Usefulness of Early Warning Scores, ROX index, and CURB-65 in the prognostic evaluation of patients with COVID-19

Objective@#Early identification of COVID-19 in patients is important to prevent significant worsening of the disease. This study was undertaken to verify whether MEWS (Modified Early Warning Score), NEWS(National Early Warning Score), ROX index, and CURB-65, which are early diagnostic tools for severe respiratory diseases, could be applied to patients visiting the emergency room for COVID-19. @*Methods@#This retrospective observational study included patients who visited an emergency medical center from September 1 to October 31, 2020, and from January 1 to February 28, 2021. Based on the vital signs and blood tests during the emergency room visit, severity evaluation tools and early diagnostic tools for severe cases were used and compared according to their area under the curve (AUC) values. The primary outcome was in-hospital mortality, while the secondary outcomes were intensive care unit admission rate and the need for mechanical ventilation based on these four tools (MEWS, NEWS, ROX index, and CURB-65). @*Results@#A total of 667 patients were analyzed. No significant difference was determined between the non-survivor group and survivor group in the MEWS values (P=0.13), but statistically significant differences were observed for NEWS (5 vs. 1, P<0.05), CURB-65 (2 vs. 1, P<0.05), and ROX index (16.61 vs. 23.1, P<0.01). The AUC value of NEWS for death prediction indicated a good predictive power at 0.80, while that of MEWS showed a low predictive power at 0.57, which was statistically significant. Moreover, the AUC values of CURB-65 and ROX index did not differ significantly from values obtained for NEWS. @*Conclusion@#As early diagnostic tools for predicting death in COVID-19 patients, NEWS, ROX index, and CURB-65 showed excellent discrimination ability, whereas MEWS showed statistically and significantly lower discrimination ability.

Mechanism of Xianlian Jiedu Prescription in Maintaining Cancer Relative Vascular Endothelial Cell Homeostasis and Inhibiting Tumor Neovascularization / 中国实验方剂学杂志

ObjectiveTo observe the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation， apoptosis， and migration of cancer-relative endothelial （CRE） cells， and to decipher the mechanism of XLJDP in regulating angiopoietin2 （Ang2） to maintain CRE cell homeostasis and inhibit tumor neovascularization. MethodHuman umbilical vein endothelial cell line （HUVEC-c） was induced into CRE cells in the human colorectal cancer HCT-116 cell-conditioned medium. The CRE cells were assigned into the blank group， conditioned medium group， and XLJDP groups （1， 2， 3 g·L-1） and treated for 48 h. The proliferation of CRE cells was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. The morphological changes of CRE cells were observed via an inverted microscope. The apoptosis rate was detected by flow cytometry. Wound healing test and Transwell migration assay were employed to detect the 2D/3D migration ability of CRE cells. The protein levels of vimentin， N-cadherin， matrix metalloproteinase-9 （MMP-9）， and Ang2 in CRE cells were measured by Western blot. ResultThe MTT results showed that the cell viability was higher in the conditioned medium group than in the blank group （P<0.05）. Compared with the conditioned medium group， XLJDP decreased the cell proliferation rate （P<0.01） and changed the cell morphology. The total apoptosis rates of all the XLJDP groups were higher than that of the conditioned medium group （P<0.01）. The 2D and 3D migration abilities of the conditioned medium group were higher than those of the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations weakened the 2D migration ability （P<0.01） and medium- and high-concentration XLJDP weakened the 3D migration ability （P<0.01）. The protein levels of N-cadherin， Vimentin， MMP-9， and Ang2 were up-regulated in the conditioned medium group compared with those in the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations down-regulated the protein level of Ang2 （P<0.05， P<0.01）， and medium- and high-concentration XLJDP down-regulated those of N-cadherin， vimentin， and MMP-9 protein （P<0.01）. ConclusionXLJDP may inhibit the proliferation， migration， differentiation， and apoptosis of CRE cells by down-regulating the expression of Ang2， inhibiting tumor neovascularization， and maintaining the cell homeostasis.

