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OBJECT: Promoting the accessibility and equity of healthcare services, as well as enhancing service capacity, are crucial for building a sound healthcare system. Particularly in the past two years of the normalized COVID-19 situation, this issue has garnered widespread attention in the academic community. This study aims to investigate and analyze the characteristics and trends of the spatial-temporal evolution of healthcare service supply levels in China. It also seeks to explore the influencing factors and pathways for development, with the goal of optimizing the allocation of healthcare resources. METHODS: This article uses the entropy weight TOPSIS method combined with Dagum Gini coefficient and Kernel density to evaluate the supply level of healthcare services in 31 provinces and cities in China from 2012 to 2020, and explores its development and spatial pattern characteristics. Then, through Moran index, panel regression model and spatial econometric testing, the spatial correlation problem and its influencing factors are further analyzed, and targeted policy recommendations are proposed based on it, laying the foundation for further promoting the balanced development of healthcare service supply capacity. RESULTS: (1) Healthcare services supply levels in various provinces and cities in China have significantly increased, with a shift in spatial distribution from 'higher in the east and lower in the west' to 'convergence between east and west, with lower levels in the central regions.' (2) Relative differences among regions are narrowing annually, primarily due to interactions between the four regions rather than within each region, with expanding impact of overlapping regions. (3) Absolute differences among regions are also decreasing, moving towards uniformity with a contraction of extension and a restraint on the trend towards multipolarization. (4) Spatial correlation between adjacent regions is weakening, eventually becoming non-significant, with fading spatial effects. (5) The correlation between local economic development, population factors, institutional arrangements, and the current state of supply is significant, and the research design and conclusions remain robust even after thorough consideration of spatial effects. The study explores the development pathways based on the objective existence of regional development and the controllable government actions. CONCLUSION: The overall level of healthcare service supply in China has improved, but regional differences still exist. The objective level of regional development and the subjective behavior of local governments have a significant impact on the supply of healthcare services. Therefore, it is recommended that each region adapt to local conditions, identify its own strengths and weaknesses, coordinate resource supply and demand, consider the impact of key factors, and optimize the allocation of healthcare development resources.
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COVID-19 , Análise Espaço-Temporal , China , Humanos , COVID-19/epidemiologia , Serviços de Saúde/provisão & distribuição , Acessibilidade aos Serviços de Saúde , SARS-CoV-2 , Atenção à Saúde/organização & administraçãoRESUMO
BACKGROUND: Though the survival of breast cancer (BC) patients with malignant pleural effusion (MPE) has been studied, this has not been specifically studied in the luminal B subtype. Therefore, this study investigated the characteristics and survival of luminal B-BC patients presenting with MPE. METHODS: We retrospectively analyzed 141 patients diagnosed with postoperative advanced Luminal B breast cancer, including 54 cases with MPE and 87 cases without MPE at the Tianjin Cancer Hospital from January 2012 to January 2015. We assessed the clinical characteristics between the groups. RESULTS: The mean age of all patients was 47 years, with no significant difference between the two groups. Altogether, 29 (33%), 24 (28%), 28 (32%), 45 (52%), and 10 (11%) patients had lung, liver, bone, lymph node, and chest wall metastases, respectively. In addition. The difference in overall survival between the two groups was not significant (P>0.05). However, cox regression analysis showed that only the tumor clinical stage at initial diagnosis was related to short overall survival. Further, we conducted a subgroup analysis and found that the higher the clinical stage at initial diagnosis in age < 50 years patients, the shorter the overall survival, while age > 50 years patients was not. (P < 0.05). CONCLUSIONS: There was no difference in the overall survival between luminal B-BC patients with MPE and those without. Clinical stages at initial diagnosis were an independent prognostic factor for age < 50 years luminal B BC with MPE overall survival. Our results may help clinicians make positive decisions regarding personalized treatment of luminal B-BC with MPE.
