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1.
International journal of molecular sciences ; 24(8), 2023.
Article in English | EuropePMC | ID: covidwho-2295334

ABSTRACT

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that β-cyclodextrin polymer (β-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host–guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host–guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3′ terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host β-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of β-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.

2.
Int J Mol Sci ; 24(8)2023 Apr 12.
Article in English | MEDLINE | ID: covidwho-2295333

ABSTRACT

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that ß-cyclodextrin polymer (ß-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host-guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host-guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3' terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host ß-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of ß-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.


Subject(s)
COVID-19 , Polymers , Humans , Polymers/chemistry , SARS-CoV-2 , Fluorescence , COVID-19/diagnosis , Pyrenes/chemistry
3.
Chin Med J (Engl) ; 2023 Mar 15.
Article in English | MEDLINE | ID: covidwho-2260375

ABSTRACT

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment (P = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS: COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

4.
Transplant Cell Ther ; 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2246470

ABSTRACT

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplant teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplant teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (AA) (13%). The PB stem cell source accounted for 41% of HIDs and 75% of MSDs. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and TBI-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.

5.
Biosensors (Basel) ; 12(11)2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2099352

ABSTRACT

Since the 2019-nCoV outbreak was first reported, hundreds of millions of people all over the world have been infected. There is no doubt that improving the cure rate of 2019-nCoV is one of the most effective means to deal with the current serious epidemic. At present, Remdesivir (RDV) has been clinically proven to be effective in the treatment of SARS-CoV-2. However, the uncertain side effects make it important to reduce the use of drugs while ensuring the self-healing effect. We report an approach here with targeted therapy for the treatment of SARS-CoV-2 and other coronaviruses illness. In this study, mesoporous silica was used as the carrier of RDV, the nucleocapsid protein (N protein) aptamer was hybridized with the complementary chain, and the double-stranded DNA was combined with gold nanoparticles as the gates of mesoporous silica pores. When the RDV-loaded mesoporous silica is incubated with the N protein, aptamer with gold nanoparticles dissociate from the complementary DNA oligonucleotide on the mesoporous silica surface and bind to the N protein. The releasing of RDV was determined by detecting the UV-vis absorption peak of RDV in the solution. These results show that the RDV delivery system designed in this work has potential clinical application for the treatment of 2019-nCoV.


Subject(s)
Aptamers, Nucleotide , COVID-19 Drug Treatment , Metal Nanoparticles , Nanoparticles , Humans , Silicon Dioxide , SARS-CoV-2 , Gold
7.
Chin Med J (Engl) ; 135(12): 1394-1403, 2022 Jun 20.
Article in English | MEDLINE | ID: covidwho-2037562

ABSTRACT

ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is a highly effective and unique medical procedure for the treatment of most hematological malignancies. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then, the field has evolved and expanded worldwide. The first successful allogenic HSCT (allo-HSCT) in China was conducted in 1981. Although the development of allo-HSCT in China lagged, China has since made considerable contributions to the process of HSCT worldwide, with more than 10,000 HSCTs performed annually. In particular, haploid HSCT (haplo-HSCT) technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in China. Currently, the number of haplo-HSCT procedures exceeds 5000 per year, and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications, relapse, and infection management. In addition, innovative haplo-HSCT technologies developed by different medical transplantation centers, such as Soochow, Zhejiang, Fujian, Chongqing, and Anhui, have emerged, providing inspiration for the refinement of global practice. This review will focus on the current activity in this field and highlight important trends that are vital in China's allo-HSCT process, examining the current viewpoint and future directions.


