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1.
Vaccine ; 42(12): 3091-3098, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38594120

RESUMO

BACKGROUND: The study evaluated the protective effect of 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against all-cause hospitalized pneumonia in children in Beijing. METHODS: Based on the vaccination record and inpatient medical record database of Beijing, children born in 2017 in Beijing, matched by age, gender, and district of the children with the ratio of 1:4, were selected as the vaccinated and unvaccinated groups according whether if vaccinated with PCV13. The incidence rate and 95 % confidence interval (95 %CI), vaccine effectiveness (VE) and direct medical costs of all-cause hospitalized pneumonia were calculated and compared within the same period of 12 months, 18 months, 24 months and 30 months after the birth of the child. RESULTS: The decreased incidence rates of all-cause hospitalized pneumonia were observed at the four points in the PCV13 vaccinated group compared to the unvaccinated group, which were significant at the points of 12 months (0.42 % vs. 0.72 %, P = 0.001), 18 months (0.90 % vs. 1.26 %, P = 0.002) and 24 months (1.37 % vs. 1.65 %, P = 0.046). The VE of PCV13 against all-cause hospitalized pneumonia within 12 months was the highest as 41.9 % (95 % CI 19.6 %, 58.0 %), followed by 29.3 % (95 % CI 11.4 %, 43.5 %) within 18 months, 17.1 % (95 % CI 0.3 %, 31.1 %) within 24 months and it almost disappeared within 30 months. The VE of 4-dose vaccination within 18 months and 24 months were 39.9 % (95 % CI 20.3 %, 54.7 %) and 27.2 % (95 % CI 8.6 %, 42.0 %), respectively. The median hospitalization cost of the children in the vaccinated group was higher at the four points but without significance. CONCLUSIONS: PCV13 had a certain protective effect on all-cause hospitalized pneumonia, and the booster immunization strategy had the best protective effect with great public health significance to enter the immunization program.


Assuntos
Infecções Pneumocócicas , Pneumonia Pneumocócica , Criança , Humanos , Lactente , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae , Pequim/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas Pneumocócicas , Hospitalização , Vacinas Conjugadas
2.
BMC Cardiovasc Disord ; 24(1): 147, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448835

RESUMO

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.


Assuntos
Anestésicos , Delírio do Despertar , Hipnóticos e Sedativos , Humanos , Anestésicos/uso terapêutico , Bradicardia , Dexmedetomidina , Delírio do Despertar/prevenção & controle , Hipnóticos e Sedativos/uso terapêutico , Midazolam , Propofol , Solução Salina , Sevoflurano , Metanálise em Rede
3.
J Ethnopharmacol ; 326: 117992, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38428654

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.


Assuntos
Medicamentos de Ervas Chinesas , Melatonina , Distúrbios do Início e da Manutenção do Sono , Humanos , Camundongos , Animais , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Triptofano , Serotonina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Melatonina/farmacologia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico
4.
Biomed Pharmacother ; 174: 116456, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38552441

RESUMO

Acute lung injury (ALI) is a common and critical respiratory disorder caused by various factors, with viral infection being the leading contributor. Dehydroandrographolide (DAP), a constituent of the Chinese herbal plant Andrographis paniculata, exhibits a range of activities including anti-inflammatory, in vitro antiviral and immune-enhancing effects. This study evaluated the anti-inflammatory effects and pharmacokinetics (PK) profile of DAP in ALI mice induced by intratracheal instillation of Poly(I:C) (PIC). The results showed that oral administration of DAP (10-40 mg/kg) effectively suppressed the increase in lung wet-dry weight ratio, total cells, total protein content, accumulation of immune cells, inflammatory cytokines and neutrophil elastase levels in bronchoalveolar lavage fluid of PIC-treated mice. DAP concentrations, determined by an LC-MS/MS method, in plasma after receiving DAP (20 mg/kg) were unchanged compared to those in normal mice. However, DAP concentrations and relative PK parameters in the lungs were significantly altered in PIC-treated mice, exhibiting a relatively higher maximum concentration, larger AUC, and longer elimination half-life than those in the lungs of normal mice. These results demonstrated that DAP could improve lung edema and inflammation in ALI mice, and suggested that lung injury might influence the PK properties of DAP, leading to increased lung distribution and residence. Our study provides evidence that DAP displays significant anti-inflammatory activity against viral lung injury and is more likely to distribute to damaged lung tissue.