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Neoplasias da Mama , Derrame Pleural Maligno , Humanos , Feminino , Pessoa de Meia-Idade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia , Derrame Pleural Maligno/etiologia , Estudos Retrospectivos , Neoplasias da Mama/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Prognóstico , Adulto , Estadiamento de Neoplasias , Idoso , China/epidemiologiaRESUMO
A common problem for Zn alloys is the trade-off between antibacterial ability and biocompatibility. This paper proposes a strategy to solve this problem by increasing release ratio of Ca2+ ions, which is realized by significant refinement of CaZn13 particles through bottom circulating water-cooled casting (BCWC) and rolling. Compared with conventionally fabricated Zn-0.3Ca alloy, the BCWC-rolled alloy shows higher antibacterial abilities against E. coli and S. aureus, meanwhile much less toxicity to MC3T3-E1 cells. Additionally, plasticity, degradation uniformity, and ability to induce osteogenic differentiation in vitro of the alloy are improved. The elongation up to 49 %, which is the highest among Zn alloys with Ca, and is achieved since the sizes of CaZn13 particles and Zn grains are small and close. As a result, the long-standing problem of low formability of Zn alloys containing Ca has also been solved due to the elimination of large CaZn13 particles. The BCWC-rolled alloy is a promising candidate of making GBR membrane.
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OBJECTIVES: To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC). METHODS: The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC. RESULTS: In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8+ T cells. Single-cell gene analysis demonstrated that CD8+ T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8+ T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR). CONCLUSIONS: Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.
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Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Feminino , Pessoa de Meia-Idade , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T CD8-Positivos/imunologia , Tomografia Computadorizada por Raios X/métodosRESUMO
RATIONALE AND OBJECTIVES: This study explored the intratumor heterogeneity (ITH) of esophageal squamous cell carcinoma (ESCC) using computed tomography (CT) and investigated the value of CT-based ITH in predicting the response to immune checkpoint inhibitor (ICI) plus chemotherapy in patients with ESCC. MATERIALS AND METHODS: This retrospective study included 416 patients with ESCC who received ICI plus chemotherapy at two independent hospitals between January 2019 and July 2022. Multiparametric CT features were extracted from ESCC lesions and screened using hierarchical clustering and dimensionality reduction algorithms. Logistic regression and machine learning models based on selected features were developed to predict treatment response and validated in separate datasets. ITH was quantified using the score calculated by the best-performing model and visualized through feature clustering and feature contribution heatmaps. A gene set enrichment analysis (GSEA) was performed to identify the biological pathways underlying the CT-based ITH. RESULTS: The extreme gradient boosting model based on CT-derived ITH had higher discriminative power, with areas under the receiver operating characteristic curve of 0.864 (95% confidence interval [CI]: 0.774-0.954) and 0.796 (95% CI: 0.698-0.893) in the internal and external validation sets. The CT-based ITH pattern differed significantly between responding and non-responding patients. The GSEA indicated that CT-based ITH was associated with immunity-, keratinization-, and epidermal cell differentiation-related pathways. CONCLUSION: CT-based ITH is an effective biomarker for identifying patients with ESCC who could benefit from ICI plus chemotherapy. Immunity-, keratinization-, and epidermal cell differentiation-related pathways may influence the patient's response to ICI plus chemotherapy.
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OBJECTIVES: To evaluate the performance of automatic deep learning (DL) algorithm for size, mass, and volume measurements in predicting prognosis of lung adenocarcinoma (LUAD) and compared with manual measurements. METHODS: A total of 542 patients with clinical stage 0-I peripheral LUAD and with preoperative CT data of 1-mm slice thickness were included. Maximal solid size on axial image (MSSA) was evaluated by two chest radiologists. MSSA, volume of solid component (SV), and mass of solid component (SM) were evaluated by DL. Consolidation-to-tumor ratios (CTRs) were calculated. For ground glass nodules (GGNs), solid parts were extracted with different density level thresholds. The prognosis prediction efficacy of DL was compared with that of manual measurements. Multivariate Cox proportional hazards model was used to find independent risk factors. RESULTS: The prognosis prediction efficacy of T-staging (TS) measured by radiologists was inferior to that of DL. For GGNs, MSSA-based CTR measured by radiologists (RMSSA%) could not stratify RFS and OS risk, whereas measured by DL using 0HU (2D-AIMSSA0HU%) could by using different cutoffs. SM and SV measured by DL using 0 HU (AISM0HU% and AISV0HU%) could effectively stratify the survival risk regardless of different cutoffs and were superior to 2D-AIMSSA0HU%. AISM0HU% and AISV0HU% were independent risk factors. CONCLUSION: DL algorithm can replace human for more accurate T-staging of LUAD. For GGNs, 2D-AIMSSA0HU% could predict prognosis rather than RMSSA%. The prediction efficacy of AISM0HU% and AISV0HU% was more accurate than of 2D-AIMSSA0HU% and both were independent risk factors. CLINICAL RELEVANCE STATEMENT: Deep learning algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma. KEY POINTS: ⢠Deep learning (DL) algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma (LUAD). ⢠For GGNs, maximal solid size on axial image (MSSA)-based consolidation-to-tumor ratio (CTR) measured by DL using 0 HU could stratify survival risk than that measured by radiologists. ⢠The prediction efficacy of mass- and volume-based CTRs measured by DL using 0 HU was more accurate than of MSSA-based CTR and both were independent risk factors.