Subject(s)
Hematopoietic Stem Cell Transplantation , Neoplasm Recurrence, Local , China , HLA Antigens , Hematopoietic Stem Cell Transplantation/methods , Humans , Retrospective Studies , Transplantation, Homologous
8.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology ; 36(Suppl 1), 2022.
Article in English | EuropePMC | ID: covidwho-1981308

ABSTRACT

Endothelial cells (ECs) are in the inner layer of blood vessels, and it controls the transportation of nutrition and essential molecules from the extracellular matrix to the intracellular space making a homeostasis environment. Vascular endothelium can be disrupted with viruses, which are among the main reasons for epidemic and pandemic outbreaks, and it leads to health issues such as cardiovascular‐related diseases. Wide range of viruses can potentially target the endothelium including Dengue virus estimated to infect 390 million people per year. Zika virus leads to pregnancy complications such as preterm birth and miscarriage. Tick‐borne encephalic damaged the central nervous system and, Hantavirus has a mortality rate of 38% through hantavirus pulmonary syndrome. Reviewing these several diseases, including SARS‐CoV‐2, has given an in‐depth look at what the endothelial cells are going through when these viruses are infecting the host bodies. Following the virus infection, ECs are going through activation mode, which is accompanied with glycocalyx degradation, plasma leakage, phosphorylation of P120, and cadherin, increased proinflammatory responses and, disruption of barrier integrity. The SARS‐CoV‐2 pandemic has taken a global toll;With a total of 362 million cases, there are 5.63 million deaths occurring. With the usage of immunofluorescence and vascular permeability assay, we monitor how Human Umbilical Vascular Endothelial Cells (HUVEC) and Human Lung Microvascular Endothelial Cells (HLMVEC) are impacted when treated with UV‐inactivated & heat‐inactivated SARS‐CoV‐2, and tumor necrosis factor (TNF)‐α. TNF‐α is an inflammatory cytokine prominent during inflammation and its known to increase the permeability of endothelium. Like the TNF‐α, both cells treated with UV‐inactivated and heat‐inactivated SARS‐CoV2 demonstrated boosted permeability. With the considerable effect of SARS‐CoV2 on the permeability of ECs, it is essential to understand the mechanisms and pathways behind the boosted leak, including the impact of the virus on the expression of adhesion molecules like platelet endothelial cell adhesion molecule (PECAM‐1). One can see in the images of HUVEC and HLMVEC that SARS‐CoV‐2 diminish the localization of PECAM‐1. On a non‐treated negative control, cells are spaced evenly and are close to another since their junctions are not targeted. Once the cells are treated with either heat‐inactivated or UV‐inactivated SARS‐CoV‐2, PECAM‐1 localization is disrupted, which can be seen from the space between cells since the PECAM‐1 has been altered and is no longer holding the cells together. From those exact images, one can detect the enlarged and irregular shapes of nucleuses and change in morphology of these cells since the SARS‐CoV‐2 is not only altering the PECAM‐1 complex but it can also modify various proteins and mRNAs. By combining information of various viruses and knowledge from our studies, we can understand the mechanisms of ECs and take measurements to protect ECs from viruses. In future experiments, we will detect if the PECAM‐1 expression is lowered when treated with SARS‐CoV‐2 and TNF‐α or if PECAM‐1 is internalized in the cell. Moreover, we can do mRNA and immunoblotting analysis to elaborate the changes in protein pathways as a consequence of COVID‐19.

9.
Biosens Bioelectron ; 213: 114436, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-1944325

ABSTRACT

The emergence of the COVID-19 epidemic has affected the lives of hundreds of millions of people globally. There is no doubt that the development of fast and sensitive detection methods is crucial while the worldwide effective vaccination programs are miles away from actualization. In this study, we have reported an electrochemical N protein aptamer sensor with complementary oligonucleotide as probe for the specific detection of COVID-19. The electrochemical aptasensor was prepared by fixing the double-stranded DNA hybrid obtained by the hybridization of N protein aptamer and its Fc-labeled complementary strand on the surface of a gold electrode. After incubation with the target, the aptamer dissociated from the labeled complementary DNA oligonucleotide hybrid to preferentially bind with N protein in the solution. The concentration of N protein was measured by detecting the changes in electrochemical current signals induced by the conformational transformation of the complementary DNA oligonucleotide left on the electrode surface. The sensor had a linear relationship between the logarithm of the N protein concentration from 10 fM to 100 nM (ΔIp = 0.098 log CN protein/fM - 0.08433, R2 = 0.99), and the detection limitation was 1 fM (S/N = 3). The electrochemical aptamer sensor was applied to test the spiked concentrations of throat swabs and blood samples from three volunteers, and the obtained results proved that the sensor has great potentials for the early detection of COVID-19 in patients.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , COVID-19 , Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods , COVID-19/diagnosis , DNA, Complementary , Electrochemical Techniques/methods , Electrodes , Gold/chemistry , Humans , Limit of Detection , Protein Binding
10.
Front Public Health ; 10: 764203, 2022.
Article in English | MEDLINE | ID: covidwho-1775974