5.
Mil Med Res ; 11(1): 19, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38549161

RESUMO

Drug delivery systems (DDS) have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery. However, the access of nanoparticles/drugs to the central nervous system (CNS) remains a challenge mainly due to the obstruction from brain barriers. Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery. Herein, we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood-brain barrier. We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS, as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases. Finally, we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.


Assuntos
Doenças do Sistema Nervoso Central , Nanopartículas , Humanos , Sistemas de Liberação de Medicamentos , Encéfalo , Barreira Hematoencefálica , Doenças do Sistema Nervoso Central/tratamento farmacológico , Nanopartículas/uso terapêutico
6.
Front Immunol ; 15: 1338096, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495892

RESUMO

Type III interferon (IFN-λ), a new member of the IFN family, was initially considered to possess antiviral functions similar to those of type I interferon, both of which are induced via the JAK/STAT pathway. Nevertheless, recent findings demonstrated that IFN-λ exerts a nonredundant antiviral function at the mucosal surface, preferentially produced in epithelial cells in contrast to type I interferon, and its function cannot be replaced by type I interferon. This review summarizes recent studies showing that IFN-λ inhibits the spread of viruses from the cell surface to the body. Further studies have found that the role of IFN-λ is not only limited to the abovementioned functions, but it can also can exert direct and/or indirect effects on immune cells in virus-induced inflammation. This review focuses on the antiviral activity of IFN-λ in the mucosal epithelial cells and its action on immune cells and summarizes the pathways by which IFN-λ exerts its action and differentiates it from other interferons in terms of mechanism. Finally, we conclude that IFN-λ is a potent epidermal antiviral factor that enhances the respiratory mucosal immune response and has excellent therapeutic potential in combating respiratory viral infections.


Assuntos
Interferon Tipo I , Viroses , Humanos , Interferon lambda , Janus Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Interferon Tipo I/metabolismo , Epitélio/metabolismo , Antivirais/farmacologia , Antivirais/uso terapêutico
7.
Curr Med Sci ; 44(1): 121-133, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38393525

RESUMO

OBJECTIVE: Human adenovirus (HAdV) infection is common and can develop to serious conditions with high mortality, yet the mechanism of HAdV infection remains unclear. In the present study, the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection (URTI) were explored. METHODS: In total, 35 patients were enrolled in the study following an outbreak of HAdV-7 in the army, of whom 14 had pneumonia and 21 had URTI. Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics. RESULTS: Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules, including glycerophospholipids, fatty acyls, and sphingolipids. The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways, including sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients, but not between the acute and recovery stages for the URTI patients. Ceramide and lactosylceramide, involved in sphingolipid metabolism, were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities [area under curve (AUC) 0.742 and 0.716, respectively; combination AUC 0.801]. CONCLUSION: Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia, especially the sphingolipid metabolism involving ceramide and lactosylceramide, which might thus be a potential intervention target in the treatment of HAdV infection.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Antígenos CD , Pneumonia , Infecções Respiratórias , Humanos , Adenovírus Humanos/genética , Lactosilceramidas , Infecções Respiratórias/epidemiologia , Pneumonia/complicações , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/metabolismo
8.
Virol J ; 21(1): 11, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191404