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Adenocarcinoma de Pulmão , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Prognóstico , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Estudos RetrospectivosRESUMO
Staphylococcus aureus often leads to severe skin infections. However, S. aureus is facing a crisis of antibiotic resistance. The combination of phage and antibiotics is effective for drug-resistant S. aureus infections. Therefore, it is worth exploiting novel antibacterial agents to cooperate with antibiotics against S. aureus infections. Herein, a novel chimeric lysin ClyQ was constructed, which was composed of a cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP) catalytic domain from S. aureus phage lysin LysGH15 and cell wall-binding domain (CBD) from Enterococcus faecalis phage lysin PlyV12. ClyQ had an exceptionally broad host range targeting streptococci, staphylococci, E. faecalis, and E. rhusiopathiae. ClyQ combined with mupirocin (2.64 log reduction) was more effective at treating S. aureus skin infections than ClyQ (0.46 log reduction) and mupirocin (2.23 log reduction) alone. Of equal importance, none of S. aureus ATCC 29213 or S3 exposed to ClyQ developed resistance, and the combination of ClyQ and mupirocin delayed the development of mupirocin resistance. Collectively, chimeric lysin ClyQ enriches the reservoirs for treating S. aureus infections. Our findings may provide a way to alleviate the current antibiotic resistance crisis. IMPORTANCE Staphylococcus aureus, as an Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogen, can escape the elimination of existing antibiotics. At present, phages and phage lysins against S. aureus infections are considered alternative antibacterial agents. However, the development of broad-spectrum chimeric phage lysins to cooperate with antibiotics against S. aureus infections remains at its initial stage. In this study, we found that the broad-host-range chimeric lysin ClyQ can synergize with mupirocin to treat S. aureus skin infections. Furthermore, the development of S. aureus resistance to mupirocin is delayed by the combination of ClyQ and mupirocin in vitro. Our results bring research attention toward the development of chimeric lysin that cooperates with antibiotics to overcome bacterial infections.
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Bacteriófagos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Mupirocina/farmacologia , Mupirocina/uso terapêutico , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVES: The genus Streptococcus contains species of important zoonotic pathogens such as those that cause bovine mastitis. Unfortunately, many Streptococcus species have developed antibiotic resistance. Phage lysins are considered promising alternatives to antibiotics because it is difficult for bacteria to develop lysin resistance. However, there remains a lack of phage lysin resources for the treatment of streptococci-induced mastitis. METHODS: We identified the prophage lysin Lys0859 from the genome of the Streptococcus suis SS0859 strain. Lys0859 was subsequently characterized to determine its host range, MIC, bactericidal activity in milk, and ability to clear biofilms in vitro. Finally, to determine the effects of Lys0859 on the treatment of both bovine mastitis and S. suis infection in vivo, we established models of Streptococcus agalactiae ATCC 13813-induced mastitis and S. suis serotype 2 SC19 systemic infection. RESULTS: Our results demonstrate that Lys0859 possesses broad-spectrum lytic activity against Streptococcus and Staphylococcus species isolated from animals with bovine mastitis and 15 serotypes of S. suis isolated from swine. Intramammary and intramuscular injection of Lys0859 reduced the number of bacteria in mammary tissue by 3.75 and 1.45 logs compared with the PBS group, respectively. Furthermore, 100 µg/mouse of Lys0859 administered intraperitoneally at 1 h post-infection protected 83.3% (5/6) of mice from a lethal dose of S. suis infection. CONCLUSIONS: Overall, our results enhance the understanding and development of new strategies to combat both streptococci-induced mastitis and S. suis infection.