Effect and Mechanism of Xianlian Jiedu Prescription Against Proliferation of Colorectal Cancer Cells in Hypoxic Microenvironment / 中国实验方剂学杂志

ObjectiveTo study the effect of Xianlian Jiedu prescription （XLJDP） on the activation of nuclear transcription factor-κB （NF-κB） signaling pathway induced by bromodomain-containing protein 4 （Brd4） in hypoxic microenvironment and to explore its mechanism in inhibiting the proliferation of colorectal cancer HT-29 cells. MethodThe human colorectal cancer HT-29 cells were cultured in a hypoxic incubator or normoxia incubator and treated with XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L-1 for 48 h， respectively. Following the detection of cell vitality using methyl thiazolyl tetrazolium （MTT） colorimetry， the effects of XLJDP （1.25，2.5，and 5 g·L-1） on the cell mitochondrial membrane potential were determined using a fluorescent probe （JC-1）， and the apoptosis of colorectal cancer HT-29 cells was detected by flow cytometry. The cell colony formation assay and 5-ethynyl-2'-deoxyuridine （EDU） staining were conducted to test the proliferation of colorectal cancer HT-29 cells. The Western blot was carried out to measure the expression levels of Brd4 and its downstream relevant proteins such as c-Myc and hexamethylene bisacetamide-inducible protein 1 （HEXIM1）， as well as the effects of XLJDP on related proteins in the NF-κB signaling pathway. ResultCompared with the blank control group， XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L-1 inhibited the vitality of colorectal cancer HT-29 cells （P<0.05 ， P<0.01）， with the median inhibitory concentration （IC50） under the hypoxic condition higher than that under the normoxia condition. Compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L-1 significantly decreased the mitochondria membrane potential， enhanced the apoptosis （P<0.05，P<0.01）， and lowered the number of cell colonies and also the EDU-positive cells （P<0.05， P<0.01）. The results of Western blot showed that compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L-1 down-regulated Brd4， c-Myc， p-NF-κB p65， and p-IκBα protein expression to varying degrees and up-regulated the expression of HEXIM1 （P<0.05， P<0.01）. ConclusionIn the hypoxic microenvironment， XLJDP inhibits the proliferation of colorectal cancer HT-29 cells regulated by Brd4， which may be related to its inhibition of the activation of NF-κB signaling pathway.

Biological fate and interaction with cytochromes P450 of the nanocarrier material, d-α-tocopheryl polyethylene glycol 1000 succinate

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

Multi-index components of Scutellariae Barbatae Herba according to UHPLC-QTRAP-MS coupled with chemometrics / 中国中药杂志

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.

Research progress and therapeutic perspective of iron transport balance based on "iron-inflammation" homeostatic coupling theory / 药学学报

The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.

Establishment of a rapid risk assessment system for imported COVID-19 cases / 中华流行病学杂志

Objective: To develop a rapid risk assessment tool for imported COVID-19 cases and provide reference evidences for prevention and control of COVID-19 at ports. Methods: The information about COVID-19 pandemic and control strategies of 12 concerned countries was collected during July to August 2021, and 12 indexes were selected to assess the importation risk of COVID-19 by risk matrix. Results: The risk for imported COVID-19 cases from 12 countries to China was high or extremely high, and the risk from Russia and the USA was highest. Conclusions: The developed rapid risk assessment tool based on the risk matrix method can be used to determine the risk level of countries for imported COVID-19 cases to China at ports, and the risk of imported COVID-19 was high at Beijing port in August 2021.

Proportion and rate: connotation and understanding route / 中华流行病学杂志

Proportion and rate have multiple and overlapping meanings, which blur their concepts. Based on the existence of the states and the occurrence of the events and their measuring process, we first put forward the concept of "cumulative number of states in point time". Considering the general meaning of "rate" in mathematics and the units of the elements in indexes, this paper puts forward the concept of "the change of cumulative number of states in point time", which is equal to the commonly acknowledged concept "number of incident event within observation period" or "absolute rate", and further constructs relative rate and proportion. Proportions can be classified into three types: time-point (or rate-type) constitutional proportion, time-period incidence proportion and their synthesis, time-period constitutional proportion. The essential difference between relative rate and time-period proportions is whether the observation period is regarded as a one-unit-length fixed period which would be further moved to the description of the indexes. Furthermore, the sources populations of relative rate and proportions are exclusively those at the beginning of the observation period. Thus, we established a unified identification route about ratios, proportions, and rates, the basic indicators of categorical data in populations. These are applicable to both fixed and dynamic populations. The paper aims to clarify the connotation of the indexes and the feasible understanding route and provide some reference for the population researchers.