RESUMO

BACKGROUND: The pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) remained unclear. We aimed to profile the metabolic alterations in urine of SFTS patients and provide new evidence for its pathogenesis. METHODS: A case-control study was conducted in the 154th hospital in China. Totally 88 cases and 22 controls aged ≥ 18 years were enrolled. The cases were selected from laboratory-confirmed SFTS patients. The controls were selected among SFTSV-negative population. Those with diabetes, cancer, hepatitis and other sexually transmitted diseases were excluded in both groups. Fatal cases and survival cases were 1:1 matched. Inter-group differential metabolites and pathways were obtained, and the inter-group discrimination ability was evaluated. RESULTS: Tryptophan metabolism and phenylalanine metabolism were the top one important metabolism pathway in differentiating the control and case groups, and the survival and fatal groups, respectively. The significant increase of differential metabolites in tryptophan metabolism, including 5-hydroxyindoleacetate (5-HIAA), L-kynurenine (KYN), 5-hydroxy-L-tryptophan (5-HTP), 3-hydroxyanthranilic acid (3-HAA), and the increase of phenylpyruvic acid and decrease of hippuric acid in phenylalanine metabolism indicated the potential metabolic alterations in SFTSV infection. The increase of 5-HIAA, KYN, 5-HTP, phenylpyruvic acid and hippuric acid were involved in the fatal progress of SFTS patients. CONCLUSIONS: Tryptophan metabolism and phenylalanine metabolism might be involved in the pathogenesis of SFTSV infection. These findings provided new evidence for the pathogenesis and treatment of SFTS.


Assuntos
Febre Grave com Síndrome de Trombocitopenia , Humanos , 5-Hidroxitriptofano , Estudos de Casos e Controles , Ácido Hidroxi-Indolacético , Triptofano , Fenilalanina
9.
Angew Chem Int Ed Engl ; 63(5): e202313030, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38072915

RESUMO

Carboxylation with carbon dioxide (CO2 ) represents one notable methodology to produce carboxylic acids. In contrast to carbon-heteroatom bonds, carbon-carbon bond cleavage for carboxylation with CO2 is far more challenging due to their inherent and less favorable orbital directionality for interacting with transition metals. Here we report a photocatalytic protocol for the deconstructive carboxylation of alkenes with CO2 to generate carboxylic acids in the absence of transition metals. It is emphasized that our protocol provides carboxylic acids with obviously unchanged carbon numbers when terminal alkenes were used. To show the power of this strategy, a variety of pharmaceutically relevant applications including the modular synthesis of propionate nonsteroidal anti-inflammatory drugs and the late-stage carboxylation of bioactive molecule derivatives are demonstrated.

10.
Molecules ; 28(23)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38067625

RESUMO

MOF (metal organic framework) materials have been used as functional materials in a number of fields due to their diverse spatial tunability, which produces rich porous structures with stable and continuous pores and a high specific surface area. A triboelectric nanogenerator can convert trace mechanical energy into electrical energy, and the application of MOF materials to triboelectric nanogenerators has been intensively studied. In this work, we report on two MOFs with similar spatial structures, and the modulation of the end microstructures was achieved using the difference in F content. The output performance of friction power generation increases with the increase in F content, and the obtained polyacidic ligand materials can be used to construct self-powered corrosion protection systems, which can effectively protect metallic materials from corrosion.