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Bacteriófagos , Mastite Bovina , Infecções Estreptocócicas , Fagos de Streptococcus , Streptococcus suis , Feminino , Bovinos , Animais , Suínos , Camundongos , Humanos , Prófagos/genética , Mastite Bovina/tratamento farmacológico , Antibacterianos/farmacologia , Infecções Estreptocócicas/microbiologiaRESUMO
Improving plasticity has been an eternal theme of developing metallic materials. It is difficult to increase room-temperature elongation of metallic materials over 100% without sacrificing strength using existing methods. Herein, surface-roughness-induced plasticity (SRIP) is discovered in biodegradable Zn-0.4Mn alloy. Surprisingly, in the good surface range that meets the international standard ISO 6892, reducing surface roughness results in significant increase in plasticity without loss of strength. From unground to 5000# sandpaper ground states, the surface roughness Ra of the alloy decreases from 0.63 to 0.05 µm, while its room temperature elongation increases from 74% to 143%. SRIP is the synergistic result of increased microstructure damage tolerance and decreased surface roughness. It provides a new method for improving plasticity.
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Background: The aim of this study was to determine the clinical characteristics and outcome of patients with aortic dissection (AD) who present with an initial manifestation of cerebral infarction. Methods: We retrospectively analyzed patients who were diagnosed with AD and admitted to the emergency department from May 1, 2017 to May 1, 2022. Data was collected for variables including age, sex, clinical manifestation, past medical history, and laboratory test results. Results: Twenty-five patients (2.61%, 22 type A and 3 type B) showed cerebral infarction as the primary presentation for acute AD, while another 933 AD patients (471 type A and 462 type B) who presented with other symptoms served as the control group. Eighteen of the 25 patients (72%) were initially diagnosed with stroke, and the diagnosis of AD was missed. However, patients with a missed diagnosis of AD did not have significantly different mortality to those in whom AD was diagnosed (chi-square test, p > 0.9999). Patients with cerebral infarction as the first presentation had a higher incidence of type A AD than the control patients (p = 0.0002), while their mortality rate was also higher than the control group of AD patients (p < 0.0001). Furthermore, patients with cerebral infarction as the first presentation were more likely to have multiple organ dysfunction. Conclusions: AD with an initial presentation of cerebral infarction is a rare condition with high mortality. However, the initial failure to diagnose AD does not further increase patient mortality.
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OBJECTIVES: Our goal in this study was to determine 1) whether there are any differences in clinical characteristics between Chinese and Western patients with aortic dissection (AD), and 2) the mortality rate of AD patients in the emergency department (ED) and identify the risk predictors for death. METHODS: We retrospectively analyzed patients who were diagnosed with AD and admitted to our ED between September 1, 2017-August 31, 2020. Data on age, gender, clinical manifestation, medical history, routine blood tests, liver and kidney function, coagulation, myocardial enzymology, and mortality were collected. RESULTS: We enrolled 535 AD patients (422 men and 113 women) with a mean age of 54.7±14.1 years. Type A AD constituted 40% of the total number of AD cases, while type B AD constituted 60%. The proportion of those who were females, 10-92 years, with type A AD, and hypertension in the Chinese population was lower than that in the Western population (P <0.05 for all). Type A AD patients had a higher proportion of acute AD clinical manifestations than did patients with type B AD (P = 0.0084, P <0.05). The mortality rate of type A AD patients (10.75%) was higher than that of type B AD patients (1.87%) (P <0.0001) in the ED. Higher values of white blood cells, neutrophils, high-density lipoprotein, activated partial thromboplastin time, and D-dimer level with worsened hepatic and renal function were found in the deceased group, and multivariate logistic regression revealed that blood urea nitrogen (BUN) levels (P = 0.0031, P <0.05) were significantly associated with death. CONCLUSION: In South China, patients with AD had a mean age of 54.7 years, with 78.88% prevalence in males and 66.92% hypertension rate. Type A AD accounted for 40% of all AD cases, and 10.70% of patients with type A AD died in the ED. Elevated BUN levels may be a risk predictor for death in patients with type A AD.
