing the MSNM@SFN with FFA. The solubility, dissolution and bioavailability of SFN in the MSNM@SFN&FFA complex was investigated in comparison with those of the MSNM@SFN. This study was performed following the National Institutes of Health guidelines for the use of experimental animals; all care and handling of animals were performed with the approval of the Experimental Animal Center of Peking University Health Science Center. The MSNM@SFN&FFA showed no significant influence on the solubility, dissolution and bioavailability of SFN when compared with the MSNM@SFN. These data indicated that FFA had almost no influence on the solubility, dissolution and bioavailability of SFN in the combined administration of MSNM@SFN and FFA, thus providing an experimental foundation for the subsequent formulation research on the combined usage of drugs.

Advanced research of lipopolysaccharide in sepsis / 中国小儿急救医学

Sepsis is a common clinical critical illness and causing serious public health problem worldwide. Lipopolysaccharide(LPS) release from the cytoderm of Gram-negative bacteria and is a pivotal initiating factor in the development of sepsis,which can induce pathological processes such as inflammation, coagulopathy and immunosuppression. Therefore,the research progress in LPS-related region is of great sig-nificance for understanding the pathogenesis of sepsis and developing new diagnostic and therapeutic methods for sepsis. This review summarized the related research progress of LPS and sepsis based on the recent litera-tures.

Interleukin-6 and sepsis / 中国小儿急救医学

Sepsis is a common critical disease, the morbidity of sepsis increases in recent years. Interleukin( IL)-6 plays an important role in the progress of sepsis. It can induce inflammation and cause coagulation. Therefore,it is particularly important to study the relationship between sepsis and IL-6. In order to provide more direction and ideas for septic treatment,this paper summarized the related research progress of IL-6 and sepsis based on the recent literature.

Advances in mechanism of autophagy in renal tubular injury / 生理学报

Autophagy is a lysosome-dependent degradation process that eliminates damaged macromolecular proteins and aging organelles to maintain intracellular homeostasis. Autophagy is observed in almost all eukaryotic cells and plays important roles in many cellular physiological processes, including the cell proliferation and growth, cellular functional alteration and phenotypical transition. Renal tubule is an important target for renal injury under different pathological conditions. Following the discoveries of the molecular basis of autophagy, accumulated lines of evidence have indicated that autophagy dysfunction in tubule is involved in the pathogenesis of many renal diseases. This review will summarize the recent progress in molecule mechanism of autophagy and its roles in renal tubular injury.

Real-time three-dimensional transesophageal echocardiography in therapy risk assessment of unusual atrial septal defect / 中国医学影像技术

Objective To evaluate the application value of real-time three-dimensional transesophageal echocardiography (RT-3DTEE) for the risk assessment of unusual atrial septal defect (ASD) in clinic therapy.Methods Accurate assessment before operation was conducted in 57 cases of patients with unusual ASD by two-dimensional transthoracic echocardiography (2DTTE),two-dimensional transesophageal echocardiography (2DTEE) and RT-3DTEE.The ultrasound manifestations were observed.And the guidance in clinic therapy were compared.Results The shape and number can be displayed clearly by 2D-TTE and 2D-TEE in 46 of 57 eases.Another 11 cases were diagnosed as irregular or two holes possibly.RT-3DTEE can help to observe the morphology and quantity of ASD visually and comprehensively in all cases.There was no statistical difference among 2DTTE,2DTEE and RT-3DTEE for the measurement of right atrium end-systolic transverse diameter (RATD),left atrium end-systolic transverse diameter (LATD),right ventricular end-diastolic diameter (RVDD) and left ventricular end-diastolic diameter (LVDD;all P＞0.05).The statistic difference for the diameter of atrial septal defect (ASDD) was found between 2D-TEE and 2D-TTE (P＜0.05) and RT-3DTEE and 2D-TTE (P＜0.05).There was no statistical difference among 2D-TEE,2DTTE and RT-3DTEE for the measurement of residual boundary condition of superior vena cava,aorta side and the top side of the atrium (all P＞0.05),whereas significant difference was found in measuring the residual boundary condition of inferior vena cava (F=50.39,P＜0.001).There were statistic differences between 2DTEE and 2DTTE,RT-3DTEE and 2DTTE,RT-3DTEE and 2DTEE (all P＜0.05).The clinic therapy can be directed by RT-3DTEE in all 57 cases.The diagnosis of 5 cases was failed by 2D-TTE,and 2 cases was failed by 2D-TEE.Conclusion Abundant image information can be offered by RT-3DTEE which plays an important role in the risk assessment of unusual atrial septal defect.