ABSTRACT

Background: Stigmatization and poor social support are challenges faced by individuals living with HIV or sexually transmitted disease, which can have a profound negative impact on their healthcare. Mother-to-child transmission of either HIV or syphilis can lead to adverse maternal and fetal outcomes. The aim of this study was to investigate stigmatization and social support of pregnant women with HIV or syphilis in eastern China. Methods: This was an explanatory sequential mixed-method study conducted in Zhejiang province, China in 2019. Stigmatization, social support, and the associated factors toward HIV or syphilis were evaluated using questionnaires. The social support rating scale was used to evaluate social support, where a score <25% was defined as poor social support. A logistic regression model was used to explore the association between stigmatization and poor social support. Results: A total of 448 women (HIV positive, N = 93; syphilis, N = 355) were recruited in this study. Higher stigmatization was observed in pregnant women with HIV compared to those with syphilis (53.76% vs. 24.36%, p < 0.001), and poorer social support was observed in women with HIV compared with those with syphilis (40.86% vs. 19.86%, p < 0.001), with significant distributions of the total social support scores (Z = -1.976, p = 0.048) and scores on objectivity (Z = -2.036, p = 0.042) and subjectivity (Z = -2.500, p = 0.012). Similar social support among HIV or syphilis pregnant women was observed in medical healthcare facilities. In multivariable logistic model analysis, stigmatization (OR adj = 2.927; 95%CI, 1.714-4.996; p < 0.001) and ethnic minority (OR adj = 2.373; 95%CI, 1.113-5.056; p = 0.025) were negatively associated with social support. Interestingly, employment status was associated with improved social support (OR adj = 0.345; 95%CI, 0.180-0.662; p = 0.001). Conclusion: Stigmatization among pregnant women with HIV or syphilis remains high. We demonstrated that stigmatization was a significant predictor of low social support in pregnant women with HIV or syphilis. The support shown in medical facilities was similar toward pregnant women with HIV or syphilis. Implementation of stigmatization eradication and social support strategies targeting pregnant women with HIV or syphilis may therefore improve the dual elimination of mother-to-child transmission service.


Subject(s)
HIV Infections , Pregnancy Complications, Infectious , Social Stigma , Social Support , Syphilis , China/epidemiology , Ethnicity , Female , HIV Infections/epidemiology , HIV Infections/psychology , Humans , Infectious Disease Transmission, Vertical , Minority Groups , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/psychology , Pregnant Women , Syphilis/epidemiology , Syphilis/psychology
13.
Diagnostics (Basel) ; 11(10)2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1480621