Clinical application of artificial dermis combined with autologous thin skin graft in the repair of burn scar contracture of joint / 中国医师杂志

Objective:To study the clinical value of artificial dermis combined with autologous thin skin graft in the repair of burn scar contracture in joints.Methods:A total of 52 patients with burn scar contractures were enrolled in the No.5 Hospital of Baoding from July 2015 to April 2018. According to different methods of repair, 26 cases were used in each group. The observation group was treated with artificial dermis combined with autologous thin skin graft. The control group was treated with medium-thickness skin grafting. The survival rate of autologous skin was compared between the two groups. The tissue of artificial dermal polyester fiber was taken and HE staining was performed to observe the pathological changes. The Vancouver skin scar assessment score (VSS), functional activity, infection rate, wound healing time, and VSS score after healing of the donor site were compared between the two groups.Results:The survival rate of autologous skin in the observation group (92.31%) was not significantly different from that in the control group (84.62%) ( P>0.05). Compared with preoperative, the VSS scores at 3, 6 months and 1 year after operation in both groups were decreased ( P<0.05). The VSS scores of the observation group were lower than those of the control group at 3, 6 months and 1 year ( P<0.05). The excellent rate of functional activity in the observation group (100.00%) was higher than that of the control group (76.92%) ( P<0.05); There was no significant difference in the infection rate (3.85% vs 7.69%) and healing time of skin grafting area between the two groups ( P>0.05). The healing time of donor site was shorter than that of the control group ( P<0.05). The VSS score of the donor site was lower than that of the control group ( P<0.05). Conclusions:Artificial dermis combined with autologous thin skin graft can be used in patients with burn scar contracture in joints, which can improve the scarring of skin grafting area and donor site, shorten the healing time of donor site and improve the function of burn scar contracture joint.

Debridement effectiveness of infected bone tissue of chronic hematogenous osteomyelitis in the lower extremities under the guidance of 99mTc-MDP SPECT/CT fused images / 中华创伤杂志

Objective:To explore the debridement effectiveness of infected bone tissue of chronic hematogenous osteomyelitis in the lower extremities under the guidance of 99mTc-MDP SPECT/CT fused images. Methods:A retrospective case series analysis was conducted on 21 patients with chronic hematogenous osteomyelitis in the lower extremities treated at Southwest Hospital of Army Medical University from May 2017 to June 2020. There were 8 males and 13 females, with the age range of 10-62 years [23(18, 37)years]. The tibial infections were found in 16 patients, and femoral infections in 5 patients. The duration of bone infection was 4-480 months [120(42, 228)months]. According to the Cierny-Mader anatomico-physiological system, 4 patients were classified as type I, 14 as type III, 3 as type IV; 18 patients were classified as type A and 3 as type B. Intraoperative debridement of infected bone tissue was operated at stage I on the region of interest (ROI) where the isocontour(ISO) value was between 30%-40%, using the preoperative 99mTc-MDP SPECT/CT fused images as the reference. The stage II bone defect reconstruction was based on autologous and / or allogeneic bone. To observe the frequency of operations regarding bone infection control in stage I. The preoperative white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), intraoperative bacterial culture and pathological examination were compared at stages I and II. The skin redness and swellings, pain, sinus tract in the infected limbs, and ossification of grafted bones in the original bone defect part were observed at stage II. The accuracy rate between ISO value in the region of interest (ROI) and set ISO figure was checked. The difference of longitudinal length of the bone debridement area in ROI area with the actual bone debridement area was observed under the coronal position. Results:All patients were followed up for 6-36 months [11(9, 29)months] after stage II operation. All of the 21 patients had undergone operations of infection control with an average number of 1.04 times in stage I. 1 patient's intraoperative frozen section indicated that neutrophils were>5/HP. The bone graft at stage II had been completed after another debridement. Comparison of preoperative inflammatory markers at stages I and II: the WBC was decreased from (5.9±1.6)×10 9/L to (5.4±1.5)×10 9/L ( P>0.05), the ESR decreased from 9(5, 26)mm/h to 4(2, 10)mm/h ( P<0.05), and the CRP decreased from 2.8(2.3, 7.7)mg/L to 2.3(1.4, 3.0)mg/L ( P>0.05). The results of bacterial culture of tissue at stage I were positive in 12 patients and negative in 9 patients. The pathological examination indicated neutrophils and lymphocyte infiltration. The results of bacterial culture of tissue at stage II were all negative. A modicum of plasmacyte and lymphocyte infiltration and the neutrophils (<5 per/Hp) had been found in the intraoperative frozen section and pathological examination. No redness, swelling or sinus tract was found in the skin after stage II surgery and ossification of grafted bone was good. The accuracy rate between ISO value in the ROI and set ISO figure was 90.5%. The comparison between longitudinal debridement scope of ROI [(86.8±31.1)mm] and actual bone tissue debridement scope [(86.0±31.3)mm] at stage I showed no significant difference ( P>0.05). Conclusions:99mTc-MDP SPECT/CT fused images can be used as an effective means to define the debridement scope of infected bone tissue preoperatively. The method can not only avoid excessive debridement, but also improve the cure rate of hematogenous osteomyelitis in the lower extremities.