Problems and countermeasures for after-sale service of medical equipment / 医疗卫生装备

Objective To explore the problems and countermeasures during the implementation of after-sale service of the medical equipment.Methods The common problems and their causes during after-sale service were analyzed,and some countermeasures were proposed from the aspects of signing purchase contract,acceptance check,operation quality,overall evaluation,personnel and etc.Results Strengthened after-sale service contributed to enhancing the medical equipment in operation quality,medical safety and efficiency.Conclusion It is important to take corresponding measures during after-sale service to improve operation quality and decrease operation cost of the medical equipment.

The effect of prophylactic phenylephrine on systemic hypotension during induction of anaesthesia with propofol in patients over 55 years old

Background: Induction of anaesthesia with propofol is often associated with a significant decrease in arterial pressure, especially in the older population. The aim of this study is to determine the efficacy of phenylephrine in two different doses i.e. 100mcg and 200mcg, given during induction to counteract the anticipated hypotensive effect of propofol in older patients aged over 55 years. Methods: Seventy-two ASA physical status I – II patients aged 55 years or older were randomly allocated to group 1 (received propofol mixed with normal saline), group 2 (propofol mixed with 100mcg of phenylephrine) or group 3 (propofol mixed with 200mcg of pheynylphrine). Anaesthesia was induced with fentanyl 1.5mcg/kg and propofol 2mg/kg (mixed with the study drug). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were recorded at 1 minute intervals for up to 5 minutes after induction. Results: SBP, MAP and DBP decreased significantly after induction in the control group and group 2 (phenylephrine 100mcg). In contrast, SBP was maintained to near baseline for the first two minutes after induction using phenylephrine 200mcg in group 3, and similar trends were seen with MAP and DBP at a lesser magnitude. Conclusion: Phenylephrine 200mcg is more effective than 100mcg in attenuating propofol induced hypotension, especially during the first two minutes after induction, in patients aged 55 years and above.

3D dynamic research on spatial lengths of functional bundles in knee cruciate ligaments / 医用生物力学

Objective To analyze patterns of functional bundles in anterior and posterior cruciate ligaments during knee joint movement, so as to provide important references for studying injury mechanism of cruciate ligaments and implant reconstruction. Methods Five healthy knee cadavers were elaborately dissected to expose insertions of functional bundles in anterior and posterior ligaments on both the femur and tibia. CT scans and 3D finite element reconstruction with Mimics and ANSYS were conducted at 0°, 30°,60°, 90°, and 120° flexion angle of the knee joint. The center points of insertions and parallel sections of functional bundles defined by the software ANSYS and CATIA were connected to the centerlines, and at five different knee flexion angles, the lengths of centerlines, defined as the bundle lengths, were measured. Results The length of anterior medial bundle (AMB) of anterior cruciate ligament (ACL) increased gradually as the flexion angle grew from 0° to 90°, but slightly decreased at 120° flexion angle; whereas the length of posterior lateral bundle (PLB) of ACL decreased as flexion angle went from 0° to 90° and slightly increased at 120° flexion angle. In posterior cruciate ligament (PCL), both anterior lateral bundle (ALB) and posterior medial bundle (PMB) extended in length as the flexion angle went from 0° to 120°. The change of ACL and PCL bundle’s length was statistically significant (P<0.05). Conclusions ACL bundles functioned in a reciprocal manner and PCL bundles functioned in a complementary manner during knee flexion. Through establishing the finite element model of functional bundles in cruciate ligaments, the actual length of cruciate ligaments could be reflected, which provided a reasonable method for studying the changes of actual length of functional bundles in cruciate ligaments during knee flexion.