11.
Immun Inflamm Dis ; 11(12): e1126, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38156379

RESUMO

BACKGROUND: The global COVID-19 pandemic presented an immense obstacle to public health, with vaccination emerging as a crucial measure to curb transmission. This study aimed to evaluate the willingness, hesitancy, and coverage of SARS-CoV-2 vaccines among healthcare workers (HCWs) in Tanzania and reveal their concerns about SARS-CoV-2 vaccines and the reasons that might prevent them from getting vaccinated. METHODS: We conducted a cross-sectional study using an anonymous online survey from October to November 2022. The multivariate logistic regression model explored the factors associated with SARS-CoV-2 vaccine willingness, hesitancy, and coverage. RESULTS: The study included 560 HCWs, with the largest group being doctors (47.9%), followed by nurses (26.9%) and other HCWs (25.2%). A total of 70.5% of HCWs reported being vaccinated against SARS-CoV-2. The primary driver for SARS-CoV-2 vaccination was collective responsibility. A total of 81.4% of HCWs reported being willing to accept SARS-CoV-2 vaccines, while 62.5% of HCWs reported vaccine hesitancy. HCWs with higher educational qualifications were likelier to take the vaccine, while the respondents aged 18-30 years had the highest SARS-CoV-2 vaccination refusal (71.9%). We also investigated the role of HCWs as a source of information to promote COVID-19 vaccine uptake. 79.4% of HCWs provided information and advice on SARS-CoV-2 vaccines. CONCLUSION: To increase vaccine acceptance among HCWs and the general population, targeted messaging is needed to deliver transparent information on vaccine safety, efficacy, and development.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Hesitação Vacinal , Tanzânia/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Pandemias , SARS-CoV-2 , Pessoal de Saúde , Vacinação
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1469-1474, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37846702

RESUMO

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BßArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION: Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.


Assuntos
Afibrinogenemia , Fibrinogênio , Humanos , Criança , Feminino , Fibrinogênio/genética , Linhagem , Afibrinogenemia/genética , Mutação , Transfusão de Sangue
13.
J Org Chem ; 88(21): 14874-14886, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37862710

RESUMO

An efficient oxidant-free, photoredox-mediated cascade cyclization strategy for the synthesis of 1,3,4-oxadiazoles by using an organo acridinium photocatalyst and a cobaloxime catalyst has been developed. Various acylhydrazones have been transformed into the corresponding 1,3,4-oxadiazole products in up to 96% yield, and H2 is the only byproduct. Mechanistic experiments and density functional theory (DFT) calculation studies indicate carbon-centered radicals rather than oxygen-centered radicals as π-radicals produced by the oxidation of photoexcited Mes-Acr+* along with deprotonation, which is responsible for this transformation. The practical utility of this method is highlighted by the one-pot gram-scale synthesis starting directly from commercially available aldehydes and acylhydrazides.

14.
BMC Pulm Med ; 23(1): 383, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817172

RESUMO

BACKGROUD: The current diagnostic criteria for refractory Mycoplasma pneumoniae pneumonia (RMPP) among Mycoplasma pneumoniae Pneumonia (MPP) are insufficient for early identification, and potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP. METHODS: A total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA). RESULTS: Multivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08-1.33, P = 0.038), fever duration (HR 1.34, 95%CI 1.20-1.50, P < 0.001), lymphocyte count (HR 0.45, 95%CI 0.23-0.89, P = 0.021), serum D-dimer (D-d) level (HR 1.70, 95%CI 1.16-2.49, P = 0.006), and pulmonary imaging score (HR 5.16, 95%CI 2.38-11.21, P < 0.001). The area under the ROC curve was 90.7% for the development cohort and 96.36% for the validation cohort. The internal and external verification calibration curves were almost linear with slopes of 1, and the DCA curve revealed a net benefit with the final predictive nomogram. CONCLUSION: This study proposes a predictive nomogram only based on five variables. The nomogram can be used for early identification of RMPP among pediatric patients with MPP, thereby facilitating more timely and effective intervention.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Criança , Humanos , Estudos Retrospectivos , Criança Hospitalizada , Nomogramas , Proteína C-Reativa/análise , L-Lactato Desidrogenase , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/epidemiologia
15.
Bioanalysis ; 15(19): 1169-1178, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37676652

RESUMO

Background: Relatively large disulfide-linked polypeptides can serve as signaling molecules for a diverse array of biological processes and may be studied in animal models to investigate their function in vivo. The aim of this work was to develop an LC-MS/MS assay to measure a model peptide, INSL3, in rat plasma. Results: A dual enrichment strategy incorporating both protein precipitation and solid phase extraction was utilized to isolate INSL3 from rat plasma, followed by targeted LC-MS/MS detection. The method was able to measure full-length INSL3 (6.1 kDa) down to 0.2 ng/ml with acceptable accuracy and precision. Conclusion: The final assay was applied to support an exploratory pharmacokinetic study to evaluate steady-state concentrations of dosed INSL3 in rat plasma.