Analysis of chemical constituents of Ginseng-Douchi compound fermentation products based on UPLC-Q-TOF-MS / 中国中药杂志

In this experiment, ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze and identify chemical constituents of Ginseng-Douchi(GD) compound fermentation, and explore the conversion rules of ginsenosides and soybean isoflavones after compound fermentation. Waters Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was adopted, with 0.1% formic acid aqueous solution(A)-0.1% formic acid acetonitrile solution(B) as mobile phase for gradient elution; electrospray ion source(ESI) was used to collect data in positive and negative ion modes; according to the exact mass number, the secondary spectrum comparison of the database and the existing literature reports, Peakview 2.0/masterview 1.0 software was used to determine the common ion structure formula. Finally, a total of 133 chemical constituents were analyzed and identified from the GD. Ginseng saponins and isoflavone glycosides were significantly converted after fermentation. Among them, peak areas of prototype ginsenosides Rk_3, Rh_1, Rh_2, Rh_3, daidzin, glycitin and genistin decreased significantly; whereas peak areas of se-condary ginsenoside Rb_1, Rb_2, Rk_1, glycitein, genistein and daidzein increased significantly. In this experiment, liquid-mass spectrometry technique was used to investigate the conversion of active ingredients of GD compound fermented products after co-fermentation, so as to provide a scientific basis for elucidating pharmacodynamics material basis and quality control.

Current drug research on intestinal mucosal healing in inflammatory bowel disease based on macrophage regulation / 药学学报

Complete healing of the intestinal mucosa is the most ideal goal in the treatment of inflammatory bowel disease (IBD). The intestinal mucosa healing not only significantly alters the course of the disease and relieves clinical symptoms, but also markedly reduces the occurrence of complications and prevents recurrence of IBD. As chronic inflammation associated with peptic ulcer damage is the main pathological feature of IBD, clinical treatment is mainly based on anti-inflammatory therapy, but such therapy cannot promote the healing of the intestinal mucosa of patients. Therefore, how to achieve long-term remission of IBD is still an urgent challenge. In the process of intestinal mucosal repair, the polarization of macrophages maintains the homeostasis of the intestinal microenvironment, which is a representative process that promotes mucosal inflammatory-repair. It is a key part of initiating tissue regeneration that should not be underestimated. In this paper, we reviewed the literature of the past decade, focusing on the promotion of intestinal mucosal healing in IBD. The discussion will highlight the importance and feasibility of regulating macrophages to promote intestinal mucosal repair. Following this thought, we discuss the shortcomings of current clinical treatments and summarize the relevant drugs which have potential to promote intestinal mucosal repair. The aim is to provide effective potential drugs and therapeutic targets for the treatment of IBD.