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Dissecção Aórtica , Hipertensão , Adulto , Idoso , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Acute liver injury is liver cell injury that occurs rapidly in a short period of time. Caffeine has been shown to maintain hepatoprotective effect with an unclear mechanism. Endoplasmic reticulum stress (ERS) has significant effects in acute liver injury. Induction of GRP78 is a hallmark of ERS. Whether or not caffeine's function is related to GRP78 remains to be explored. METHODS: Acute liver injury model was established by LPS-treated L02 cells and in vivo administration of LPS/D-Gal in mice. Caffeine was pre-treated in L02 cells or mice. Gene levels was determined by real-time PCR and western blot. Cell viability was tested by CCK-8 assay and cell apoptosis was tested by flow cytometry. The interaction of GRP78 and NEDD4L was determined by Pull-down and co-immunoprecipitation (Co-IP) assay. The ubiquitination by NEDD4L on GRP78 was validated by in vitro ubiquitination assay. RESULTS: Caffeine protected liver cells against acute injury induced cell apoptosis and ERS both in vitro and in vivo. Suppression of GRP78 could block the LPS-induced cell apoptosis and ERS. NEDD4L was found to interact with GRP78 and ubiquitinate its lysine of 324 site directly. Caffeine treatment induced the expression of NEDD4L, resulting in the ubiquitination and inhibition of GRP78. CONCLUSION: Caffeine mitigated the acute liver injury by stimulating NEDD4L expression, which inhibited GRP78 expression via ubiquitination at its K324 site. Low dose of caffeine could be a promising therapeutic treatment for acute liver injury.
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Cafeína , Doença Hepática Induzida por Substâncias e Drogas , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Ubiquitina-Proteína Ligases Nedd4 , Animais , Camundongos , Apoptose , Cafeína/farmacologia , Cafeína/uso terapêutico , Chaperona BiP do Retículo Endoplasmático/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Ubiquitinação , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológicoRESUMO
In this study, we used genotyping by sequencing (GBS) to examine the genetic diversity of 22 strains of Lingzhi and the quality differences in 15 fruit bodies of Lingzhi from different Chinese regions. The phylogenetic trees of 22 strains were constructed based on ITS (Internal transcribed spacer) and SNP (single nucleotide polymorphism). Moisture, ash, water-soluble extracts, alcohol-soluble extracts, polysaccharides, and triterpenoids from 15 fruit bodies of Lingzhi were detected and analyzed based on Chinese Pharmacopoeia and the US Pharmacopoeia references. Moreover, the monosaccharide composition of polysaccharides was studied using PMP-HPLC, and the effect of polysaccharides on the proliferation rate of splenocytes was investigated in vitro. The identification results of these strains by the phylogenetic trees which were constructed based on ITS sequences and SNPs showed that most of the strains applied in the main producing areas of Lingzhi in China were accurate except for a few inaccurate strains. The moisture, ash, water and alcohol soluble extractive, polysaccharide and triterpenoid content of all samples were meet the requirements of the Chinese Pharmacopoeia, while the polysaccharide and triterpenoid content of less than half of the samples meet the requirements of the U.S. Pharmacopoeia. The polysaccharide extracted from these samples have different effects on the proliferation rate of spleen cells. To sum up, this is the first study that reported on the differences in Lingzhi strains from the main producing areas in China. The quality of some fruit bodies did not meet the pharmacopeia requirements, and wrong strains were used in some production areas; thus, strains should be given special attention before legal processing.
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PURPOSE: To determine the clinical manifestations and results of adult hemophagocytic lymphohistiocytosis (HLH) patients in our emergency department. METHODS: We retrospectively evaluated patients with HLH from 1 April 2018 to 31 December 2020. The clinical data of these patients (basic information, symptoms, vital signs, laboratory results, HLH diagnostic criteria, H Score, main treatments, outcomes) were collected. RESULTS: Thirty-three patients (23 males and 10 females; 40.55±18.78 years) with 34 clinical episodes (one male had two clinical episodes and died during the second episode) were enrolled. Twenty-five patients were placed in a "survivor" group, and nine patients were categorized into a "deceased" group. Fever, splenomegaly, hemoglobin <90 g/L and platelet count <100×109/L most commonly met the diagnostic standard for HLH. The H Score results in the survival group and deceased group was 212.4±37.18 and 252.1±40.95, respectively. Viral infection was the most common reason for HLH, followed by immune-system disease and cancer. Laboratory tests showed that deceased-group patients had multiple-organ dysfunction. Multivariate logistic regression showed that the lactate dehydrogenase (lactate dehydrogenase) level (P = 0.039; odds ratio, 0.999) was significantly related to death. CONCLUSION: In the emergency department, HLH should be considered for critically ill patients with fever, splenomegaly, low hemoglobin and low platelet count. The H Score might be useful to diagnose HLH quickly. In our study, 26.47% of HLH patients died in the emergency department, and patients with a significantly increased lactate dehydrogenase level had a markedly increased risk of death.