ABSTRACT

OBJECTIVE: To provide the quantitative volumetric data of the total lung and lobes in inspiration and expiration from healthy adults, and to explore the value of paired inspiratory-expiratory chest CT scan in pulmonary ventilatory function and further explore the influence of each lobe on ventilation. METHODS: A total of 65 adults (29 males and 36 females) with normal clinical pulmonary function test (PFT) and paired inspiratory-expiratory chest CT scan were retrospectively enrolled. The inspiratory and expiratory volumetric indexes of the total lung (TL) and 5 lobes (left upper lobe [LUL], left lower lobe [LLL], right upper lobe [RUL], right middle lobe [RML], and right lower lobe [RLL]) were obtained by Philips IntelliSpace Portal image postprocessing workstation, including inspiratory lung volume (LVin), expiratory lung volume (LVex), volume change (∆LV), and well-aerated lung volume (WAL, lung tissue with CT threshold between -950 and -750 HU in inspiratory scan). Spearman correlation analysis was used to explore the correlation between CT quantitative indexes of the total lung and ventilatory function indexes (including total lung capacity [TLC], residual volume [RV], and force vital capacity [FVC]). Multiple stepwise regression analysis was used to explore the influence of each lobe on ventilation. RESULTS: At end-inspiratory phase, the LVin-TL was 4664.6 (4282.7, 5916.2) mL, the WALTL was 4173 (3639.6, 5250.9) mL; both showed excellent correlation with TLC (LVin-TL: r = 0.890, p < 0.001; WALTL: r = 0.879, p < 0.001). From multiple linear regression analysis with lobar CT indexes as variables, the LVin and WAL of these two lobes, LLL and RUL, showed a significant relationship with TLC. At end-expiratory phase, the LVex-TL was 2325.2 (1969.7, 2722.5) mL with good correlation with RV (r = 0.811, p < 0.001), of which the LVex of RUL and RML had a significant relationship with RV. For the volumetric change within breathing, the ∆LVTL was 2485.6 (2169.8, 3078.1) mL with good correlation with FVC (r = 0.719, p < 0.001), moreover, WALTL showed a better correlation with FVC (r = 0.817, p < 0.001) than that of ∆LVTL. Likewise, there was also a strong association between ∆LV, WAL of these two lobes (LLL and RUL), and FVC. CONCLUSIONS: The quantitative indexes derived from paired inspiratory-expiratory chest CT could reflect the clinical pulmonary ventilatory function, LLL, and RUL give greater impact on ventilation. Thus, the pulmonary functional evaluation needs to be more precise and not limited to the total lung level.

14.
Mech Soft Mater ; 2(1): 11, 2020.
Article in English | MEDLINE | ID: covidwho-1384771

ABSTRACT

A critical event during the process of cell infection by a viral particle is attachment, which is driven by adhesive interactions and resisted by bending and tension. The biophysics of this process has been studied extensively, but the additional role of externally applied force or displacement has generally been neglected. In this work, we study the adhesive force-displacement response of viral particles against a cell membrane. We have built two models: one in which the viral particle is cylindrical (say, representative of a filamentous virus such as Ebola) and another in which it is spherical (such as SARS-CoV-2 and Zika). Our interest is in initial adhesion, in which case deformations are small, and the mathematical model for the system can be simplified considerably. The parameters that characterize the process combine into two dimensionless groups that represent normalized membrane bending stiffness and tension. In the limit where bending dominates, for sufficiently large values of normalized bending stiffness, there is no adhesion between viral particles and the cell membrane without applied force. (The zero external force contact width and pull-off force are both zero.) For large values of normalized membrane tension, the adhesion between virus and cell membrane is weak but stable. (The contact width at zero external force has a small value.) Our results for pull-off force and zero force contact width help to quantify conditions that could aid the development of therapies based on denying the virus entry into the cell by blocking its initial adhesion.

15.
Pharmacol Res ; 161: 105290, 2020 11.
Article in English | MEDLINE | ID: covidwho-1318948

ABSTRACT

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.


Subject(s)
COVID-19 Drug Treatment , Drugs, Chinese Herbal/therapeutic use , Adult , Aged , Aged, 80 and over , China , Cohort Studies , Female , Follow-Up Studies , Humans , Length of Stay , Male , Middle Aged , Time-to-Treatment , Treatment Outcome , Young Adult
16.
Pharmacol Res ; 157: 104820, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318923