Influence Factors for Competitive Performance of Alpine Skiers in the View of Biomechanics / 医用生物力学

Under the background of technological assistance to prepare for the Beijing Winter Olympics in China, the biomechanical research highlights and the latest achievements related to competitive performance of alpine skiers in recent years were systematically analyzed in this paper, so as to determine biomechanical factors affecting competitive performance of alpine skiers, including aerodynamic drag, frictional forces, ground reaction force (GRF), energy dissipation, turn radius, trajectory of the skis and/or center of mass (COM). In addition, biomechanical differences in turn techniques, multiple turns connections and abilities of individuals were also considered as important factors affecting the alpine skiing performance. In the case of slalom and giant slalom events, the earlier initiation of turns, longer path length and trajectory, earlier and smoother application of GRF, and carbene technique carving to reduce the ski-snow friction and thereby dissipate energy should be used to improve sports performance. During speed skiing, minimizing the exposed frontal area and positioning the arms close to the body can reduce the energy loss caused by aerodynamic drag, thereby improving sports performance. Top-level alpine skiers will always perform well on different courses, terrains and snow conditions during the race. Excellent alpine ski performance from a biomechanical perspective includes the efficient use of potential energy, minimizing ski-snow friction and aerodynamic drag, choosing optimal trajectory and maintaining high-speed skiing. Individual tactics and techniques should be valued in training and competition. For better results, the same performance on multiple sections and on different terrains is more important than excellence in individual sections and specific conditions.

Clinical Characteristics of Patients with Adrenal Insufficiency and Fever

Background@#Because persistent fever often occurs in adrenal insufficiency, it might be confused with infectious diseases. This study aimed to identify clinical characteristics and risk factors of patients with adrenal insufficiency and fever. @*Methods@#All adult patients (n = 150) admitted to a tertiary care hospital in South Korea and diagnosed with adrenal insufficiency between 1 March 2018, and 30 June 2019, were recruited. Patients were excluded if they had: 1) proven structural problems in the adrenal or pituitary gland; 2) a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency; and 3) other medical conditions that may cause fever. @*Results@#Among the included patients, 45 (30.0%) had fever at the time of the diagnosis of adrenal insufficiency. The mean C-reactive protein level was higher (11.25 ± 8.54 vs. 4.36 ± 7.13 mg/dL) in patients with fever than in those without fever. A higher proportion of patients with fever changed antibiotics (33.3% vs. 1.0%). On multivariate logistic regression analysis, female sex (odds ratio [OR], 0.32) lowered the risk of adrenal insufficiency with fever, while a history of surgery within 6 months (OR, 4.35), general weakness (OR, 7.21), and cough (OR, 17.29) were significantly associated with that. @*Conclusion@#The possibility of adrenal insufficiency should be considered in patients with fever of unknown origin, especially those with risk factors.

Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

Role of asymptomatic hyperuricemia in the progression of chronic kidney disease and cardiovascular disease

Previous research has investigated whether hyperuricemia serves as an independent risk factor for cardiovascular and renal diseases. Hyperuricemia is defined as an abnormally high level of uric acid (UA; i.e., serum urate level > 6.8 mg/dL). Hyperuricemia has been considered a complication of chronic kidney disease (CKD). However, it seems to play a pathogenic role in the progression of renal diseases. There has been increasing focus on the link between hyperuricemia and CKD. The results of randomized controlled trials have implied independent associations between hyperuricemia and the progression of cardiovascular and renal morbidities. These associations may be mediated by renin-angiotensin system activation, nitric oxide synthase inhibition, and macrovascular/microvascular disease development. There remains controversy regarding the use of serum UA level as an indirect index of renal vascular disease. This literature review focuses on the role of asymptomatic hyperuricemia in the progression of CKD, as well as the association between hyperuricemia and cardiovascular disease. It also provides a general overview of the physiological metabolism of UA.

Monocytes Contribute to IFN-β Production via the MyD88-Dependent Pathway and Cytotoxic T-Cell Responses against Mucosal Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children. However, little is known about the contribution of monocytes to antiviral responses against RSV infection. We identified the IFN-β production of monocytes using IFN-β/YFP reporter mice. The kinetic analysis of IFN-β-producing cells in in vivo RSV-infected lung cells indicated that monocytes are recruited to the inflamed lung during the early phase of infection. These cells produced IFN-β via the myeloid differentiation factor 88-mediated pathway, rather than the TLR7- or mitochondrial antiviral signaling protein-mediated pathway. In addition, monocyte-ablated mice exhibited decreased numbers of IFN-γ-producing and RSV Ag-specific CD8 + T cells. Collectively, these data indicate that monocytes play pivotal roles in cytotoxic T-cell responses and act as type I IFN producers during RSV infection.