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Bioassay-guided fractionation led to the isolation of a series of triterpenoids (1-46) including 12 new ones (1-12) from the mushroom Inonotus obliquus. The structures of all the compounds were elucidated by spectroscopic analysis as well as by comparison with literature data. Triterpenoids 1-3, 6, 7, 16, 24, 25, 27, 38, 43, 44 and 46 showed strong α-glucosidase inhibition, with IC50 values from 11.5 to 81.8 µM. Their structure-activity relationships were discussed. Inonotusol F (24) showed the strongest inhibitory activity and it presented noncompetitive inhibition against α-glucosidase. Molecular docking and molecular dynamics stimulation further demonstrated that GLU302 and PHE298 were key amino acids for the inhibition of inonotusol F (24) towards α-glucosidase. This study indicates the vital role of triterpenoids in explaining hypoglycemic effect of Inonotus obliquus and provides important evidence for further development and utilization of this mushroom.
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Agaricales/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Triterpenos/farmacologia , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Cinética , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening and easily misdiagnosed thrombotic microangiopathy disease. Few studies have reported the use of therapeutic plasma exchange (TPE) for TTP in emergency departments in China. The present study was a retrospective analysis of patients with TTP who were treated with TPE in our emergency intensive care unit (EICU). METHODS: This study retrospectively analyzed patients with TTP who received TPE management from July 1, 2014 to February 1, 2020. The following clinical data of these patients were collected: laboratory results, first symptoms, ADAMTS13 levels, glucocorticoid levels, TPE times and outcomes. RESULTS: The study included 19 patients (9 male and 10 female) with 20 clinical episodes, and 1 female patient had two episodes. TPE was used in 17 patients, and TPE was performed once every 2-3 days in patients. The volume for each TPE treatment was 2000 ml. In total, 4 male patients died, and 15 patients survived. One female experienced a relapse. No significant differences in age, RBC, HGB, PLT, ALT, AST, BUN, Cr, LDH, or bilirubin were noted between the survival and death groups. The mortality rate of male patients was significantly higher than that of female patients(p = 0.0325, p < 0.05), and the mean age of deceased patients was 64.25 ± 4.78 years, which was older than the mean age of survivors (47.38 ± 4.30). However, no significant difference was noted (p = 0.0787). CONCLUSION: TPE had satisfactory results for TTP patients although it was not performed every day. Older male TTP patients exhibited a relatively increased risk of death.
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Serviço Hospitalar de Emergência , Troca Plasmática/métodos , Púrpura Trombocitopênica Trombótica/terapia , Proteína ADAMTS13/sangue , Adulto , Idoso , China , Feminino , Glucocorticoides/sangue , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/sangue , Estudos Retrospectivos , Adulto JovemAssuntos
Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia/terapia , Tigeciclina/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Hospitais , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
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The aim of the present study was to investigate the effect of ulinastatin (UTI) alone or combined with mild therapeutic hypothermia (MTH) on intestinal barrier dysfunction following cardiopulmonary resuscitation (CPR) in rats. A total of 25 adult male Sprague-Dawley rats were randomly organized into five groups: Sham; control; UTI; MTH; and the combined group. The latter four groups were induced with the asphyxiated cardiac arrest rat model and treated with different interventions. After 6 h of treatment, the intestinal tissues of the rats were examined by electron microscopy, and the levels of intestinal malondialdehyde (MDA) and superoxide dismutase (SOD) were determined. The results of the present study indicated that the target temperature had successfully been attained in MTH and the combined group, and the other three groups of rats all survived at a normal temperature. In the rats treated with UTI or MTH, the epithelial cells exhibited pathological changes in their tight junctions and epithelial cell surface microvilli compared with the sham group. In the rats treated with a combination of UTI and MTH, whilst the epithelial cells exhibited a few slight changes, including mitochondrial edema, they were largely similar to the normal epithelial cells. However, there were significant differences in the levels of MDA and SOD between the different treatment groups. UTI combined with MTH may serve a protective role by suppressing oxidative stress in the small intestinal mucosa following CPR in rats compared with either UTI or MTH treatment alone.