17.
Int J Antimicrob Agents ; 62(5): 106972, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37741585

RESUMO

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) is challenging due to multi-drug resistance of strains and biofilm formation, the latter of which is an important barrier to the penetration of antibiotics and host defences. As such, there is an urgent need to discover and develop novel agents to fight MRSA-associated infection. In this study, HL-J6, a novel indolylbenzoquinone compound, was shown to inhibit S. aureus strains, with a minimum inhibitory concentration against MRSA252 of 2 µg/mL. Moreover, HL-J6 exhibited potent antibiofilm activity in vitro and was able to kill bacteria in biofilm. In the mouse models of wound infection, HL-J6 treatment reduced the MRSA load significantly and inhibited biofilm formation on the wounds. The potent targets of its antibiofilm activity were explored by real-time reverse transcriptase polymerase chain rection, which indicated that HL-J6 downregulated the transcription levels of sarA, atlAE and icaADBC. Moreover, Western blot results showed that HL-J6 reduced the secretion level of α-toxin, a major virulence factor. These findings indicate that HL-J6 is a promising lead compound for the development of novel drugs against MRSA biofilm infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Camundongos , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Testes de Sensibilidade Microbiana
18.
EBioMedicine ; 96: 104807, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37738834

RESUMO

BACKGROUND: Optimal treatment strategy for severe fever with thrombocytopenia syndrome (SFTS) remained unknown. We aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) on SFTS. METHODS: A retrospective cohort study was conducted based on medical records of the laboratory-confirmed SFTS patients hospitalized during 2010-2020 in the 154th hospital, China. A 1:1 propensity score matching with age, sex, the interval from symptom onset to admission, presence of chronic viral hepatitis, diabetes and disease severity was performed between Non-IVIG group (supportive therapy) and IVIG group (IVIG plus supportive therapy). The matching variables were adjusted to compare the case fatality rates (CFRs), viral load and laboratory parameters between the two groups. Risk ratio (RR) and 95% confidence interval (CI) were reported. FINDINGS: Totally 2219 SFTS patients were recruited. CFRs were significantly higher in 1051 patients in IVIG group than 1168 patients in Non-IVIG group (19.0% vs. 4.6%, RR = 4.30, 95% CI 3.12-5.93). The difference remained significant after matching (17.2% vs. 5.1%, RR = 4.02, 95% CI 2.71-5.97). The CFR of IVIG group was significantly higher in all age groups, two IVIG therapy delay groups and two therapy duration groups compared to that of Non-IVIG group (all P < 0.05). IVIG therapy was related to higher viral loads and reduced counts of lymphocytes, T cells, CD4+ T cells and natural killer cells in the blood (all P < 0.05). INTERPRETATION: No obvious efficacy of IVIG in saving life or improving outcome of SFTS was observed. Caution is needed for clinical physicians to continue prescribing IVIG for SFTS patients. FUNDING: Natural Science Foundation of China.

19.
iScience ; 26(9): 107488, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37636039

RESUMO

Pneumonia complicated by preterm birth is related to adverse clinical sequelae from the neonatal period to childhood. Children with pneumonia during 2009-2021 were enrolled at the Children's Hospital of Chongqing Medical University. Altogether 20 respiratory pathogens were detected and compared. Among 8,206 children, 779 were in the preterm group with 246 of early-preterm and 533 of late preterm. The positive rates for all viral pathogens were comparable between the preterm group and the full-term group. For bacterial pathogens, higher positive rates for Escherichia coli and Klebsiella pneumoniae were observed in the preterm group. Severe pneumonia developed in 16.52% of all, which was higher in the preterm group than in the full-term group. A significantly higher rate of severe pneumonia was observed in the early-preterm group compared to the late-preterm group. Preterm birth has an impact on the detection of bacterial pathogens in children and is a risk factor for severe pneumonia.

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