Reoperation for cardiac myxoma: report of 23 cases / 中华胸心血管外科杂志

Objective:To summarize the experience of reoperation for 23 cases of cardiac myxoma recurrence.Methods:From January 2002 to December 2018, 1106 patients with cardiac myxoma underwent surgical treatment. Among them, 23 patients underwent reoperation after recurrence. 10 males and 13 females with an average age of (50.5±10.8) years old. There were 22 patients with secondary operation and 1 patient with four operations. 3 cases with mitral insufficiency and 1 case with tricuspid insufficiency. There were 20 patients with NYHA Ⅰ-Ⅱ and 3 patients with Ⅲ-Ⅳ. A total of 1 083 patients with cardiac myxoma undergoing primary operation were selected as the control group. The operation time, cardiopulmonary bypass time, aortic clamping time, ICU monitoring time, ventilator assisted breathing time, postoperative hospital stay, in-hospital mortality and cardiac ejection fraction at discharge were compared between the two groups.Results:8 cases (34.8%) had the first onset in the left atrial septum, and 15 cases (65.2%) in other parts. Recurrence site: left atrium in 17 cases(73.9%), left ventricle in 2 cases (8.7%), right atrium in 3 cases (13.0%), right ventricle in 1 case (4.3%). Reoperation accounted for 2.1% of cardiac myxoma surgery in the same period. The median recurrence time of 13 patients was 24 months. During the same period, mitral valve replacement was performed in 2 cases, mitral valvuloplasty in 1 case and tricuspid valve plasty in 1 case. The average operation time was (3.9±2.8) h, cardiopulmonary bypass time was (107.6±33.8) min, aortic clamping time was (64.9±23.8) min, ICU monitoring time was (20.1±16.0) h, ventilator assisted breathing time was (16.9±8.5) h, cardiac ejection fraction at discharge was 0.51±0.10, postoperative hospital stay was (8.3±1.5) days. The median follow-up time was 5 (1-18) years. One case (4.3%) died of all causes. There was no significant difference in ICU monitoring time, ventilator assisted breathing time, discharge cardiac ejection fraction, postoperative hospital stay and hospital mortality between reoperation patients and one operation ( P>0.05). Conclusion:Atypical cardiac myxoma has a high recurrence tendency after operation. Regular follow-up after the first operation of cardiac myxoma is a necessary means to early detect recurrence and avoid complications. Reoperation after recurrence can still achieve satisfactory results.

Clinical Characteristics of Patients with Adrenal Insufficiency and Fever

Background@#Because persistent fever often occurs in adrenal insufficiency, it might be confused with infectious diseases. This study aimed to identify clinical characteristics and risk factors of patients with adrenal insufficiency and fever. @*Methods@#All adult patients (n = 150) admitted to a tertiary care hospital in South Korea and diagnosed with adrenal insufficiency between 1 March 2018, and 30 June 2019, were recruited. Patients were excluded if they had: 1) proven structural problems in the adrenal or pituitary gland; 2) a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency; and 3) other medical conditions that may cause fever. @*Results@#Among the included patients, 45 (30.0%) had fever at the time of the diagnosis of adrenal insufficiency. The mean C-reactive protein level was higher (11.25 ± 8.54 vs. 4.36 ± 7.13 mg/dL) in patients with fever than in those without fever. A higher proportion of patients with fever changed antibiotics (33.3% vs. 1.0%). On multivariate logistic regression analysis, female sex (odds ratio [OR], 0.32) lowered the risk of adrenal insufficiency with fever, while a history of surgery within 6 months (OR, 4.35), general weakness (OR, 7.21), and cough (OR, 17.29) were significantly associated with that. @*Conclusion@#The possibility of adrenal insufficiency should be considered in patients with fever of unknown origin, especially those with risk factors.

Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.