Fabrication of Ascorbic Acid Sensor Based on Phosphotungstic Acid/ZnO Nanofibers / 分析化学

A ZnO nanofibers carrier on the Pt electrode via electrospinning technology was prepared and then the Keggin phosphotungstic acid was deposited on the ZnO/Pt electrode using electrodeposition technology. The scanning electron microscopy showed that the zinc oxide fibers presented net structure and the diameter of its fiber was about 300 nanometers. The fourier transform infrared spectroscopy confirmed that the phosphotungstic acid adhered to the fiber surface. The electrochemical property of the modified electrode showed that it exhibited rapid response, excellent sensitivity and good stability, achieving rapid and accurate determination. The electrode responded linearly to ascorbic acid ( AA) in a concentration range from 8. 8 × 10-7 to 3. 3 × 10-4 mol/L with a low detection limit of 2. 5 × 10-7 mol/L. The method is promising for the development of AA detecting instrument.

Epithelial-mesenchymal transition and cancer stem cells in tumor metastasis / 第二军医大学学报

The epithelial-mesenchymal transition (EMT) is characterized by absence of epithelial phenotype and acquiring of mesenchymal properties. EMT participates not only in normal embryonic development, wound healing and tissue reconstruction, but also in various pathologic processes, including fibrosis and carcinogenesis. EMT can facilitate the invasion and metastasis of cancer cells to distant tissues, and confer the metastatic cancer cells self-renewal ability of stem cells, contributing to macroscopical metastasis formation and multiple resistance to treatment. Recent studies have revealed that several transcription factors, signaling pathways, microRNAs and microenvironment components are involved in this process. Here we summarize the recent progress on the roles of EMT and cancer stem cells in tumor metastasis, hoping to provide new insights in target therapy of tumor metastasis and recurrence.

Congenital myopathy with type 1 fiber predominance in two children / 中国当代儿科杂志

Non-progressive congenital myopathy is a group of muscle diseases occurring at birth or during teenage years. A number of new reports of congenital myopathy, such as homogeneous bodies myopathy, muscle quality control myopathy and type 1 fiber predominance have recently been reported, but they lack of sufficient quantity and constant clinico-pathologic manifestations. This paper reports two cases of congenital myopathy with type 1 fiber predominance confirmed by muscle biopsy. The clinical manifestations of the two children (a 4.5-year-old girl and an 11-year-old boy) included non-progressive symptoms of muscle weakness, skeletal deformities and other clinical features of congenital myopathy. The physical examinations showed a long face or figure and funnel chest or kyphosis/scoliosis, high palatal arch and wing-like shoulder. Serum levels of creatine kinase were normal but slightly elevated serum lactate dehydrogenase levels were noted in the two children. The skeletal muscle biopsy by ATPase staining showed that type 1 fibers accounted for more than 90% of the total number of muscle fibers. No other abnormal pathological changes, such as central cores, muscle tube and central nuclei, were found in the two children.

A possible mechanism linking hyperglycemia and reduced high-density lipoprotein cholesterol levels in diabetes / 华中科技大学学报（医学）（英德文版）

This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol (HDL-C). Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco's modified Eagle's medium (DMEM) containing glucose of various concentrations. The cells were divided into 3 groups in terms of different glucose concentrations in the cultures: Control group (5.6 mmol/L glucose), high glucose concentration groups (16.7 mmol/L and 30 mmol/L glucose). ATP-binding cassette transporter A1 (ABCA1) mRNA expression in the macrophages was detected by semi-quantitative RT-PCR 24, 48 and 72 h after glucose treatment. The results showed that ABCA1 mRNA expression in the 16.7 mmol/L glucose group was not significantly different from that in the control group at all testing time points (P>0.05 for each). In the 30 mmol/L glucose group, macrophage ABCA1 mRNA expression was not changed significantly at 24 h (P=0.14), but was substantially decreased by 40.4% at 48 h (P=0.009) and by 48.1% at 72 h (P=0.015) as compared with that in the control group. It was concluded that ABCA1 is of vital importance for HDL-C biogenesis. High glucose may hamper HDL-C biogenesis by decreasing ABCA1 expression, which contributes to low HDL-C level in diabetes.