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45 %), glycosides (15 %), carboxylic acids (10 %), and saponins (5 %). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Pneumonia, Viral/drug therapy , Animals , Anti-Inflammatory Agents/analysis , Anti-Inflammatory Agents/pharmacology , COVID-19 , Cells, Cultured , Computer Simulation , Coronavirus Infections/genetics , Gene Expression/drug effects , Glycyrrhizic Acid/pharmacology , Humans , Interleukin-6/metabolism , Lipopeptides/antagonists & inhibitors , Lipopeptides/pharmacology , Lipopolysaccharides , Male , Pandemics , Pneumonia/chemically induced , Pneumonia/metabolism , Pneumonia, Viral/genetics , Rats , SARS-CoV-2 , Signal Transduction/drug effects , Thrombin/metabolism , Toll-Like Receptors/metabolism
17.
Transplant Cell Ther ; 27(10): 870.e1-870.e7, 2021 10.
Article in English | MEDLINE | ID: covidwho-1292829

ABSTRACT

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.


Subject(s)
Hematopoietic Stem Cell Transplantation , Pneumonia , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Pneumonia/diagnosis , Prognosis , Retrospective Studies , Transplantation, Homologous
18.
Pathog Dis ; 78(3)2020 04 01.
Article in English | MEDLINE | ID: covidwho-616784

ABSTRACT

The coronavirus disease 2019 (COVID-2019) that emerged in Wuhan, China, has rapidly spread to many countries across all six WHO regions. However, its pathobiology remains incompletely understood and many efforts are underway to study it worldwide. To clarify its pathogenesis to some extent, it will inevitably require lots of COVID-2019-associated pathological autopsies. Pathologists from all over the world have raised concerns with pathological autopsy relating to COVID-2019. The issue of whether a person died from COVID-2019 infection or not is always an ambiguous problem in some cases, and ongoing epidemiology from China may shed light on it. This review retrospectively summarizes the research status of pathological autopsy for COVID-2019 deaths in China, which will be important for the cause of death, prevention, control and clinical strategies of COVID-2019. Moreover, it points out several challenges at autopsy. We believe pathological studies from China enable to correlate clinical symptoms and pathological features of COVID-2019 for doctors and provide an insight into COVID-2019 disease.


Subject(s)
Autopsy , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Betacoronavirus , COVID-19 , Cause of Death , China , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/mortality , SARS-CoV-2
19.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2249-2256, 2020 May.
Article in Chinese | MEDLINE | ID: covidwho-398787

ABSTRACT

The study aimed to investigate the multi-constituent, multi-target mechanism of Xuanfei Baidu Tang(XFBD) in the treatment of coronavirus disease 2019(COVID-19), through exploring the main ingredients and effective targets of XFBD, as well as analyzing the correlation between XFBD targets and COVID-19. The compounds of each herb in XFBD were collected from TCM-PTD, ETCM, TCMSP and SymMap database. Next, the information of meridian tropisms was collected from Chinese Pharmacopoeia(2015 edition), and the target information of the major constituents of XFBD were obtained from TCM-PTD, ETCM, TCMSP and TargetNet database. Subsequently, the target network model and the major modules were generated by Cytoscape, and the functional enrichment analysis of XFBD targets were completed by DAVID and STRING. As a result, ten of the 13 herbs in XFBD belonged to the lung meridian, and 326 of the 1 224 putative XFBD targets were associated with the disease target of COVID-19, among which 109 targets were enriched in the disease pathways of viral infection and lung injury. The main biological pathways regulated by the key XFBD targets included viral infection, energy metabolism, immunity and inflammation, parasites and bacterial infections. In conclusion, the therapeutic mechanism of XFBD in COVID-19 showed a multi-herb, multi-constituent, multi-target pattern, with lung as the chief targeted organ. By regulating a series of biological pathways closely related to the occurrence and development of diseases, XFBD plays a role in balancing immunity, eliminating inflammation, regulating hepatic and biliary metabolism and recovering energy metabolism balance.


Subject(s)
Betacoronavirus , Coronavirus Infections , Drugs, Chinese Herbal/therapeutic use , Pandemics , Pneumonia, Viral , COVID-19 , Coronavirus Infections/drug therapy , Humans , Medicine, Chinese Traditional , Pneumonia, Viral/drug therapy , SARS-CoV-2 , COVID-19 Drug Treatment
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